The glymphatic system of the brain is a recently discovered pathway allowing cerebrospinal fluid to drain from the brain into the body, carrying metabolic waste with it. Another path through pores in the cribriform plate behind the nose also appears important. Both of these drainage pathways decline in efficacy with age. It is thought that this loss of function allows various forms of metabolic waste, such as the protein aggregates characteristic of neurodegenerative conditions, to accumulate in the brain. This provokes cells into dysfunction and inflammatory behavior.
The glymphatic system theory introduces a new perspective on fluid flow and homeostasis in the brain. Here, cerebrospinal fluid and interstitial fluid (CSF-ISF) moves from the perivascular spaces (PVS) of arteries to those of veins for drainage. Aquaporin-4 (AQP4) plays a crucial role in driving fluid within the PVS. The impairment of AQP4 is closely linked to the dysfunction of the glymphatic system. The function of the glymphatic system is less active during waking but enhanced during sleep.
The efficiency of the glymphatic system decreases with aging. Damage to the glymphatic system will give rise to the development and progression of many brain diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), chronic traumatic encephalopathy (CTE), and vascular dementia (VaD). Here, we reviewed previous research associated with the glymphatic system, including its concepts, principles, and influencing factors. We hypothesize that AQP4 could be a target for the prevention and treatment of certain brain diseases through the regulation on the glymphatic system.
Link: https://doi.org/10.3...el.2025.1528995
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