Department of Neurosurgery, Medical College of Georgia, Augusta University, Augusta, GA, USA.
Department of Neurosurgery, Medical College of Georgia, Augusta University, Augusta, GA, USA.
Neurochem Int. 2021 Nov;150:105192. doi: 10.1016/j.neuint.2021.105192. Epub 2021 Sep 22.
Mitochondria are dynamic organelles responsible for cellular energy production. Besides, regulating energy homeostasis, mitochondria are responsible for calcium homeostasis, signal transmission, and the fate of cellular survival in case of injury and pathologies. Accumulating reports have suggested multiple roles of mitochondria in neuropathologies, neurodegeneration, and immune activation under physiological and pathological conditions. Mitochondrial dysfunction, which occurs at the initial phase of brain injury, involves oxidative stress, inflammation, deficits in mitochondrial bioenergetics, biogenesis, transport, and autophagy. Thus, development of targeted therapeutics to protect mitochondria may improve functional outcomes following traumatic brain injury (TBI) and intracerebral hemorrhages (ICH). In this review, we summarize mitochondrial dysfunction related to TBI and ICH, including the mechanisms involved, and discuss therapeutic approaches with special emphasis on past and current clinical trials.
线粒体是负责细胞能量产生的动态细胞器。此外,除了调节能量稳态外,线粒体还负责钙稳态、信号转导以及细胞在受伤和病理情况下的生存命运。越来越多的报告表明,在线粒体在生理和病理条件下的神经病理学、神经退行性变和免疫激活中具有多种作用。线粒体功能障碍发生在脑损伤的初始阶段,涉及氧化应激、炎症、线粒体生物能学、生物发生、运输和自噬的缺陷。因此,开发靶向治疗以保护线粒体可能会改善创伤性脑损伤 (TBI) 和脑出血 (ICH) 后的功能结果。在这篇综述中,我们总结了与 TBI 和 ICH 相关的线粒体功能障碍,包括所涉及的机制,并讨论了治疗方法,特别强调了过去和当前的临床试验。