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.

Optic nerves of stage 54-56 Xenopus laevis tadpoles were either transected or crushed, and subsequent Wallerian degeneration, regeneration, and remyelination were examined. After 4 days, normal myelinated fibres were no longer present in the distal stump, and only a few unmyelinated fibres remained. After 10-13 days, the distal nerve consisted mainly of a core of reactive astrocytes with enlarged processes and scattered oligodendrocytes which persisted throughout the degenerative period. Regenerating axons traversed the site of the lesion and extended into the distal stump within 13-15 days. As regeneration progressed, astrocytic processes extended radially from the optic nerve's central cellular core and formed longitudinal compartments for regenerating axons. Between 15-19 days, a few regenerating fibres were remyelinated and by 35 days, more axons were surrounded either by thin collars of oligodendrocyte cytoplasm or by 1-3 spiral turns of myelin membrane. By 95 days, the number of myelinated fibres had increased to about 50% of those present in control nerves. Their myelin sheaths were normal in appearance and thickness relative to their respective axon diameters. The largest axons were surrounded by compact sheaths with 4-9 lamellae.

To extend earlier observations on Schwann cell remyelination in multiple sclerosis (MS) lesions (Itoyama et al. 1983) we immunostained spinal cord sections from eight Japanese MS patients with antiserum to Po glycoprotein, a major constituent of peripheral nervous system (PNS) myelin, myelin basic protein (MBP), and glial fibrillary acidic protein (GFAP). Spinal cord sections from six of the eight Japanese MS patients contained large clusters of peripheral myelin sheaths with anti-Po immunoreactivity. In lesions found in four of the six patients, thousands of Po-stained PNS myelin sheaths were present. Necrosis was prominent in these lesions which included more than half of the spinal cord's transverse area. The number and density of regenerating myelin sheaths of peripheral origin were much greater than we observed in MS spinal cord lesions of white people (Itoyama et al. 1983). Anti-GFAP immunoreactivity was present in most brain and spinal cord lesions. However, the areas in lesions that contained large groups of PNS myelin sheaths lacked anti-GFAP immunoreactivity. Our data suggest that spinal MS lesions that are large, severely demyelinated, and partially necrotic may contain factors that inhibit fibrous astrogliosis. These factors, other substances in the large lesions and/or the lack of astrocytic scarring could then promote Schwann cell invasion, multiplication, and remyelination of surviving axons.