Investigation of the Possible Protective Effects of Ketamine and Dantrolene on the Hippocampal Apoptosis and Spatial Learning in Rats Exposed to Repeated Electroconvulsive Seizures as a Model of Status Epilepticus

Abstract

AIM: To evaluate the possible neuroprotective effects of ketamine and dantrolene on the hippocampal apoptosis and spatial learning in rats exposed to repeated electroconvulsive seizures (ECS) as a model of status epilepticus (SE).

MATERIAL and METHODS: Twenty-four rats were assigned to 4 groups. 1st Group was Sham. 2nd Group was ECS: ECS was induced by ear electrodes via electrical stimulation. The same ECS protocol was applied to the 3th and 4th Groups which received ketamine (40 mg/kg s.c.) or dantrolene (5 mg/kg i.p.) 1 h before each ECS, respectively. Following 30 days of recovery, the cognitive status of the animals was evaluated via Morris Water Maze (MWM). The same experimental protocol was repeated 14 days afterward to evaluate the retention of the memory. Hippocampal apoptosis was examined in corresponding experimental groups.

RESULTS: All the animals in four groups learned the task with no significant difference between groups in MWM. The ECS+ketamine group showed memory impairment 14 days afterward. ECS+dantrolene group was not different from controls. ECS caused long term apoptotic processes in dentate gyrus (DG) and non-apoptotic neuronal injury in CA1 and CA2.

CONCLUSION: Dantrolene and ketamine inhibited apoptosis and showed neuroprotective effects. Although ketamine and dantrolene inhibited ECS-induced apoptosis and non-apoptotic injury, they did not produce similar effects on memory retention. It will be warranted to evaluate cognitive dysfunction by taking into consideration the other factors in addition to apoptosis and neurodegenerative changes.