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HALL_Physiological_Measurement_Apr_2021.pdf (2.59 MB)

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

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posted on 2023-06-09, 23:46 authored by Selena Milanovic, Kira ShawKira Shaw, Catherine HallCatherine Hall, Stephen John Payne
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 signalling 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 1mm 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 1s. 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.

History

Publication status

  • Published

File Version

  • Accepted version

Journal

Physiological Measurement

ISSN

0967-3334

Publisher

IOP Publishing

Department affiliated with

  • Psychology Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2021-05-06

First Open Access (FOA) Date

2021-05-06

First Compliant Deposit (FCD) Date

2021-05-05

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    University of Sussex (Publications)

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