Efeito do 17β-estradiol na performance locomotora de ratas submetidas à lesão medular por compressão

Detalhes bibliográficos
Autor(a) principal: Silva, Fernanda Kohn Bastos da
Data de Publicação: 2014
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da UFRRJ
Texto Completo: https://rima.ufrrj.br/jspui/handle/20.500.14407/14933
Resumo: Uma lesão traumática na medula espinal promove rápida morte celular no epicentro da lesão e desencadeia uma série de eventos vasculares, celulares e bioquímicos, denominados danos secundários, que culminam em morte de células que estavam intactas após o trauma inicial e, desta forma, amplifica a lesão e a disfunção tecidual. O 17β-estradiol (E2) é um hormônio esteroide endógeno produzido principalmente pelas gônadas e que tem demonstrado efeito neuroprotetor in vitro e in vivo, em diversas doenças e traumas no sistema nervoso central (SNC). Na lesão medular espinal o E2 tem evidenciado múltiplas ações neuroprotetoras por modular diversos danos secundários à lesão, tais como: inflamação, apoptose, estresse oxidativo e alterações vasculares. Nesse sentido, o objetivo desse estudo foi avaliar se, de forma aguda, o E2 promove recuperação locomotora em ratas ovariectomizadas submetidas à lesão medular por compressão. Neste estudo foram utilizadas ratas Wistar que foram submetidas a ovariectomia bilateral (OVX) e após uma semana foi induzida a lesão medular através da inflação do balão de um cateter Fogarty 2F de embolectomia, inflado com 15μl de solução salina no espaço epidural entre as vértebras T8 e T9 durante 5 minutos. Quinze minutos após a cirurgia de lesão medular foi administrado por via subcutânea uma dose única de 100 μg/Kg de E2 diluído em óleo (grupo OVX+E2) ou somente o veículo óleo (grupo OVX+óleo). Uma parte dos animais foi submetida a OVX e após uma semana foi realizada apenas a laminectomia vertebral (grupo OVX+sham). A performance locomotora dos animais foi avaliada através do teste BBB durante 14 dias e foi detectado uma significativa melhora na recuperação locomotora do grupo OVX+E2 comparado ao grupo OVX+óleo no 10º e 14º dia após a lesão medular. Para verificar se essa melhor capacidade locomotora dos animais tratados com E2 esta relacionada com a menor quantidade de lesão no tecido medular, foi realizada a análise histopatológica de cortes longitudinais de tecido medular desses animais. Na avaliação histopatológica da medula foi detectado que o grupo OVX+E2 apresentou lesões significativamente menores sob os aspectos de comprimento, largura e área da lesão comparado ao grupo OVX+óleo. Nesse sentido, os resultados sugerem que o E2 é capaz de promover recuperação locomotora após uma lesão moderada na medula espinal, sendo esse efeito associado ao menor tamanho de lesão no tecido, corroborando com a hipótese de que o E2 é um hormônio neuroprotetor.
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spelling Silva, Fernanda Kohn Bastos daMedeiros, Magda Alves de03659248738http://lattes.cnpq.br/6392136073564306Almeida, Norma Aparecida dos SantosResende, Victor Túlio Ribeiro de11013489764http://lattes.cnpq.br/07931074817479362023-12-22T03:08:30Z2023-12-22T03:08:30Z2014-08-29SILVA, Fernanda Kohn Bastos da. Efeito do 17β-estradiol na performance locomotora de ratas submetidas à lesão medular por compressão. 2014. 79 f. Dissertação (Mestrado Multicêntrico em Ciências Fisiológicas) - Instituto de Ciências Biológicas e da Saúde, Universidade Federal Rural do Rio de Janeiro, Seropédica - RJ, 2014.https://rima.ufrrj.br/jspui/handle/20.500.14407/14933Uma lesão traumática na medula espinal promove rápida morte celular no epicentro da lesão e desencadeia uma série de eventos vasculares, celulares e bioquímicos, denominados danos secundários, que culminam em morte de células que estavam intactas após o trauma inicial e, desta forma, amplifica a lesão e a disfunção tecidual. O 17β-estradiol (E2) é um hormônio esteroide endógeno produzido principalmente pelas gônadas e que tem demonstrado efeito neuroprotetor in vitro e in vivo, em diversas doenças e traumas no sistema nervoso central (SNC). Na lesão medular espinal o E2 tem evidenciado múltiplas ações neuroprotetoras por modular diversos danos secundários à lesão, tais como: inflamação, apoptose, estresse oxidativo e alterações vasculares. Nesse sentido, o objetivo desse estudo foi avaliar se, de forma aguda, o E2 promove recuperação locomotora em ratas ovariectomizadas submetidas à lesão medular por compressão. Neste estudo foram utilizadas ratas Wistar que foram submetidas a ovariectomia bilateral (OVX) e após uma semana foi induzida a lesão medular através da inflação do balão de um cateter Fogarty 2F de embolectomia, inflado com 15μl de solução salina no espaço epidural entre as vértebras T8 e T9 durante 5 minutos. Quinze minutos após a cirurgia de lesão medular foi administrado por via subcutânea uma dose única de 100 μg/Kg de E2 diluído em óleo (grupo OVX+E2) ou somente o veículo óleo (grupo OVX+óleo). Uma parte dos animais foi submetida a OVX e após uma semana foi realizada apenas a laminectomia vertebral (grupo OVX+sham). A performance locomotora dos animais foi avaliada através do teste BBB durante 14 dias e foi detectado uma significativa melhora na recuperação locomotora do grupo OVX+E2 comparado ao grupo OVX+óleo no 10º e 14º dia após a lesão medular. Para verificar se essa melhor capacidade locomotora dos animais tratados com E2 esta relacionada com a menor quantidade de lesão no tecido medular, foi realizada a análise histopatológica de cortes longitudinais de tecido medular desses animais. Na avaliação histopatológica da medula foi detectado que o grupo OVX+E2 apresentou lesões significativamente menores sob os aspectos de comprimento, largura e área da lesão comparado ao grupo OVX+óleo. Nesse sentido, os resultados sugerem que o E2 é capaz de promover recuperação locomotora após uma lesão moderada na medula espinal, sendo esse efeito associado ao menor tamanho de lesão no tecido, corroborando com a hipótese de que o E2 é um hormônio neuroprotetor.Conselho Nacional de Desenvolvimento Científico e Tecnológico - CNPQTraumatic spinal cord injury promotes rapid cell death at the lesion epicenter and triggers a series of vascular, cellular and biochemical events, known as secondary damage, which culminate in more cell death, amplifying the injury and tissue dysfunction. The 17β-estradiol (E2) is an endogenous steroid hormone produced primarily by the gonads that has demonstrated neuroprotective effect in vitro and in vivo in several diseases and trauma to the central nervous system (CNS). E2 has shown multiple neuroprotective effects after spinal cord injury by modulating many secondary damage, such as: inflammation, apoptosis, oxidative stress and vascular changes. Accordingly, the aim of this study was to assess whether, acutely, the E2 promotes locomotor recovery in ovariectomized rats subjected to spinal cord compression injury. In the present study, female Wistar rats were subjected to bilateral ovariectomy (OVX) and after one week spinal cord injury was induced by inflation of a embolectomy catheter balloon (Fogarty 2F) with 15μl of saline into the epidural space between T8 and T9 vertebrae for 5 minutes. Fifteen minutes after spinal cord injury surgery a single dose of 100 μg/Kg of E2 diluted in oil (OVX+E2 group) or oil vehicle alone (OVX+oil group) was administered subcutaneously. Some of the animals were subjected to OVX and after a week was performed only spinal laminectomy (OVX+sham group). The locomotor performance of the animals was assessed using the BBB test for 14 days and it was detected significant improvement in locomotor recovery in OVX+E2 group compared to OVX+oil group at 10 and 14 days after spinal cord injury. To verify that better locomotor ability of animals treated with E2 is related with the least amount of damage to the spinal cord tissue, the cross-sections of the histopathological analysis of spinal cord tissue of these animals was performed. The histopathological evaluation detected that the OVX+E2 group showed significantly less tissue damage under the aspects of length, width and area of the lesion compared to OVX+oil group. Accordingly, the results suggest that E2 is able to promote locomotor recovery after a mild compression injury to the spinal cord, and this effect is associated with a reduction of the damage to the spinal cord tissue, supporting the hypothesis that E2 is a neuroprotective hormoneapplication/pdfporUniversidade Federal Rural do Rio de JaneiroPrograma Multicêntrico de Pós-Graduação em Ciências FisiológicasUFRRJBrasilInstituto de Ciências Biológicas e da SaúdeLesão medular espinal17β-estradiolneuroproteçãoSpinal cord injury17β-estradiolneuroprotectionFisiologiaEfeito do 17β-estradiol na performance locomotora de ratas submetidas à lesão medular por compressãoEffect of 17β-estradiol on locomotor performance in rats subjected to spinal cord compression injuryinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisAKASSOGLOU, K.; BAUER, J.; KASSIOTIS, G.; PASPARAKIS, M.; LASSMANN, H.; KOLLIAS, G.; PROBERT, L. Oligodendrocyte apoptosis and primary demyelination induced by local TNF/p55TNF receptor signaling in the central nervous system of transgenic mice: models for multiple sclerosis with primary oligodendrogliopathy. The American Journal of Pathology, v. 153, n. 3, p. 801-813, 1998. ALMEIDA, M.; MARTIN‐MILLAN, M.; AMBROGINI, E.; BRADSHER, R.; HAN, L.; CHEN, X. D.; ROBERSON, P. K.; WEINSTEIN, R. S.; O'BRIEN, C. A.; JILKA, R. L.; MANOLAGAS, S. C. Estrogens attenuate oxidative stress and the differentiation and apoptosis of osteoblasts by DNA‐binding‐independent actions of the ERα. Journal of Bone and Mineral Research, v. 25, n. 4, p. 769-781, 2010. AMANTEA, D.; RUSSO, R.; BAGETTA, G.; CORASANITI, M. T. From clinical evidence to molecular mechanisms underlying neuroprotection afforded by estrogens. Pharmacological Research, v. 52, n. 2, p. 119-132, 2005. ANDERSEN M.L.; TUFIK S. Animal models as ethical tools in biomedical research. CLR Balieiro Editores, São Paulo, 1ª ed., 2010. ARNOLD, S.; BEYER, C. Neuroprotection by estrogen in the brain: the mitochondrial compartment as presumed therapeutic target. Journal of Neurochemistry, v. 110, n. 1, p. 1-11, 2009. BACHIS, A.; COLANGELO, A. M.; VICINI, S.; DOE, P. P.; DE BERNARDI, M. A.; BROOKER, G.; MOCCHETTI, I. Interleukin-10 prevents glutamate-mediated cerebellar granule cell death by blocking caspase-3-like activity. The Journal of Neuroscience, v. 21, n. 9, p. 3104-3112, 2001. BAO F.; LIU D. Peroxynitrite generated in the rat spinal cord induces apoptotic cell death and activates caspase-3. Neuroscience, v. 116, n. 1, p. 59–70, 2003. BARTHOLDI, D.; SCHWAB, M. E. Expression of pro‐inflammatory cytokine and chemokine mRNA upon experimental spinal cord injury in mouse: An in situ hybridization study. European Journal of Neuroscience, v. 9, n. 7, p. 1422-1438, 1997. BASSO, M. D.; BEATTIE, M. S.; BRESNAHAN, J. C. A sensitive and reliable locomotor rating scale for open field testing in rats. Journal of Neurotrauma, v. 12, n. 1, p. 1-21, 1995. BASSO, D. M.; BEATTIE, M. S.; BRESNAHAN, J. C. Graded histological and locomotor outcomes after spinal cord contusion using the NYU weight-drop deviceversus transection. Exp Neurol., v. 139, n. 2, p. 244-256, 1996. BASSO, D. M. Behavioral testing after spinal cord injury: congruities, complexities, and controversies. Journal of Neurotrauma, v. 21, n. 4, p. 395-404, 2004. BASSO, D. M.; FISHER, L. C.; ANDERSON, A. J.; JAKEMAN, L. B.; MCTIGUE, D. M.; POPOVICH, P. G. Basso Mouse Scale for locomotion detects differences in recovery after spinal cord injury in five common mouse strains. Journal of Neurotrauma, v. 23, n. 5, p. 635-659, 2006. 