Stimulation-induced increases in cerebral blood flow and local capillary vasoconstriction depend on conducted vascular responses

Abstract

Functional neuroimaging, such as fMRI, is based on coupling neuronal activity and accompanying changes in cerebral blood flow (CBF) and metabolism. However, the relationship between CBF and events at the level of the penetrating arterioles and capillaries is not well established. Recent findings suggest an active role of capillaries in CBF control, and pericytes on capillaries may be major regulators of CBF and initiators of functional imaging signals. Here, using two-photon microscopy of brains in living mice, we demonstrate that stimulation-evoked increases in synaptic activity in the mouse somatosensory cortex evokes capillary dilation starting mostly at the first- or second-order capillary, propagating upstream and downstream at 5-20 µm/s. Therefore, our data support an active role of pericytes in cerebrovascular control. The gliotransmitter ATP applied to first- and second-order capillaries by micropipette puffing induced dilation, followed by constriction, which also propagated at 5-20 µm/s. ATP-induced capillary constriction was blocked by purinergic P2 receptors. Thus, conducted vascular responses in capillaries may be a previously unidentified modulator of cerebrovascular function and functional neuroimaging signals.

Precapillary sphincters maintain perfusion in the cerebral cortex

“…Increased Ca 2+ in neurons and astrocytes triggers the release of vasoactive compounds that dilate capillaries and penetrating arterioles (PAs) and thereby increases blood flow. The activity-induced flow increase is based on coordinated changes in vessel diameters, which are regulated by Ca 2+ fluctuations within the vascular smooth muscle cells (VSMCs) that circumscribe arteries and larger arterioles and the pericytes that ensheathe capillaries close to the PA [5][6][7][8] . PAs branch into capillary networks that supply each cortical layer with oxygen and glucose 9 .…”

Metabolic‐vascular coupling in skeletal muscle: A potential role for capillary pericytes?

“…In the brain, pericytes form an interconnected network within the microvasculature and are capable of transmitting signals upstream to activate adjacent pericytes . A recent study calculated that the speed of these conducted responses ranges from 5 to 20 μm/s and that the signal was transmitted both up and downstream of the initiating pericyte . This rapid cell–cell communication is particularly intriguing and suggests that rather than acting independently on single capillaries, pericytes may regulate and co‐ordinate networks of capillaries through an integrated and interconnected response to meet tissue metabolic demand.…”

Bioenergy Crisis in Coronavirus Diseases?

“…Therefore, investigation of an adjunct therapy targeting dysfunctional mitochondrial metabolism [13] is proposed, including photobiomodulation [14], since ATP acts as a purinergic feedback signaling molecule where low ATP concentrations almost exclusively recruit microglial cells [15]. Purinergic signaling cascade is also involved with the complex vascular response at the capillaries (pericytes) [16], which can be partly responsible for the cerebrovascular complications of COVID-19 [7]. We further postulate that continuous fNIRS-EEG joint monitoring can be a useful bedside multimodal monitoring tool in neuro ICU [17] to detect transient neurovascular uncoupling.…”