Damage, reorganization, and abnormal neocortical hyperexcitability in the pilocarpine model of temporal lobe epilepsy

• Autor(a) principal: Sanabria, Emilio Rafael Garrido [UNIFESP]
• Data de Publicação: 2002
• Outros Autores: Silva, Alexandre Valotta da [UNIFESP], Spreafico, R., Cavalheiro, Esper Abrão [UNIFESP]
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNIFESP
• Texto Completo: http://repositorio.unifesp.br/handle/11600/26683; http://dx.doi.org/10.1046/j.1528-1157.43.s.5.31.x
• topic: neocortex; epilepsy; pilocarpine; immunocytochemistry; burst

Purpose: Clinical, neuropathological, and electro-physiological data have shown that limbic structures are involved in the pathogenesis of temporal lobe epilepsy (TLE). in most cases, limbic-originated seizures frequently spread to extrahippocampal areas. It is unclear whether such distant circuitries, especially the neocortex, exhibit abnormal electrophysiology as consequences of a chronic epileptogenic process. the present research studied neuropathological abnormalities and in vitro electrophysiological properties of sensorimotor neocortex in pilocarpine-treated epileptic rats.Methods: Adult epileptic animals showing six to seven seizures/week and saline-injected rats were selected for neurohistology. Coronal sections were sampled throughout the anteroposterior extent of the diencephalon and stained with cresyl violet (Nissl). Immunocytochemistry (ICC) was performed using anti-neurofilament (SMI-311) antibody. Extracellular (layer II/III) and intracellular (layer V) recordings were per-formed in coronal sensorimotor neocortical slices. Several electrophysiological aspects were examined such as evoked responses, intrinsic properties, and firing patterns of layer V pyramidal cells.Results: Niss1 staining showed a significant decrease of cortical thickness in epileptic rats when compared with controls, particularly in superficial layers (II-IV). Such abnormalities were also revealed by SMI-311 staining. SMI-311-labeled dendrite arborizations were more complex in layers I-II of epileptic rats. Epileptic rats manifested several abnormalities in extracellular field responses including hyperresponsiveness and presence of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA)-mediated polysynaptic activity. Although no significant changes were observed concerning passive intrinsic properties, it was possible to detect a higher proportion of bursting neurons distributed in layer V (60%) of epileptic rats compared with 22% in control slices.Conclusions: Taken together, our findings indicate damage, reorganization, and chronic hyperexcitability of sensorimotor neocortex in experimental TLE.