Advancement in modulation of brain extracellular space and unlocking its potential for intervention of neurological diseases

Abstract

Cells in the brain are surrounded by extracellular space (ECS), which forms porous nets and interconnected routes for molecule transportation. Our view of brain ECS has changed from a largely static compartment to dynamic and diverse structures that actively regulate neural activity and brain states. Emerging evidence supports that dysregulation of brain ECS contributes to the pathogenesis and development of many neurological disorders, highlighting the importance of therapeutic modulation of brain ECS function. Here, we aim to provide an overview of the regulation and dysfunction of ECS in healthy and pathological brains, as well as advanced tools to investigate properties of brain ECS. This review emphasizes modulation methods to manipulate ECS with implications to restore their function in brain diseases. Graphical Abstract