64 BAYIR, H.; MARION, D. W.; PUCCIO, A. M.; WISNIEWSKI, S. R.; JANESKO, K. L.; CLARK, R. S.; KOCHANEK, P. M. Marked gender effect on lipid peroxidation after severe traumatic brain injury in adult patients. Journal of Neurotrauma, v. 21, n. 1, p. 1-8, 2004. BEATTIE, M. S.; FAROOQUI, A. A.; BRESNAHAN, J. C. Review of current evidence for apoptosis after spinal cord injury. Journal of Neurotrauma, v. 17, n. 10, p. 915-925, 2000. BECK K. D.; NGUYEN H. X.; GALVAN M. D.; SALAZAR D. L.; WOODRUFF T. M.; ANDERSON A. J. Quantitative analysis of cellular inflammation after traumatic spinal cord injury: evidence for a multiphasic inflammatory response in the acute to chronic environment. Brain, v.;133, n. 2, p. 433–47, 2010 BEHL, C.; WIDMANN, M.; TRAPP, T.; HOLSBOER, F. 17-[beta] Estradiol protects neurons from oxidative stress-induced cell death in vitro. Biochemical and Biophysical Research Communications, v. 216, n. 2, p. 473-482, 1995 BEHL, C.; SKUTELLA, T.; FRANK, L. H.; POST, A.; WIDMANN, M.; NEWTON, C. J.; HOLSBOER, F. Neuroprotection against oxidative stress by estrogens: structure-activity relationship. Molecular Pharmacology, v. 51, n. 4, p. 535-541, 1997. BEHL, C. Oestrogen as a neuroprotective hormone. Nature Reviews Neuroscience, v. 3, n. 6, p. 433-442, 2002a. BEHL, C. Estrogen can protect neurons: modes of action. The Journal of Steroid Biochemistry and Molecular Biology, v. 83, n. 1, p. 195-197, 2002b. BEHRMANN, D. L.; BRESNAHAN, J. C.; BEATTIE, M. S.; SHAH, B. R. Spinal cord injury produced by consistent mechanical displacement of the cord in rats: behavioral and histologic analysis. Journal of Neurotrauma, v. 9, n. 3, p. 197-217, 1992. BETHEA, J. R.; NAGASHIMA, H.; ACOSTA, M. C.; BRICENO, C.; GOMEZ, F.; MARCILLO, A. E.; DIETRICH, W. D. Systemically administered interleukin-10 reduces tumor necrosis factor-alpha production and significantly improves functional recovery following traumatic spinal cord injury in rats. Journal of Neurotrauma, v. 16, n. 10, p. 851-863, 1999. BETHEA J.R. Spinal cord injury-induced inflammation: a dual-edged sword. Prog Brain Res, v. 128, p. 33–42, 2000. BETHEA, J. R.; DIETRICH, D. W. Targeting the host inflammatory response in traumatic spinal cord injury. Current Opinion in Neurology, v. 15, n. 3, p. 355-360, 2002. BIEWENGA, E.; CABELL, L.; AUDESIRK, T. Estradiol and raloxifene protect cultured SN4741 neurons against oxidative stress. Neuroscience Letters, v. 373, n. 3, p. 179-183, 2005. BISHOP, J.; SIMPKINS, J. W. Estradiol Treatment Increases Viability of Glioma and Neuroblastoma Cells in vitro. Molecular and Cellular Neuroscience, v. 5, n. 4, p. 303-308, 1994. BLIGHT, A. R. Cellular morphology of chronic spinal cord injury in the cat: analysis of myelinated axons by line-sampling. Neuroscience, v. 10, n. 2, p. 521-543, 1983. 65 BLIGHT, A. R.; TOOMBS, J. P.; BAUER, M. S.; WIDMER, W. R. The effects of 4-aminopyridine on neurological deficits in chronic cases of traumatic spinal cord injury in dogs: a phase I clinical trial. Journal of Neurotrauma, v. 8, n. 2, p. 103-119, 1991. BORGENS, R. B.; SHI, R. Immediate recovery from spinal cord injury through molecular repair of nerve membranes with polyethylene glycol. The FASEB Journal, v. 14, n. 1, p. 27-35, 2000. BOTELHO, R. V., DANIEL, J. W., BOULOSA, J. L. R., COLLI, B. O., FARIAS, R. D. L., MORAES, O. J. S., PIMENTA JR., W. E.; RIBEIRO, C. H.; RIBEIRO, F. R. B.; TARICCO, M. A.; CARVALHO, M. V.; BERNARDO, W. M. Effectiveness of methylprednisolone in the acute phase of spinal cord injuries: a systematic review of randomized controlled trials. Revista da Associação Médica Brasileira, v. 55, n. 6, p. 729-737, 2009. BRACKEN, M. B.; COLLINS, W. F.; FREEMAN, D. F.; SHEPARD, M. J.; WAGNER, F. W. SILTEN, R. M.; HELLENBRAND, G. K.; RANSOHOFF, J.; HUNT, W. E.; PEROT JR, P. L.; GROSSMAN, R. G.; GREEN, B. A.; EISENBERG, H. M.; RIFKINSON, N.; GOODMAN, J. H.; MEAGHER, J. N.; FISCHER, B.; CLIFTON, G. L.; FLAMM, E. S.; STEPHEN E.; RAWE, S. E. Efficacy of methylprednisolone in acute spinal cord injury. Jama, v. 251, n. 1, p. 45-52, 1984. BRACKEN, M. B.; SHEPARD, M. J.; COLLINS, W. F.; HOLFORD, T. R.; YOUNG, W.; BASKIN, D. S.; EISENBERG, H. M.; FLAMM, E.; LEO-SUMMERS, L.; MAROON, J.; MARSHALL, L. F.; PEROT, JR., P. L.; PIEPMEIER, J.; SONNTAG, V. K. H.; WAGNER, F. C.; WILBERGER, J. E.; WINN, H. R. A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury: results of the Second National Acute Spinal Cord Injury Study. New England Journal of Medicine, v. 322, n. 20, p. 1405-1411, 1990. BRACKEN, M. B.; SHEPARD, M. J.; HOLFORD, T. R.; LEO-SUMMERS, L.; ALDRICH, E. F.; FAZL, M.; FEHLINGS, M.; HERR, D. L.; HITCHON, P. W.; MARSHALL, L. F.; NOCKELS, R. P.; PASCALE, V.; PEROT JR, P. L.; PIEPMEIER, J.; SONNTAG, V. K. H.; WAGNER, F.; WILBERGER, J. E.; WINN, H. R.; YOUNG, W. Administration of methylprednisolone for 24 or 48 hours or tirilazad mesylate for 48 hours in the treatment of acute spinal cord injury: results of the Third National Acute Spinal Cord Injury Randomized Controlled Trial. Jama, v. 277, n. 20, p. 1597-1604, 1997. BRANN, D. W.; DHANDAPANI, K.; WAKADE, C.; MAHESH, V. B.; KHAN, M. M. Neurotrophic and neuroprotective actions of estrogen: basic mechanisms and clinical implications. Steroids, v. 72, n. 5, p. 381-405, 2007. BREWER, K. L.; BETHEA, J. R.; YEZIERSKI, R. P. Neuroprotective effects of interleukin-10 following excitotoxic spinal cord injury. Experimental Neurology, v. 159, n. 2, p. 484-493, 1999. BUNGE, R. P.; PUCKETT, W. R.; BECERRA, J. L.; MARCILLO, A.; QUENCER, R. M. Observations on the pathology of human spinal cord injury. A review and classification of 22 new cases with details from a case of chronic cord compression with extensive focal demyelination. Advances in Neurology, v. 59, p. 75, 1993. BYDON, M., LIN, J., MACKI, M., GOKASLAN, Z. L., & BYDON, A. The current role of steroids in acute spinal cord injury. World Neurosurgery, 2013. 66 CAMPBELL, S. J.; JIANG, Y.; DAVIS, A. E.; FARRANDS, R.; HOLBROOK, J.; LEPPERT, D.; ANTHONY, D. C. Immunomodulatory effects of etanercept in a model of brain injury act through attenuation of the acute‐phase response. Journal of Neurochemistry, v. 103, n. 6, p. 2245-2255, 2007. CARBONE, D. L.; HANDA, R. J. Sex and stress hormone influences on the expression and activity of brain-derived neurotrophic factor. Neuroscience, v. 239, p. 295-303, 2013. CARDONA‐GÓMEZ, G. P.; CHOWEN, J. A.; GARCIA‐SEGURA, L. M. Estradiol and progesterone regulate the expression of insulin‐like growth factor‐I receptor and insulin‐like growth factor binding protein‐2 in the hypothalamus of adult female rats. Journal of Neurobiology, v. 43, n. 3, p. 269-281, 2000. CARLSON, D.; GORDEN, C. Current developments in spinal cord injury research. The Spine Journal, v. 2, n. 2, p. 116-128, 2002. CASHA, S. W. R. Y.; YU, W. R.; FEHLINGS, M. G. Oligodendroglial apoptosis occurs along degenerating axons and is associated with FAS and p75 expression following spinal cord injury in the rat. Neuroscience, v. 103, n. 1, p. 203-218, 2001. CHAOVIPOCH, P.; JELKS, K. A. B.; GERHOLD, L. M.; WEST, E. J.; CHONGTHAMMAKUN, S.; FLOYD, C. L. 17 β-Estradiol Is Protective in Spinal Cord Injury in Post-and Pre-Menopausal Rats. Journal of Neurotrauma, v. 23, n. 6, p. 830-852, 2006. CHI, X.; KALE, J.; LEBER, B.; ANDREWS, D. W. Regulating cell death at, on, and in membranes. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, v. 1843, p. 2100-2113, 2014. CHOI, D. W. Calcium-mediated neurotoxicity: relationship to specific channel types and role in ischemic damage. Trends in Neurosciences, v. 11, n. 10, p. 465-469, 1988. CITRON, B. A.; ARNOLD, P. M.; SEBASTIAN, C.; QIN, F.; MALLADI, S.; AMEENUDDIN, S.; LANDIS, M. E.; FESTOFF, B. W. Rapid upregulation of caspase-3 in rat spinal cord after injury: mRNA, protein, and cellular localization correlates with apoptotic cell death. Experimental Neurology, v. 166, n. 2, p. 213-226, 2000. CREGG, J. M.; DEPAUL, M. A.; FILOUS, A. R.; LANG, B. T.; TRAN, A.; SILVER, J. Functional regeneration beyond the glial scar. Experimental Neurology, v. 253, p. 197-207, 2014. CROWE, M. J.; BRESNAHAN, J. C.; SHUMAN, S. L.; MASTERS, J. N.; CROWE, M. S. Apoptosis and delayed degeneration after spinal cord injury in rats and monkeys. Nature Medicine, v. 3, n. 1, p. 73-76, 1997. CUZZOCREA, S.; GENOVESE, T.; MAZZON, E.; ESPOSITO, E.; DI PAOLA, R.; MUIA, C.; CRISAFULLI, C.; PELI, A.; BRAMANTI, P.; CHAUDRY, I. H. Effect of 17β-estradiol on signal transduction pathways and secondary damage in experimental spinal cord trauma. Shock, v. 29, n. 3, p. 362-371, 2008. DAS, A.; SMITH, J. A.; GIBSON, C.; VARMA, A. K.; RAY, S. K.; BANIK, N. L. Estrogen receptor agonists and estrogen attenuate TNF-α-induced apoptosis in VSC4.1 motoneurons. J Endocrinol., v. 208, n. 2, p. 171-182, 2011. 67 DESJARDINS, G.C.; BEAUDET, A.; MEANEY, M.J.; BRAWER, J.R. Estrogen-induced hypothalamic beta-endorphin neuron loss: a possible model of hypothalamic aging. Exp. Gerontol., v. 30, n. 3-4, p. 253-267, 1995. DIMAYUGA, F. O.; REED, J. L.; CARNERO, G. A.; WANG, C.; DIMAYUGA, E. R.; DIMAYUGA, V. M.; PERGER, A.; WILSON, M. E.; KELLER, J. N.; BRUCE-KELLER, A. J. Estrogen and brain inflammation: effects on microglial expression of MHC, costimulatory molecules and cytokines. Journal of Neuroimmunology, v. 161, n. 1, p. 123-136, 2005. DODEL, R. C.; DU, Y.; BALES, K. R.; GAO, F.; PAUL, S. M. Sodium salicylate and 17beta-estradiol attenuate nuclear transcription factor NF-kappaB translocation in cultured rat astroglial cultures following exposure to amyloid A beta(1±40) and lipopolysaccharides. J. Neurochem., v. 73, n. 4, p. 1453-1460, 1999. DOMENICONI, M.; CAO, Z.; SPENCER, T.; SIVASANKARAN, R.; WANG, K. C.; NIKULINA, E.; FILBIN, M. T. Myelin-associated glycoprotein interacts with the Nogo66 receptor to inhibit neurite outgrowth. Neuron, v. 35, n. 2, p. 283-290, 2002. DONCARLOS, L. L.; AZCOITIA, I.; GARCIA-SEGURA, L. M. Neuroprotective actions of selective estrogen receptor modulators. Psychoneuroendocrinology, v. 34, p. S113-S122, 2009. DONG, L.; WANG, W.; WANG, F.; STONER, M.; REED, J. C.; HARIGAI, M.; SAMUDIO, I.; KLADDE, M. P.; VYHLIDAL, C.; SAFE S. Mechanisms of transcriptional activation of bcl-2 gene expression by 17beta-estradiol in breast cancer cells. J Biol Chem., v. 274, n. 45, p. 32099-32107, 1999. DONNELLY, D. J.; POPOVICH, P. G. Inflammation and its role in neuroprotection, axonal regeneration and functional recovery after spinal cord injury. Experimental Neurology, v. 209, n. 2, p. 378-388, 2008. DUBAL, D. B.; SHUGHRUE, P. J.; WILSON, M. E.; MERCHENTHALER, I.; WISE, P. M. Estradiol modulates bcl-2 in cerebral ischemia: a potential role for estrogen receptors. The Journal of Neuroscience, v. 19, n. 15, p. 6385-6393, 1999. DUBREUIL, C. I.; WINTON, M. J.; MCKERRACHER, L. Rho activation patterns after spinal cord injury and the role of activated Rho in apoptosis in the central nervous system. The Journal of Cell Biology, v. 162, n. 2, p. 233-243, 2003. ELDADAH, B. A.; FADEN, A. I. Caspase pathways, neuronal apoptosis, and CNS injury. Journal of Neurotrauma, v. 17, n. 10, p. 811-829, 2000. ELKABES, S., NICOT, A.B.. Sex steroids and neuroprotection in spinal cord injury: A review of preclinical investigations, Exp. Neurol., 2014. Disponível em <http://dx.doi.org/10.1016/j.expneurol.2014.01.008>. Retirado 27 de jun 2014. EMERY, E.; ALDANA, P.; BUNGE, M. B.; PUCKETT, W.; SRINIVASAN, A.; KEANE, R. W.; LEVI, A. D. Apoptosis after traumatic human spinal cord injury. Journal of Neurosurgery, v. 89, n. 6, p. 911-920, 1998. FAROOQUE, M.; SUO, Z.; ARNOLD, P. M.; WULSER, M. J.; CHOU, C. T.; VANCURA, R. W.; S FOWLER, S.; FESTOFF, B. W. Gender-related differences in recovery of locomotor function after spinal cord injury in mice. Spinal Cord, v. 44, n. 3, p. 182-187, 2006. 