Departments of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
J Cereb Blood Flow Metab. 2010 Apr;30(4):757-68. doi: 10.1038/jcbfm.2009.259. Epub 2009 Dec 30.
Recently, a universal, simple, and fail-safe mechanism has been proposed by which cerebral blood flow (CBF) might be coupled to oxygen metabolism during neuronal activation without the need for any tissue-based mechanism. According to this concept, vasodilation occurs by local erythrocytic release of nitric oxide or ATP wherever and whenever hemoglobin is deoxygenated, directly matching oxygen demand and supply in every tissue. For neurovascular coupling in the brain, we present experimental evidence challenging this view by applying an experimental regime operating without deoxy-hemoglobin. Hyperbaric hyperoxygenation (HBO) allowed us to prevent hemoglobin deoxygenation, as the oxygen that was physically dissolved in the tissue was sufficient to support oxidative metabolism. Regional CBF and regional cerebral blood oxygenation were measured using a cranial window preparation in anesthetized rats. Hemodynamic and neuronal responses to electrical forepaw stimulation or cortical spreading depression (CSD) were analyzed under normobaric normoxia and during HBO up to 4 ATA (standard atmospheres absolute). Inconsistent with the proposed mechanism, during HBO, CBF responses to functional activation or CSD were unchanged. Our results show that activation-induced CBF regulation in the brain does not operate through the release of vasoactive mediators on hemoglobin deoxygenation or through a tissue-based oxygen-sensing mechanism.
最近，人们提出了一种通用、简单且万无一失的机制，通过该机制，在神经元激活过程中，脑血流（CBF）可能无需任何基于组织的机制而与氧代谢相偶联。根据这一概念，只要血红蛋白脱氧，无论在何处，红细胞都会释放一氧化氮或 ATP 引起血管扩张，从而直接匹配每个组织中的氧气供需。对于大脑中的神经血管偶联，我们提出了实验证据，通过应用在没有脱氧血红蛋白的情况下运行的实验方案对此观点提出了挑战。高压氧（HBO）使我们能够防止血红蛋白脱氧，因为物理溶解在组织中的氧气足以支持氧化代谢。在麻醉大鼠中使用颅窗制备来测量局部脑血流量（CBF）和局部脑血氧饱和度。在常氧和高达 4 ATA（标准大气压绝对）的 HBO 条件下，分析了电前爪刺激或皮质扩散性抑制（CSD）下的血液动力学和神经元反应。与提出的机制不一致的是，在 HBO 期间，功能激活或 CSD 引起的 CBF 反应没有变化。我们的结果表明，大脑中激活诱导的 CBF 调节不是通过血红蛋白脱氧时释放血管活性介质或通过基于组织的氧感应机制来实现的。
