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Pyruvate dehydrogenase complex in cerebral ischemia-reperfusion injury
Alexa Thibodeau1, Xiaokun Geng2, Lauren E Previch1, Yuchuan Ding3
1 Department of Neurological Surgery, Wayne State University School of Medicine, Detroit, MI, USA
2 Department of Neurological Surgery, Wayne State University School of Medicine, Detroit, MI, USA; China-America Institute of Neuroscience; Department of Neurology, Luhe Hospital, Capital Medical University, Beijing, China
3 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
Correspondence Address:
Xiaokun Geng
Department of Neurology, Luhe Hospital, Capital Medical University, No. 82 Xinhua South Road, Tongzhou District, Beijing 101149, China
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/2394-8108.186256
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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. |
