Microglia help regulate blood flow and maintain the brain’s critical blood vessels, University of Virginia School of Medicine researchers have found. It is an important but previously unknown role for these immune cells that protect the brain from disease and injury.

The findings1 may prove important in cognitive decline, dementia and stroke, among other conditions linked to diseases of the brain’s small vessels.

Precise blood vessel function is critical to accommodate the extreme energy demands of the brain for normal brain function. These findings suggest previously unknown roles for these brain cells in the proper maintenance of blood delivery to the brain and provide novel opportunities to intervene in contexts where blood perfusion to the brain is impaired,

said Ukpong B. Eyo of UVA’s Department of Neuroscience.

Brain Support Staff

Scientists have known that microglia play many important roles in the brain. For example, the cells police the blood-brain barrier that protects the organ from harmful germs in the bloodstream.

Microglia also facilitate the formation of the brain’s complex network of blood vessels during development. And they are known to be important in many diseases. In Alzheimer’s disease, for example, recent work suggests2 that the loss of the immune cells is thought to increase harmful plaque buildup in the brain.

ramified myeloid cells

Ramified CX3CR1 myeloid cells associate with brain capillaries. Credit: Bisht et al, CC-BY

Scientists have been unsure, however, what role microglia play in maintaining blood vessels in a normal, healthy brain. The new research from Eyo and his colleagues reveals that the cells are critical support staff, tending the vessels and even regulating blood flow.

Capillary-associated Microglia

The UVA researchers identified microglia associating with the brain’s capillaries, determined what the immune cells do there and revealed what controls those interactions.

 neurovascular unit illustration of microglia

(a) An illustration showing the neurovascular unit consisting of astrocytes (ACs), pericytes (PCs), microglial cells (MGs), neurons, and the associated vasculature. The black box indicates a zoomed-in region depicted in (b), showing microglial expression of the P2RY12 and capillary expression of the ATP permeable integral membrane protein PANX1. (c) P2RY12–PAN1 coupling mediate microglial interactions with the vasculature, where those microglia whose cell bodies reside on the vasculature are referred to as capillary-associated microglia (CAMs). Knockout of PANX1, microglial depletion with PLX3397, or knockout of the P2RY12 as depicted in (d) all lead to (e), reduced CAM interactions, increased capillary diameter and cerebral blood flow, and an impaired vasodilatory response to carbon dioxide (CO2). Credit: Bisht et al, CC-BY

Among the cells' important responsibilities is helping to regulate the diameter of the capillaries and possibly restricting or increasing blood flow as needed.

Researchers have been studying these cells in the living brain for over two decades, but this is the first time we are able to get an idea of these mechanisms of microglia-blood vessel interaction. It’s an exciting time to be the first to make these findings here at UVA,

said Eyo.

The researchers believe their new findings could have significant implications for diseases that affect the small vessels of the brain. These conditions are thought to contribute to strokes, Alzheimer’s, loss of balance and mental decline, among other serious health problems.

This research was supported by The National Institutes of Health, and by the Owens Family Foundation.

  1. Bisht, K., Okojie, K.A., Sharma, K. et al. Capillary-associated microglia regulate vascular structure and function through PANX1-P2RY12 coupling in mice. Nat Commun 12, 5289 (2021). ↩︎

  2. Spangenberg, E. et al. Sustained microglial depletion with CSF1R inhibitor impairs parenchymal plaque development in an Alzheimer’s disease model. Nat. Commun. 10, 3758 (2019). ↩︎

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