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.
Humans ; Neuroglia ; Nervous System Diseases ; Blood-Brain Barrier ; Alzheimer Disease ; Glymphatic System

The glymphatic system can remove metabolic wastes from the brain, which plays a significant role in maintaining the homeostasis of the central nervous system. It is an important basis for advanced cognitive functions such as learning and memory. Studies have analyzed the function of glymphatic system by diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) recently. Compared with other invasive examinations that require fluorescent tracer technique or the injection of contrast agents, DTI-ALPS can evaluate the hydromechanics of the glymphatic system via quantifying the diffusion rate of water molecules in different directions, which turns out to be a non-invasive in vivo neuroimaging method. The ALPS-index calculated by the DTI-ALPS method is significantly correlated with the cognitive function in diseases of central nervous system and other system and can reflect the dynamic changes of diseases. In general, ALPS-index is expected to become a novel neuroimaging biomarker for predicting prognosis and clinical effects.
Glymphatic System/diagnostic imaging* ; Diffusion Tensor Imaging ; Brain/diagnostic imaging* ; Central Nervous System ; Cognition