The goals of this project are to study the glial gene expression of growth factors, myelin-related proteins and other glial proteins during nervous system injury and regeneration. Previous studies have shown that hypertropic astrocytes in lesions of acute experimental autoimmune encephalomyelitis (EAE) synthesize insulin-like growth factor I (IGF-I). In addition, during clinical recovery and demyelination, oligodendrocytes (the cells responsible for CNS myelin synthesis) express the IGF-I receptor. The EAE lesions in which IGF-I expression occurs are characterized by breakdown of the blood-brain barrier, immune-mediated inflammation, severe demyelination and relative preservation of axons. Since they closely resemble those seen during active demyelination in multiple sclerosis, studies this year were designed to test whether IGF-I treatment of Lewis rats with this type of EAE would significantly alter clinical deficits and lesion severity. About 12 days after EAE induction, pairs of rats with the same degree of mild but definite weakness were selected and given intravenous placebo or IGF-I twice daily for 8 days. IGF-I treated rats had less severe clinical deficits and began recovering sooner. Compared to placebo-treated rats, those treated with IGF-I had reduced permeability of the blood-brain barrier and fewer inflammatory demyelinating lesions; these lesions also were smaller. In lesions of IGF-I treated rats, there also were fewer demyelinated axons, higher levels of myelin protein messenger RNAs, and more regenerating myelin sheaths. This evidence suggests that IGF-I may be useful in treating patients with multiple sclerosis and other demyelinating diseases.
