Regional Blood Flow in the Normal and Ischemic Brain Is Controlled by Arteriolar Smooth Muscle Cell Contractility and Not by Capillary Pericytes

The precise regulation of cerebral blood flow is critical for normal brain function, and its disruption underlies many neuropathologies. The extent to which smooth muscle-covered arterioles or pericyte-covered capillaries control vasomotion during neurovascular coupling remains controversial. We fou... Full description

The precise regulation of cerebral blood flow is critical for normal brain function, and its disruption underlies many neuropathologies. The extent to which smooth muscle-covered arterioles or pericyte-covered capillaries control vasomotion during neurovascular coupling remains controversial. We found that capillary pericytes in mice and humans do not express smooth muscle actin and are morphologically and functionally distinct from adjacent precapillary smooth muscle cells (SMCs). Using optical imaging we investigated blood flow regulation at various sites on the vascular tree in living mice. Optogenetic, whisker stimulation, or cortical spreading depolarization caused microvascular diameter or flow changes in SMC but not pericyte-covered microvessels. During early stages of brain ischemia, transient SMC but not pericyte constrictions were a major cause of hypoperfusion leading to thrombosis and distal microvascular occlusions. Thus, capillary pericytes are not contractile, and regulation of cerebral blood flow in physiological and pathological conditions is mediated by arteriolar SMCs. •Pericytes are morphologically and functionally distinct from precapillary SMCs•Capillary pericytes lack smooth muscle actin and are not contractile in vivo•Neurovascular coupling is mediated by arteriolar smooth muscle contractility•Ischemia causes transient SMC constrictions that lead to capillary thrombosis The extent to which arteriolar smooth muscle cell or capillary pericyte contractility regulates regional cerebral blood flow is debated. Hill et al. use optogenetic, whisker stimulation, spreading depolarization, and transient cerebral ischemia to demonstrate that capillary pericytes are not contractile in vivo and that arteriolar smooth muscle cells mediate physiological and pathological vasomotion.