68 FAWCETT, J. W.; ASHER, R. A. The glial scar and central nervous system repair. Brain Research Bulletin, v. 49, n. 6, p. 377-391, 1999. FEHLINGS, M. G.; NGUYEN, D. H. Immunoglobulin G: a potential treatment to attenuate neuroinflammation following spinal cord injury. Journal of Clinical Immunology, v. 30, n. 1, p. 109-112, 2010. FLEMING, J. C.; NORENBERG, M. D.; RAMSAY, D. A.; DEKABAN, G. A.; MARCILLO, A. E.; SAENZ, A. D.; WEAVER, L. C. The cellular inflammatory response in human spinal cords after injury. Brain, v. 129, n. 12, p. 3249-3269, 2006. FORYST-LUDWIG, A.; KINTSCHER, U. Metabolic impact of estrogen signalling through ERalpha and ERbeta. The Journal of Steroid Biochemistry and Molecular Biology, v. 122, n. 1, p. 74-81, 2010. GARCIA-SEGURA, L. M.; CARDONA-GOMEZ, P.; NAFTOLIN, F.; CHOWEN, J. A. Estradiol upregulates Bcl-2 expression in adult brain neurons. Neuroreport, v. 9, n. 4, p. 593-597, 1998. GARCIA-SEGURA, L. M.; WOZNIAK, A.; AZCOITIA, I.; RODRIGUEZ, J. R.; HUTCHISON, R. E.; HUTCHISON, J. B. Aromatase expression by astrocytes after brain injury: implications for local estrogen formation in brain repair. Neuroscience, v. 89, n. 2, p. 567-578, 1999. GARCIA-SEGURA, L. M.; AZCOITIA, I.; DONCARLOS, L. L. Neuroprotection by estradiol. Progress in Neurobiology, v. 63, n. 1, p. 29-60, 2001. GIBBS, R. B. Treatment with estrogen and progesterone affects relative levels of brain-derived neurotrophic factor mRNA and protein in different regions of the adult rat brain. Brain Research, v. 844, n. 1, p. 20-27, 1999. GIRAUD, S. N.; CARON, C. M.; PHAM-DINH, D.; KITABGI, P.; NICOT, A. B. Estradiol inhibits ongoing autoimmune neuroinflammation and NFkappaB-dependent CCL2 expression inreactive astrocytes. Proc Natl Acad Sci U S A., v. 107, n. 18, p. 8416-8421, 2010. GOLDBERGER, M. E.; BREGMAN, B. S.; VIERCK JR, C. J.; BROWN, M. Criteria for Assessing Recovery of Function After Spinal Cord Injury: Behavioral Methods. Journal of Neurotrauma, v. 8, n. 1, p. 3-9, 1991. GRANT, G. Rat Nervous System. Elsevier, 2004. GREEN, P. S.; SIMPKINS, J. W. Neuroprotective effects of estrogens: potential mechanisms of action. International Journal of Developmental Neuroscience, v. 18, n. 4, p. 347-358, 2000. GRUNER, JOHN A. A monitored contusion model of spinal cord injury in the rat. Journal of Neurotrauma, v. 9, n. 2, p. 123-128, 1992. GRUOL, D. L.; NELSON, T. E. Physiological and pathological roles of interleukin-6 in the central nervous system. Molecular Neurobiology, v. 15, n. 3, p. 307-339, 1997. GUERRERO, A. R.; UCHIDA, K.; NAKAJIMA, H.; WATANABE, S.; NAKAMURA, M.; JOHNSON, W. E.; BABA, H. Blockade of interleukin-6 signaling inhibits the classic 69 pathway and promotes an alternative pathway of macrophage activation after spinal cord injury in mice. J Neuroinflammation, v. 9, n. 1, p. 40, 2012. GUPTARAK, J.; WIKTOROWICZ, J. E.; SADYGOV, R. G.; ZIVADINOVIC, D.; PAULUCCI-HOLTHAUZEN, A. A.; VERGARA, L.; NESIC, O. The cancer drug tamoxifen: a potential therapeutic treatment for spinal cord injury. J Neurotrauma., v. 31, n. 3, p. 268-283, 2014. HAGE, F. G.; OPARIL, S. Ovarian hormones and vascular disease. Current Opinion in Cardiology, v. 28, n. 4, p. 411-416, 2013. HAGG, T.; OUDEGA, M. Degenerative and spontaneous regenerative processes after spinal cord injury. Journal of Neurotrauma, v. 23, n. 3-4, p. 263-280, 2006. HAPPEL, R. D.; Smith, K. P.; BANIK, N. L.; Powers, J.M.; Hogan, E. L.; Balentine, D.J. Ca2+ accumulation in experimental spinal cord trauma. Brain Research, v. 211, n. 2, p. 476-479, 1981. HAUSMANN, O. N. Post-traumatic inflammation following spinal cord injury. Spinal Cord, v. 41, n. 7, p. 369-378, 2003. HAYES, K. C.; KAKULAS, B. A. Neuropathology of human spinal cord injury sustained in sports-related activities. J Neurotrauma., v. 14, n. 4, 235-248, 1997. HISAHARA, S.; SHOJI, S. I.; OKANO, H.; MIURA, M. ICE/CED‐3 Family Executes Oligodendrocyte Apoptosis by Tumor Necrosis Factor. Journal of Neurochemistry, v. 69, n. 1, p. 10-20, 1997. HU, R.; SUN, H.; ZHANG, Q.; CHEN, J.; WU, N.; MENG, H.; CUI, G.; HU, S.; LI, F.; LIN, J.; WAN, Q.; FENG, H. G-protein coupled estrogen receptor 1 mediated estrogenic neuroprotection against spinal cord injury*. Critical Care Medicine, v. 40, n. 12, p. 3230-3237, 2012. HULSEBOSCH, C. E. Recent advances in pathophysiology and treatment of spinal cord injury. Advances in Physiology Education, v. 26, n. 4, p. 238-255, 2002. IMAIZUMI, T.; KOCSIS, J. D.; WAXMAN, S. G. Anoxie Injury in the Rat Spinal Cord: Pharmacological Evidence for Multiple Steps in Ca2+-Dependent Injury of the Dorsal Columns. Journal of Neurotrauma, v. 14, n. 5, p. 299-311, 1997. ISMAILOĞLU, O.; ORAL, B.; GÖRGÜLÜ, A.; SÜTÇÜ, R.; DEMIR, N. Neuroprotective effects of tamoxifen on experimental spinal cord injury in rats. J Clin Neurosci., v 17, n. 10, p. 1306-1310, 2010. ISMAILOĞLU, Ö.; ORAL, B.; SÜTCÜ, R.; KARA, Y.; TOMRUK, O.; DEMIR, N. Neuroprotective effects of raloxifene on experimental spinal cord injury in rats. Am J Med Sci., v. 345, n. 1, p. 39-44, 2013. KACHADROKA, S.; HALL, A. M.; NIEDZIELKO, T. L.; CHONGTHAMMAKUN, S.; FLOYD, C. L. Effect of Endogenous Androgens on 17 β-Estradiol-Mediated Protection after Spinal Cord Injury in Male Rats. Journal of Neurotrauma, v. 27, n. 3, p. 611-626, 2010. KANDEL E.R.; SCHWARTZ J.M.; JESSELL T.M. Principles of Neuronal Science. The McGraw-Hill Companies, EUA, 4ed., 2000. 70 KARKI, P.; SMITH, K.; JOHNSON, J. J.; LEE, E. Astrocyte-derived growth factors and estrogen neuroprotection: role of transforming growth factor-α in estrogen-induced upregulation of glutamate transporters in astrocytes. Mol Cell Endocrinol., v. 389, n. 1-2, p. 58-64, 2014. KLOOS A.D.; FISHER L.C.; DETLOFF M.R.; HASSENZAHL D.L.; BASSO D.M. Stepwise motor and all-or-none sensory recovery is associated with nonlinear sparing after incremental spinal cord injury in rats. Exp Neurol, v. 191, n.2, p. 251–265, 2005. KNOBLACH, S. M.; HUANG, X.; VANGELDEREN, J.; CALVA‐CERQUEIRA, D.; FADEN, A. I. Selective caspase activation may contribute to neurological dysfunction after experimental spinal cord trauma. Journal of Neuroscience Research, v. 80, n. 3, p. 369-380, 2005. KRAFT, A. D.; HARRY, G. J. Features of microglia and neuroinflammation relevant to environmental exposure and neurotoxicity. International Journal of Environmental Research and Public Health, v. 8, n. 7, p. 2980-3018, 2011. KWON, B. K.; BORISOFF, J. F.; TETZLAFF, W. Molecular targets for therapeutic intervention after spinal cord injury. Molecular Interventions, v. 2, n. 4, p. 244, 2002a. KWON, B. K.; OXLAND, T. R.; TETZLAFF, W. Animal models used in spinal cord regeneration research. Spine, v. 27, n. 14, p. 1504-1510, 2002b. KWON, B. K.; TETZLAFF, W.; GRAUER, J. N.; BEINER, J.; VACCARO, A. R. Pathophysiology and pharmacologic treatment of acute spinal cord injury. The Spine Journal, v. 4, n. 4, p. 451-464, 2004. KWON, B. K.; OKON, E.; HILLYER, J.; MANN, C.; BAPTISTE, D.; WEAVER, L. C.; FEHLINGS, M. G.; TETZLAFF, W. A systematic review of non-invasive pharmacologic neuroprotective treatments for acute spinal cord injury. Journal of Neurotrauma, v. 28, n. 8, p. 1545-1588, 2011. KWON, B. K.; GHAG, A.; REICHL, L.; DVORAK, M. F.; ILLES, J.; TETZLAFF, W. Opinions on the preclinical evaluation of novel therapies for spinal cord injury: a comparison between researchers and spinal cord-injured individuals. J Neurotrauma., v. 29, n. 14, p. 2367-2374, 2012. LANKHORST, A. J.; TER LAAK, M. P.; HAMERS, F.; GISPEN, W. H. Combined treatment with αMSH and methylprednisolone fails to improve functional recovery after spinal injury in the rat. Brain Research, v. 859, n. 2, p. 334-340, 2000. LAWRENCE T. The nuclear factor NF-kappaB pathway in inflammation. Cold Spring Harb Perspect Biol., v. 1, n. 6, 2009. doi: 10.1101/cshperspect.a001651. Disponpivel em: <cshperspectives.cshlp.org>. Retirado 04 de out. 2013. LEE, B. B.; CRIPPS, R. A.; FITZHARRIS, M.; WING, P. C. The global map for traumatic spinal cord injury epidemiology: update 2011, global incidence rate. Spinal Cord, v. 52, n. 2, p. 110-116, 2013. LEE, H. R.; KIM, T. H.; CHOI, K. C. Functions and physiological roles of two types of estrogen receptors, ERα and ERβ, identified by estrogen receptor knockout mouse. Laboratory Animal Research, v. 28, n. 2, p. 71-76, 2012a. 71 LEE, J. Y.; CHOI, S. Y.; OH, T. H.; YUNE, T. Y.17β-Estradiol inhibits apoptotic cell death of oligodendrocytes by inhibiting RhoA-JNK3 activation after spinal cord injury. Endocrinology, v. 153, n. 8, p. 3815-3827, 2012b. LEE, Y. B.; YUNE, T. Y.; BAIK, S. Y.; SHIN, Y. H.; DU, S.; RHIM, H.; LEE, E. B.; KIM, Y. C.; SHIN, M. L.; MARKELONIS, G. J.; OH, T. H. Role of Tumor Necrosis Factor-α in Neuronal and Glial Apoptosis after Spinal Cord Injury. Exp Neurol., v. 166, n. 1, p. 190-195, 2000. LENT R. Cem bilhões de neurônios: Conceitos Fundamentais de Neurociência. Editora Atheneu, 2ª ed., 2010. LI, Q. M.; TEP, C.; YUNE, T. Y.; ZHOU, X. Z.; UCHIDA, T.; LU, K. P.; YOON, S. O. Opposite regulation of oligodendrocyte apoptosis by JNK3 and Pin1 after spinal cord injury. The Journal of Neuroscience, v. 27, n. 31, p. 8395-8404, 2007. LIANZA, S.; CASALIS, M.E.P.; GREVE, J.M.D.; EICHBERG, R. Lesão medular. In: Lianza S. Medicina de Reabilitação. Guanabara-Koogan, São Paulo, 3ª. ed., p. 299-321, 2001. LIU, X. Z.; XU, X. M.; HU, R.; DU, C.; ZHANG, S. X.; MCDONALD, J. W.; CHOI, D. W. Neuronal and glial apoptosis after traumatic spinal cord injury. The Journal of Neuroscience, v. 17, n. 14, p. 5395-5406, 1997. LIVERMAN T.C.; ALTEVOGT M.B.; JOY E.J.; JOHNSON T.R. Spinal cord injury: progress, promise, and priorities. National Academy of Sciences. N.W. Washington, DC., 2005. LOANE, D. J.; BYRNES, K. R. Role of microglia in neurotrauma. Neurotherapeutics, v. 7, n. 4, p. 366-377, 2010. MACHADO, Â. Neuroanatomia Funcional. Editora Ateneu, São Paulo, 2ª ed., 2007. MAIER B.; LEHNERT M.; LAURER H. L.; MAUTES A. E.; STEUDEL W. I.; MARZI I. Delayed elevation of soluble tumor necrosis factor receptors p75 and p55 in cerebrospinal fluid and plasma after traumatic brain injury. Shock, v. 26, n. 2, p. 122-127, 2006. MANTHEY, D.; BEHL, C. From structural biochemistry to expression profiling: neuroprotective activities of estrogen. Neuroscience, v. 138, n. 3, p. 845-850, 2006. MARTIN, L. J. Neuronal cell death in nervous system development, disease, and injury (Review). International Journal of Molecular Medicine, v. 7, n. 5, p. 455-478, 2001. MERRILL, J. E.; BENVENISTE, E. N. Cytokines in inflammatory brain lesions: helpful and harmful. Trends in Neurosciences, v. 19, n. 8, p. 331-338, 1996. MILLER, V. M.; DUCKLES, S. P. Vascular actions of estrogens: functional implications. Pharmacological Reviews, v. 60, n. 2, p. 210-241, 2008. MODI, H. N.; SUH, S. W.; HONG, J. Y.; YANG, J. H. The effects of spinal cord injury induced by shortening on motor evoked potentials and spinal cord blood flow: an experimental study in Swine. J Bone Joint Surg Am., v. 93, n. 19, p. 1781-1789, 2011. 