HLY78 protects blood-brain barrier integrity through Wnt/β-catenin signaling pathway following subarachnoid hemorrhage in rats.

Wnt/β-catenin signaling plays an essential role in blood-brain barrier (BBB) formation and maintenance under pathophysiological conditions. HLY78, a lycorine derivative, has been identified as a novel activator of Wnt/β-catenin signaling in vitro. However, the effects of HLY78 on the BBB function in subarachnoid hemorrhage (SAH) are not yet validated. The present study was designed to investigate the impacts of HLY78 on the BBB in an endovascular perforation induced SAH model of Sprague-Dawley rats. Western blot, immunofluorescence staining, neurological function, brain water content, and Evans blue assay were performed after SAH induction. The results revealed that the expression of phosphorylated low-density lipoprotein receptor-related protein 6 (p-LRP6) was significantly increased after SAH and further augmented by HLY78. Administration of HLY78 significantly improved neurobehavioral functions and attenuated BBB leakage following SAH. Moreover, HLY78 markedly increased the β-catenin expression followed with the up-regulation of Occludin, ZO-1, and Claudin-5 after SAH, which was reversed by LRP6 siRNA. In conclusion, HLY78 could preserve BBB integrity, possibly through the Wnt/β-catenin signaling pathway. HLY78 might be a potential treatment option to protect BBB integrity following SAH.