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.
大脑的血流动态长期以来被与神经活动联系在一起，并且构成BOLD (blood-oxygen-level-dependent)功能成像的基础。但这种血流变化是怎样被介导的却仍有争议。在这项研究中，David Attwell及同事揭示了神经活动何以能使“周细胞”高度极化、导致它们松弛和毛细管扩张。神经活动相关的血流增加量的84%是由毛细管扩张造成的，所以在缺血期间由于“周细胞”死亡而发生的不可逆的毛细管封闭会损伤血-脑屏障和加重伤害。如果谷氨酸盐受体信号作用被抑制的话，病理条件下的“周细胞”死亡可以减少。这项工作表明，“周细胞”是大脑血液流动的主要调控因子，可能会启动BOLD成像信号。