Effects Of WNT3A On Neurogenesis In Rats During Early Brain Injury After Subarachnoid Hemorrhage

Objective:To investigate the effects and possible mechanisms of Wnt3a on neurogenesis in rats during early brain injury after subarachnoid hemorrhage (SAH), by the way of detecting the neurogenesis and the expressing leve of Dvl-1and β-catenin located in hippocampus.Methods:Seventy adult male SD rats were randomly divided into seven groups:the sham operation groups, the SAH groups, the Wnt3a Ⅰ groups, the Wnt3a Ⅱ groups, the Wnt3a Ⅲgroups, the Wnt3a Ⅳgroups and the DKK-1groups. The SAH model was established by injecting autologous blood into cisterna magna. Rats are labelled with BrdU using intraperitoneal injection, each rat with the dose of50mg/kg. Wnt3a and DKK-1, which can be instead of saline if necessary, are injected into cisterna magna6h before establishing SAH model. An immunofluorescence technique was used to detective neurogenesis by investigating the BrdU-positive cells located in the dentate gyrus of hippocampus of rats. Western blotting was performed to analyze dishevelled-1(Dvl-1) and β-catenin expression.Results:After injected with5,10,20and40μg/mL Wnt3a into cisterna magna, the percentages of BrdU-positive cells increased gradually(P<0.05). The expression levels of Dvl-1and β-catenin protein were also upregulated in a dose-dependant manner (P<0.05). After injected with DKK-1as an inhibitor of classical Wnt signaling pathway, the percentage of BrdU-positive cells decreased obviously (P<0.05), and the activities of Dvl-1and P-catenin were also inhibited (P<0.05). Therefore, by the way of immunofluorescence technique we found that Wnt3a can promote neurogenesis in early brain injury after subarachnoid hemorrhage. Using western blotting we proved that neurogenesis may be promoted through the canonical Wnt signaling pathway.Conclusions:Wnt3a may have the potential to promote neurogenesis via activating canonical Wnt-signaling pathway during early brain injury after SAH, which can contribute to the protection and reparation of central nervous system.