Laboratory of Neuroendocrinology, Pavlov Institute of Physiology, Russian Academy of Sciences, Makarova 6, 199034 St. Petersburg, Russian Federation.
Neurosci Lett. 2012 Mar 28;513(1):100-5. doi: 10.1016/j.neulet.2012.02.019. Epub 2012 Feb 15.
A potent neuroprotective effect of ischemic postconditioning has previously been described using cerebral artery occlusion but this is not a practical therapeutic option. The present study has been performed to determine whether postconditioning by mild episodes of hypobaric hypoxia (hypoxic postconditioning, HP) can reduce post-hypoxic brain injury in rats. Male Wistar rats were submitted to severe hypobaric hypoxia (180 Torr, 3 h) followed by HP (360 Torr, 2 h, 3 trials spaced at 24 h) starting either 3h (early HP) or 24 h (delayed HP) after severe hypoxia. The structural and functional brain injury was assessed by a complex of histological techniques, behavioral methods, and by testing the functions of the hypothalamic-pituitary-adrenal axis (HPA). It was found that early and delayed HP considerably attenuated post-hypoxic injury, reducing pyknosis, hyperchromatosis, and interstitial brain edema, as well as the rates of neuronal loss in hippocampus and neocortex. Delayed HP produced prominent anxiolytic effect on rat behavior, preventing development of post-hypoxic anxiety. Both modes of HP had beneficial effect on the functioning of HPA, but only delayed HP normalized completely the baseline HPA activity and its reactivity to stress. The results obtained demonstrate that postconditioning by using repetitive episodes of mild hypobaric hypoxia may provide a powerful neuroprotective procedure that can be easily adopted for clinical practice and recommended as a research tool for identification of endogenous mechanisms involved in post-ischemic neuroprotection.
缺血后处理的强大神经保护作用以前曾在脑动脉闭塞中描述过，但这不是一种实用的治疗选择。本研究旨在确定轻度低氧（低氧后处理，HP）是否可以减轻大鼠缺氧后的脑损伤。雄性 Wistar 大鼠接受严重低氧（180 毫托，3 小时），然后进行 HP（360 毫托，2 小时，3 次试验间隔 24 小时），开始于严重缺氧后 3 小时（早期 HP）或 24 小时（延迟 HP）。通过一系列组织学技术、行为方法以及测试下丘脑-垂体-肾上腺轴（HPA）的功能，评估了结构和功能脑损伤。结果发现，早期和晚期 HP 可显著减轻缺氧后损伤，减少嗜碱性粒细胞核固缩、深染和间质脑水肿，以及海马和新皮质神经元的丢失率。延迟 HP 对大鼠行为产生明显的抗焦虑作用，防止缺氧后焦虑的发展。两种 HP 模式均对 HPA 的功能产生有益影响，但只有延迟 HP 可完全使 HPA 基线活动及其对应激的反应正常化。研究结果表明，使用轻度低氧重复发作的后处理可能提供一种强大的神经保护程序，该程序易于在临床实践中采用，并推荐作为鉴定缺血后神经保护中涉及的内源性机制的研究工具。
