PDF(Pubmed)
Abstract：
Hypoxia stabilizes hypoxia-inducible factors (HIFs), facilitating adaptation to hypoxic conditions. Appropriate hypoxia is pivotal for neurovascular regeneration and immune cell mobilization. However, in central nervous system (CNS) injury, prolonged and severe hypoxia harms the brain by triggering neurovascular inflammation, oxidative stress, glial activation, vascular damage, mitochondrial dysfunction, and cell death. Diminished hypoxia in the brain improves cognitive function in individuals with CNS injuries. This review discusses the current evidence regarding the contribution of severe hypoxia to CNS injuries, with an emphasis on HIF-1α-mediated pathways. During severe hypoxia in the CNS, HIF-1α facilitates inflammasome formation, mitochondrial dysfunction, and cell death. This review presents the molecular mechanisms by which HIF-1α is involved in the pathogenesis of CNS injuries, such as stroke, traumatic brain injury, and Alzheimer\'s disease. Deciphering the molecular mechanisms of HIF-1α will contribute to the development of therapeutic strategies for severe hypoxic brain diseases.
摘要：
缺氧稳定缺氧诱导因子（HIF），促进适应缺氧条件。适当的缺氧对于神经血管再生和免疫细胞动员至关重要。然而,中枢神经系统（CNS）损伤，长期和严重的缺氧通过引发神经血管炎症损害大脑，氧化应激，胶质激活，血管损伤,线粒体功能障碍，细胞死亡。大脑中缺氧的减少改善了中枢神经系统损伤个体的认知功能。这篇综述讨论了目前关于严重缺氧对中枢神经系统损伤的贡献的证据。重点是HIF-1α介导的途径。在中枢神经系统严重缺氧期间，HIF-1α促进炎性体形成，线粒体功能障碍，细胞死亡。本文综述了HIF-1α参与中枢神经系统损伤发病的分子机制。如中风，创伤性脑损伤,和老年痴呆症。破译HIF-1α的分子机制将有助于开发严重缺氧性脑疾病的治疗策略。
