Insulin-like growth factor I treatment reduces clinical deficits and lesion severity in acute demyelinating experimental autoimmune encephalomyelitis.
Our goal was to test the effects of insulin-like growth factor I (IGF-I) treatment on clinical deficits, lesion number and lesion size in acute demyelinating experimental autoimmune encephalomyelitis (EAE) induced in Lewis rats with an emulsion containing guinea pig spinal cord. In this EAE model, there is severe immune-mediated demyelination, which resembles that seen in actively demyelinating MS lesions. On day 12-13 after EAE induction, a total of 23 pairs of rats with the same mild degree of tail and hind limb weakness were given either intravenous IGF-I or placebo twice daily for 8 days. The daily IGF-I dose used in the first trial was 200 micrograms (about 0.6 mg kg-1) and in the second and third trials was 1 mg (about 3.0 mg kg-1). IGF-I treatment reduced permeability of the blood-spinal cord barrier to Evans blue-albumin. Maximum clinical deficit scores of IGF-I-treated rats were significantly lower and treated rats recovered faster than controls. IGF-I treatment produced significant reductions in weight loss and hind limb weakness. Treatment also improved treadmill walking, stride length and climbing performance. Morphometric analysis showed that spinal cord inflammatory lesions were significantly smaller and fewer in IGF-I-treated rats. The higher IGF-I dose produced a greater reduction in clinical and pathological deficits. We conclude that IGF-I treatment promotes clinical recovery by reducing EAE-induced blood-spinal cord barrier changes and the associated immune-mediated inflammatory lesions. Our results suggest that IGF-I may be useful in treating patients with multiple sclerosis and other demyelinating diseases.
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Laboratory of Experimental Neuropathology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Yao
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Webster
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D000208:Acute Disease; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000187:drug effects; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000473:pathology*; D005121:Extremities / Q000503:physiopathology; D005684:Gait / Q000187:drug effects; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011917:Rats, Inbred Lew; D012720:Severity of Illness Index; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology; D013997:Time Factors
D007334:Insulin-Like Growth Factor I