Progressive Evaluation of Memory and Hippocampal Histomorphology in Adult Wistar Rats Following Lithium-Pilocarpine-induced Temporal Lobe Epilepsy

Epilepsy is the third most common neurologic disorder, following stroke and Alzheimer's disease. It affects an estimated 1% of the world's population and has no respect for age and gender. This study was designed to examine the histomorphology of neurons in the different sub-fields of the hippocampus, assess the neurobehavioral changes of memory and investigate the time-line dynamics of the above parameters at different phases of epileptogenesis following lithium-pilocarpine-induced TLE in Wistar rats. Sixty 12 weeks old Wistar rats were randomly assigned into 3 groups viz; Control group (15 rats) received 2ml/kg of normal saline intraperitoneally. Sham group (15 rats) was administered diazepam (10 mg/kg) and normal saline 2mL/kg intraperitoneally. Experimental group (30 rats) was administered lithium chloride (127 mg/kg) subcutaneously 24 hours before administration of pilocarpine (30 mg/kg) intraperitoneally. At 90 minutes after seizure onset, the rats received diazepam injection (10 mg/kg) intraperitoneally. The rats were observed for 7-day transient seizure-free period (latent phase), followed by the 7- day spontaneous recurrent seizure period (chronic phase). 5 rats each (from the control and sham groups) and 10 rats from the experimental group were sacrificed at the end of the acute, latent and chronic phases of epileptogenesis. In the acute, latent and chronic phases, there is a significant increase in degenerating neuronal density in the experimental group when compared with control [(p<0.001), (p<0.001) and (p<0.001) respectively] and sham [(p<0.001), (p<0.001) and (p<0.001) respectively] groups, but no significant difference was noted between the control and sham groups [(p=0.11), (p=0.62) and (p=0.57) respectively] across the phases. Memory impairment was only observed when experimental groups were compared with control and sham groups across the three phases of epileptogenesis. Neurodegenerative features observed in different hippocampal sub-fields gives a better explanation about memory impairment associated with this condition and further unravels the scientific basis of epileptogenesis following lithium-pilocarpine-induced TLE.

Key Words: TLE, lithium-pilocarpine, epileptogenesis, memory, hippocampus.