Precapillary sphincters maintain perfusion in the cerebral cortex

Abstract

Active nerve cells release vasodilators that increase their energy supply by dilating local blood vessels, a mechanism termed neurovascular coupling and the basis of BOLD functional neuroimaging signals. Here, we reveal a mechanism for cerebral blood flow control, a precapillary sphincter at the transition between the penetrating arteriole and first order capillary, linking blood flow in capillaries to the arteriolar inflow. The sphincters are encircled by contractile mural cells, which are capable of bidirectional control of the length and width of the enclosed vessel segment. The hemodynamic consequence is that precapillary sphincters can generate the largest changes in the cerebrovascular flow resistance of all brain vessel segments, thereby controlling capillary flow while protecting the downstream capillary bed and brain tissue from adverse pressure fluctuations. Cortical spreading depolarization constricts sphincters and causes vascular trapping of blood cells. Thus, precapillary sphincters are bottlenecks for brain capillary blood flow.

Brain Microvascular Pericytes in Vascular Cognitive Impairment and Dementia

“…The definition of the vessels, however, has varied depending on the studies. While some studies have defined all vessels including proximal and distal branches coming off penetrating arterioles as capillaries (Peppiatt et al, 2006;Hall et al, 2014;Cai et al, 2018;Khennouf et al, 2018;Grubb et al, 2020), others have defined proximal branches as precapillary arterioles (Fernández-Klett et al, 2010;Hartmann et al, 2015;Hill et al, 2015). To make matters more complicated, Hill et al (2015), have asserted that the mural cells on the proximal FIGURE 1 | Brain vessels and mural cells.…”

“…Because these pericytes are positioned at the transition between arterioles and capillaries, and have shared some characteristics with SMCs, the terminology and classification of these mural cells have been hotly debated. The cells have been variably called as ensheathing pericytes Grant et al, 2019), transition/transitional pericytes (Kisler et al, 2017a;Arango-Lievano et al, 2018), pre-capillary pericytes (Zimmermann, 1923), simply 'pericytes' or 'capillary pericytes' (Hall et al, 2014;Attwell et al, 2016;Cai et al, 2018;Khennouf et al, 2018;Grubb et al, 2020), smooth muscle-pericyte hybrids (Hartmann et al, 2015;Yang et al, 2017;Dalkara, 2019), arteriole SMC (aaSMC) (Vanlandewijck et al, 2018), or pre-capillary SMCs (Hill et al, 2015). At the same time, the vessels of proximal branches coming off penetrating arterioles are also differently defined as pre-capillary arterioles (Fernández-Klett et al, 2010;Hartmann et al, 2015;Hill et al, 2015;Berthiaume et al, 2018;Erdener and Dalkara, 2019;Grant et al, 2019), post-arteriole capillaries (Gould et al, 2016) or a part of capillaries (Hall et al, 2014;Attwell et al, 2016;Cai et al, 2018;Khennouf et al, 2018;Grubb et al, 2020).…”

“…The cells in this proximal branches (especially, 1st to 2nd branches) coming off arterioles has drawn attention as they highly contribute to neurovascular coupling (NVC) (Hall et al, 2014;Hill et al, 2015;Cai et al, 2018;Khennouf et al, 2018;Rungta et al, 2018;Grubb et al, 2020) and no-reflow phenomenon after acute ischemia (Hall et al, 2014;Hill et al, 2015). Although referring to these mural cells as a subtype of "pericytes" has become almost a consensus, the shifting nomenclature of these cells and vessels has been the root of recent controversies on pericyte roles as regulators of CBF (discussed below).…”

Retina-specific targeting of pericytes reveals structural diversity and enables control of capillary blood flow

“…First, using the Cspg4-Cre-Tom line, we anatomically characterized sphincter pericytes. In the brain, they control blood inflow from an artery into a capillary branch [21,38]. We found that this is a single cell fully encircling the opening into the branching vessel; the cell had relatively low SMA expression and was heavily insulated by the basement membrane.…”

“…Using the Cspg4-Cre-Tom mouse, we evaluated the sphincter cells (Figure 2i-n), a unique structure that is believed to play a role in gating blood inflow into the arterial branch [21][22][23].…”