Investigating the role of pericytes in cerebral autoregulation: A modeling study
Journal
Physiological Measurement
Journal Volume
42
Journal Issue
5
Date Issued
2021
Author(s)
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. ? 2021 Institute of Physics and Engineering in Medicine.
Subjects
autoregulation
CBF regulation
haemodynamic
mathematical modeling
pericytes
Blood
Blood pressure
Blood vessels
Feedback control
Metabolism
Microcirculation
Arterial blood pressure
Autoregulations
Cerebral autoregulation
Cerebral blood flow
Cerebral blood flow regulation
Feedback mechanisms
Flow regulation
Haemodynamics
Mathematical modeling
Pericytes
Nutrients
arterial pressure
brain circulation
capillary
homeostasis
pericyte
Arterial Pressure
Capillaries
Cerebrovascular Circulation
Homeostasis
Type
journal article