Research Paper Volume 16, Issue 4 pp 3404—3419
Orexin-A alleviates ferroptosis by activating the Nrf2/HO-1 signaling pathway in traumatic brain injury
- 1 Department of Rehabilitation Medicine, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, PR China
- 2 First Department of Rehabilitation Medicine, Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi 330006, China
Received: June 15, 2023 Accepted: November 30, 2023 Published: February 12, 2024
https://doi.org/10.18632/aging.205541How to Cite
Copyright: © 2024 Kang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.