brin-derived γ377-395 peptide inhibits microglia activation and suppresses relapsing paralysis in central nervous system autoimmune disease

JEM © The Rockefeller University Press $15.00 Vol. 204, No. 3, March 19, 2007 571–582 www.jem.org/cgi/doi/10.1084/jem.20061931 571 powerful target for therapeutic intervention (4), the mechanisms of perivascular microglia activation in infl ammatory demyelination as well as a strategy to limit their activation in MS have not been identifi ed. In MS lesions, perivascular activation of microglia colocalizes with areas of bloodbrain barrier (BBB) disruption (5). Magnetic resonance imaging studies link BBB breakdown with clinical relapse (6). Moreover, in vivo live imaging showed that BBB disruption provokes the immediate and focal activation of microglia (7). However, the molecular mechanism that links BBB disruption with microglia activation and disease pathogenesis remains elusive. One of the earliest events coupled to BBB disruption in MS is leakage of the blood protein fi brinogen in the nervous system that results in perivascular deposition of fi brin (8-11). Although fi brinogen has been primarily studied for its functions The fi brin-derived γ377-395 peptide inhibits microglia activation and suppresses relapsing paralysis in central nervous system autoimmune disease