The role of orexin A in the pathogenesis of ischaemic stroke at high altitude.

Abstract

Orexin offers protection against cerebral ischaemia-reperfusion injury, with high altitude playing a key role in modulating its expression. This study aimed to investigate the effect of high altitude on orexin expression and its pathophysiological mechanisms involved in high altitude stroke injury. In this study, changes of orexin expression were observed by simulating hypoxia at different altitudes, and the changes of orexin and its receptor were analysed by constructing a middle cerebral artery occlusion (MCAO) model after high altitude simulation. Finally, the protective effect of orexin on cerebral ischaemia-reperfusion injury was evaluated by exogenous orexin intervention. The results indicated that at an altitude of 4000 m, orexin expression was increased, but then decreased at higher altitudes. Rats exposed to 4000 m hypoxia simulation and MCAO exhibited increased orexin and type 1 receptor expression. Exogenous orexin A administration reduced infarct size, improved microcirculation blood flow in the ischaemic cortex, accelerated blood flow, elevated blood oxygen saturation and mitigated systemic oxidative stress and inflammation. These findings confirm our hypothesis that 4000 m altitude promotes orexin expression, thereby attenuating cerebral ischaemia-reperfusion injury through enhanced microcirculation, reduced oxidative stress and inflammation.