Dynamic Intravital Imaging Of Immune Cells During The Initiating Events Of Experimental Autoimmune Encephalomyelitis

Experimental autoimmune encephalomyelitis (EAE) is a murine model of central nervous system (CNS) inflammatory disease resulting in immune cell accumulation, neuronal tissue destruction and paralysis. With this work, we endeavor to reconcile the literature on EAE, from the action of pertussis toxin (PTx) in the initiation of inflammation through to infiltration of CD4+T cells. We show for the first time that localized, transient vessel leak initiates an inflammatory state within the CNS that results in microglia activation, and recruitment of dendritic cells (DCs). We also show for the first time that microgliaare able to project extensions into the blood vessel with an intact blood brain barrier under non-inflammatory conditions and that the number of projections increase during the first 12 days of EAE induction. These resident microglia and peripheral DCs accumulate near vessel leaks and recruit myelin-specific T cells to cause subsequent tissue damage and plaque formation. This inflammatory process, serial immune cell infiltration and tissue destruction can be dampened by the use of anti-histamines to inhibit the activation of microglia at the onset of disease initiation.