Fibrin deposition in the central nervous system correlates with the degree of Theiler's murine encephalomyelitis virus-induced demyelinating disease.
We examined the role of coagulation-fibrinolysis system in Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD). The degree of fibrin deposition around the vessels in the spinal cord was significantly higher in susceptible SJL/J mice on 30 days post intracerebral injection (i.c.) than resistant C57BL/6 mice on 30 days post i.c. or mock infected SJL/J mice. Treatment with batroxobin (30 BU/kg/day), which is a thrombin-like defibrinogenating enzyme, causing a profound degree of afibrinogenemia, suppressed clinical signs of TMEV-IDD. Plasma fibrinogen concentration was significantly decreased in batroxobin-treated mice. Histologically, though the degree of perivascular mononuclear cell infiltration in the spinal cord was not suppressed in batroxobin-treated mice compared to saline-treated control mice, fibrin deposition was markedly suppressed in batroxobin-treated mice. These findings suggest that batroxobin suppresses TMEV-IDD through its defibrination effect, and provide evidence that CNS-associated deposition of fibrin and ensuing fibrinolysis, together with increased permeability of the blood-brain barrier (BBB), are prerequisite events for clinical manifestations of TMEV-IDD.
Inoue
A
A
Department of Medicine (Neurology), Shinshu University School of Medicine, Matsumoto, Japan.
Koh
C S
CS
Yamazaki
M
M
Yanagisawa
N
N
Ishihara
Y
Y
Kim
B S
BS
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D003711:Demyelinating Diseases / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D004198:Disease Susceptibility; D005260:Female; D005337:Fibrin / Q000276:immunology / Q000378:metabolism*; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000821:virology; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D011051:Poliomyelitis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D012965:Sodium Chloride / Q000494:pharmacology; D013116:Spinal Cord / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology; D017945:Theilovirus / Q000276:immunology*
D000914:Antibodies, Viral; D012965:Sodium Chloride; D005337:Fibrin