Ebselen Relieve Ferroptosis Induced By DMT1 In Experimental Rats After Subarachnoid Hemorrhage

ObjectivesTo investigate the expression of Divalent mental transporter 1 and ferroptosis after SAH,and the neuroprotective effect of ebselen by inhibiting DMT1 in early brain injury after SAH.MethodsSAH rats were constructed by intravascular punture.Immunofluorescence was introduced to indentify the location of DMT1 and GPX4 in the brain cortex.Ebselen were administered by intracerebroventricular injection to the SAH,WB detected the expression of DMT and GPX4 in 72 h and after the intervention of ebselen;iron,MDA,GSH were introduced to evaluate the ferroptosis;Neurological deficits,brain edema,were recommend for early brain injury.ResultsImmunofluorescence indentified DMT1 and GPX4 were both in the cytoplasm of neuro in the brain cortex.Western blot results revealed that DMT1 increased then decreased at 24 h,48 h increased till 72 h(P<0.01),while GPX4 decreased in at 24 h,then decreased till 72 h(P<0.01),compared with the sham groups.A suppresant of DMT1,ebselen,were injected 1,2,4 mg/kg from lateral ventricles before SAH.Western blot results showed that,compared with the SAH and vehicle groups,(1)ebselen 1 mg/kg,DMT1 decreased(P<0.01),reversely,GPX4 increased(P<0.01),(2)ebselen 2 mg/kg,DMT1 decreased(P>0.01),GPX4 increased(P<0.01),(3)ebselen 4 mg/kg,DMT1 decreased(P>0.01),GPX4 increased(P>0.01).The results indicated that ebselen 4 mg/kg could decrease iron(P<0.01),MDA(P<0.01)and improve GSH(P<0.01),GPX 4(P<0.01),at last relieved ferroptosis.Ebselen 4 mg/kg improved neurological deficits(P<0.01),augmented brain edema(P<0.01),then defended early brain injury.ConclusionEbselen could suppress the exprssion of DMT1 then decrease the ferroptosis and protect the early brain injury after SAH.