72 MOLINA, A. E. I. S. Análise da sensibilidade e reprodutibilidade da escala de Basso, Beattie e Bresnahan (BBB) em ratos Wistar. Tese de Doutorado. Universidade de São Paulo, São Paulo, 2006. MOOSMANN, B.; BEHL, C. The antioxidant neuroprotective effects of estrogens and phenolic compounds are independent from their estrogenic properties. Proceedings of the National Academy of Sciences, v. 96, n. 16, p. 8867-8872, 1999. MORIARTY, K.; KIM, K. H.; BENDER, J. R. Estrogen receptor-mediated rapid signaling. Endocrinology, v. 147, n. 12, p. 5557-5563, 2006. MOSQUERA, L.; COLÓN, J. M.; SANTIAGO, J. M.; TORRADO, A. I.; MELÉNDEZ, M.; SEGARRA, A. C.; RODRÍGUEZ-ORENGO, J. F.; MIRANDA, J. D. Tamoxifen and estradiol improved locomotor function and increased spared tissue in rats after spinal cordinjury: their antioxidant effect and role of estrogen receptor alpha. Brain Res., v. 1561, p. 11-22, 2014. NAKAJIMA, H.; UCHIDA, K.; KOBAYASHI, S.; INUKAI, T.; HORIUCHI, Y.; YAYAMA, T.; SATO, R.; BABA, H. Rescue of rat anterior horn neurons after spinal cord injury by retrograde transfection of adenovirus vector carrying brain-derived neurotrophic factor gene. Journal of Neurotrauma, v. 24, n. 4, p. 703-712, 2007. NAKAMURA, M.; HOUGHTLING, R. A.; MACARTHUR, L.; BAYER, B. M.; BREGMAN, B. S. Differences in cytokine gene expression profile between acute and secondary injury in adult rat spinal cord. Experimental Neurology, v. 184, n. 1, p. 313-325, 2003. NICHOLSON, D. W.; THORNBERRY, N. A. Caspases: killer proteases. Trends in Biochemical Sciences, v. 22, n. 8, p. 299-306, 1997. NILSEN, J. Estradiol and neurodegenerative oxidative stress. Frontiers in Neuroendocrinology, v. 29, n. 4, p. 463-475, 2008. NILSEN, J.; BRINTON, R. D. Mechanism of estrogen-mediated neuroprotection: regulation of mitochondrial calcium and Bcl-2 expression. Proceedings of the National Academy of Sciences, v. 100, n. 5, p. 2842-2847, 2003. NILSEN, J.; BRINTON, R. D. Mitochondria as therapeutic targets of estrogen action in the central nervous system. Current Drug Targets-CNS & Neurological Disorders, v. 3, n. 4, p. 297-313, 2004. NILSSON, S.; MÄKELÄ, S.; TREUTER, E.; TUJAGUE, M.; THOMSEN, J.; ANDERSSON, G.; ENMARK E.; PETTERSSON K.; WARN M.; GUSTAFSSON, J. Å. Mechanisms of estrogen action. Physiological Reviews, v. 81, n. 4, p. 1535-1565, 2001. NOBLE, L. J.;WRATHALL, J. R. Spinal cord contusion in the rat: morphometric analyses of alterations in the spinal cord. Exp Neurol., v. 88, n. 1, p. 135-149, 1985. NORENBERG, M. D.; SMITH, J.; MARCILLO, A. The pathology of human spinal cord injury: defining the problems. Journal of Neurotrauma, v. 21, n. 4, p. 429-440, 2004. NUMAKAWA, Y.; MATSUMOTO, T.; YOKOMAKU, D.; TAGUCHI, T.; NIKI, E.; HATANAKA H.; KUNUGI, H.; NUMAKAWA, T. 17beta-estradiol protects cortical neurons against oxidative stress-induced cell death through reduction in the activity of mitogen- 73 activated protein kinase and in the accumulation of intracellular calcium. Endocrinology, v. 148, n. 2, p. 627-637, 2007. OYINBO, C. A. Secondary injury mechanisms in traumatic spinal cord injury: a nugget of this multiply cascade. Acta Neurobiol Exp (Wars), v. 71, n. 2, p. 281-299, 2011. PAN, J. Z.; NI, L.; SODHI, A.; AGUANNO, A.; YOUNG, W.; HART, R. P. Cytokine activity contributes to induction of inflammatory cytokine mRNAs in spinal cord following contusion. Journal of Neuroscience Research, v. 68, n. 3, p. 315-322, 2002. PAPKA, R. E.; STOREY-WORKLEY M.; SHUGHRUE, P. J.; MERCHENTHALER, I.; COLLINS, J. J.; USIP, S.; SAUNDERS, P. T.; SHUPNIK, M. Estrogen receptor-alpha and beta-immunoreactivity and mRNA in neurons of sensory and autonomicganglia and spinal cord. Cell Tissue Res., v. 304, n. 2, p. 193-214, 2001. PEDRAM, A.; RAZANDI, M.; AITKENHEAD, M.; LEVIN, E. R. Estrogen inhibits cardiomyocyte hypertrophy in vitro Antagonism of calcineurin-related hypertrophy through induction of MCIP1. Journal of Biological Chemistry, v. 280, n. 28, p. 26339-26348, 2005. PEREZ-POLO, J. R.; HALL, K.; LIVINGSTON, K.; WESTLUND, K. Steroid induction of nerve growth factor synthesis in cell culture. Life Sciences, v. 21, n. 10, p. 1535-1543, 1977. PIKE, C.J. Estrogen modulates neuronal Bcl-XL expression and beta-amyloid-induced apoptosis: relevance to Alzheimer's disease. J. Neurochem, v. 72, n. 4, p. 1552-1563, 1999. PINEAU I.; LACROIX S. Proinflammatory cytokine synthesis in the injured mouse spinal cord: multiphasic expression pattern and identification of the celltypes involved. Journal of Comparative Neurology, v. 500, n. 2, p. 267–85, 2007. PLUNKETT, J. A.; YU, C. G.; EASTON, J. M.; BETHEA, J. R.; YEZIERSKI, R. P. Effects of interleukin-10 (IL-10) on pain behavior and gene expression following excitotoxic spinal cord injury in the rat. Experimental Neurology, v. 168, n. 1, p. 144-154, 2001 POZZI, S.; BENEDUSI, V.; MAGGI, A.; VEGETO, E. Estrogen action in neuroprotection and brain inflammation. Annals of the New York Academy of Sciences, v. 1089, n. 1, p. 302-323, 2006. PROFYRIS, C.; CHEEMA, S. S.; ZANG, D.; AZARI, M. F.; BOYLE, K.; PETRATOS, S. Degenerative and regenerative mechanisms governing spinal cord injury. Neurobiology of Disease, v. 15, n. 3, p. 415-436, 2004. PROKAI, L.; SIMPKINS, J. W. Structure–nongenomic neuroprotection relationship of estrogens and estrogen-derived compounds. Pharmacology & Therapeutics, v. 114, n. 1, p. 1-12, 2007. RAFF, M. Cell suicide for beginners. Nature, v. 396, n. 6707, p. 119-119, 1998. RAY, S. K.; DIXON, C. E.; BANIK, N. L. Molecular mechanisms in the pathogenesis of traumatic brain injury. Histol Histopathol., v. 17, n. 4, p. 1137-1152, 2002. RAY, S. K.; HOGAN, E. L.; BANIK, N. L. Calpain in the pathophysiology of spinal cord injury: neuroprotection with calpain inhibitors. Brain Research Reviews, v. 42, n. 2, p. 169-185, 2003. 74 REXED B. A cytoarchitectonic atlas of the spinal cord in cat. J Comp Neurol., v. 100, p. 297-379, 1954. RITZ, M. F.; HAUSMANN, O. N. Effect of 17β-estradiol on functional outcome, release of cytokines, astrocyte reactivity and inflammatory spreading after spinal cord injury in male rats. Brain Research, v. 1203, p. 177-188, 2008. RIVLIN, A. S.; TATOR, C. H. Effect of duration of acute spinal cord compression in a new acute cord injury model in the rat. Surgical Neurology, v. 10, n. 1, p. 38-43, 1978. ROSELLI, C. F. Brain aromatase: roles in reproduction and neuroprotection. The Journal of Steroid Biochemistry and Molecular Biology, v. 106, n. 1, p. 143-150, 2007. SAMANTARAY, S.; SRIBNICK, E. A.; DAS, A.; THAKORE, N. P.; MATZELLE, D.; YU, S. P.; RAY, S. K.; WEI, L.; BANIK, N. L. Neuroprotective efficacy of estrogen in experimental spinal cord injury in rats. Annals of the New York Academy of Sciences, v. 1199, n. 1, p. 90-94, 2010a. SAMANTARAY, S.; MATZELLE, D. D.; RAY, S. K.; BANIK, N. L. Physiological low dose of estrogen‐protected neurons in experimental spinal cord injury. Annals of the New York Academy of Sciences, v. 1199, n. 1, p. 86-89, 2010b. SAMANTARAY, S.; SMITH, J. A.; DAS, A.; MATZELLE, D. D.; VARMA, A. K.; RAY, S. K.; BANIK, N. L. Low dose estrogen prevents neuronal degeneration and microglial reactivity in an acute model of spinal cord injury: effect of dosing, route of administration, and therapy delay. Neurochemical Research, v. 36, n. 10, p. 1809-1816, 2011. SAWADA, M.; SUZUMURA, A.; HOSOYA, H.; MARUNOUCHI, T.; NAGATSU, T. Interleukin‐10 Inhibits Both Production of Cytokines and Expression of Cytokine Receptors in Microglia. Journal of Neurochemistry, v. 72, n. 4, p. 1466-1471, 1999. SAYER, F. T.; KRONVALL, E.; NILSSON, O. G. Methylprednisolone treatment in acute spinal cord injury: the myth challenged through a structured analysis of published literature. The Spine Journal, v. 6, n. 3, p. 335-343, 2006. SCHILLER, M. D.; MOBBS, R. J.; LEE, B.B.; STANFORD, R.E.; MARIAL, O. Acute care for spinal cord injured patients at spinal injury units: the influence of early and direct admission on complications and length of stay. ANZCoS Brisbane, Australia, 2011. SCHNELL, L.; FEARN, S.; KLASSEN, H.; SCHWAB, M. E.; PERRY, V. H. Acute inflammatory responses to mechanical lesions in the CNS: differences between brain and spinal cord. European Journal of Neuroscience, v. 11, n. 10, p. 3648-3658, 1999a. SCHNELL, L.; FEARN, S.; SCHWAB, M. E.; PERRY, V. H.; ANTHONY, D. C. Cytokine-induced acute inflammation in the brain and spinal cord. Journal of Neuropathology & Experimental Neurology, v. 58, n. 3, p. 245-254, 1999b. SCHWAB J. M.; BRECHTEL K.; MUELLER C. A.; FAILLI V.; KRAPS H. P.; TULI S. K.; SCHLUESENER H. J. Experimental strategies to promote spinal cord regeneration—an integrative perspective. Progress in Neurobiology, v. 78, n. 2, p. 91–116, 2006. SCHWAB, M. E. Nogo and axon regeneration. Current Opinion in Neurobiology, v. 14, n. 1, p. 118-124, 2004. 75 SCHWARTZ, M.; MOALEM, G.; LEIBOWITZ-AMIT, R.; COHEN, I. R. Innate and adaptive immune responses can be beneficial for CNS repair. Trends in Neurosciences, v. 22, n. 7, p. 295-299, 1999. SCOTT, E.; ZHANG, Q. G.; WANG, R.; VADLAMUDI, R.; BRANN, D. Estrogen neuroprotection and the critical period hypothesis. Frontiers in Neuroendocrinology, v. 33, n. 1, p. 85-104, 2012. SIEGENTHALER, M. M.; TU, M. K.; KEIRSTEAD, H. S. The extent of myelin pathology differs following contusion and transection spinal cord injury. Journal of Neurotrauma, v. 24, n. 10, p. 1631-1646, 2007. SILVA, N. A.; SOUSA, N.; REIS, R. L.; SALGADO, A. J. From basics to clinical: a comprehensive review on spinal cord injury. Progress in Neurobiology, v. 114, p. 25-57, 2014. SIMON M.C.; SHARIF S.; TAN P.R.; LAPLACA C.M. Spinal Cord Contusion Causes Acute Plasma Membrane Damage. J Neurotrauma, v. 26, n. 4, p. 563–574, 2009. SIMONCINI, T.; RABKIN, E.; LIAO, J. K. Molecular basis of cell membrane estrogen receptor interaction with phosphatidylinositol 3-kinase in endothelial cells. Arteriosclerosis, Thrombosis, and Vascular Biology, v. 23, n. 2, p. 198-203, 2003. SIMPKINS, J. W.; DYKENS, J. A. Mitochondrial mechanisms of estrogen neuroprotection. Brain Research Reviews, v. 57, n. 2, p. 421-430, 2008. SIMPKINS, J. W.; YI, K. D.; YANG, S. H.; DYKENS, J. A. Mitochondrial mechanisms of estrogen neuroprotection. Biochimica et Biophysica Acta (BBA)-General Subjects, v. 1800, n. 10, p. 1113-1120, 2010. SIPSKI, M. L.; JACKSON, A. B.; GÓMEZ-MARÍN, O.; ESTORES, I.; STEIN, A. Effects of gender on neurologic and functional recovery after spinal cord injury. Archives of Physical Medicine and Rehabilitation, v. 85, n. 11, p. 1826-1836, 2004. SIRIPHORN, A.; CHOMPOOPONG, S.; FLOYD, C. L. 17β‐Estradiol protects Schwann cells against H2O2‐induced cytotoxicity and increases transplanted Schwann cell survival in a cervical hemicontusion spinal cord injury model. Journal of Neurochemistry, v. 115, n. 4, p. 864-872, 2010. SIRIPHORN, A.; DUNHAM, K. A.; CHOMPOOPONG, S.; FLOYD, C. L. Postinjury administration of 17β‐estradiol induces protection in the gray and white matter with associated functional recovery after cervical spinal cord injury in male rats. Journal of Comparative Neurology, v. 520, n. 12, p. 2630-2646, 2012. SOHRABJI, F.; MIRANDA, R. C.; TORAN-ALLERAND, C. Dominique. Identification of a putative estrogen response element in the gene encoding brain-derived neurotrophic factor. Proceedings of the National Academy of Sciences, v. 92, n. 24, p. 11110-11114, 1995. SOLTYSIK, K.; CZEKAJ, P. Membrane estrogen receptors-is it an alternative way of estrogen action?. J Physiol Pharmacol, v. 64, p. 129-42, 2013. SPRINGER, J. E.; AZBILL, R. D.; KNAPP, P. E. Activation of the caspase-3 apoptotic cascade in traumatic spinal cord injury. Nature Medicine, v. 5, n. 8, p. 943-946, 1999. 76 SRIBNICK, E. A.; WINGRAVE, J. M.; MATZELLE, D. D.; WILFORD, G. G.; RAY, S. K.; BANIK, N. L. Estrogen attenuated markers of inflammation and decreased lesion volume in acute spinal cord injury in rats. Journal of Neuroscience Research, v. 82, n. 2, p. 283-293, 2005. SRIBNICK, E. A.; MATZELLE, D. D.; RAY, S. K.; BANIK, N. L. Estrogen treatment of spinal cord injury attenuates calpain activation and apoptosis. Journal of Neuroscience Research, v. 84, n. 5, p. 1064-1075, 2006. SRIBNICK, E. A.; DEL RE, A. M.; RAY, S. K.; WOODWARD, J. J.; BANIK, N. L. Estrogen attenuates glutamate-induced cell death by inhibiting Ca2+ influx through L-type voltage-gated Ca2+ channels. Brain Res.,v. 1276, p. 159-170, 2009. SRIBNICK, E. A.; SAMANTARAY, S.; DAS, A.; SMITH, J.; MATZELLE, D. D.; RAY, S. K.; BANIK, N. L. Postinjury estrogen treatment of chronic spinal cord injury improves locomotor function in rats. J Neurosci Res., v. 88, n. 8, p. 1738-1750, 2010. STEFANO, G. B.; PREVOT, V.; BEAUVILLAIN, J. C.; FIMIANI, C.; WELTERS, I.; CADET, P.; BREATON, C.; PESTEL, J.; SALZET, M.; BILFINGER, T. V. Estradiol coupling to human monocyte nitric oxide release is dependent on intracellular calcium transients: evidence for an estrogen surface receptor. The Journal of Immunology, v. 163, n. 7, p. 3758-3763, 1999. STOLL G.; JANDER S.; SCHROETER M. Detrimental and beneficial effects of injury-induced inflammation and cytokine expression in the nervous system. Adv Exp Med Biol, v. 513, p. 87–113, 2002. STREIT, W. J.; SEMPLE-ROWLAND, S. L.; HURLEY, S. D.; MILLER, R. C.; POPOVICH, P. G.; STOKES, B. T. Cytokine mRNA profiles in contused spinal cord and axotomized facial nucleus suggest a beneficial role for inflammation and gliosis. Experimental Neurology, v. 152, n. 1, p. 74-87, 1998. SUGAWARA T.; LEWEN A.; GASCHE Y, Y. U. F.; CHAN P.H. Overexpression of sod1 protects vulnerable motor neurons after spinal cord injury by attenuating mitochondrial cytochrome c release. FASEB J, v.16, p.1997–1999, 2002. SUGIOKA, K.; SHIMOSEGAWA, Y.; NAKANO, M. Estrogens as natural antioxidants of membrane phospholipid peroxidation. FEBS Lett., v. 210, n. 1, p. 37-39, 1987. SWARTZ, K. R.; FEE, D. B.; JOY, K. M.; ROBERTS, K. N.; SUN, S.; SCHEFF, N. N.; WILSON, M. E.; SCHEFF, S. W. Gender differences in spinal cord injury are not estrogen-dependent. Journal of Neurotrauma, v. 24, n. 3, p. 473-480, 2007. TAKAO, T., FLINT, N., LEE, L., YING, X., MERRILL, J., CHANDROSS, K. J. 17beta‐estradiol protects oligodendrocytes from cytotoxicity induced cell death. Journal of Neurochemistry, v. 89, n. 3, p. 660-673, 2004. TATOR, C. H. Update on the pathophysiology and pathology of acute spinal cord injury. Brain Pathol., v. 5, n. 4 p. 407– 413, 1995. TATOR, C. H.; FEHLINGS, M. G. Review of the secondary injury theory of acute spinal cord trauma with emphasis on vascular mechanisms. Journal of Neurosurgery, v. 75, n. 1, p. 15-26, 1991. 