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

Overview

Journal Neuron

Publisher Cell Press

Specialty Neurology

Date 2015 Jun 30

PMID 26119027

Citations 382

Authors

Robert A Hill

Lei Tong

Peng Yuan

Sasidhar Murikinati

Shobhana Gupta

Jaime Grutzendler

Affiliations

Soon will be listed here.

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.

Citing Articles

Modeling of Blood Flow Dynamics in Rat Somatosensory Cortex.

Battini S, Cantarutti N, Kotsalos C, Roussel Y, Cattabiani A, Arnaudon A Biomedicines. 2025; 13(1).

PMID: 39857656 PMC: 11761867. DOI: 10.3390/biomedicines13010072.

Response of capillaries and small arterioles to full-field flicker is not dependent on local ganglion cell thickness.

Sobczak M, Walker B, Gast T, Cassavaugh N, Carmichael-Martins A, Burns S Biomed Opt Express. 2025; 16(1):42-56.

PMID: 39816155 PMC: 11729286. DOI: 10.1364/BOE.544772.

From Mechanisms to Medicine: Neurovascular Coupling in the Diagnosis and Treatment of Cerebrovascular Disorders: A Narrative Review.

Yang L, Zhao W, Kan Y, Ren C, Ji X Cells. 2025; 14(1.

PMID: 39791717 PMC: 11719775. DOI: 10.3390/cells14010016.

Unlocking the potential of photobiomodulation therapy for brain neurovascular coupling: The biological effects and medical applications.

Yan B, Zhou J, Yan F, Gao M, Tang J, Huang L J Cereb Blood Flow Metab. 2025; :271678X241311695.

PMID: 39763390 PMC: 11705326. DOI: 10.1177/0271678X241311695.

Label free, capillary-scale blood flow mapping in vivo reveals that low-intensity focused ultrasound evokes persistent dilation in cortical microvasculature.

Shen Y, Jethe J, Reid A, Hehir J, Amaral M, Ren C Commun Biol. 2025; 8(1):12.

PMID: 39762513 PMC: 11704147. DOI: 10.1038/s42003-024-07356-2.

References

Krueger M, Bechmann I . CNS pericytes: concepts, misconceptions, and a way out. Glia. 2009; 58(1):1-10. DOI: 10.1002/glia.20898. View

Del Zoppo G, Schmid-Schonbein G, Mori E, Copeland B, Chang C . Polymorphonuclear leukocytes occlude capillaries following middle cerebral artery occlusion and reperfusion in baboons. Stroke. 1991; 22(10):1276-83. DOI: 10.1161/01.str.22.10.1276. View

Chaigneau E, Oheim M, Audinat E, Charpak S . Two-photon imaging of capillary blood flow in olfactory bulb glomeruli. Proc Natl Acad Sci U S A. 2003; 100(22):13081-6. PMC: 240748. DOI: 10.1073/pnas.2133652100. View

Hamel E . Perivascular nerves and the regulation of cerebrovascular tone. J Appl Physiol (1985). 2006; 100(3):1059-64. DOI: 10.1152/japplphysiol.00954.2005. View

LEAO A . Further observations on the spreading depression of activity in the cerebral cortex. J Neurophysiol. 2010; 10(6):409-14. DOI: 10.1152/jn.1947.10.6.409. View

Attwell D, Iadecola C . The neural basis of functional brain imaging signals. Trends Neurosci. 2002; 25(12):621-5. DOI: 10.1016/s0166-2236(02)02264-6. View

Logothetis N, Pauls J, Augath M, Trinath T, Oeltermann A . Neurophysiological investigation of the basis of the fMRI signal. Nature. 2001; 412(6843):150-7. DOI: 10.1038/35084005. View

Somjen G . Mechanisms of spreading depression and hypoxic spreading depression-like depolarization. Physiol Rev. 2001; 81(3):1065-96. DOI: 10.1152/physrev.2001.81.3.1065. View

Zhu X, Hill R, Dietrich D, Komitova M, Suzuki R, Nishiyama A . Age-dependent fate and lineage restriction of single NG2 cells. Development. 2011; 138(4):745-53. PMC: 3026417. DOI: 10.1242/dev.047951. View

10.

Zariwala H, Borghuis B, Hoogland T, Madisen L, Tian L, De Zeeuw C . A Cre-dependent GCaMP3 reporter mouse for neuronal imaging in vivo. J Neurosci. 2012; 32(9):3131-41. PMC: 3315707. DOI: 10.1523/JNEUROSCI.4469-11.2012. View

11.

Yemisci M, Gursoy-Ozdemir Y, Vural A, Can A, Topalkara K, Dalkara T . Pericyte contraction induced by oxidative-nitrative stress impairs capillary reflow despite successful opening of an occluded cerebral artery. Nat Med. 2009; 15(9):1031-7. DOI: 10.1038/nm.2022. View

12.

OFarrell F, Attwell D . A role for pericytes in coronary no-reflow. Nat Rev Cardiol. 2014; 11(7):427-32. DOI: 10.1038/nrcardio.2014.58. View

13.

Wendling O, Bornert J, Chambon P, Metzger D . Efficient temporally-controlled targeted mutagenesis in smooth muscle cells of the adult mouse. Genesis. 2008; 47(1):14-8. DOI: 10.1002/dvg.20448. View

14.

Vanzetta I, Hildesheim R, Grinvald A . Compartment-resolved imaging of activity-dependent dynamics of cortical blood volume and oximetry. J Neurosci. 2005; 25(9):2233-44. PMC: 6726087. DOI: 10.1523/JNEUROSCI.3032-04.2005. View

15.

Winkler E, Sagare A, Zlokovic B . The pericyte: a forgotten cell type with important implications for Alzheimer's disease?. Brain Pathol. 2014; 24(4):371-86. PMC: 4423607. DOI: 10.1111/bpa.12152. View

16.

Winkler E, Bell R, Zlokovic B . Central nervous system pericytes in health and disease. Nat Neurosci. 2011; 14(11):1398-1405. PMC: 4020628. DOI: 10.1038/nn.2946. View

17.

Simard M, Arcuino G, Takano T, Liu Q, Nedergaard M . Signaling at the gliovascular interface. J Neurosci. 2003; 23(27):9254-62. PMC: 6740832. View

18.

Armulik A, Genove G, Mae M, Nisancioglu M, Wallgard E, Niaudet C . Pericytes regulate the blood-brain barrier. Nature. 2010; 468(7323):557-61. DOI: 10.1038/nature09522. View

19.

Hill R, Grutzendler J . In vivo imaging of oligodendrocytes with sulforhodamine 101. Nat Methods. 2014; 11(11):1081-2. PMC: 4539948. DOI: 10.1038/nmeth.3140. View

20.

Faraci F . Protecting against vascular disease in brain. Am J Physiol Heart Circ Physiol. 2011; 300(5):H1566-82. PMC: 3094081. DOI: 10.1152/ajpheart.01310.2010. View