The Effect And Mechanism Of Intranasal Wnt-3a Administration In Early Brain Injury Post Subarachnoid Hemorrhage In Rats

PurposeNeuronal apoptosis has since long been a focus in the pathophysiology of early brain injury(EBI)after subarachnoid hemorrhage(SAH).Wnt-3a,one of the endogenous wnt ligands,has been shown to be beneficial in the treatment of ischemic stroke.The glycolytic enzyme aldolase C and ribosome biogenesis component PPAN were revealed to be related to canonical wnt signaling pathway.The present study was designed to explore the anti-apoptotic property of wnt-3a through Frizzled-1(Frz-1)/aldolase C/PPAN pathway in SAH via intranasal route.MethodsMethods for experimental evaluation consisted of Garcia test,SAH grade,brain water content test,rotarod test,Morris water maze test,western blot,immunofluorescence and transmission electron microscopy(TEM).ResultsThe results showed that wnt-3a improved brain water content and both short-and long-term neurofunctional deficits induced by SAH.The protein level of Frz-1,aldolase C,?-catenin,PPAN and the Bcl-2/Bax ratio was increased by wnt-3a treatment;and that of axin and cleaved caspase-3(CC-3)was decreased significantly.The anti-apoptotic property of wnt-3a was further supported by immunofluorescence and TEM.Frz-1 si RNA and aldolase C si RNA counterbalanced the effects of wnt-3a;and salvage of aldolase C by aldolase C CRISPR in Frz-1 si RNA preconditioned SAH rats restored the level of Frz-1,aldolase C,PPAN and reduced axin and CC-3.ConclusionIn conclusion,intranasal administration of exogenous wnt-3a ameliorates neuronal apoptosis through Frz-1/aldolase C/PPAN pathway in EBI of SAH.The practical intranasal administration as well as the long-term neuroprotection of wnt-3a is of great promise for future clinical application.