Orexin-A alleviates ferroptosis by activating the Nrf2/HO-1 signaling pathway in traumatic brain injury.

ABSTRACT

BACKGROUND: Traumatic Brain Injury (TBI) has high disability and mortality rate. Oxidative stress and ferroptosis are important pathophysiological characteristics after TBI. Orexin-A (OXA) can alleviate neuronal damage in diverse neurological disorders. Nevertheless, the role and mechanism of OXA in TBI stay unknown. OBJECTIVES: The research investigated protection influence of OXA on TBI and its potential mechanisms. METHODS: Male Sprague-Dawley rats were randomly grouped into sham, TBI, TBI + normal saline (NS) and TBI+OXA groups. TBI model was constructed in rat via modified Feeney's approach, and OXA treatment was administered following construction of TBI model. RESULTS: Relative to TBI+NS group, TBI+OXA group displayed greatly recovered tissue damage and neurological deficits. Additionally, OXA eased oxidative stress as well as ferroptosis in cerebral cortex of rats following TBI. Furthermore, OXA increased Nrf2 expression and regulating factors HO-1 and NQO1 in cerebral cortex of TBI rats. CONCLUSIONS: Our research found OXA may restrain ferroptosis via Nrf2/HO-1 signaling pathway activation, thereby reducing brain injury after TBI.