Role Of Dexras1-mediated Inflammatory Response In White Matter Injury After Subarachnoid Hemorrhage

Objective To explore the mechanisms by which Dexras1 promotes inflammation and participates in white matter damage(WMD)in subarachnoid hemorrhage(SAH).Methods One hundred and six healthy male SD rats were used as research objects,and they were randomly divided into control group,SAH group,SAH time group,SAH+LV-Scramble group,SAH+LV-Dexras1~+group,and SAH+LV-Dexras1~-group,the number of rats in each group was 14.Using lentivirus for intervention,intravascular puncture method was used to construct a rat model of subarachnoid hemorrhage.Immunofluorescence,electron microscopy and Luxol fast blue staining were used to detect myelin changes in each group;The changes of neurological function were detected by neurobehavioral scores;And Western blot analysis was used to detect the expression of Dexras1,NG2,CREB,pCREB,CNPase,TNF-a,IL-1βand MBP in each group.Results Compared with the sham group,Dexras1,NG2,GFAP,TNF-a,and IL-1βwere significantly increased in the brain tissue of rats after SAH(P<0.05),MBP,CREB,pCREB and CNPase was significantly reduced(P<0.05),and obvious neurological deficits,astrocyte activation,cerebral edema,inflammatory cell infiltration,oligodendrocyte precursor cell differentiation disorders,and myelin loss and injury.Compared with the SAH+LV-Scramble group,brain tissue Dexras1,NG2,GFAP,TNF-a,and IL-1βof rats in the SAH+LV-Dexras1~+group continued to increase(P<0.01),MBP,CREB,pCREB and CNPase was further reduced(P<0.05),and neurological deficits,cerebral edema,oligodendrocyte precursor cell differentiation disorder,myelin loss and damage were significantly worsened,inflammatory cell infiltration and astrocyte activation were also significantly increased;In the SAH+LV-Dexras1~-group,brain tissue Dexras1,NG2,GFAP,TNF-a,and IL-1βof rats were significantly reduced(P<0.01),MBP,CREB,pCREB and CNPase was increased(P<0.05),and neurological deficits,cerebral edema,oligodendrocyte precursor cell differentiation disorder,myelin loss and damage were significantly improved,inflammatory cell infiltration and astrocyte activation were also significantly reduced;Conclusion Dexras1 after subarachnoid hemorrhage may promote inflammatory response and astrocyte activation and lead to oligodendrocyte precursor cell differentiation disorder,thereby participating in the role of demyelination and white matter damage after subarachnoid hemorrhage.