Valproic acid attenuates the severity of astrogliosis in the hippocampus of animal models of temporal lobe epilepsy

Reactive astrogliosis is one of the most frequency neuropathological alterations in the hippocampus of animal models and patients with temporal lobe epilepsy (TLE). Valproic acid (VPA), a widely used antiepileptic drug (AED), acts by blocking ion channels and enhancing GABAergic activity. This study investigated the effects of VPA on hippocampal astrogliosis in a rat model of TLE. The results demonstrated that chronic administration of VPA at a dose of 200 mg/kg significantly reduced the severity of astrogliosis and ameliorated neuronal loss in the hippocampus at the early and middle stages post-status epilepticus (SE), while also improving cognitive impairments at the middle and late stages in KA-SE rats. Long-term administration of VPA at 400 mg/kg attenuated astrogliosis in the hippocampus at the middle stage post-SE, but lacked neuroprotective effects and exacerbated cognitive impairments at the late stage. These findings suggest that VPA at an appropriate dose could mitigate hippocampal astrogliosis, potentially offering a new antiepileptic mechanism for its long-term use.