Department of Neuroscience, Physiology & Pharmacology University College London, Gower St., London, WC1E 6BT, UK.
Department of Neuroscience & Pharmacology and Center for Healthy Aging, and Department of Clinical Neurophysiology, Glostrup Hospital, University of Copenhagen, DK-2200 Copenhagen N, Denmark.
Nature. 2014 Apr 3;508(7494):55-60. doi: 10.1038/nature13165. Epub 2014 Mar 26.
Increases in brain blood flow, evoked by neuronal activity, power neural computation and form the basis of BOLD (blood-oxygen-level-dependent) functional imaging. Whether blood flow is controlled solely by arteriole smooth muscle, or also by capillary pericytes, is controversial. We demonstrate that neuronal activity and the neurotransmitter glutamate evoke the release of messengers that dilate capillaries by actively relaxing pericytes. Dilation is mediated by prostaglandin E2, but requires nitric oxide release to suppress vasoconstricting 20-HETE synthesis. In vivo, when sensory input increases blood flow, capillaries dilate before arterioles and are estimated to produce 84% of the blood flow increase. In pathology, ischaemia evokes capillary constriction by pericytes. We show that this is followed by pericyte death in rigor, which may irreversibly constrict capillaries and damage the blood-brain barrier. Thus, pericytes are major regulators of cerebral blood flow and initiators of functional imaging signals. Prevention of pericyte constriction and death may reduce the long-lasting blood flow decrease that damages neurons after stroke.
神经元活动引起的脑血流增加，为神经计算提供动力，并构成 BOLD（血氧水平依赖）功能成像的基础。血流是仅由小动脉平滑肌控制，还是也由毛细血管周细胞控制，这是有争议的。我们证明，神经元活动和神经递质谷氨酸引发信使的释放，通过主动松弛周细胞来扩张毛细血管。扩张是由前列腺素 E2 介导的，但需要一氧化氮释放来抑制收缩性 20-HETE 的合成。在体内，当感觉输入增加血流量时，毛细血管在小动脉之前扩张，据估计可产生 84%的血流量增加。在病理状态下，缺血通过周细胞引起毛细血管收缩。我们表明，随后是在僵硬状态下的周细胞死亡，这可能会使毛细血管不可逆地收缩并损害血脑屏障。因此，周细胞是脑血流的主要调节者，也是功能成像信号的启动者。预防周细胞收缩和死亡可能会减少中风后损害神经元的持久血流减少。
