Bennet Laura, Roelfsema Vincent, Dean Justin M, Wassink Guido, Power Gordon G, Jensen Ellen C, Gunn Alistair Jan
Department of Physiology, The University of Auckland, Private Bag 92019, Auckland, New Zealand.
Am J Physiol Regul Integr Comp Physiol. 2007 Apr;292(4):R1569-76. doi: 10.1152/ajpregu.00743.2006. Epub 2006 Dec 14.
The preterm fetus is capable of surviving prolonged periods of severe hypoxia without neural injury for much longer than at term. To evaluate the hypothesis that regulated suppression of brain metabolism contributes to this remarkable tolerance, we assessed changes in the redox state of cytochrome oxidase (CytOx) relative to cerebral heat production, and cytotoxic edema measured using cerebral impedance, during 25 min of complete umbilical cord occlusion or sham occlusion in fetal sheep at 0.7 gestation. Occlusion was followed by rapid, profound reduction in relative cerebral oxygenation and EEG intensity and an immediate increase in oxidized CytOx, indicating a reduction in electron flow down the mitochondrial electron transfer chain. Confirming rapid suppression of cerebral metabolism there was a loss of the temperature difference between parietal cortex and body at a time when carotid blood flow was maintained at control values. As occlusion continued, severe hypotension/hypoperfusion developed, with a further increase in CytOx levels to a plateau between 8 and 13 min and a progressive rise in cerebral impedance. In conclusion, these data strongly suggest active regulation of cerebral metabolism during the initial response to severe hypoxia, which may help to protect the immature brain from injury.
早产胎儿在严重缺氧的长时间内能够存活而不发生神经损伤，其耐受时间比足月胎儿长得多。为了评估大脑代谢的调节性抑制有助于这种显著耐受性的假说，我们在妊娠0.7期的胎羊中，在完全脐带闭塞或假闭塞25分钟期间，评估了细胞色素氧化酶（CytOx）的氧化还原状态相对于脑产热的变化，以及使用脑阻抗测量的细胞毒性水肿。闭塞后，相对脑氧合和脑电图强度迅速大幅降低，氧化型CytOx立即增加，表明线粒体电子传递链上的电子流减少。在颈动脉血流维持在对照值时，顶叶皮层与身体之间的温差消失，证实了脑代谢的快速抑制。随着闭塞的持续，出现严重的低血压/低灌注，CytOx水平进一步升高至8至13分钟之间的平台期，脑阻抗逐渐上升。总之，这些数据有力地表明，在对严重缺氧的初始反应期间，大脑代谢存在主动调节，这可能有助于保护未成熟脑免受损伤。