77 TATOR, C. H.; MCCORMICK, P. C.; PIEPMEIER, J. M.; BENZEL, E. C.; YOUNG, W. Biology of neurological recovery and functional restoration after spinal cord injury. J Neurosurg, v. 42, p. 696–708, 1998. TIAN, D. S.; LIU, J. L.; XIE, M. J.; ZHAN, Y.; QU, W. S.; YU, Z. Y.; TANG, Z. P.; PAN, D. J.; WANG, W. Tamoxifen attenuates inflammatory‐mediated damage and improves functional outcome after spinal cord injury in rats. Journal of Neurochemistry, v. 109, n. 6, p. 1658-1667, 2009. TRIVEDI, A.; OLIVAS, A. D.; NOBLE-HAEUSSLEIN, L. J. Inflammation and spinal cord injury: infiltrating leukocytes as determinants of injury and repair processes. Clinical Neuroscience Research, v. 6, n. 5, p. 283-292, 2006. TUNA, M.; POLAT, S.; ERMAN, T.; ILDAN, F.; GÖÇER, A. I.; TUNA, N.; TAMER, L.; KAYA, M.; CETINALP, E. Effect of anti-rat interleukin-6 antibody after spinal cord injury in the rat: inducible nitric oxide synthaseexpression, sodium- and potassium-activated, magnesium-dependent adenosine-5'-triphosphatase and superoxide dismutase activation, and ultrastructural changes. J Neurosurg., v. 95, n. 1, p. 64-73, 2001. VANICKÝ, I.; URDZÍKOVÁ, L.; SAGANOVÁ, K.; CÍZKOVÁ, D.; GÁLIK, J. A simple and reproducible model of spinal cord injury induced by epidural balloon inflation in the rat. Journal of Neurotrauma, v. 18, n. 12, p. 1399-1407, 2001. VEGETO, E.; BENEDUSI, V.; MAGGI, A. Estrogen anti-inflammatory activity in brain: a therapeutic opportunity for menopause and neurodegenerative diseases. Frontiers in Neuroendocrinology, v. 29, n. 4, p. 507-519, 2008. VIDAL, P. M.; LEMMENS, E.; DOOLEY, D.; HENDRIX, S. The role of “anti-inflammatory” cytokines in axon regeneration. Cytokine & Growth Factor Reviews, v. 24, n. 1, p. 1-12, 2013. WANG, C. X.; SHUAIB, A. Involvement of inflammatory cytokines in central nervous system injury. Progress in Neurobiology, v. 67, n. 2, p. 161-172, 2002. WANG, K. C.; KOPRIVICA, V.; KIM, J. A.; SIVASANKARAN, R.; GUO, Y.; NEVE, R. L.; HE, Z. Oligodendrocyte-myelin glycoprotein is a Nogo receptor ligand that inhibits neurite outgrowth. Nature, v. 417, n. 6892, p. 941-944, 2002. WANG, X.; DYKENS, J. A.; PEREZ, E.; LIU, R.; YANG, S.; COVEY, D. F.; SIMPKINS, J. W. Neuroprotective effects of 17β-estradiol and nonfeminizing estrogens against H2O2 toxicity in human neuroblastoma SK-N-SH cells. Molecular Pharmacology, v. 70, n. 1, p. 395-404, 2006. WATSON C.; PAXINOS G.; KAYALIOGLU G. The Spinal Cord - A Chritopher and Dana Reeve Foundation Text and Atlas. Elsevier, 2009. WEAVER, C. E. J.; PARK-CHUNG, M., GIBBS, T. T.; FARB, D. H. 17β-Estradiol protects against NMDA-induced excitotoxicity by direct inhibition of NMDA receptors. Brain Research, v. 761, n. 2, p. 338-341, 1997. WELLS, J. E.; HURLBERT, R. J.; FEHLINGS, M. G.; YONG, V. W. Neuroprotection by minocycline facilitates significant recovery from spinal cord injury in mice. Brain, v. 126, n. 7, p. 1628-1637, 2003. 78 WINTERLE, J. S.; MILL, T.; HARRIS, T.; GOLDBECK, R. A. Absolute kinetic characterization of 17-beta-estradiol as a radical-scavenging, antioxidant synergist. Arch Biochem Biophys., v. 392, n. 2, p. 233-244, 2001. WISE, P. M. Estrogens and neuroprotection. Trends in Endocrinology & Metabolism, v. 13, n. 6, p. 229-230, 2002. WISE, P. M.; DUBAL, D. B.; WILSON, M. E.; RAU, S. W.; BÖTTNER, M.; ROSEWELL, K. L.. Estradiol is a protective factor in the adult and aging brain: understanding of mechanisms derived from in vivo and in vitro studies. Brain Research Reviews, v. 37, n. 1, p. 313-319, 2001. WONG, M.; MOSS, R. L. Long-term and short-term electrophysiological effects of estrogen on the synaptic properties of hippocampal CA1 neurons. The Journal of Neuroscience, v. 12, n. 8, p. 3217-3225, 1992. WU, W. F.; TAN, X. J.; DAI, Y. B.; KRISHNAN, V.; WARNER, M.; GUSTAFSSON, J. Å. Targeting estrogen receptor β in microglia and T cells to treat experimental autoimmune encephalomyelitis. Proceedings of the National Academy of Sciences, v. 110, n. 9, p. 3543-3548, 2013. WYSS-CORAY, T.; MUCKE, L. Inflammation in neurodegenerative disease—a double-edged sword. Neuron, v. 35, n. 3, p. 419-432, 2002. XING, D.; NOZELL, S.; CHEN, Y. F.; HAGE, F.; OPARIL, S. Estrogen and mechanisms of vascular protection. Arteriosclerosis, Thrombosis, and Vascular Biology, v. 29, n. 3, p. 289-295, 2009. XIONG, Y.; RABCHEVSKY, A. G.; HALL, E. D. Role of peroxynitrite in secondary oxidative damage after spinal cord injury. Journal of Neurochemistry, v. 100, n. 3, p. 639-649, 2007. YAKOVLEV, A. G.; FADEN, A. I. Caspase-dependent apoptotic pathways in CNS injury. Molecular Neurobiology, v. 24, n. 1-3, p. 131-144, 2001. YANG, L.; BLUMBERGS, P. C.; JONES, N. R.; MANAVIS, J.; SARVESTANI, G. T.; GHABRIEL, M. N. Early expression and cellular localization of proinflammatory cytokines interleukin-1β, interleukin-6, and tumor necrosis factor-α in human traumatic spinal cord injury. Spine, v. 29, n. 9, p. 966-971, 2004. YANG, L.; JONES, N. R.; BLUMBERGS, P. C.; VAN DEN HEUVEL, C.; MOORE, E. J.; MANAVIS, J.; SARVESTAN, G. T.; GHABRIEL, M. N. Severity-dependent expression of pro-inflammatory cytokines in traumatic spinal cord injury in the rat. Journal of Clinical Neuroscience, v. 12, n. 3, p. 276-284, 2005. YU, X., RAJALA, R. V., MCGINNIS, J. F., LI, F., ANDERSON, R. E., YAN, X., LI, S.; ELIAS, R. V.; KNAPP, R. R.; ZHOU, X.; CAO, W. Involvement of insulin/phosphoinositide 3-kinase/Akt signal pathway in 17β-estradiol-mediated neuroprotection. Journal of Biological Chemistry, v. 279, n. 13, p. 13086-13094, 2004. YUNE, T. Y.; KIM, S. J.; LEE, S. M.; LEE, Y. K.; OH, Y. J.; KIM, Y. C.; MARKELONIS, G. J.; OH, T. H. Systemic administration of 17β-estradiol reduces apoptotic cell death and improves functional recovery following traumatic spinal cord injury in rats. Journal of Neurotrauma, v. 21, n. 3, p. 293-306, 2004. 79 YUNE, T. Y.; PARK, H. G.; LEE, J. Y.; OH, T. H. Estrogen-induced Bcl-2 expression after spinal cord injury is mediated through phosphoinositide-3-kinase/Akt-dependent CREB activation. Journal of Neurotrauma, v. 25, n. 9, p. 1121-1131, 2008. ZHENG, J.; RAMIREZ, V. D. Rapid inhibition of rat brain mitochondrial proton FoF1-ATPase activity by estrogens: comparison with Na+, K+-ATPase of porcine cortex. Euro. J. 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dc.title.por.fl_str_mv Efeito do 17β-estradiol na performance locomotora de ratas submetidas à lesão medular por compressão
dc.title.alternative.eng.fl_str_mv Effect of 17β-estradiol on locomotor performance in rats subjected to spinal cord compression injury
title Efeito do 17β-estradiol na performance locomotora de ratas submetidas à lesão medular por compressão
spellingShingle Efeito do 17β-estradiol na performance locomotora de ratas submetidas à lesão medular por compressão
Silva, Fernanda Kohn Bastos da
Lesão medular espinal
17β-estradiol
neuroproteção
Spinal cord injury
17β-estradiol
neuroprotection
Fisiologia
title_short Efeito do 17β-estradiol na performance locomotora de ratas submetidas à lesão medular por compressão
title_full Efeito do 17β-estradiol na performance locomotora de ratas submetidas à lesão medular por compressão
title_fullStr Efeito do 17β-estradiol na performance locomotora de ratas submetidas à lesão medular por compressão
title_full_unstemmed Efeito do 17β-estradiol na performance locomotora de ratas submetidas à lesão medular por compressão
title_sort Efeito do 17β-estradiol na performance locomotora de ratas submetidas à lesão medular por compressão
author Silva, Fernanda Kohn Bastos da
author_facet Silva, Fernanda Kohn Bastos da
author_role author
dc.contributor.author.fl_str_mv Silva, Fernanda Kohn Bastos da
dc.contributor.advisor1.fl_str_mv Medeiros, Magda Alves de
dc.contributor.advisor1ID.fl_str_mv 03659248738
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/6392136073564306
dc.contributor.referee1.fl_str_mv Almeida, Norma Aparecida dos Santos
dc.contributor.referee2.fl_str_mv Resende, Victor Túlio Ribeiro de
dc.contributor.authorID.fl_str_mv 11013489764
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/0793107481747936
contributor_str_mv Medeiros, Magda Alves de
Almeida, Norma Aparecida dos Santos
Resende, Victor Túlio Ribeiro de
dc.subject.por.fl_str_mv Lesão medular espinal
17β-estradiol
neuroproteção
topic Lesão medular espinal
17β-estradiol
neuroproteção
Spinal cord injury
17β-estradiol
neuroprotection
Fisiologia
dc.subject.eng.fl_str_mv Spinal cord injury
17β-estradiol
neuroprotection
dc.subject.cnpq.fl_str_mv Fisiologia
description Uma lesão traumática na medula espinal promove rápida morte celular no epicentro da lesão e desencadeia uma série de eventos vasculares, celulares e bioquímicos, denominados danos secundários, que culminam em morte de células que estavam intactas após o trauma inicial e, desta forma, amplifica a lesão e a disfunção tecidual. O 17β-estradiol (E2) é um hormônio esteroide endógeno produzido principalmente pelas gônadas e que tem demonstrado efeito neuroprotetor in vitro e in vivo, em diversas doenças e traumas no sistema nervoso central (SNC). Na lesão medular espinal o E2 tem evidenciado múltiplas ações neuroprotetoras por modular diversos danos secundários à lesão, tais como: inflamação, apoptose, estresse oxidativo e alterações vasculares. Nesse sentido, o objetivo desse estudo foi avaliar se, de forma aguda, o E2 promove recuperação locomotora em ratas ovariectomizadas submetidas à lesão medular por compressão. Neste estudo foram utilizadas ratas Wistar que foram submetidas a ovariectomia bilateral (OVX) e após uma semana foi induzida a lesão medular através da inflação do balão de um cateter Fogarty 2F de embolectomia, inflado com 15μl de solução salina no espaço epidural entre as vértebras T8 e T9 durante 5 minutos. Quinze minutos após a cirurgia de lesão medular foi administrado por via subcutânea uma dose única de 100 μg/Kg de E2 diluído em óleo (grupo OVX+E2) ou somente o veículo óleo (grupo OVX+óleo). Uma parte dos animais foi submetida a OVX e após uma semana foi realizada apenas a laminectomia vertebral (grupo OVX+sham). A performance locomotora dos animais foi avaliada através do teste BBB durante 14 dias e foi detectado uma significativa melhora na recuperação locomotora do grupo OVX+E2 comparado ao grupo OVX+óleo no 10º e 14º dia após a lesão medular. Para verificar se essa melhor capacidade locomotora dos animais tratados com E2 esta relacionada com a menor quantidade de lesão no tecido medular, foi realizada a análise histopatológica de cortes longitudinais de tecido medular desses animais. Na avaliação histopatológica da medula foi detectado que o grupo OVX+E2 apresentou lesões significativamente menores sob os aspectos de comprimento, largura e área da lesão comparado ao grupo OVX+óleo. Nesse sentido, os resultados sugerem que o E2 é capaz de promover recuperação locomotora após uma lesão moderada na medula espinal, sendo esse efeito associado ao menor tamanho de lesão no tecido, corroborando com a hipótese de que o E2 é um hormônio neuroprotetor.
