Vascular Compartmentalization of Functional Hyperemia from the Synapse to the Pia

Rungta, Ravi L.; Chaigneau, Emmanuelle; Osmanski, Bruno-Félix; Charpak, Serge

doi:10.1016/j.neuron.2018.06.012

Cited by 210 publications

(255 citation statements)

References 49 publications

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“…Thus, the signal originated in capillaries may need to travel upstream toward the feeding artery to produce there a stronger vasomotor response. While this spatial separation of the signal reception from the major vasomotor response element was also noted in various regions of the CNS (Iadecola, Yang, Ebner, & Chen, ; Kornfield & Newman, ; Rungta, Chaigneau, Osmanski, & Charpak, ), the structure mediating the signal propagation remained unclear. Here we describe a vascular relay region, a transition between the capillary and the feeding artery with a unique string‐like expression of Cx43.…”

Section: Discussionmentioning

confidence: 82%

Domain‐specific distribution of gap junctions defines cellular coupling to establish a vascular relay in the retina

Ivanova

Kovács-Öller

Sagdullaev

2019

J of Comparative Neurology

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In the retina, diverse functions of neuronal gap junctions (GJs) have been established. However, the distribution and function of vascular GJs are less clear. Here in the mouse retina whole mounts, we combined structural immunohistochemical analysis and a functional assessment of cellular coupling with a GJ‐permeable tracer Neurobiotin to determine distribution patterns of three major vascular connexins. We found that Cx43 was expressed in punctate fashion on astroglia, surrounding all types of blood vessels and in continuous string‐like structures along endothelial cell contacts in specialized regions of the vascular tree. Specifically, these Cx43‐positive strings originated at the finest capillaries and extended toward the feeding artery. As this structural arrangement promoted strong and exclusive coupling of pericytes and endothelial cells along the corresponding branch, we termed this region a “vascular relay.” Cx40 expression was found predominantly along the endothelial cell contacts of the primary arteries and did not overlap with Cx43‐positive strings. At their occupied territories, Cx43 and Cx40 clustered with tight junctions and, to a lesser extent, with adhesion contacts, both key elements of the blood–retina barrier. Finally, Cx37 puncta were associated with the entire surface of both mural and endothelial cells across all regions of the vascular tree. This combinatorial analysis of vascular connexins and identification of the vascular relay region will serve as a structural foundation for future studies of neurovascular signaling in health and disease.

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Section: Discussionmentioning

confidence: 82%

Domain‐specific distribution of gap junctions defines cellular coupling to establish a vascular relay in the retina

Ivanova

Kovács-Öller

Sagdullaev

2019

J of Comparative Neurology

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“…Firstly, at least some of these pericytes express the contractile protein SMA (though in a form that is less stable than in smooth muscle cells and ensheathing pericytes 28 ). Secondly, their level of intracellular calcium decreases in response to neuronal activity (consistent with a relaxation of contractile machinery 24 ). Finally, their dilations seem to mediate a large proportion of the overall increase in blood flow 24,25 .…”

Section: Discussionmentioning

confidence: 90%

“…Secondly, their level of intracellular calcium decreases in response to neuronal activity (consistent with a relaxation of contractile machinery 24 ). Finally, their dilations seem to mediate a large proportion of the overall increase in blood flow 24,25 .…”

Section: Discussionmentioning

confidence: 90%

“…Firstly, pericytes were longer in HC than V1, suggesting functional differences that are likely to include a lower contractility, because shorter mural cells are more contractile and pericyte contractility is greatest near the soma 12,15 . Ensheathing pericytes initiate the dilatory response to sensory stimulation in the olfactory bulb 24 , and are amongst the earliest to respond in the neocortex 25 . They tended to be longer in HC, so may be less contractile, helping to shape the weaker neurovascular coupling responses there.…”

Section: Discussionmentioning

confidence: 99%

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Hippocampus has lower oxygenation and weaker control of brain blood flow than cortex, due to microvascular differences

Shaw

Bell

Boyd

et al. 2019

Preprint

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The hippocampus is essential for spatial and episodic memory but is damaged early in Alzheimer's disease and is very sensitive to hypoxia. Understanding how it regulates its oxygen supply is therefore key for designing interventions to preserve its function. However, studies of neurovascular function in the hippocampus in vivo have been limited by its relative inaccessibility.Here we compared hippocampal and visual cortical neurovascular function in awake mice, using two photon imaging of individual neurons and vessels and measures of regional blood flow and haemoglobin oxygenation. We show that blood flow, blood oxygenation and neurovascular coupling were decreased in the hippocampus compared to neocortex, because of differences in both the vascular network and pericyte and endothelial cell function. Modelling oxygen diffusion indicates that these features of the hippocampal vasculature could explain its sensitivity to damage during neurological conditions, including Alzheimer's disease, where the brain's energy supply is decreased.

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“…Arterial dilations during functional hyperemia can drive fluid exchange in the PVS While cardiac pulsations are small in size, the arterial dilations that accompany increases in local neural activity are substantially larger and longer lasting. In response to increases in local neural activity, cerebral arteries can dilate by 20% or more in non-anesthetized animals [26][27][28][29] and are the basis for the blood-oxygen-level dependent (BOLD), functional magnetic resonance imaging (fMRI) [30][31][32][33] signal. In contrast with arterial pulsations which occur at the heart rate, these neurally-induced arterial dilation take one to three seconds to peak and last for several seconds in response to a brief increase in neural activity.…”

Section: Ignoring Brain Deformability Leads To Implausibly High Pressmentioning

confidence: 99%

Functional hyperemia drives fluid exchange in the paravascular space

Kedarasetti

Turner

Echagarruga

et al. 2019

Preprint

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Maintaining the ionic and chemical composition of the extracellular spaces in the brain is extremely important for its health and function. However, the brain lacks a conventional lymphatic system to remove metabolic waste. It has been proposed that the fluid movement through the paravascular space (PVS) surrounding penetrating arteries can help remove metabolites from the brain. The dynamics of fluid movement in the PVS and its interaction with arterial dilation and brain mechanics are not well understood. Here, we performed simulations to understand how arterial pulsations and dilations interact with brain deformability to drive fluid flow in the PVS. In simulations with compliant brain tissue, arterial pulsations did not drive appreciable flows in the PVS. In contrast, when the artery dilated with dynamics like those seen during functional hyperemia, there was a marked movement of fluid through the PVS. Our simulations suggest that in addition to its other purposes, functional hyperemia may serve to increase fluid exchange between the PVS and the subarachnoid space, improving the clearance of metabolic waste. We measured displacement of the blood vessels and the brain tissue simultaneously in awake, headfixed mice using two-photon microscopy. Our measurements show that brain tissue can deform in response to fluid movement in the PVS, as predicted by simulations. The results from our simulations and experiments show that the deformability of the soft brain tissue needs to be accounted for when studying fluid flow and metabolite transport in the brain.

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Vascular Compartmentalization of Functional Hyperemia from the Synapse to the Pia

Cited by 210 publications

References 49 publications

Domain‐specific distribution of gap junctions defines cellular coupling to establish a vascular relay in the retina

Domain‐specific distribution of gap junctions defines cellular coupling to establish a vascular relay in the retina

Hippocampus has lower oxygenation and weaker control of brain blood flow than cortex, due to microvascular differences

Functional hyperemia drives fluid exchange in the paravascular space

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