The Role Of Kr(?)ppel-like Factor 11 Genetic Deletion On Ischemic Brain Injury

Backgroud: Ischemic stroke is one of the common diseases seriously threaten human health which characterized as high morbidity,mortality and high morbidity.After stroke a series of cellular and molecular signaling cascades are activated that eventually lead to neuronal death in the ischemic brain.However,the underlying mechanisms of stroke-induced pathophysiological events are not completely understood.Kr(?)ppel-like factors(KLFs),belong to the zinc finger family,has diverseregulatory functions in cell growth,differentiation,proliferation,migration,apoptosis,metabolism,and inflammation.Recently,accumulative studies have showed their involvement in the pathological process of vascular diseases.Objectives: The aim of this study is to determine the role of KLF11 in cerebravascular function and the pathogenesis of ischemic stroke.Methods: Transient middle cerebral artery occlusion(MCAO)was performed in KLF11 knockout(KO)and wild-type(WT)and the change of cerebral blood flow(CBF)was detected by laser speckle imaging during the operation.The infarction volumn of brain was analyzed by TTC staining.Neurobehavioral deficits were determined by the adhesive tape removal test,foot fault test,and rotarod test.Brain water content was measured by the dry-wet method.BBB integrity was assessed by using Evans Blue and TMR-Dextran extravasation assays.Western Blot,qPCR and enzyme linked immunosorbent assay(ELISA)were performed to test the change of proteins or mRNA of series inflammatory facors.Results: KLF11 KO mice exhibited significantly larger brain infarction and poorer neurological outcomes after ischemic insults.Genetic deficiency of KLF11 in mice also significantly aggravated ischemia-induced BBB disruption by increasingcerebrovascular permeability and edema.Mechanistically,it was found that the expression of IL-6 was increased in the brains of KLF11 KO mice after MCAO compared with WT group.Conclusion: Genetic deficiency of KLF11 in mice aggrevates ischemic brain injury and increases the disruption of BBB and the expression of IL-6.These findings suggest that KLF11 might act as a potential protective factor in ischemic stroke.