Thibodeau Alexa, Geng Xiaokun, Previch Lauren E, Ding Yuchuan
Department of Neurological Surgery, Wayne State University School of Medicine, Detroit, MI, USA.
China-America Institute of Neuroscience, Luhe Hospital, Capital Medical University, Beijing, China.
Brain Circ. 2016 Apr-Jun;2(2):61-66. doi: 10.4103/2394-8108.186256. Epub 2016 Jul 13.
Pyruvate dehydrogenase (PDH) complex is a mitochondrial matrix enzyme that serves a critical role in the conversion of anaerobic to aerobic cerebral energy. The regulatory complexity of PDH, coupled with its significant influence in brain metabolism, underscores its susceptibility to, and significance in, ischemia-reperfusion injury. Here, we evaluate proposed mechanisms of PDH-mediated neurodysfunction in stroke, including oxidative stress, altered regulatory enzymatic control, and loss of PDH activity. We also describe the neuroprotective influence of antioxidants, dichloroacetate, acetyl-L-carnitine, and combined therapy with ethanol and normobaric oxygen, explained in relation to PDH modulation. Our review highlights the significance of PDH impairment in stroke injury through an understanding of the mechanisms by which it is modulated, as well as an exploration of neuroprotective strategies available to limit its impairment.
丙酮酸脱氢酶（PDH）复合体是一种线粒体基质酶，在脑能量从无氧代谢向有氧代谢的转换过程中发挥关键作用。PDH的调节复杂性，及其对脑代谢的重大影响，凸显了其在缺血再灌注损伤中的易感性及重要性。在此，我们评估了PDH介导的中风神经功能障碍的潜在机制，包括氧化应激、调节酶控制改变以及PDH活性丧失。我们还描述了抗氧化剂、二氯乙酸、乙酰左旋肉碱以及乙醇与常压氧联合治疗的神经保护作用，并从PDH调节的角度进行了解释。我们的综述强调了通过了解PDH的调节机制以及探索限制其损伤的神经保护策略，来认识PDH损伤在中风损伤中的重要性。
