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. 2006 Oct 12;443(7112):700-4.
doi: 10.1038/nature05193. Epub 2006 Oct 1.

Bidirectional control of CNS capillary diameter by pericytes

Claire M Peppiatt  1 , Clare Howarth, Peter Mobbs, David Attwell
Affiliations

Bidirectional control of CNS capillary diameter by pericytes

Claire M Peppiatt et al. Nature. .

Abstract

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.

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Figures

Figure 1
Figure 1
Pericyte anatomy confers flow regulating capability downstream of arterioles. a Potential blood flow control sites in cerebral vasculature: arteriolar smooth muscle, and pericytes on capillaries. b Cerebellar molecular layer arteriole (left), surrounded by smooth muscle (SM), giving off a capillary. Capillary labelled with isolectin B4 (green); pericytes labelled for NG2 (red) are on the straight part of capillaries (arrow heads) and at junctions (arrows). c Retinal capillaries. d Soma (s) of cerebellar pericyte gives off processes (p) running along/around capillary. e Dye fill of retinal pericyte reveals processes running around capillary (dashed lines).
Figure 2
Figure 2
Electrical stimulation evokes a Ca2+-dependent localized constriction of retinal pericytes. a-c Capillary with pericytes (black arrows) before (a), during (b) and after (c) stimulation. Erthyrocytes are present within capillary; thin structures outside capillary are astrocyte endfeet. d Diameter of capillary in a-c at stimulated pericyte and a non-pericyte site (white arrow). e Mean (±s.e.m.) constriction when stimulating at pericyte or non-pericyte sites. f Effect of removing extracellular Ca2+ on resting diameter and response to pericyte stimulation, at pericyte and nearby non-pericyte sites. g Dilation produced by removing Ca2+. h Effect of Ca2+-removal on pericyte constriction, as in f.
Figure 3
Figure 3
Propagation and transmitter-evocation of retinal pericyte constriction. a Electrically stimulating a pericyte (black arrow) evokes local constriction (red dashes show vessel diameter) followed by constriction of distant pericytes (blue). b No constriction of intervening non-pericyte regions (green). c,d UTP constricts two pericytes (arrows) but not at non-pericyte region. e Mean (±s.e.m.) UTP-evoked constriction. f,g Pericyte constriction (top arrows; lower arrows show another pericyte) evoked by electrical stimulation (electrode, right) near inner plexiform layer. h,i Constriction of pericyte (top arrows; lower arrows show another pericyte) evoked by puffing GABA receptor blockers (electrode, top left) near inner plexiform layer.
Figure 4
Figure 4
Effects of neurotransmitters on cerebellar molecular layer capillary, and of ischaemia on retinal capillary. a Localized noradrenaline-evoked constriction near pericytes (black arrows, clearest in panel 4), and dilation by superimposed glutamate. Noradrenaline-evoked constriction cannot reflect fluid movement caused by arterioles constricting, because this would make the capillary dilate. b Diameter at pericyte; numbers show image times above. c Mean (±s.e.m.) constriction by noradrenaline, at pericyte and non-pericyte sites. d Dilation (reduction of noradrenaline-evoked constriction) by glutamate (as percentage of pre-noradrenaline diameter). e Retinal capillary before ischaemia and in ischaemia before anoxic depolarization. f Diameter at pericyte in e.
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