Peppiatt Claire M, Howarth Clare, Mobbs Peter, Attwell David
Department of Physiology, University College London, Gower Street, London WC1E 6BT, UK.
Nature. 2006 Oct 12;443(7112):700-4. doi: 10.1038/nature05193. Epub 2006 Oct 1.
Neural activity increases local blood flow in the central nervous system (CNS), which is the basis of BOLD (blood oxygen level dependent) and PET (positron emission tomography) functional imaging techniques. Blood flow is assumed to be regulated by precapillary arterioles, because capillaries lack smooth muscle. However, most (65%) noradrenergic innervation of CNS blood vessels terminates near capillaries rather than arterioles, and in muscle and brain a dilatory signal propagates from vessels near metabolically active cells to precapillary arterioles, suggesting that blood flow control is initiated in capillaries. Pericytes, which are apposed to CNS capillaries and contain contractile proteins, could initiate such signalling. Here we show that pericytes can control capillary diameter in whole retina and cerebellar slices. Electrical stimulation of retinal pericytes evoked a localized capillary constriction, which propagated at approximately 2 microm s(-1) to constrict distant pericytes. Superfused ATP in retina or noradrenaline in cerebellum resulted in constriction of capillaries by pericytes, and glutamate reversed the constriction produced by noradrenaline. Electrical stimulation or puffing GABA (gamma-amino butyric acid) receptor blockers in the inner retina also evoked pericyte constriction. In simulated ischaemia, some pericytes constricted capillaries. Pericytes are probably modulators of blood flow in response to changes in neural activity, which may contribute to functional imaging signals and to CNS vascular disease.
神经活动会增加中枢神经系统(CNS)的局部血流量,这是血氧水平依赖性功能磁共振成像(BOLD)和正电子发射断层扫描(PET)功能成像技术的基础。由于毛细血管缺乏平滑肌,血流量被认为是由毛细血管前小动脉调节的。然而,中枢神经系统血管的大部分(65%)去甲肾上腺素能神经支配在毛细血管附近而非小动脉处终止,并且在肌肉和大脑中,扩张信号从代谢活跃细胞附近的血管传播到毛细血管前小动脉,这表明血流量控制始于毛细血管。与中枢神经系统毛细血管相邻且含有收缩蛋白的周细胞可能启动这种信号传导。在这里,我们表明周细胞可以控制整个视网膜和小脑切片中的毛细血管直径。对视网膜周细胞进行电刺激会引起局部毛细血管收缩,该收缩以约2微米/秒的速度传播以收缩远处的周细胞。视网膜中灌注的ATP或小脑中的去甲肾上腺素会导致周细胞引起毛细血管收缩,而谷氨酸会逆转去甲肾上腺素产生的收缩。在内视网膜中电刺激或吹入γ-氨基丁酸(GABA)受体阻滞剂也会引起周细胞收缩。在模拟缺血时,一些周细胞会收缩毛细血管。周细胞可能是响应神经活动变化的血流量调节因子,这可能有助于功能成像信号和中枢神经系统血管疾病。