Remodeling of the Neurovascular Unit Following Cerebral Ischemia and Hemorrhage

Abstract

Formulated as a group effort of the stroke community, the transforming concept of the neurovascular unit (NVU) depicts the structural and functional relationship between brain cells and the vascular structure. Composed of both neural and vascular elements, the NVU forms the blood–brain barrier that regulates cerebral blood flow to meet the oxygen demand of the brain in normal physiology and maintain brain homeostasis. Conversely, the dysregulation and dysfunction of the NVU is an essential pathological feature that underlies neurological disorders spanning from chronic neurodegeneration to acute cerebrovascular events such as ischemic stroke and cerebral hemorrhage, which were the focus of this review. We also discussed how common vascular risk factors of stroke predispose the NVU to pathological changes. We synthesized existing literature and first provided an overview of the basic structure and function of NVU, followed by knowledge of how these components remodel in response to ischemic stroke and brain hemorrhage. A greater understanding of the NVU dysfunction and remodeling will enable the design of targeted therapies and provide a valuable foundation for relevant research in this area.

Mechanistic Insights, Treatment Paradigms, and Clinical Progress in Neurological Disorders: Current and Future Prospects

“…comprising the continuous brain microvascular endothelium, its underlying basement membrane, the pericytes that tightly encircle the endothelium, and the adjacent tissue space made up of astrocytes (Figure 2) [68]. The BBB avails itself of several transport systems, such as carrier-mediated transport (CMT), receptor-mediated transport (RMT), efflux transporters, and ion transporters, by which ions or small molecules can pass into the CNS (Figure 2).…”

“…Therefore, dysregulation in the maintenance of the blood vessels within the NVU may lead to a wide spectrum of NDs. Hence, for a healthy brain, there is a need for a balance in the physiological communication between the individual CNS microenvironments [ 67 , 68 , 69 ]. The BBB is a physical barrier separating the CNS from the systemic circulation, comprising the continuous brain microvascular endothelium, its underlying basement membrane, the pericytes that tightly encircle the endothelium, and the adjacent tissue space made up of astrocytes ( Figure 2 ) [ 68 ].…”

“…Hence, for a healthy brain, there is a need for a balance in the physiological communication between the individual CNS microenvironments [ 67 , 68 , 69 ]. The BBB is a physical barrier separating the CNS from the systemic circulation, comprising the continuous brain microvascular endothelium, its underlying basement membrane, the pericytes that tightly encircle the endothelium, and the adjacent tissue space made up of astrocytes ( Figure 2 ) [ 68 ]. The BBB avails itself of several transport systems, such as carrier-mediated transport (CMT), receptor-mediated transport (RMT), efflux transporters, and ion transporters, by which ions or small molecules can pass into the CNS ( Figure 2 ).…”

“…Permission has been taken from the author and this work is licensed under a Creative Commons Attribution 4.0 International License Copyright © 2022. All rights reserved [ 68 ].…”

m6A methylation: Critical roles in aging and neurological diseases

“…NVU emphasizes the symbiotic relationship between the nervous system and the microenvironment, which is a dynamic interaction between multiple cells instead of a simple nutritional relationship. The dysfunction of NVU is an important pathological feature underlying neurological disorders and during aging process ( Sato et al, 2022 ). When that happens, cells and other constituents in NVU interact with each other to maintain homeostasis and promote NVU recovery.…”