Suppression of clinical signs of cell-transferred experimental allergic encephalomyelitis and altered cerebrovascular permeability in Lewis rats treated with a plasminogen activator inhibitor.
The purpose of this study was to determine whether fibrinolysis resulting from activation of the clotting cascade in juxtaposition to endothelial cells of the central nervous system (CNS) microvasculature is important for development of clinical signs of experimental allergic encephalomyelitis (EAE) in recipient Lewis rats. Rats were injected with previously primed syngeneic lymph node cells, activated in vitro with guinea pig myelin basic protein, and subsequently treated daily with trans-4-(aminomethyl)cyclohexanecarboxylic acid (AMCA), a synthetic inhibitor of plasminogen activator. Clinical signs of EAE were significantly suppressed in AMCA-treated rats compared to saline-treated control recipient animals. Furthermore, suppression of clinical signs in AMCA-treated rats was accompanied by a significant curtailment in EAE-associated increased permeability of the blood-brain barrier (BBB). These findings provide evidence that CNS-associated deposition of fibrin and ensuing fibrinolysis, together with increased permeability of the BBB, are related prerequisite events for expression of clinical manifestations of EAE.
D000818:Animals; D001777:Blood Coagulation; D001812:Blood-Brain Barrier; D002470:Cell Survival / Q000187:drug effects; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D007111:Immunity, Cellular; D007116:Immunization, Passive; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology; D008297:Male; D004676:Myelin Basic Protein / Q000276:immunology; D010960:Plasminogen Activators / Q000037:antagonists & inhibitors*; D015849:Plasminogen Inactivators; D051381:Rats; D011917:Rats, Inbred Lew; D013997:Time Factors; D014148:Tranexamic Acid / Q000494:pharmacology*
D003509:Cyclohexanecarboxylic Acids; D004676:Myelin Basic Protein; D015849:Plasminogen Inactivators; D014148:Tranexamic Acid; D010960:Plasminogen Activators