The decrease of Tie-2 receptor phosphorylation in microvascular endothelial cells is involved in early brain injury after subarachnoid hemorrhage

Abstract

PurposeLoose endothelial cells and the destruction of the blood–brain barrier (BBB) are one of the pathophysiological mechanisms of early brain injury (EBI) after subarachnoid hemorrhage (SAH). Tie-2 receptor phosphorylation is important for maintaining integrity of microvascular endothelial cells and BBB. This study aimed to explore the role and changes of Tie-2 receptor phosphorylation levels in EBI after SAH. MethodsThis study used an endovascular puncture model of rat to simulate the occurrence and development of aneurysmal subarachnoid hemorrhage. The location of Tie-2 receptor in brain tissues was determined by immunofluorescence. Immunofluorescence and western blot was carried out to observe the expression of Claudin-5 and Occludin in cortex and hippocampus. We chose to observe the Tie-2 receptor phosphorylation level in hippocampus according western blot. Evans blue viability assay was used to evaluate BBB permeability. ResultsThe results suggested that Tie-2 receptor mainly expressed around the vascular endothelial cells in brain. Following SAH, the Tie-2 receptor phosphorylation level and expression of tight junction protein (claudin-5 and occluding) decreased. Both of these downtrends were reversed by exogenous Angiopoietin-1 (Ang-1). Finally, injection of exogenous Ang-1 reduced SAH-associated BBB leakage. ConclusionsOur study indicated that Tie-2 receptor phosphorylation in microvascular endothelial cells was involved in pathophysiological process after SAH, and the decline of Tie-2 receptor phosphorylation might increase blood–brain barrier permeability by decreasing the tight junction protein expression.