Effects of long term NOS inhibition on disease and the immune system in MOG induced EAE.
Hypothesising that systemically and intrathecally produced nitric oxide might play different roles in the EAE pathogenesis, we administered the NOS inhibitor N-nitro-methyl-L-arginine-ester intrathecally or systemically via osmotic minipumps to DA rats with MOG induced EAE. We demonstrate an protective effect of the NOS inhibitor on EAE severity, the extent of CNS inflammation, and demyelination. Intrathecal administration was more effective when compared to systemic administration. The observed effect was accompanied by enhanced anti-MOG IgG1 production. In our model, the therapeutic effect was concluded to be due to direct inhibition of the NO pathway in the CNS.
Danilov
Alexandre I
AI
Department of Clinical Neuroscience, Division of Neurology, Karolinska Institutet, Stockholm, Sweden. alexandre.danilov@cmm.ki.se
Jagodic
Maja
M
Wiklund
N Peter
NP
Olsson
Tomas
T
Brundin
Lou
L
D000818:Animals; D000906:Antibodies / Q000097:blood; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology*; D063308:Myelin-Oligodendrocyte Glycoprotein; D019331:NG-Nitroarginine Methyl Ester / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000097:blood; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D000906:Antibodies; D004791:Enzyme Inhibitors; C571328:Mog protein, rat; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester