Damage, reorganization, and abnormal neocortical hyperexcitability in the pilocarpine model of temporal lobe epilepsy.
OBJECTIVE
Clinical, neuropathological, and electrophysiological 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 performed 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
Nissl 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-isoxazolepropionate (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.
Sanabria
Emilio R Garrido
ER
Laboratório de Neurologia Experimental, Universidade Federal de São Paulo-Escola Paulista de Medicina, Rua Botucatu 862, CEP 04023-900, São Paulo, SP, Brazil.
Silva
Alexandre V da
AV
Spreafico
Roberto
R
Cavalheiro
Esper A
EA
D000818:Animals; D003292:Convulsants; D004594:Electrophysiology; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced* / Q000503:physiopathology*; D007150:Immunohistochemistry; D008297:Male; D019579:Neocortex / Q000473:pathology* / Q000503:physiopathology*; D009473:Neuronal Plasticity; D010862:Pilocarpine; D051381:Rats; D017208:Rats, Wistar
D003292:Convulsants; D010862:Pilocarpine