Spontaneous remyelination following prolonged inhibition of alpha4 integrin in chronic EAE.
Inhibition of alpha(4)beta(1) integrin blocks immune cell influx into the CNS providing benefit to patients with multiple sclerosis and in animal model systems. We have used this mechanism to examine whether the presence of inflammatory cells suppresses spontaneous myelin repair in experimental autoimmune encephalomyelitis. We observed (1) 87% of plaques showed remyelination after 40 days of treatment; (2) myelin repair occurred in half of the total lesion area; (3) half of the animals regained motor function. There was no significant repair or gain of motor function in vehicle-treated animals. Therefore, prolonged inhibition of CNS inflammation, in the absence of targeted myelin repair, facilitates mechanisms of spontaneous remyelination.
Piraino
P S
PS
Department of Physiology and Pharmacology, University of Western Ontario, Medical Sciences Building, Room 223, London, ON, Canada.
Yednock
T A
TA
Messersmith
E K
EK
Pleiss
M A
MA
Freedman
S B
SB
Hammond
R R
RR
Karlik
S J
SJ
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000097:blood / Q000627:therapeutic use; D002908:Chronic Disease; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D005260:Female; D006168:Guinea Pigs; D007150:Immunohistochemistry / Q000379:methods; D039441:Integrin alpha4 / Q000502:physiology*; D009043:Motor Activity / Q000187:drug effects; D009186:Myelin Sheath / Q000378:metabolism*; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology*; D020127:Recovery of Function; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D013601:T-Lymphocytes / Q000187:drug effects; D013997:Time Factors
D000893:Anti-Inflammatory Agents; D039441:Integrin alpha4