publishDate 2014
dc.date.issued.fl_str_mv 2014-08-29
dc.date.accessioned.fl_str_mv 2023-12-22T03:08:30Z
dc.date.available.fl_str_mv 2023-12-22T03:08:30Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.citation.fl_str_mv SILVA, Fernanda Kohn Bastos da. Efeito do 17β-estradiol na performance locomotora de ratas submetidas à lesão medular por compressão. 2014. 79 f. Dissertação (Mestrado Multicêntrico em Ciências Fisiológicas) - Instituto de Ciências Biológicas e da Saúde, Universidade Federal Rural do Rio de Janeiro, Seropédica - RJ, 2014.
dc.identifier.uri.fl_str_mv https://rima.ufrrj.br/jspui/handle/20.500.14407/14933
identifier_str_mv SILVA, Fernanda Kohn Bastos da. Efeito do 17β-estradiol na performance locomotora de ratas submetidas à lesão medular por compressão. 2014. 79 f. Dissertação (Mestrado Multicêntrico em Ciências Fisiológicas) - Instituto de Ciências Biológicas e da Saúde, Universidade Federal Rural do Rio de Janeiro, Seropédica - RJ, 2014.
url https://rima.ufrrj.br/jspui/handle/20.500.14407/14933
dc.language.iso.fl_str_mv por
language por
dc.relation.references.por.fl_str_mv AKASSOGLOU, K.; BAUER, J.; KASSIOTIS, G.; PASPARAKIS, M.; LASSMANN, H.; KOLLIAS, G.; PROBERT, L. Oligodendrocyte apoptosis and primary demyelination induced by local TNF/p55TNF receptor signaling in the central nervous system of transgenic mice: models for multiple sclerosis with primary oligodendrogliopathy. The American Journal of Pathology, v. 153, n. 3, p. 801-813, 1998. ALMEIDA, M.; MARTIN‐MILLAN, M.; AMBROGINI, E.; BRADSHER, R.; HAN, L.; CHEN, X. D.; ROBERSON, P. K.; WEINSTEIN, R. S.; O'BRIEN, C. A.; JILKA, R. L.; MANOLAGAS, S. C. Estrogens attenuate oxidative stress and the differentiation and apoptosis of osteoblasts by DNA‐binding‐independent actions of the ERα. Journal of Bone and Mineral Research, v. 25, n. 4, p. 769-781, 2010. AMANTEA, D.; RUSSO, R.; BAGETTA, G.; CORASANITI, M. T. From clinical evidence to molecular mechanisms underlying neuroprotection afforded by estrogens. Pharmacological Research, v. 52, n. 2, p. 119-132, 2005. ANDERSEN M.L.; TUFIK S. Animal models as ethical tools in biomedical research. CLR Balieiro Editores, São Paulo, 1ª ed., 2010. ARNOLD, S.; BEYER, C. Neuroprotection by estrogen in the brain: the mitochondrial compartment as presumed therapeutic target. Journal of Neurochemistry, v. 110, n. 1, p. 1-11, 2009. BACHIS, A.; COLANGELO, A. M.; VICINI, S.; DOE, P. P.; DE BERNARDI, M. A.; BROOKER, G.; MOCCHETTI, I. Interleukin-10 prevents glutamate-mediated cerebellar granule cell death by blocking caspase-3-like activity. The Journal of Neuroscience, v. 21, n. 9, p. 3104-3112, 2001. BAO F.; LIU D. Peroxynitrite generated in the rat spinal cord induces apoptotic cell death and activates caspase-3. Neuroscience, v. 116, n. 1, p. 59–70, 2003. BARTHOLDI, D.; SCHWAB, M. E. Expression of pro‐inflammatory cytokine and chemokine mRNA upon experimental spinal cord injury in mouse: An in situ hybridization study. European Journal of Neuroscience, v. 9, n. 7, p. 1422-1438, 1997. BASSO, M. D.; BEATTIE, M. S.; BRESNAHAN, J. C. A sensitive and reliable locomotor rating scale for open field testing in rats. Journal of Neurotrauma, v. 12, n. 1, p. 1-21, 1995. BASSO, D. M.; BEATTIE, M. S.; BRESNAHAN, J. C. Graded histological and locomotor outcomes after spinal cord contusion using the NYU weight-drop deviceversus transection. Exp Neurol., v. 139, n. 2, p. 244-256, 1996. BASSO, D. M. Behavioral testing after spinal cord injury: congruities, complexities, and controversies. Journal of Neurotrauma, v. 21, n. 4, p. 395-404, 2004. BASSO, D. M.; FISHER, L. C.; ANDERSON, A. J.; JAKEMAN, L. B.; MCTIGUE, D. M.; POPOVICH, P. G. Basso Mouse Scale for locomotion detects differences in recovery after spinal cord injury in five common mouse strains. Journal of Neurotrauma, v. 23, n. 5, p. 635-659, 2006. 64 BAYIR, H.; MARION, D. W.; PUCCIO, A. M.; WISNIEWSKI, S. R.; JANESKO, K. L.; CLARK, R. S.; KOCHANEK, P. M. Marked gender effect on lipid peroxidation after severe traumatic brain injury in adult patients. Journal of Neurotrauma, v. 21, n. 1, p. 1-8, 2004. BEATTIE, M. S.; FAROOQUI, A. A.; BRESNAHAN, J. C. Review of current evidence for apoptosis after spinal cord injury. Journal of Neurotrauma, v. 17, n. 10, p. 915-925, 2000. BECK K. D.; NGUYEN H. X.; GALVAN M. D.; SALAZAR D. L.; WOODRUFF T. M.; ANDERSON A. J. Quantitative analysis of cellular inflammation after traumatic spinal cord injury: evidence for a multiphasic inflammatory response in the acute to chronic environment. Brain, v.;133, n. 2, p. 433–47, 2010 BEHL, C.; WIDMANN, M.; TRAPP, T.; HOLSBOER, F. 17-[beta] Estradiol protects neurons from oxidative stress-induced cell death in vitro. Biochemical and Biophysical Research Communications, v. 216, n. 2, p. 473-482, 1995 BEHL, C.; SKUTELLA, T.; FRANK, L. H.; POST, A.; WIDMANN, M.; NEWTON, C. J.; HOLSBOER, F. Neuroprotection against oxidative stress by estrogens: structure-activity relationship. Molecular Pharmacology, v. 51, n. 4, p. 535-541, 1997. BEHL, C. Oestrogen as a neuroprotective hormone. Nature Reviews Neuroscience, v. 3, n. 6, p. 433-442, 2002a. BEHL, C. Estrogen can protect neurons: modes of action. The Journal of Steroid Biochemistry and Molecular Biology, v. 83, n. 1, p. 195-197, 2002b. BEHRMANN, D. L.; BRESNAHAN, J. C.; BEATTIE, M. S.; SHAH, B. R. Spinal cord injury produced by consistent mechanical displacement of the cord in rats: behavioral and histologic analysis. Journal of Neurotrauma, v. 9, n. 3, p. 197-217, 1992. BETHEA, J. R.; NAGASHIMA, H.; ACOSTA, M. C.; BRICENO, C.; GOMEZ, F.; MARCILLO, A. E.; DIETRICH, W. D. Systemically administered interleukin-10 reduces tumor necrosis factor-alpha production and significantly improves functional recovery following traumatic spinal cord injury in rats. Journal of Neurotrauma, v. 16, n. 10, p. 851-863, 1999. BETHEA J.R. Spinal cord injury-induced inflammation: a dual-edged sword. Prog Brain Res, v. 128, p. 33–42, 2000. BETHEA, J. R.; DIETRICH, D. W. Targeting the host inflammatory response in traumatic spinal cord injury. Current Opinion in Neurology, v. 15, n. 3, p. 355-360, 2002. BIEWENGA, E.; CABELL, L.; AUDESIRK, T. Estradiol and raloxifene protect cultured SN4741 neurons against oxidative stress. Neuroscience Letters, v. 373, n. 3, p. 179-183, 2005. BISHOP, J.; SIMPKINS, J. W. Estradiol Treatment Increases Viability of Glioma and Neuroblastoma Cells in vitro. Molecular and Cellular Neuroscience, v. 5, n. 4, p. 303-308, 1994. BLIGHT, A. R. Cellular morphology of chronic spinal cord injury in the cat: analysis of myelinated axons by line-sampling. Neuroscience, v. 10, n. 2, p. 521-543, 1983. 65 BLIGHT, A. R.; TOOMBS, J. P.; BAUER, M. S.; WIDMER, W. R. The effects of 4-aminopyridine on neurological deficits in chronic cases of traumatic spinal cord injury in dogs: a phase I clinical trial. Journal of Neurotrauma, v. 8, n. 2, p. 103-119, 1991. BORGENS, R. B.; SHI, R. Immediate recovery from spinal cord injury through molecular repair of nerve membranes with polyethylene glycol. The FASEB Journal, v. 14, n. 1, p. 27-35, 2000. BOTELHO, R. V., DANIEL, J. W., BOULOSA, J. L. R., COLLI, B. O., FARIAS, R. D. L., MORAES, O. J. S., PIMENTA JR., W. E.; RIBEIRO, C. H.; RIBEIRO, F. R. B.; TARICCO, M. A.; CARVALHO, M. V.; BERNARDO, W. M. Effectiveness of methylprednisolone in the acute phase of spinal cord injuries: a systematic review of randomized controlled trials. Revista da Associação Médica Brasileira, v. 55, n. 6, p. 729-737, 2009. BRACKEN, M. B.; COLLINS, W. F.; FREEMAN, D. F.; SHEPARD, M. J.; WAGNER, F. W. SILTEN, R. M.; HELLENBRAND, G. K.; RANSOHOFF, J.; HUNT, W. E.; PEROT JR, P. L.; GROSSMAN, R. G.; GREEN, B. A.; EISENBERG, H. M.; RIFKINSON, N.; GOODMAN, J. H.; MEAGHER, J. N.; FISCHER, B.; CLIFTON, G. L.; FLAMM, E. S.; STEPHEN E.; RAWE, S. E. Efficacy of methylprednisolone in acute spinal cord injury. Jama, v. 251, n. 1, p. 45-52, 1984. BRACKEN, M. B.; SHEPARD, M. J.; COLLINS, W. F.; HOLFORD, T. R.; YOUNG, W.; BASKIN, D. S.; EISENBERG, H. M.; FLAMM, E.; LEO-SUMMERS, L.; MAROON, J.; MARSHALL, L. F.; PEROT, JR., P. L.; PIEPMEIER, J.; SONNTAG, V. K. H.; WAGNER, F. C.; WILBERGER, J. E.; WINN, H. R. A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury: results of the Second National Acute Spinal Cord Injury Study. New England Journal of Medicine, v. 322, n. 20, p. 1405-1411, 1990. BRACKEN, M. B.; SHEPARD, M. J.; HOLFORD, T. R.; LEO-SUMMERS, L.; ALDRICH, E. F.; FAZL, M.; FEHLINGS, M.; HERR, D. L.; HITCHON, P. W.; MARSHALL, L. F.; NOCKELS, R. P.; PASCALE, V.; PEROT JR, P. L.; PIEPMEIER, J.; SONNTAG, V. K. H.; WAGNER, F.; WILBERGER, J. E.; WINN, H. R.; YOUNG, W. Administration of methylprednisolone for 24 or 48 hours or tirilazad mesylate for 48 hours in the treatment of acute spinal cord injury: results of the Third National Acute Spinal Cord Injury Randomized Controlled Trial. Jama, v. 277, n. 20, p. 1597-1604, 1997. BRANN, D. W.; DHANDAPANI, K.; WAKADE, C.; MAHESH, V. B.; KHAN, M. M. Neurotrophic and neuroprotective actions of estrogen: basic mechanisms and clinical implications. Steroids, v. 72, n. 5, p. 381-405, 2007. BREWER, K. L.; BETHEA, J. R.; YEZIERSKI, R. P. Neuroprotective effects of interleukin-10 following excitotoxic spinal cord injury. Experimental Neurology, v. 159, n. 2, p. 484-493, 1999. BUNGE, R. P.; PUCKETT, W. R.; BECERRA, J. L.; MARCILLO, A.; QUENCER, R. M. Observations on the pathology of human spinal cord injury. A review and classification of 22 new cases with details from a case of chronic cord compression with extensive focal demyelination. Advances in Neurology, v. 59, p. 75, 1993. BYDON, M., LIN, J., MACKI, M., GOKASLAN, Z. L., & BYDON, A. The current role of steroids in acute spinal cord injury. World Neurosurgery, 2013. 