Inhibition of ferroptosis processes ameliorates cognitive impairment in kainic acid-induced temporal lobe epilepsy in rats.

Hippocampal neuronal death plays a causal role in the cognitive impairment of temporal lobe epilepsy (TLE). Ferroptosis, a novel form of regulated cell death, is strongly linked to cognitive impairment. However, whether ferroptosis is associated with cognitive comorbidities of TLE is unknown. In this study, it was demonstrated that ferroptosis occurs in the hippocampus following kainic acid (KA)-induced TLE in rats. Treatment with ferrostatin-1, a specific inhibitor of ferroptosis, prevented the initiation and progression of ferroptosis in the hippocampus of KA-treated rats. This was through decreased expression of glutathione peroxidase 4, glutathione (GSH) depletion as well as lipid peroxides and iron accumulation. It was also found that ferrostatin-1 prevented hippocampal neuronal loss and rescued cognitive function in KA-induced TLE in rats. These results suggest that ferroptosis is involved in the cognitive impairment of KA-induced TLE in rats, and inhibition of ferroptosis processes ameliorates cognitive impairment in KA-induced TLE in rats.