QUANTITATIVE-EVALUATION OF NEURONAL LOSS IN THE DORSAL HIPPOCAMPUS INRATS WITH LONG-TERM PILOCARPINE SEIZURES

Systemic administration of the cholinergic agonist pilocarpine (350-40 0 mg/kg, i.p.) to rats induces acute behavioral and EEG status epilept icus followed by apparent complete neurological recovery. In rats rece iving higher doses of pilocarpine (i.e., 380-400 mg/kg), recurrent sei zures reappear 2-2.5 weeks later and continue to occur as long as the rats are kept alive. Stereological estimates of neurons in regions CA1 , CA3 and the dentate granule cell layer in the dorsal hippocampus sho w a dose-dependent neuronal loss in the CA3 and CA1 subregions. The gr anule cell layer of the dentate gyrus is not affected. No progressive neuronal loss was observed in the regions studied after 3, 6 and 12 we eks during which the animals displayed spontaneous recurrent seizures. The temporal profile of the epileptic condition induced by pilocarpin e and the resulting pattern of neuronal loss in the rat hippocampus ar e similar to those seen in many cases of human temporal lobe epilepsy. The neuronal loss is dose-dependent and primarily results from the ac ute pilocarpine-induced seizures as chronic seizures do not produce an y measurable additional cell loss in the regions examined in the exper imental model used in this study.