Bidirectional control of CNS capillary diameter by pericytes

Bidirectional control of CNS capillary diameter by pericytes

2006 October 12 | Claire M. Peppiatt, Clare Howarth, Peter Mobbs, and David Attwell
Pericytes regulate capillary diameter in the CNS, playing a key role in blood flow control. This study shows that pericytes can constrict capillaries in the retina and cerebellum in response to electrical stimulation, neurotransmitters like ATP and noradrenaline, and glutamate. Pericytes are located along and around capillaries and contain contractile proteins, suggesting they can initiate blood flow regulation at the capillary level. Electrical stimulation of pericytes evokes localized capillary constriction that propagates at ~2 μm/sec to constrict distant pericytes. ATP and noradrenaline constrict capillaries, while glutamate reverses this effect. Pericytes also respond to GABA receptor blockers and simulated ischaemia. These findings suggest that pericytes are likely modulators of blood flow in response to neural activity, contributing to functional imaging signals and CNS vascular disease. Pericytes are found in both retinal and cerebellar capillaries, with distinct classes located on straight parts of capillaries and at junctions. Pericytes have processes that wrap around capillaries, providing an anatomical basis for capillary constriction. Electrical stimulation of pericytes evokes a localized constriction that propagates to distant pericytes, indicating pericyte-to-pericyte communication. The speed of this propagation is ~2 μm/sec, suggesting a non-glial mechanism. ATP and noradrenaline constrict capillaries, while glutamate dilates them, indicating that pericytes can be regulated by multiple neurotransmitters. The effects of these neurotransmitters are not uniform, with some pericytes not responding, possibly due to variable receptor expression. Pericytes are likely involved in regulating blood flow in the brain, as noradrenaline constricts capillaries in the cerebellum. This suggests that pericytes can regulate blood flow throughout the brain, not just in the retina. The study also shows that pericytes can dilate capillaries when extracellular calcium is removed, indicating that pericyte contractile tone can be modulated. This could contribute to the increase in blood flow evoked by neural activity. Pericytes may also contribute to the vascular response to ischaemia, as they constrict capillaries during simulated ischaemia. The study challenges the idea that arterioles are solely responsible for the blood flow increase evoked by neural activity, suggesting that pericytes may mediate this response. Pericytes are likely involved in regulating cerebral blood flow in health and disease, as spatially restricted constrictions of brain microvessels may be mediated by pericytes rather than arteriole smooth muscle. These findings highlight the importance of pericytes in CNS blood flow regulation and their potential role in functional imaging and vascular disease.Pericytes regulate capillary diameter in the CNS, playing a key role in blood flow control. This study shows that pericytes can constrict capillaries in the retina and cerebellum in response to electrical stimulation, neurotransmitters like ATP and noradrenaline, and glutamate. Pericytes are located along and around capillaries and contain contractile proteins, suggesting they can initiate blood flow regulation at the capillary level. Electrical stimulation of pericytes evokes localized capillary constriction that propagates at ~2 μm/sec to constrict distant pericytes. ATP and noradrenaline constrict capillaries, while glutamate reverses this effect. Pericytes also respond to GABA receptor blockers and simulated ischaemia. These findings suggest that pericytes are likely modulators of blood flow in response to neural activity, contributing to functional imaging signals and CNS vascular disease. Pericytes are found in both retinal and cerebellar capillaries, with distinct classes located on straight parts of capillaries and at junctions. Pericytes have processes that wrap around capillaries, providing an anatomical basis for capillary constriction. Electrical stimulation of pericytes evokes a localized constriction that propagates to distant pericytes, indicating pericyte-to-pericyte communication. The speed of this propagation is ~2 μm/sec, suggesting a non-glial mechanism. ATP and noradrenaline constrict capillaries, while glutamate dilates them, indicating that pericytes can be regulated by multiple neurotransmitters. The effects of these neurotransmitters are not uniform, with some pericytes not responding, possibly due to variable receptor expression. Pericytes are likely involved in regulating blood flow in the brain, as noradrenaline constricts capillaries in the cerebellum. This suggests that pericytes can regulate blood flow throughout the brain, not just in the retina. The study also shows that pericytes can dilate capillaries when extracellular calcium is removed, indicating that pericyte contractile tone can be modulated. This could contribute to the increase in blood flow evoked by neural activity. Pericytes may also contribute to the vascular response to ischaemia, as they constrict capillaries during simulated ischaemia. The study challenges the idea that arterioles are solely responsible for the blood flow increase evoked by neural activity, suggesting that pericytes may mediate this response. Pericytes are likely involved in regulating cerebral blood flow in health and disease, as spatially restricted constrictions of brain microvessels may be mediated by pericytes rather than arteriole smooth muscle. These findings highlight the importance of pericytes in CNS blood flow regulation and their potential role in functional imaging and vascular disease.
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