The Implication and Application of Brain Glymphatic System in Multiple Diseases

The glymphatic system within the central nervous system (CNS) facilitates the exchange and elimination of cerebrospinal fluid (CSF) and interstitial fluid (ISF), aiding in the removal of potentially poisonous metabolic wastes to maintain brain stability. Sleep and Aquaporin-4 (AQP-4) expression positively regulate the glymphatic system. When sleep is disturbed and AQP-4 polarization is inhibited, the glymphatic system is impaired, leading to the inability to effectively eliminate soluble wastes from the brain. This disruption can potentially contribute to, or accelerate, the progression of various CNS diseases, such as Alzheimer's disease and Parkinson's disease, as well as non-CNS diseases, like diabetes mellitus and hypertension. Therefore, the normal functioning of the glymphatic system is essential for the recovery from both CNS diseases and non-CNS diseases. In this review, an overview of the constituents and functions of the glymphatic system in the brain, specifically highlighting the glymphatic system lesions in different diseases is provided. Additionally, currently unresolved questions pertaining to this topic are summarized. Ultimately, the cerebral glymphatic system is expected to be a novel and promising target for the diagnosis and treatment of multiple diseases.