Abstract
The neurovascular mechanisms underpinning the local regulation of cerebral blood flow (CBF) and oxygen transport remain elusive. In this study we have combined novel in vivo imaging of cortical microvascular and mural cell architecture with mathematical modelling of blood flow and oxygen transport, to provide new insights into CBF regulation that would be inaccessible in a conventional experimental context. Our study indicates that vasoconstriction of smooth muscle actin-covered vessels, rather than pericyte-covered capillaries, induces stable reductions in downstream intravascular capillary and tissue oxygenation. We also propose that seemingly paradoxical observations in the literature around reduced blood velocity in response to arteriolar constrictions might be caused by a propagation of constrictions to upstream penetrating arterioles. We provide support for pericytes acting as signalling conduits for upstream smooth muscle activation, and erythrocyte deformation as a complementary regulatory mechanism. Finally, we caution against the use of blood velocity as a proxy measurement for flow. Our combined imaging-modelling platform complements conventional experimentation allowing cerebrovascular physiology to be probed in unprecedented detail.
Highlights
The mammalian brain has evolved complex neurovascular coupling mechanisms to regulate the flow of blood to tissue in response to neuronal activity
It is generally accepted that arteriolar smooth muscle cells (SMCs) are contractile cells which have a role in regulating cerebral blood flow (CBF)
Our study used in vivo imaging data from the mouse cortex, acquired with a two-photon microscope (Praire Technologies)
Summary
The mammalian brain has evolved complex neurovascular coupling mechanisms to regulate the flow of blood to tissue in response to neuronal activity. Studies suggest that neurotransmitter-mediated signalling plays a key role in regulating CBF by contributing to the vascular tone of capillaries as well as arterioles[2,3,4]. The extraction of cerebral vascular network structure enabled the parametrisation of two comprehensive, coupled mathematical models for blood flow and oxygen transport, which facilitated physiologically realistic in silico experiments to be performed. These allowed us to examine the complex interactions between coupled physiological phenomena, occurring in spatially isolated regions within the cortical vasculature.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
