title: Regional Blood Flow in the Normal and Ischemic Brain Is Controlled by Arteriolar Smooth Muscle Cell Contractility and Not by Capillary Pericytes.
abstract: 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.
authors.affiliation: Department of Neurology, Yale School of Medicine, New Haven, CT 06510, USA; Department of Neurobiology, Yale School of Medicine, New Haven, CT 06510, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hill
authors.affiliation: Department of Neurology, Yale School of Medicine, New Haven, CT 06510, USA; Department of Neurobiology, Yale School of Medicine, New Haven, CT 06510, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Tong
authors.affiliation: Department of Neurology, Yale School of Medicine, New Haven, CT 06510, USA; Department of Neurobiology, Yale School of Medicine, New Haven, CT 06510, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Yuan
authors.affiliation: Department of Neurology, Yale School of Medicine, New Haven, CT 06510, USA; Department of Neurobiology, Yale School of Medicine, New Haven, CT 06510, USA.
authors.forename: Sasidhar
authors.initials: S
authors.lastname: Murikinati
authors.affiliation: Department of Neurology, Yale School of Medicine, New Haven, CT 06510, USA; Department of Neurobiology, Yale School of Medicine, New Haven, CT 06510, USA.
authors.forename: Shobhana
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Department of Neurology, Yale School of Medicine, New Haven, CT 06510, USA; Department of Neurobiology, Yale School of Medicine, New Haven, CT 06510, USA. Electronic address: jaime.grutzendler@yale.edu.
authors.forename: Jaime
authors.initials: J
authors.lastname: Grutzendler
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001160:Arterioles / Q000502:physiology; D001921:Brain / Q000098:blood supply; D002545:Brain Ischemia; D002118:Calcium / Q000378:metabolism; D002196:Capillaries / Q000502:physiology; D002540:Cerebral Cortex / Q000098:blood supply*; D002560:Cerebrovascular Circulation / Q000502:physiology*; D006801:Humans; D051379:Mice; D009119:Muscle Contraction / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000502:physiology*; D020286:Pericytes / Q000502:physiology*
chemical_list: D000199:Actins; D002118:Calcium