66 CAMPBELL, S. J.; JIANG, Y.; DAVIS, A. E.; FARRANDS, R.; HOLBROOK, J.; LEPPERT, D.; ANTHONY, D. C. Immunomodulatory effects of etanercept in a model of brain injury act through attenuation of the acute‐phase response. Journal of Neurochemistry, v. 103, n. 6, p. 2245-2255, 2007. CARBONE, D. L.; HANDA, R. J. Sex and stress hormone influences on the expression and activity of brain-derived neurotrophic factor. Neuroscience, v. 239, p. 295-303, 2013. CARDONA‐GÓMEZ, G. P.; CHOWEN, J. A.; GARCIA‐SEGURA, L. M. Estradiol and progesterone regulate the expression of insulin‐like growth factor‐I receptor and insulin‐like growth factor binding protein‐2 in the hypothalamus of adult female rats. Journal of Neurobiology, v. 43, n. 3, p. 269-281, 2000. CARLSON, D.; GORDEN, C. Current developments in spinal cord injury research. The Spine Journal, v. 2, n. 2, p. 116-128, 2002. CASHA, S. W. R. Y.; YU, W. R.; FEHLINGS, M. G. Oligodendroglial apoptosis occurs along degenerating axons and is associated with FAS and p75 expression following spinal cord injury in the rat. Neuroscience, v. 103, n. 1, p. 203-218, 2001. CHAOVIPOCH, P.; JELKS, K. A. B.; GERHOLD, L. M.; WEST, E. J.; CHONGTHAMMAKUN, S.; FLOYD, C. L. 17 β-Estradiol Is Protective in Spinal Cord Injury in Post-and Pre-Menopausal Rats. Journal of Neurotrauma, v. 23, n. 6, p. 830-852, 2006. CHI, X.; KALE, J.; LEBER, B.; ANDREWS, D. W. Regulating cell death at, on, and in membranes. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, v. 1843, p. 2100-2113, 2014. CHOI, D. W. Calcium-mediated neurotoxicity: relationship to specific channel types and role in ischemic damage. Trends in Neurosciences, v. 11, n. 10, p. 465-469, 1988. CITRON, B. A.; ARNOLD, P. M.; SEBASTIAN, C.; QIN, F.; MALLADI, S.; AMEENUDDIN, S.; LANDIS, M. E.; FESTOFF, B. W. Rapid upregulation of caspase-3 in rat spinal cord after injury: mRNA, protein, and cellular localization correlates with apoptotic cell death. Experimental Neurology, v. 166, n. 2, p. 213-226, 2000. CREGG, J. M.; DEPAUL, M. A.; FILOUS, A. R.; LANG, B. T.; TRAN, A.; SILVER, J. Functional regeneration beyond the glial scar. Experimental Neurology, v. 253, p. 197-207, 2014. CROWE, M. J.; BRESNAHAN, J. C.; SHUMAN, S. L.; MASTERS, J. N.; CROWE, M. S. Apoptosis and delayed degeneration after spinal cord injury in rats and monkeys. Nature Medicine, v. 3, n. 1, p. 73-76, 1997. CUZZOCREA, S.; GENOVESE, T.; MAZZON, E.; ESPOSITO, E.; DI PAOLA, R.; MUIA, C.; CRISAFULLI, C.; PELI, A.; BRAMANTI, P.; CHAUDRY, I. H. Effect of 17β-estradiol on signal transduction pathways and secondary damage in experimental spinal cord trauma. Shock, v. 29, n. 3, p. 362-371, 2008. DAS, A.; SMITH, J. A.; GIBSON, C.; VARMA, A. K.; RAY, S. K.; BANIK, N. L. Estrogen receptor agonists and estrogen attenuate TNF-α-induced apoptosis in VSC4.1 motoneurons. J Endocrinol., v. 208, n. 2, p. 171-182, 2011. 67 DESJARDINS, G.C.; BEAUDET, A.; MEANEY, M.J.; BRAWER, J.R. Estrogen-induced hypothalamic beta-endorphin neuron loss: a possible model of hypothalamic aging. Exp. Gerontol., v. 30, n. 3-4, p. 253-267, 1995. DIMAYUGA, F. O.; REED, J. L.; CARNERO, G. A.; WANG, C.; DIMAYUGA, E. R.; DIMAYUGA, V. M.; PERGER, A.; WILSON, M. E.; KELLER, J. N.; BRUCE-KELLER, A. J. Estrogen and brain inflammation: effects on microglial expression of MHC, costimulatory molecules and cytokines. Journal of Neuroimmunology, v. 161, n. 1, p. 123-136, 2005. DODEL, R. C.; DU, Y.; BALES, K. R.; GAO, F.; PAUL, S. M. Sodium salicylate and 17beta-estradiol attenuate nuclear transcription factor NF-kappaB translocation in cultured rat astroglial cultures following exposure to amyloid A beta(1±40) and lipopolysaccharides. J. Neurochem., v. 73, n. 4, p. 1453-1460, 1999. DOMENICONI, M.; CAO, Z.; SPENCER, T.; SIVASANKARAN, R.; WANG, K. C.; NIKULINA, E.; FILBIN, M. T. Myelin-associated glycoprotein interacts with the Nogo66 receptor to inhibit neurite outgrowth. Neuron, v. 35, n. 2, p. 283-290, 2002. DONCARLOS, L. L.; AZCOITIA, I.; GARCIA-SEGURA, L. M. Neuroprotective actions of selective estrogen receptor modulators. Psychoneuroendocrinology, v. 34, p. S113-S122, 2009. DONG, L.; WANG, W.; WANG, F.; STONER, M.; REED, J. C.; HARIGAI, M.; SAMUDIO, I.; KLADDE, M. P.; VYHLIDAL, C.; SAFE S. Mechanisms of transcriptional activation of bcl-2 gene expression by 17beta-estradiol in breast cancer cells. J Biol Chem., v. 274, n. 45, p. 32099-32107, 1999. DONNELLY, D. J.; POPOVICH, P. G. Inflammation and its role in neuroprotection, axonal regeneration and functional recovery after spinal cord injury. Experimental Neurology, v. 209, n. 2, p. 378-388, 2008. DUBAL, D. B.; SHUGHRUE, P. J.; WILSON, M. E.; MERCHENTHALER, I.; WISE, P. M. Estradiol modulates bcl-2 in cerebral ischemia: a potential role for estrogen receptors. The Journal of Neuroscience, v. 19, n. 15, p. 6385-6393, 1999. DUBREUIL, C. I.; WINTON, M. J.; MCKERRACHER, L. Rho activation patterns after spinal cord injury and the role of activated Rho in apoptosis in the central nervous system. The Journal of Cell Biology, v. 162, n. 2, p. 233-243, 2003. ELDADAH, B. A.; FADEN, A. I. Caspase pathways, neuronal apoptosis, and CNS injury. Journal of Neurotrauma, v. 17, n. 10, p. 811-829, 2000. ELKABES, S., NICOT, A.B.. Sex steroids and neuroprotection in spinal cord injury: A review of preclinical investigations, Exp. Neurol., 2014. Disponível em <http://dx.doi.org/10.1016/j.expneurol.2014.01.008>. Retirado 27 de jun 2014. EMERY, E.; ALDANA, P.; BUNGE, M. B.; PUCKETT, W.; SRINIVASAN, A.; KEANE, R. W.; LEVI, A. D. Apoptosis after traumatic human spinal cord injury. Journal of Neurosurgery, v. 89, n. 6, p. 911-920, 1998. FAROOQUE, M.; SUO, Z.; ARNOLD, P. M.; WULSER, M. J.; CHOU, C. T.; VANCURA, R. W.; S FOWLER, S.; FESTOFF, B. W. Gender-related differences in recovery of locomotor function after spinal cord injury in mice. Spinal Cord, v. 44, n. 3, p. 182-187, 2006. 68 FAWCETT, J. W.; ASHER, R. A. The glial scar and central nervous system repair. Brain Research Bulletin, v. 49, n. 6, p. 377-391, 1999. FEHLINGS, M. G.; NGUYEN, D. H. Immunoglobulin G: a potential treatment to attenuate neuroinflammation following spinal cord injury. Journal of Clinical Immunology, v. 30, n. 1, p. 109-112, 2010. FLEMING, J. C.; NORENBERG, M. D.; RAMSAY, D. A.; DEKABAN, G. A.; MARCILLO, A. E.; SAENZ, A. D.; WEAVER, L. C. The cellular inflammatory response in human spinal cords after injury. Brain, v. 129, n. 12, p. 3249-3269, 2006. FORYST-LUDWIG, A.; KINTSCHER, U. Metabolic impact of estrogen signalling through ERalpha and ERbeta. The Journal of Steroid Biochemistry and Molecular Biology, v. 122, n. 1, p. 74-81, 2010. GARCIA-SEGURA, L. M.; CARDONA-GOMEZ, P.; NAFTOLIN, F.; CHOWEN, J. A. Estradiol upregulates Bcl-2 expression in adult brain neurons. Neuroreport, v. 9, n. 4, p. 593-597, 1998. GARCIA-SEGURA, L. M.; WOZNIAK, A.; AZCOITIA, I.; RODRIGUEZ, J. R.; HUTCHISON, R. E.; HUTCHISON, J. B. Aromatase expression by astrocytes after brain injury: implications for local estrogen formation in brain repair. Neuroscience, v. 89, n. 2, p. 567-578, 1999. GARCIA-SEGURA, L. M.; AZCOITIA, I.; DONCARLOS, L. L. Neuroprotection by estradiol. Progress in Neurobiology, v. 63, n. 1, p. 29-60, 2001. GIBBS, R. B. Treatment with estrogen and progesterone affects relative levels of brain-derived neurotrophic factor mRNA and protein in different regions of the adult rat brain. Brain Research, v. 844, n. 1, p. 20-27, 1999. GIRAUD, S. N.; CARON, C. M.; PHAM-DINH, D.; KITABGI, P.; NICOT, A. B. Estradiol inhibits ongoing autoimmune neuroinflammation and NFkappaB-dependent CCL2 expression inreactive astrocytes. Proc Natl Acad Sci U S A., v. 107, n. 18, p. 8416-8421, 2010. GOLDBERGER, M. E.; BREGMAN, B. S.; VIERCK JR, C. J.; BROWN, M. Criteria for Assessing Recovery of Function After Spinal Cord Injury: Behavioral Methods. Journal of Neurotrauma, v. 8, n. 1, p. 3-9, 1991. GRANT, G. Rat Nervous System. Elsevier, 2004. GREEN, P. S.; SIMPKINS, J. W. Neuroprotective effects of estrogens: potential mechanisms of action. International Journal of Developmental Neuroscience, v. 18, n. 4, p. 347-358, 2000. GRUNER, JOHN A. A monitored contusion model of spinal cord injury in the rat. Journal of Neurotrauma, v. 9, n. 2, p. 123-128, 1992. GRUOL, D. L.; NELSON, T. E. Physiological and pathological roles of interleukin-6 in the central nervous system. Molecular Neurobiology, v. 15, n. 3, p. 307-339, 1997. GUERRERO, A. R.; UCHIDA, K.; NAKAJIMA, H.; WATANABE, S.; NAKAMURA, M.; JOHNSON, W. E.; BABA, H. Blockade of interleukin-6 signaling inhibits the classic 69 pathway and promotes an alternative pathway of macrophage activation after spinal cord injury in mice. J Neuroinflammation, v. 9, n. 1, p. 40, 2012. GUPTARAK, J.; WIKTOROWICZ, J. E.; SADYGOV, R. G.; ZIVADINOVIC, D.; PAULUCCI-HOLTHAUZEN, A. A.; VERGARA, L.; NESIC, O. The cancer drug tamoxifen: a potential therapeutic treatment for spinal cord injury. J Neurotrauma., v. 31, n. 3, p. 268-283, 2014. HAGE, F. G.; OPARIL, S. Ovarian hormones and vascular disease. Current Opinion in Cardiology, v. 28, n. 4, p. 411-416, 2013. HAGG, T.; OUDEGA, M. Degenerative and spontaneous regenerative processes after spinal cord injury. Journal of Neurotrauma, v. 23, n. 3-4, p. 263-280, 2006. HAPPEL, R. D.; Smith, K. P.; BANIK, N. L.; Powers, J.M.; Hogan, E. L.; Balentine, D.J. Ca2+ accumulation in experimental spinal cord trauma. Brain Research, v. 211, n. 2, p. 476-479, 1981. HAUSMANN, O. N. Post-traumatic inflammation following spinal cord injury. Spinal Cord, v. 41, n. 7, p. 369-378, 2003. HAYES, K. C.; KAKULAS, B. A. Neuropathology of human spinal cord injury sustained in sports-related activities. J Neurotrauma., v. 14, n. 4, 235-248, 1997. HISAHARA, S.; SHOJI, S. I.; OKANO, H.; MIURA, M. ICE/CED‐3 Family Executes Oligodendrocyte Apoptosis by Tumor Necrosis Factor. Journal of Neurochemistry, v. 69, n. 1, p. 10-20, 1997. HU, R.; SUN, H.; ZHANG, Q.; CHEN, J.; WU, N.; MENG, H.; CUI, G.; HU, S.; LI, F.; LIN, J.; WAN, Q.; FENG, H. G-protein coupled estrogen receptor 1 mediated estrogenic neuroprotection against spinal cord injury*. Critical Care Medicine, v. 40, n. 12, p. 3230-3237, 2012. HULSEBOSCH, C. E. Recent advances in pathophysiology and treatment of spinal cord injury. Advances in Physiology Education, v. 26, n. 4, p. 238-255, 2002. IMAIZUMI, T.; KOCSIS, J. D.; WAXMAN, S. G. Anoxie Injury in the Rat Spinal Cord: Pharmacological Evidence for Multiple Steps in Ca2+-Dependent Injury of the Dorsal Columns. Journal of Neurotrauma, v. 14, n. 5, p. 299-311, 1997. ISMAILOĞLU, O.; ORAL, B.; GÖRGÜLÜ, A.; SÜTÇÜ, R.; DEMIR, N. Neuroprotective effects of tamoxifen on experimental spinal cord injury in rats. J Clin Neurosci., v 17, n. 10, p. 1306-1310, 2010. ISMAILOĞLU, Ö.; ORAL, B.; SÜTCÜ, R.; KARA, Y.; TOMRUK, O.; DEMIR, N. Neuroprotective effects of raloxifene on experimental spinal cord injury in rats. Am J Med Sci., v. 345, n. 1, p. 39-44, 2013. KACHADROKA, S.; HALL, A. M.; NIEDZIELKO, T. L.; CHONGTHAMMAKUN, S.; FLOYD, C. L. Effect of Endogenous Androgens on 17 β-Estradiol-Mediated Protection after Spinal Cord Injury in Male Rats. Journal of Neurotrauma, v. 27, n. 3, p. 611-626, 2010. KANDEL E.R.; SCHWARTZ J.M.; JESSELL T.M. Principles of Neuronal Science. The McGraw-Hill Companies, EUA, 4ed., 2000. 