Mdivi-1 Attenuates Early Brain Injury After Subarachnoid Hemorrhage Via Inhibition Of The Mitochondria-dependent Apoptosis Pathway

PurposeDynamin-related protein 1(Drp1),which is predominantly dominated protein of mitochondrial fission,has been reported to play an important role in mitochondrial apoptosis pathway.However,the role of Drpl remains unknown in early brain injury after SAH.This study was performed to character the effect of Drpl on early brain injury secondary to SAH and the underlying mechanism.MethodsWe used endovascular perforation model to induce SAH in rats.Ninety-eight male SD rats were at random allotted into three group:the sham group,SAH + vehicle group and SAH + Drp1 inhibitor(Mdivi-1)group.Mdivi-1(1.2 mg/kg)or vehicle(0.9%NaCl)were given intravenously at 5 min after SAH induction.Mortality,neurological function,SAH grades,brain tissue water content,immunofluorescence staining and western blot were operated at 24h after SAH.ResultsOur research indicated that the activation of Drp1 in the mitochondria was increased after subarachnoid hemorrhage.Inhibition of Drpl by Mdivi-1 reduced brain edema,improved neurological function and decreased the numbers of neuron death in the rats after SAH.In addition,Mdivi-I restrained the translocation of apoptosis-inducing factor(AIF)and cytochrome C(CytC)into cytosol from mitochondria,decreased expression of promoted-apoptosis protein such as Caspase-3 and Bax as well as increased Bcl-2 expression.ConclusionActivation of Drpl in the mitochondria was increased after subarachnoid hemorrhage.Inhibition of Drpl by Mdivi-1 improved neurological function,attenuated neuronal death and brain edema in rats secondary to SAH.The underlying mechanisms might involve in suppression of CytC and AIF-dependent mitochondrial apoptosis pathway...