The effect of pericyte changes on the glymphatic system in the EAE mouse model

Abstract

Multiple sclerosis (MS) is the most common non-traumatic neurodegenerative disease of the central nervous system (CNS) in young adults. Thus far, there is no curative treatment for MS, indicating a clear need for research into the pathological mechanisms of MS to provide a clear focus for developing novel therapies. The glymphatic system is a recently discovered waste clearance pathway in the CNS. It comprises a network of perivascular that facilitate cerebrospinal fluid (CSF) movement throughout the brain. Pericytes are mural cells that are in close association with these channels. We hypothesize that their dysfunction lies at the heart of glymphatic system and blood-brain barrier (BBB) dysfunction. We found that blood vessel-associated pericyte loss in the experimental autoimmune encephalomyelitis (EAE) model is accompanied by BBB disruption. This was indicated by decreased claudin-5 expression and Evans Blue dye leakage across the BBB. Furthermore, we find that pericytes might play a role in regulating the expression of AQP4, a critical regulator of the glymphatic system. Lastly, we find that the glymphatic system is implicated in the chronic stages of EAE. This study is a significant step forward in our understanding of the role of pericytes in maintaining BBB integrity and glymphatic function. By elucidating these mechanisms, we pave the way for innovative therapeutic interventions targeting pericytes.