Mitochondrial ATP-sensitive potassium channel, MitoKATP, ameliorates mitochondrial dynamic disturbance induced by temporal lobe epilepsy.

Temporal lobe epilepsy leads to a disturbance in the function and dynamic of the mitochondria. The mitoKATP channel is an important factor in controlling mitochondrial function. In this study, the protective role of mitoKATP was studied in temporal lobe epilepsy through the regulation of mitochondrial dynamic proteins. After induction of epilepsy, 5-HD (the inhibitor of mitoKATP) was administered daily for either 24 or 72 h. The results revealed an imbalance in dynamic proteins after epilepsy, specifically in the first 72 h. The disturbance in the mitochondrial dynamic worsened after blocking mitoKATP. In conclusion, mitoKATP has an important role in balancing mitochondrial dynamic proteins in epilepsy.

Evaluation of the ameliorative effects of oral administration of metformin on epileptogenesis in the temporal lobe epilepsy model in rats.

AIMS: Understanding the underlying molecular mechanisms involved in epileptogenesis is necessary to target the best therapeutic interventions in epilepsy. Recently, it has been postulated that metformin, an old antidiabetic oral drug, has anti-seizure properties mostly due to its antioxidant activities. This study was designed to evaluate the ameliorative effects of metformin on the progression of epilepsy in the temporal lobe epilepsy model in rats. MAIN METHODS: Temporal lobe Epilepsy was induced by intracerebroventricular microinjection of kainic acid. Metformin was orally administered for two weeks before induction of epilepsy. Anti-epileptogenic activity of metformin was evaluated by intracranial electroencepholography (IEEG) recording to detect spontaneous seizures, mossy fiber sprouting by Timm staining, neurogenesis by BrdU staining. KEY FINDINGS: Oral administration of metformin prior to kainite-induced status epilepticus blocked the variant characterizations of epileptogenesis like neuronal cell death, aberrant neurogenesis, mossy fiber sprouting, and spontaneous seizures. SIGNIFICANCE: These findings indicate that metformin has potential anti-epileptogenic properties in temporal lobe epilepsy.

The possible role of progranulin on anti-inflammatory effects of metformin in temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is the most prevalent and drug-resistant form of parietal epilepsy. TLE is accompanied by neuroinflammation in the brain, which involves reactive glial cells. Metformin is an old antidiabetic drug with anti-inflammatory and neuroprotective effects. Considering the importance of inflammation in epilepsy, we have investigated the effect of metformin on astrogliosis markers as well as pro and anti-inflammatory cytokines and its effect on progranulin expression (an important neuroprotective protein in epilepsy) in a rat TLE model. TLE was induced by intracerebroventricular microinjection of kainic acid. Metformin was orally administered for two weeks before the induction of epilepsy. Astrogliosis markers (GFAP and S100B), as well as IL-1ß and IL- 10 levels, were detected by ELISA. The progranulin level was measured by Western blotting and immunohistochemistry in the hippocampus. Our results showed basal levels of GFAP, S100B, and pro-inflammatory cytokine increased in the epileptic rats but were significantly ameliorated after pretreatment with metformin. However, anti-inflammatory cytokine and progranulin also increased in the pre-treated rats and metformin alone group. An increment in the progranulin level emphasizes the importance of this protein in epilepsy. Hence, metformin may exert at least some of its anti-inflammatory effects by increasing progranulin level. In sum, we have concluded that progranulin can be a key mediator in epilepsy, and the anti-inflammatory action of metformin in status epilepticus is through increasing the secretion of IL-10 and inhibiting IL-1 ß and astrogliosis.