Behavioral and histological assessment of the effect of intermittent feeding in the pilocarpine model of temporal lobe epilepsy

Abstract

Temporal lobe epilepsy (TLE) is the most resistant type of epilepsy. Currently available drugs for epilepsy are not antiepileptogenic. A novel treatment for epilepsy would be to block or reverse the process of epileptogenesis. We used intermittent feeding (IF) regimen of the dietary restriction (DR) to study its effect on epileptogenesis and neuroprotection in the pilocarpine model of TLE in rats. The effect of IF regimen on the induction of status epilepticus (SE), the duration of latent period, and the frequency, duration, severity and the time of occurrence of Spontaneous Recurrent Seizures (SRS) were investigated. We also studied the effect of IF regimen on hippocampal neurons against the excitotoxic damage of prolonged SE (about 4h) induced by pilocarpine. The animals (Wistar, male, 200-250g) were divided into four main groups: AL-AL (ad libitum diet throughout), AL-IF (PfS) [IF post-first seizure], AL-IF (PSE) [IF post-SE] and IF-IF (IF diet throughout), and two AL and IF control groups. SE was induced by pilocarpine (350mg/kg, i.p.) and with diazepam (6mg/kg, i.p.) injected after 3h, the behavioral signs of SE terminated at about 4h (AL animals, n=29, 260.43+/-8.74min; IF animals, n=19, 224.32+/-20.73min). Behavioral monitoring was carried out by 24h video recording for 3 weeks after the first SRS. Rat brains were then prepared for histological study with Nissl stain and cell counting was done in CA1, CA2 and CA3 regions of the hippocampus. The results show that the animals on IF diet had significantly less SE induction and significantly longer duration of latent period (the period of epileptogenesis) was seen in IF-IF group compared to the AL-AL group. The severity of SRS was significantly more in AL-IF (PfS) compared to the AL-IF (PSE) group. These results indicate that IF diet can make rats resistant to the induction of SE and can prolong the process of epileptogenesis. The results of the histological study show that the number of pyramidal neurons was statistically less in CA1, CA2 and CA3 of the hippocampus in the experimental groups compared to the control groups. However, IF regimen could not protect the hippocampal neurons against the excitotoxic injury caused by a prolonged SE. We conclude that IF regimen can significantly influence various behavioral characteristics of pilocarpine model of TLE. Further studies can elaborate the exact mechanisms as well as its possible role in the treatment of human TLE.