Pericytes: Intrinsic Transportation Engineers of the CNS Microcirculation.

Ahmed M Eltanahy,Albert Gonzales,Yara A Koluib

doi:10.3389/fphys.2021.719701

Ahmed M Eltanahy, Albert Gonzales + Show 1 more

Open Access

https://doi.org/10.3389/fphys.2021.719701

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Abstract

Pericytes in the brain are candidate regulators of microcirculatory blood flow because they are strategically positioned along the microvasculature, contain contractile proteins, respond rapidly to neuronal activation, and synchronize microvascular dynamics and neurovascular coupling within the capillary network. Analyses of mice with defects in pericyte generation demonstrate that pericytes are necessary for the formation of the blood-brain barrier, development of the glymphatic system, immune homeostasis, and white matter function. The development, identity, specialization, and progeny of different subtypes of pericytes, however, remain unclear. Pericytes perform brain-wide ‘transportation engineering’ functions in the capillary network, instructing, integrating, and coordinating signals within the cellular communicome in the neurovascular unit to efficiently distribute oxygen and nutrients (‘goods and services’) throughout the microvasculature (‘transportation grid’). In this review, we identify emerging challenges in pericyte biology and shed light on potential pericyte-targeted therapeutic strategies.

Highlights

Our definition and understanding of pericytes within the capillary network have evolved from their initial discovery as simple mural cells with a distinctive “bump-on-a-log” morphology to a kind of a cellular jack-of-all-trades
The functional linkage between neuronal activity and blood flow, a process termed neurovascular coupling that is responsible for the activity-dependent increase in local blood flow, was previously thought to be solely mediated by changes in the tone of the smooth muscle cells that form a continuous layer around the endothelial cell lining of arterioles
Pericyte loss leads to a breakdown and reorganization of the capillary network (Bergers and Song, 2005), and we propose that a bioengineered organoid system can efficiently provide a means of jumpstarting the angiogenic, or vascular replacement process

Summary

INTRODUCTION

Our definition and understanding of pericytes within the capillary network have evolved from their initial discovery as simple mural cells with a distinctive “bump-on-a-log” morphology to a kind of a cellular jack-of-all-trades. Nelson and colleagues further provided novel observations establishing a post-arteriole transitional zone containing junctional contractile pericytes, demonstrating that capillary pericytes in this region control the morphology of capillary junctions and blood flow between branches to ensure efficient function of the capillary network and optimal perfusion of the brain (Gonzales et al, 2020) These observations and others from prominent investigators in the field (Fernández-Klett et al, 2010; Hamilton et al, 2010; Grubb et al, 2020) have lifted pericytes from obscurity and into the limelight as cells important for the construction, maintenance, and function of the capillary network. We embellish on this conceptual role of pericytes as vascular transportation engineers of the central nervous system (CNS) in health and disease

TRANSPORTATION ENGINEERS OF THE MICROVASCULATURE

WHEN MICROVASCULAR TRANSPORTATION ENGINEERS GO MISSING

Do Pericytes Determine Stroke Outcome?

RETURN OF THE TRANSPORTATION ENGINEERS

Findings

CONCLUSION