Updated Understanding of the Glial-Vascular Unit in Central Nervous System Disorders

 Di Yao1  · Ruoying Zhang1  · Minjie Xie1  · Fengfei Ding2  · Minghuan Wang1  · Wei Wang1,3
1 Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China 
2 Department of Pharmacology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China 
3 Key Laboratory of Neurological Diseases of the Chinese Ministry of Education, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China

Abstract
The concept of the glial-vascular unit (GVU) was raised recently to emphasize the close associations between brain cells and cerebral vessels, and their coordinated reactions to diverse neurological insults from a “glio-centric” view. GVU is a multicellular structure composed of glial cells, perivascular cells, and perivascular space. Each component is closely linked, collectively forming the GVU. The central roles of glial and perivascular cells and their multi-level interconnections in the GVU under normal conditions and in central nervous system (CNS) disorders have not been elucidated in detail. Here, we comprehensively review the intensive interactions between glial cells and perivascular cells in the niche of perivascular space, which take part in the modulation of cerebral blood flow and angiogenesis, formation of the blood-brain barrier, and clearance of neurotoxic wastes. Next, we discuss dysfunctions of the GVU in various neurological diseases, including ischemic stroke, spinal cord injury, Alzheimer’s disease, and major depression disorder. In addition, we highlight the possible therapies targeting the GVU, which may have potential clinical applications.

Keywords
Glial-vascular unit; Perivascular space; Blood-brain barrier; Glymphatic system; Ischemic stroke; Spinal cord injury; Alzheimer's disease; Major depression disorder