Department of Neuropsychiatry and Laboratory of Molecular Psychiatry, Charité-Universitätsmedizin Berlin, D-10117 Berlin, Germany.
Proc Natl Acad Sci U S A. 2010 Dec 21;107(51):22290-5. doi: 10.1073/pnas.1011321108. Epub 2010 Dec 6.
Modern functional imaging techniques of the brain measure local hemodynamic responses evoked by neuronal activity. Capillary pericytes recently were suggested to mediate neurovascular coupling in brain slices, but their role in vivo remains unexplored. We used two-photon microscopy to study in real time pericytes and the dynamic changes of capillary diameter and blood flow in the cortex of anesthetized mice, as well as in brain slices. The thromboxane A(2) analog, 9,11-dideoxy-9α,11α-methanoepoxy Prostaglandin F2α (U46619), induced constrictions in the vicinity of pericytes in a fraction of capillaries, whereas others dilated. The changes in vessel diameter resulted in changes in capillary red blood cell (RBC) flow. In contrast, during brief epochs of seizure activity elicited by local administration of the GABA(A) receptor antagonist, bicuculline, capillary RBC flow increased without pericyte-induced capillary diameter changes. Precapillary arterioles were the smallest vessels to dilate, together with penetrating and pial arterioles. Our results provide in vivo evidence that pericytes can modulate capillary blood flow in the brain, which may be important under pathological conditions. However, our data suggest that precapillary and penetrating arterioles, rather than pericytes in capillaries, are responsible for the blood flow increase induced by neural activity.
现代脑功能成像技术测量由神经元活动引起的局部血液动力学反应。最近有研究表明,脑片中层细胞能够介导神经血管耦联,但它们在体内的作用仍未得到探索。我们使用双光子显微镜实时研究了麻醉小鼠皮层中的周细胞以及毛细血管直径和血流的动态变化,同时也研究了脑片。血栓素 A2 类似物 9,11-二去氧-9α,11α-亚甲氧基前列腺素 F2α(U46619)在一部分毛细血管附近诱导周细胞附近的血管收缩,而其他部分则扩张。血管直径的变化导致毛细血管红细胞(RBC)流的变化。相比之下,在局部给予 GABA(A) 受体拮抗剂荷包牡丹碱诱发短暂癫痫活动期间,毛细血管 RBC 流增加,而周细胞诱导的毛细血管直径变化则没有。微动脉是扩张的最小血管,与穿透性和脑膜性微动脉一起。我们的研究结果提供了体内证据,表明周细胞可以调节大脑中的毛细血管血流,这在病理条件下可能很重要。然而,我们的数据表明,神经活动诱导的血流增加是由前毛细血管和穿透性微动脉而不是毛细血管中的周细胞引起的。