Reciprocal Effects Of Glymphatic Function And The Experimental Autoimmune Encephalomyelitis (EAE) Model Of Multiple Sclerosis

Hanna Vinitsky, Iben Lundgaard, Shane O’neil, Wei Wang, Ben Reeves, Ezra Yang, Steven Goldman, Maiken Nedergaard Iben Lundgaard 

Multiple Sclerosis (MS) is an autoimmune disease targeting myelin in the central nervous system. Lesions in MS patients and in the experimental autoimmune (EAE) model of MS are characterized by immune cell infiltration, often forming peri-vascular cuffing around blood vessels. Here we used the EAE mouse model of MS and investigated glymphatic function dynamics using a fluorescent cerebrospinal fluid (CSF) tracer. The glymphatic system is a brain-wide clearance system using peri-vascular pathways for transport. We found that glymphatic influx to the brain was reduced and influx to the spinal cord was severely diminished. The distribution of CSF tracer was inversely correlated with the number of lesions, suggesting that EAE tissue pathology affects the glymphatic system in acute and chronic disease. Intriguingly, inhibition of the glymphatic function using acetazolamide and cisterna magna puncture (CMP) in the pre-symptomatic phase significantly ameliorated EAE clinical symptoms. This shows that glymphatic function is affected in EAE, but that disease progression might be aided by the glymphatic system in the early phase. This preliminary data suggests that targeting the glymphatic system in the early phase of MS might be a novel mechanism to curb disease.