Investigating the role of pericytes in cerebral autoregulation: a modeling study

Selena Milanovic,Catherine Hall,Kira Shaw,Stephen Payne

doi:10.1088/1361-6579/abfb0a

Selena Milanovic, Catherine Hall + Show 2 more

Open Access

https://doi.org/10.1088/1361-6579/abfb0a

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Abstract

The brain’s inability to store nutrients for more than a few seconds makes it one of the most tightly regulated systems in the body. Driven by metabolic demand, cerebral autoregulation (CA) ensures a constant cerebral blood flow (CBF) over a ±50% change in arterial blood pressure (ABP) from baseline. Recent evidence suggests that pericytes, contractile cells in the capillary bed, play a previously-ignored regulatory role. To elucidate the CA phenomenon, the role of oxygen metabolism, pericyte activity and neural signaling in CBF modulation were quantified. Driven by nutrient metabolism in the tissue and pressure sensitivity in the vasculature, the model introduced here successfully replicates CA. To highlight the role of different vessel sizes, vessels with a diameter above 1 mm were represented using a lumped parameter model while the microvasculature was illustrated as a branching tree network model. This novel approach elucidated the relationship between the microvasculature’s nutrient supply and arterial regulation. Capillary responses to local increases in neuronal activity were experimentally determined, showing that pericytes can increase the diameter of the adjacent vessel by 2.5% in approximately 1 s. Their response was quantified and included in the computational model as an active component of the capillary bed. To compare the efficacy model presented here to existing ones, four feedback mechanisms were tested. To simulate dynamic CBF regulation a 10% increase in ABP was imposed. This resulted in a 23.79%–34.33% peak increase in CBF, depending on the nature of the feedback mechanism of the model. The four feedback mechanisms that were studied significantly differ in the response time, ultimately highlighting that capillaries play a fundamental role in the rapid regulation of CBF. Conclusively, this study indicates that while pericytes do not greatly alter the peak CBF change, they play a fundamental role in the speed of regulation.

Highlights

To ensure an adequate tissue perfusion, the brain relies on a tightly regulated system of vessels
With the aim of designing a physiologically representative cerebral blood flow (CBF) regulation mechanism, the computational model presented here comprises two parts: the first part consists of large arteries and veins whose response is modelled through an electrical equivalent model while the second part extrapolates from experimental data on pericyte-induced dilation, which are included in a microvasculature network model
Pericyte activity was quantified in terms of capillary dilation magnitude and response time

Summary

Introduction

To ensure an adequate tissue perfusion, the brain relies on a tightly regulated system of vessels. Both large and small, each vessel category has a specific and indispensable function. Being highly sensitive to perfusion changes, the brain relies on an autoregulation mechanism, driven by an active response of the arteries and arterioles. [3],[4] Global and local regulating mechanisms are interlinked and changes in one result in an alteration in behaviour of the other. Sometimes these mechanisms compensate for each other’s deficiency, yet the magnitude of their importance of governing agents is yet to be defined. Contractile cells found on capillary vessels, have been recently proved to actively regulate capillary vessel diameter. [5] A dysfunction xxxx-xxxx/xx/xxxxxx

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