CRYOGENIC SPINAL-CORD INJURY INDUCES ASTROCYTIC GENE-EXPRESSION OF INSULIN-LIKE GROWTH-FACTOR-I AND INSULIN-LIKE GROWTH-FACTOR BINDING-PROTEIN-2 DURING MYELIN REGENERATION

To study injury-induced astrocytic responses associated with regrowth of axons and regeneration of myelin, the method of Collins and colleag ues was used to make focal cryogenic lesions in spinal cords of adult rats (Collins et al.: J Neuropathol Exp Neurol 45: 742-757, 1986). The duration of cryogenic injury (CI), the size of the cryode, and its te mperature were chosen to destroy all myelin sheaths and axons without producing cavities or hemorrhages, Messenger RNA and peptide distribut ions of insulin-like growth factor I (IGF-I), IGF-I receptor (IGFR-I), IGF binding protein 2 (IGFBP-2), glial fibrillary acidic protein (GFA P), and myelin basic protein (MBP) were studied 3-56 days after CI by in situ hybridization and immunocytochemistry, At 3 days, vimentin-pos itive, GFAP-negative astrocyte-like cells in the lesion expressed IGF- I mRNA and peptide and 7 days after CI, both were expressed by typical GFAP-positive, hypertrophic astrocytes, many of which also were vimen tin-positive. Levels of IGF-I, IGFBP-2, and GFAP mRNA and peptide were higher in lesion astrocytes after 14 days, They attained maximum leve ls at 21-28 days before declining to near control levels at 56 days, D ecreasing relative levels of oligodendroglial MBP mRNA were found in a nd around lesions 7-14 days after CI; subsequently, rising levels acco mpanied remyelination, At 28 and 56 days after CI, some transferrin-po sitive, oligodendroglia-like cells also were immunostained by anti-IGF R-I. Our findings suggest that early astrocytic production of IGF-I an d IGFBP-2 may be involved in the myelin regeneration which occurs in t his model of spinal cord injury. (c) 1995 Wiley-Liss, Inc.()