A selective inhibitor of Drp1, mdivi-1, protects against cell death of hippocampal neurons in pilocarpine-induced seizures in rats.

Mdivi-1 is a selective inhibitor of a mitochondrial fission protein Drp1. Recent studies demonstrated that inhibition of Drp1 provides neuroprotection in vitro and in vivo. In this study, we examined the role of mdivi-1 in hippocampal neuron death after seizures induced by pilocarpine. Our data showed that pretreatment with mdivi-1 (1.25 mg/kg) significantly attenuated the neuronal death in hippocampus induced by seizures. This neuroprotective effect was dose-dependent. In addition, the seizures resulted in up-regulation of Drp1 expression and mdivi-1 treatment had no effect on the expression. Moreover, we also found that mdivi-1 (1.25 mg/kg) treatment reversed the release of cytochrome c (CytC), translocation of apoptosis-inducing factor (AIF) induced by seizures while inhibiting the activated caspase-3. Altogether, our data suggested that mdivi-1 exerts neuroprotective effects against cell death of hippocampal neurons induced by seizures, and the underlying mechanism may be through inhibiting CytC release, AIF translocation and suppression of the mitochondrial apoptosis pathway.