Withanolide-A treatment exerts a neuroprotective effect via inhibiting neuroinflammation in the hippocampus after pilocarpine-induced status epilepticus

Abstract

Status epilepticus (SE) is a medical emergency with high mortality and a risk factor for the development of chronic epilepsy. Given that effective treatments for the pathophysiology following SE are still lacking, suppressing pathophysiological mechanisms of SE may be important to inhibit epileptogenesis. Withanolide-A (WA), a major bioactive component of Withania somnifera, is a potential medicinal natural compound showing improvement of some neurological diseases, such as cerebral ischemia. In the present study, we examined whether administration of WA can exert the beneficial effects involved in neuroprotection and anti-inflammatory effects in a mouse model of pilocarpine-induced SE. Our results showed that WA treatment ameliorated SE-induced apoptotic neuronal cell death in the hippocampus. Moreover, WA treatment reduced immunoreactivity of both ionized calcium binding adapter molecule 1-positive microglia/macrophage and glial fibrillary acidic protein-positive reactive astrocytes, and the SE-induced increase in both interleukin-1 β and tumor necrosis factor in the hippocampus, suggesting that inhibiting pro-inflammatory factors by WA treatment might induce neuroprotection after SE. These results suggest that WA may be useful in improving the treatment efficacy for pathophysiology following SE.