Human serum albumin attenuates global cerebral ischemia/reperfusion-induced brain injury in a Wnt/β-Catenin/ROS signaling-dependent manner in rats

[Display omitted] •Global cerebral ischemia (GCI) causes severe cerebral damage and a high fatality rate.•We tested human serum albumin (HSA) therapy on a GCI rat model.•HSA treatment reduced neuronal injury and behavioral deficits in rats after GCI.•This effect was mediated via Wnt/β-Catenin/ROS signaling. This study sought to clarify the role and underlying mechanisms of human serum albumin (HSA) therapy in global cerebral ischemia/reperfusion (GCI/R)-induced brain damage in rats. Five groups of adult male Wistar rats (n = 12 per group) were created as follows: sham operation (Sham), global cerebral ischemia/reperfusion (GCI/R), HSA treatment (GCI/R + HSA), Dickkopf-1 (DDK1) treatment (GCI/R + DDK1), and DDK1 plus HSA treatment (GCI/R + DKK1 + HSA). The GCI/R injury model was created using the modified Pusinelli four-vessel occlusion method. After 24 h, rats were evaluated using neurological scoring, Nissl staining, and brain tissue water content. The mRNA expression of Wnt, GSK3β, and β-Catenin in the brain were detected by quantitative real time polymerase chain reaction. The protein expression of β-Catenin and GSK-3β were investigated by western blot and immunohistochemical analysis in the presence and absence of the Wnt/β-Catenin antagonist, DKK-1. Complex I activity and ROS content were also measured. After 24 h of reperfusion, the behavior score and brain tissue water content in the GCI/R + HSA group were lower than that in the GCI/R group. In addition, the degree of neuronal injury was significantly reduced in the GCI/R + HSA group (P