The Role Of Celastrol In Early Brain Injury After Experimental Subarachnoid Hemorrhage In Rats

Purpose The purpose of this study was to investigate whether necroptosis was involved in early brain injury after subarachnoid hemorrhage(SAH),and to assess a potential role of celastrol and its related mechanism in early brain injury after SAH.Methods Adult male Sprague-Dawley rats were randomly divided into sham,SAH+celastrol(SAH+cel),and SAH+vehicle groups.The SAH model was induced by endovascular perforation.After 72 h of SAH,the expression of cerebral RIP3 and MLKL in all groups were assayed.Propidium iodide(PI)was used to label necrotic cell death.Neurological scores were recorded at 24,48 and 72 h after SAH induction.PI was used to label the plasma membrane ruptured cells.Results Compared with the sham group,the SAH+vehicle group animals significantly up-regulated the expression of RIP3 and MLKL,increased PI-positive cells,and deteriorated neurological dysfunction.Treatment with celastrol suppressed the expression of RIP3 and MLKL,and reduced PI-positive cells and neurological dysfunction.Conclusion These results indicated that necroptosis was an important mechanism of cell death involved in the early brain injury after SAH.Celastrol perhaps could serve as a protective role against necroptosis in early brain injury after SAH.