Pharmacological Inhibition of Microglial Proliferation Supports Blood-Brain Barrier Integrity in Experimental Autoimmune Encephalomyelitis.

Abstract

Blood-brain barrier dysfunction (BBB) is a primary characteristic of experimental autoimmune encephalomyelitis (EAE), an experimental model of multiple sclerosis (MS). We have previously shown that blocking microglial proliferation using GW2580, a selective inhibitor of CSF1R (Colony stimulating factor 1 receptor), reduced disease progression and severity and prevented the relapse phase. However, whether this was due to effects of GW2580 on the functional integrity of the BBB was not determined. Therefore, here, we examine BBB properties in rats during EAE under GW2580 treatment. Our data suggest that blocking early microglial proliferation through selective targeting of CSF1R signaling has a therapeutic effect in EAE by protecting BBB integrity and reducing peripheral immune cell infiltration. Taken together, our results identify a novel mechanism underlying the effects of GW2580, which could offer a novel therapy for MS.