70 KARKI, P.; SMITH, K.; JOHNSON, J. J.; LEE, E. Astrocyte-derived growth factors and estrogen neuroprotection: role of transforming growth factor-α in estrogen-induced upregulation of glutamate transporters in astrocytes. Mol Cell Endocrinol., v. 389, n. 1-2, p. 58-64, 2014. KLOOS A.D.; FISHER L.C.; DETLOFF M.R.; HASSENZAHL D.L.; BASSO D.M. Stepwise motor and all-or-none sensory recovery is associated with nonlinear sparing after incremental spinal cord injury in rats. Exp Neurol, v. 191, n.2, p. 251–265, 2005. KNOBLACH, S. M.; HUANG, X.; VANGELDEREN, J.; CALVA‐CERQUEIRA, D.; FADEN, A. I. Selective caspase activation may contribute to neurological dysfunction after experimental spinal cord trauma. Journal of Neuroscience Research, v. 80, n. 3, p. 369-380, 2005. KRAFT, A. D.; HARRY, G. J. Features of microglia and neuroinflammation relevant to environmental exposure and neurotoxicity. International Journal of Environmental Research and Public Health, v. 8, n. 7, p. 2980-3018, 2011. KWON, B. K.; BORISOFF, J. F.; TETZLAFF, W. Molecular targets for therapeutic intervention after spinal cord injury. Molecular Interventions, v. 2, n. 4, p. 244, 2002a. KWON, B. K.; OXLAND, T. R.; TETZLAFF, W. Animal models used in spinal cord regeneration research. Spine, v. 27, n. 14, p. 1504-1510, 2002b. KWON, B. K.; TETZLAFF, W.; GRAUER, J. N.; BEINER, J.; VACCARO, A. R. Pathophysiology and pharmacologic treatment of acute spinal cord injury. The Spine Journal, v. 4, n. 4, p. 451-464, 2004. KWON, B. K.; OKON, E.; HILLYER, J.; MANN, C.; BAPTISTE, D.; WEAVER, L. C.; FEHLINGS, M. G.; TETZLAFF, W. A systematic review of non-invasive pharmacologic neuroprotective treatments for acute spinal cord injury. Journal of Neurotrauma, v. 28, n. 8, p. 1545-1588, 2011. KWON, B. K.; GHAG, A.; REICHL, L.; DVORAK, M. F.; ILLES, J.; TETZLAFF, W. Opinions on the preclinical evaluation of novel therapies for spinal cord injury: a comparison between researchers and spinal cord-injured individuals. J Neurotrauma., v. 29, n. 14, p. 2367-2374, 2012. LANKHORST, A. J.; TER LAAK, M. P.; HAMERS, F.; GISPEN, W. H. Combined treatment with αMSH and methylprednisolone fails to improve functional recovery after spinal injury in the rat. Brain Research, v. 859, n. 2, p. 334-340, 2000. LAWRENCE T. The nuclear factor NF-kappaB pathway in inflammation. Cold Spring Harb Perspect Biol., v. 1, n. 6, 2009. doi: 10.1101/cshperspect.a001651. Disponpivel em: <cshperspectives.cshlp.org>. Retirado 04 de out. 2013. LEE, B. B.; CRIPPS, R. A.; FITZHARRIS, M.; WING, P. C. The global map for traumatic spinal cord injury epidemiology: update 2011, global incidence rate. Spinal Cord, v. 52, n. 2, p. 110-116, 2013. LEE, H. R.; KIM, T. H.; CHOI, K. C. Functions and physiological roles of two types of estrogen receptors, ERα and ERβ, identified by estrogen receptor knockout mouse. Laboratory Animal Research, v. 28, n. 2, p. 71-76, 2012a. 71 LEE, J. Y.; CHOI, S. Y.; OH, T. H.; YUNE, T. Y.17β-Estradiol inhibits apoptotic cell death of oligodendrocytes by inhibiting RhoA-JNK3 activation after spinal cord injury. Endocrinology, v. 153, n. 8, p. 3815-3827, 2012b. LEE, Y. B.; YUNE, T. Y.; BAIK, S. Y.; SHIN, Y. H.; DU, S.; RHIM, H.; LEE, E. B.; KIM, Y. C.; SHIN, M. L.; MARKELONIS, G. J.; OH, T. H. Role of Tumor Necrosis Factor-α in Neuronal and Glial Apoptosis after Spinal Cord Injury. Exp Neurol., v. 166, n. 1, p. 190-195, 2000. LENT R. Cem bilhões de neurônios: Conceitos Fundamentais de Neurociência. Editora Atheneu, 2ª ed., 2010. LI, Q. M.; TEP, C.; YUNE, T. Y.; ZHOU, X. Z.; UCHIDA, T.; LU, K. P.; YOON, S. O. Opposite regulation of oligodendrocyte apoptosis by JNK3 and Pin1 after spinal cord injury. The Journal of Neuroscience, v. 27, n. 31, p. 8395-8404, 2007. LIANZA, S.; CASALIS, M.E.P.; GREVE, J.M.D.; EICHBERG, R. Lesão medular. In: Lianza S. Medicina de Reabilitação. Guanabara-Koogan, São Paulo, 3ª. ed., p. 299-321, 2001. LIU, X. Z.; XU, X. M.; HU, R.; DU, C.; ZHANG, S. X.; MCDONALD, J. W.; CHOI, D. W. Neuronal and glial apoptosis after traumatic spinal cord injury. The Journal of Neuroscience, v. 17, n. 14, p. 5395-5406, 1997. LIVERMAN T.C.; ALTEVOGT M.B.; JOY E.J.; JOHNSON T.R. Spinal cord injury: progress, promise, and priorities. National Academy of Sciences. N.W. Washington, DC., 2005. LOANE, D. J.; BYRNES, K. R. Role of microglia in neurotrauma. Neurotherapeutics, v. 7, n. 4, p. 366-377, 2010. MACHADO, Â. Neuroanatomia Funcional. Editora Ateneu, São Paulo, 2ª ed., 2007. MAIER B.; LEHNERT M.; LAURER H. L.; MAUTES A. E.; STEUDEL W. I.; MARZI I. Delayed elevation of soluble tumor necrosis factor receptors p75 and p55 in cerebrospinal fluid and plasma after traumatic brain injury. Shock, v. 26, n. 2, p. 122-127, 2006. MANTHEY, D.; BEHL, C. From structural biochemistry to expression profiling: neuroprotective activities of estrogen. Neuroscience, v. 138, n. 3, p. 845-850, 2006. MARTIN, L. J. Neuronal cell death in nervous system development, disease, and injury (Review). International Journal of Molecular Medicine, v. 7, n. 5, p. 455-478, 2001. MERRILL, J. E.; BENVENISTE, E. N. Cytokines in inflammatory brain lesions: helpful and harmful. Trends in Neurosciences, v. 19, n. 8, p. 331-338, 1996. MILLER, V. M.; DUCKLES, S. P. Vascular actions of estrogens: functional implications. Pharmacological Reviews, v. 60, n. 2, p. 210-241, 2008. MODI, H. N.; SUH, S. W.; HONG, J. Y.; YANG, J. H. The effects of spinal cord injury induced by shortening on motor evoked potentials and spinal cord blood flow: an experimental study in Swine. J Bone Joint Surg Am., v. 93, n. 19, p. 1781-1789, 2011. 72 MOLINA, A. E. I. S. Análise da sensibilidade e reprodutibilidade da escala de Basso, Beattie e Bresnahan (BBB) em ratos Wistar. Tese de Doutorado. Universidade de São Paulo, São Paulo, 2006. MOOSMANN, B.; BEHL, C. The antioxidant neuroprotective effects of estrogens and phenolic compounds are independent from their estrogenic properties. Proceedings of the National Academy of Sciences, v. 96, n. 16, p. 8867-8872, 1999. MORIARTY, K.; KIM, K. H.; BENDER, J. R. Estrogen receptor-mediated rapid signaling. Endocrinology, v. 147, n. 12, p. 5557-5563, 2006. MOSQUERA, L.; COLÓN, J. M.; SANTIAGO, J. M.; TORRADO, A. I.; MELÉNDEZ, M.; SEGARRA, A. C.; RODRÍGUEZ-ORENGO, J. F.; MIRANDA, J. D. Tamoxifen and estradiol improved locomotor function and increased spared tissue in rats after spinal cordinjury: their antioxidant effect and role of estrogen receptor alpha. Brain Res., v. 1561, p. 11-22, 2014. NAKAJIMA, H.; UCHIDA, K.; KOBAYASHI, S.; INUKAI, T.; HORIUCHI, Y.; YAYAMA, T.; SATO, R.; BABA, H. Rescue of rat anterior horn neurons after spinal cord injury by retrograde transfection of adenovirus vector carrying brain-derived neurotrophic factor gene. Journal of Neurotrauma, v. 24, n. 4, p. 703-712, 2007. NAKAMURA, M.; HOUGHTLING, R. A.; MACARTHUR, L.; BAYER, B. M.; BREGMAN, B. S. Differences in cytokine gene expression profile between acute and secondary injury in adult rat spinal cord. Experimental Neurology, v. 184, n. 1, p. 313-325, 2003. NICHOLSON, D. W.; THORNBERRY, N. A. Caspases: killer proteases. Trends in Biochemical Sciences, v. 22, n. 8, p. 299-306, 1997. NILSEN, J. Estradiol and neurodegenerative oxidative stress. Frontiers in Neuroendocrinology, v. 29, n. 4, p. 463-475, 2008. NILSEN, J.; BRINTON, R. D. Mechanism of estrogen-mediated neuroprotection: regulation of mitochondrial calcium and Bcl-2 expression. Proceedings of the National Academy of Sciences, v. 100, n. 5, p. 2842-2847, 2003. NILSEN, J.; BRINTON, R. D. Mitochondria as therapeutic targets of estrogen action in the central nervous system. Current Drug Targets-CNS & Neurological Disorders, v. 3, n. 4, p. 297-313, 2004. NILSSON, S.; MÄKELÄ, S.; TREUTER, E.; TUJAGUE, M.; THOMSEN, J.; ANDERSSON, G.; ENMARK E.; PETTERSSON K.; WARN M.; GUSTAFSSON, J. Å. Mechanisms of estrogen action. Physiological Reviews, v. 81, n. 4, p. 1535-1565, 2001. NOBLE, L. J.;WRATHALL, J. R. Spinal cord contusion in the rat: morphometric analyses of alterations in the spinal cord. Exp Neurol., v. 88, n. 1, p. 135-149, 1985. NORENBERG, M. D.; SMITH, J.; MARCILLO, A. The pathology of human spinal cord injury: defining the problems. Journal of Neurotrauma, v. 21, n. 4, p. 429-440, 2004. NUMAKAWA, Y.; MATSUMOTO, T.; YOKOMAKU, D.; TAGUCHI, T.; NIKI, E.; HATANAKA H.; KUNUGI, H.; NUMAKAWA, T. 17beta-estradiol protects cortical neurons against oxidative stress-induced cell death through reduction in the activity of mitogen- 73 activated protein kinase and in the accumulation of intracellular calcium. Endocrinology, v. 148, n. 2, p. 627-637, 2007. OYINBO, C. A. Secondary injury mechanisms in traumatic spinal cord injury: a nugget of this multiply cascade. Acta Neurobiol Exp (Wars), v. 71, n. 2, p. 281-299, 2011. PAN, J. Z.; NI, L.; SODHI, A.; AGUANNO, A.; YOUNG, W.; HART, R. P. Cytokine activity contributes to induction of inflammatory cytokine mRNAs in spinal cord following contusion. Journal of Neuroscience Research, v. 68, n. 3, p. 315-322, 2002. PAPKA, R. E.; STOREY-WORKLEY M.; SHUGHRUE, P. J.; MERCHENTHALER, I.; COLLINS, J. J.; USIP, S.; SAUNDERS, P. T.; SHUPNIK, M. Estrogen receptor-alpha and beta-immunoreactivity and mRNA in neurons of sensory and autonomicganglia and spinal cord. Cell Tissue Res., v. 304, n. 2, p. 193-214, 2001. PEDRAM, A.; RAZANDI, M.; AITKENHEAD, M.; LEVIN, E. R. Estrogen inhibits cardiomyocyte hypertrophy in vitro Antagonism of calcineurin-related hypertrophy through induction of MCIP1. Journal of Biological Chemistry, v. 280, n. 28, p. 26339-26348, 2005. PEREZ-POLO, J. R.; HALL, K.; LIVINGSTON, K.; WESTLUND, K. Steroid induction of nerve growth factor synthesis in cell culture. Life Sciences, v. 21, n. 10, p. 1535-1543, 1977. PIKE, C.J. Estrogen modulates neuronal Bcl-XL expression and beta-amyloid-induced apoptosis: relevance to Alzheimer's disease. J. Neurochem, v. 72, n. 4, p. 1552-1563, 1999. PINEAU I
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