Researcher discovers previously rejected function in the brain’s blood vessels

Summary: Despite previous findings, researchers have found precapillary sphincters in the brain. The study reports the precapillary sphincters may play a major role in disturbances of the brain’s blood supply and blood pressure.

Source: University of Copenhagen

Allegedly, they should not exist in the brain, the so-called precapillary sphincters – a kind of squeezing ‘muscle clamp’ between the larger and smaller vessels of the bloodstream.

Nevertheless, Assistant Professor Søren Grubb from the Department of Neuroscience at the University of Copenhagen has indeed shown the sphincters in mice.

‘In the early ’10s, a Japanese review study concluded that there was no evidence that pre-capillary sphincters should exist in the heart, brain and muscular connective tissue,’ he says and continues:

‘Since then, scientists have focused a lot on pericytes – muscle cells that can regulate the resistance in the smallest blood vessels. At the same time, however, they have somehow missed a great resistance right between some arterioles and capillaries: The sphincters. Perhaps because the discovery of the pericytes has received more attention among all the blood vessels of the brain’.

Functions as a water faucet or a sluice system

As blood flows through the brain, it flows from arteriole to vein through the capillaries. The latter are the smallest blood vessels in the body, but incredibly important. It is here that the blood and the brain exchange oxygen and nutrients.

Søren Grubb explains that the precapillary sphincters may be compared to a kind of thermostat that distributes the pressure between the branches of the blood vessels. A bit like a faucet adjusting the pressure between a water pipe and a garden hose.

As the muscle clamp relaxes, more blood cells will flow through its passage and the pressure in the following blood vessels will increase. When the clamp contracts, a bottleneck forms, which lowers the pressure further down the blood flow.

‘In this way, it also works a bit like a sluice system to irrigate fields: You may have a roaring river, but by diverting water from the river and making sluices that can regulate the amount of water for each field, you can distribute the water to many areas, says Søren Grubb.

‘Conversely, if the sluice shuts down or is clogged, the field will quickly dry out’, he adds.

Potential for dementia and migraine

Based on that picture, Søren Grubb assumes that the pre-capillary sphincters may play a major role for disturbances of the brain’s blood supply and blood pressure.

If the assumption holds true, the discovery of the clamping muscles in the brain will potentially affect the treatment of diseases such as migraine, Alzheimer’s and vascular dementia – all associated with an accumulation of waste products that may stem from blood vessel defects.

This shows a precapillary sphincter
Close-up of precapillary sphincter (the strong red mark in the middle of the greenly marked blood flow) from two-photon microscope. According to the research results, these squeezing muscle cells are in the brain most often found at the early branches of blood vessels in the upper layers of the cerebral cortex. Image is credited to Lauritzen Lab, University of Copenhagen.

Already, the research group Lauritzen Lab, of which Søren Grubb is part, has tested a model for migraine with aura. The model confirms the hypothesis, but the Assistant Professor emphasises that further research is still needed in connection with disorders:

‘We have shown that the precapillary sphincter is found in the brain. The rest is still speculative. But perhaps more researchers will start working on it, now that they know that the sphincters are there’.

About this neuroscience research article

University of Copenhagen
Media Contacts:
Søren Grubb – University of Copenhagen
Image Source:
The image is credited to Lauritzen Lab, University of Copenhagen.

Original Research: Open access
“Precapillary sphincters maintain perfusion in the cerebral cortex”. Søren Grubb, Changsi Cai, Bjørn O. Hald, Lila Khennouf, Reena Prity Murmu, Aske G. K. Jensen, Jonas Fordsmann, Stefan Zambach & Martin Lauritzen.
Nature Communications doi:10.1038/s41467-020-14330-z.


Precapillary sphincters maintain perfusion in the cerebral cortex

Active nerve cells release vasodilators that increase their energy supply by dilating local blood vessels, a mechanism termed neurovascular coupling and the basis of BOLD functional neuroimaging signals. Here, we reveal a mechanism for cerebral blood flow control, a precapillary sphincter at the transition between the penetrating arteriole and first order capillary, linking blood flow in capillaries to the arteriolar inflow. The sphincters are encircled by contractile mural cells, which are capable of bidirectional control of the length and width of the enclosed vessel segment. The hemodynamic consequence is that precapillary sphincters can generate the largest changes in the cerebrovascular flow resistance of all brain vessel segments, thereby controlling capillary flow while protecting the downstream capillary bed and brain tissue from adverse pressure fluctuations. Cortical spreading depolarization constricts sphincters and causes vascular trapping of blood cells. Thus, precapillary sphincters are bottlenecks for brain capillary blood flow.

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