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Temporal lobe epilepsy (TLE) is a common form of drug-resistant epilepsy that sometimes responds to dietary manipulation such as the 'ketogenic diet'. Here we have investigated the effects of metformin in the rat pilocaroin model of TLE. Male rats were treated with intra peritoneal injection of pilocarpine hydrochloride, in dose of 360 mg/kg to induce status epilepticus (SE). At 45 day after induction of SE, metformin was injected intraperitoneally in dose of 250 mg/kg/day for 5 days. We show that metformin potently reduces the progression of seizures and blocks seizure-induced over-expression of brain-derived neurotropic factor (BDNF) and its receptor, Tropomyosin receptor kinase B (TrkB). We have shown that this reduced expression pattern is mediated by the transcriptional co-repressor CtBP (C-terminal binding protein). Moreover, metformin decreased mechanistic target of rapamycin (mTOR) activation through activation of AMP-activated protein kinase (AMPK) signaling pathway. Our findings have been shown that metformin has anticonvulsant and antiepileptic properties, and suggesting that antiglycolytic compounds such as metformin may represent a new class of drugs for treating epilepsy.

Introduction:Cerebral ischemia and reperfusion causes physiological and biochemical changes in the neuronal cells that will eventually lead to cell damage. Evidence indicates that exercise reduces the ischemia and reperfusion-induced brain damages in animal models of stroke. In the present study, the effect of exercise preconditioning on brain edema and neurological movement disorders following the cerebral ischemia and reperfusion in rats was investigated.Methods:Twenty-one adult male wistar rats (weighing 260–300 g) were randomly divided into three groups: sham operated, exercise plus ischemia, and ischemia group (7 rats per group). The rats in exercise group were trained to run on a treadmill 5 days a week for 4 weeks. Transient focal cerebral ischemia and reperfusion were induced by middle cerebral artery occlusion (MCAO) for 60 minutes, followed by reperfusion for 23 hours. After 24 hours ischemia, movement disorders were tested by a special neurological examination. Also, cerebral edema was assessed by determining the brain water content.Results:The results showed that pre-ischemic exercise significantly reduced brain edema (P<0.05). In addition, exercise preconditioning decreased the neurological movement disorders caused by brain ischemia and reperfusion (P<0.05).Conclusion:Preconditioning by exercise had neuroprotective effects against brain ischemia and reperfusion-induced edema and movement disorders. Thus, it could be considered as a useful strategy for prevention of ischemic injuries, especially in people at risk.