Insulin-like growth factor-1 reduces postischemic white matter injury in fetal sheep

Insulin-like growth factor-1 (IGF-1) is known to be important for oligodend rocyte survival and myelination. In the current study, the authors examined the hypothesis that exogenous IGF-I could reduce postischemic white matter injury. Bilateral brain injury was induced in near-term fetal sheep by 30 minutes of reversible carotid artery occlusion. Ninety minutes after ischem ia, either vehicle (n = 8) or a single dose of 3 mug IGF-1 (n = 9) was infu sed intracerebroventricularly over 1 hour. White matter changes were assess ed after 4 days recovery in the parasagittal intragyral white matter and un derlying corona radiata. Proteolipid protein (PLP) mRNA staining was used t o identify bioactive oligodendrocytes. Glial fibrillary acidic protein (GFA P) and isolectin B-4 immunoreactivity were used to label astrocytes and mic roglia, respectively. Myelin basic protein (MBP) density and the area of th e intragyral white matter tracts were determined by image analysis. Insulin -like growth factor-1 treatment was associated with significantly reduced l oss of oligodendrocytes in the intragyral white matter (P < 0.05), with imp roved MBP density (P < 0.05), reduced tissue swelling, and increased number s of GFAP and isolectin B-4 positive cells compared with vehicle treatment. After ischemia there was a close association of PLP mRNA labeled cells wit h reactive astrocytes and macrophages/microglia. In conclusion, IGF-I can p revent delayed, postischemic oligodendrocyte cell loss and associated demye lination.