Department of Biochemistry, School of Medicine, Keio University, Shinjuku-ku, Tokyo, Japan.
Antioxid Redox Signal. 2010 Oct;13(8):1157-67. doi: 10.1089/ars.2010.3290.
Local responses of energy metabolism during brain ischemia are too heterogeneous to decipher redox distribution between anoxic core and adjacent salvageable regions such as penumbra. Imaging mass spectrometry combined by capillary electrophoresis/mass spectrometry providing quantitative metabolomics revealed spatio-temporal changes in adenylates and NADH in a mouse middle-cerebral artery occlusion model. Unlike the core where ATP decreased, the penumbra displayed paradoxical elevation of ATP despite the constrained blood supply. It is noteworthy that the NADH elevation in the ischemic region is clearly demarcated by the ATP-depleting core. Results suggest that metabolism in ischemic penumbra does not respond passively to compromised circulation, but actively compensates energy charges.
在脑缺血期间,能量代谢的局部反应非常复杂,难以解析缺氧核心区与缺血半暗带等可挽救区域之间的氧化还原分布。结合毛细管电泳/质谱联用的成像质谱分析提供了定量代谢组学,揭示了在小鼠大脑中动脉闭塞模型中腺苷酸和 NADH 的时空变化。与核心区 ATP 减少不同,尽管血液供应受限,缺血半暗带仍显示出 ATP 的反常升高。值得注意的是,缺血区域 NADH 的升高与耗竭 ATP 的核心区明显分界。结果表明,缺血半暗带的代谢不是被动地对循环受损做出反应,而是积极地补偿能量电荷。