The locus coeruleus-norepinephrine network optimizes coupling of cerebral blood volume with oxygen demand
The locus coeruleus-norepinephrine network optimizes coupling of cerebral blood volume with oxygen demand
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DOI：
10.1038/jcbfm.2012.115
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发表时间：
2012-12-01
影响因子：
6.3
通讯作者：
Nedergaard, Maiken
中科院分区：
文献类型：
--
作者：
Bekar, Lane K.;Wei, Helen S.;Nedergaard, Maiken
鉴于大脑独特的高细胞密度和接近缺氧的组织氧水平，快速精确地将血流与不断变化的神经活动模式相匹配的能力是脑血管调节的基本特征。蓝斑-去甲肾上腺素（LC-NE）投射支配脑血管并可介导血管收缩。然而，LC介导的收缩在血流调节中的功能从未得到解决。在这里，使用内在的光学成像加上麻醉方案，只有最低限度地干扰LC活动，我们表明，NE增强小鼠体感皮层的功能性充血的空间和时间方面。使用α（2）-肾上腺素能受体拮抗剂增加皮质中NE水平反而减少了功能性充血的程度，同时增强了周围血流减少。然而，NE介导的血管收缩优化了充血反应的空间和时间聚焦，导致血容量和需氧量之间的差异减少了六倍。此外，NE介导的血管收缩加速再分布到随后的活动区域，增强血液输送的时间同步性。这些观察结果表明，NE在优化神经血管耦合的重要作用。由于LC神经元损失在阿尔茨海默病和帕金森病中是突出的，因此将血容量与氧需求耦合的能力降低可能有助于其发病机制。Journal of Cerebral Blood Flow & Metabolism（2012）32，2135-2145; doi：10.1038/jcbfm.2012.115; 2012年8月8日在线发表
Given the brain's uniquely high cell density and tissue oxygen levels bordering on hypoxia, the ability to rapidly and precisely match blood flow to constantly changing patterns in neural activity is an essential feature of cerebrovascular regulation. Locus coeruleus-norepinephrine (LC-NE) projections innervate the cerebral vasculature and can mediate vasoconstriction. However, function of the LC-mediated constriction in blood-flow regulation has never been addressed. Here, using intrinsic optical imaging coupled with an anesthesia regimen that only minimally interferes with LC activity, we show that NE enhances spatial and temporal aspects of functional hyperemia in the mouse somatosensory cortex. Increasing NE levels in the cortex using an alpha(2)-adrenergic receptor antagonist paradoxically reduces the extent of functional hyperemia while enhancing the surround blood-flow reduction. However, the NE-mediated vasoconstriction optimizes spatial and temporal focusing of the hyperemic response resulting in a sixfold decrease in the disparity between blood volume and oxygen demand. In addition, NE-mediated vasoconstriction accelerated redistribution to subsequently active regions, enhancing temporal synchronization of blood delivery. These observations show an important role for NE in optimizing neurovascular coupling. As LC neuron loss is prominent in Alzheimer and Parkinson diseases, the diminished ability to couple blood volume to oxygen demand may contribute to their pathogenesis. Journal of Cerebral Blood Flow & Metabolism (2012) 32, 2135-2145; doi:10.1038/jcbfm.2012.115; published online 8 August 2012