Division of Glia Disease and Therapeutics, Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, New York, USA.
J Cereb Blood Flow Metab. 2012 Dec;32(12):2135-45. doi: 10.1038/jcbfm.2012.115. Epub 2012 Aug 8.
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 α(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.
鉴于大脑具有独特的高细胞密度和接近缺氧的组织氧水平，快速而精确地将血液流量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一个基本特征。蓝斑去甲肾上腺素（LC-NE）投射支配脑血管，可以介导血管收缩。然而，LC 介导的收缩在血流调节中的功能尚未得到解决。在这里，我们使用与麻醉方案相结合的固有光学成像，该方案仅最小程度地干扰 LC 活性，表明 NE 增强了小鼠体感皮层中功能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层中的 NE 水平，反而会减少功能充血的程度，同时增强周围的血流减少。然而，NE 介导的血管收缩优化了充血反应的时空聚焦，导致血液体积和氧气需求之间的差异减少了六倍。此外，NE 介导的血管收缩加速了向随后活跃区域的重新分布，增强了血液输送的时间同步性。这些观察结果表明 NE 在优化神经血管耦联中起着重要作用。由于 LC 神经元在阿尔茨海默病和帕金森病中明显丢失，因此将血液体积与氧气需求相耦联的能力下降可能导致其发病机制。
