Vascular and apoptotic changes in the placode of myelomeningocele mice during the final stages of in utero development

• Autor(a) principal: Reis, J.L.
• Data de Publicação: 2008
• Outros Autores: Correia-Pinto, J., Monteiro, M.P., Costa, M., Hutchins, G.M.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.16/424
• topic: apoptosis; immunocytochemistry; endothelium; inflammation

JOAQUIM L. REIS, M.D., PH.D.,1,2 JORGE CORREIA-PINTO, M.D., PH.D.,3,4 MARIANA P. MONTEIRO, M.D., PH.D.,1 MADALENA COSTA, B.SC.,1 AND GROVER M. HUTCHINS, M.D.5 1Department of Anatomy, Abel Salazar Institute for the Biomedical Sciences and Unit for Multidisciplinary Biomedical Research, University of Porto; 2Department of Neurosurgery, Santo António General Hospital; 4Department of Pediatric Surgery, São João Hospital, Porto; 3Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Braga, Portugal; and 5Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland Object. Myelomeningocele (MMC) is a primary neurulation defect that is associated with devastating neurological disabilities in affected newborns. To better characterize the in utero neurodegenerative process of MMC, the authors investigated the changes in vascular organization, apoptosis, and the presence of inflammatory cells during gestation by using a mutant mouse model of MMC. Methods. The curly tail/loop tail (ct/lp) mutant mouse model of MMC was chosen to obtain fetuses at different stages of gestation. Mouse fetuses harboring MMC were harvested by caesarean section at embryonic Days 14.5, 16.5, and 18.5 (complete mouse gestation at 19 days, 6 mice/group); littermate fetuses with the same gestational age but without an MMC were used as controls. Samples of the MMC placode or normal spinal cord were stained for immunocytochemical labeling with caveolin antibody (endothelium marker) and activated caspase-3 antibody (apoptosis marker). Samples were morphometrically analyzed with a computer-assisted image analyzer. Results. The MMC mice presented with an increase in vascular density from embryonic Days 16.5–18.5 and an enhanced number of apoptotic cells at embryonic Day 18.5, compared with controls. There were scarce signals of an inflammatory reaction in the MMC placode, as a few infiltrating neutrophils were seen only at embryonic Day 18.5. Conclusions. Fetal placodes in MMC mice showed evidence of increased vascular density since embryonic Day 16.5 and increased apoptosis at embryonic Day 18.5. These new data support the view that in utero changes of the MMC placode, occurring during the last stages of gestation, contribute to the neuropathological manifestations in fullterm newborns with MMC. (DOI: 10.3171/PED/2008/2/8/150)