INCREASE OF INSULIN-LIKE GROWTH-FACTOR (IGF)-1, IGF BINDING-PROTEIN-2AND BINDING-PROTEIN-4 MESSENGER-RNAS FOLLOWING CEREBRAL CONTUSION

The insulin-like growth factor (IGF) system has a role in repair follo wing hypoxic-ischemic injury in many tissues including the brain. To s tudy the involvement of the IGF system following head trauma, we used a rat contusion model, which produces a focal lesion of the cerebral c ortex. Molecules in the IGF system were analyzed using in situ hybridi zation at different times following impact. We observed a dramatic up- regulation of insulin-like growth factor binding protein-2 (IGFBP-2) m RNA in cortical areas adjacent to the injury 24 h after impact, with a peak 10-fold increase engaging most of the ipsilateral cortex 2 and 3 days post-contusion. Seven days after the contusion, IGFBP-2 expressi on was only moderately up-regulated and again concentrated around the injury. IGFBP-4 mRNA levels increased 4-fold ipsilateral to the site o f injury, with retained pattern of cortical expression. IGFBP-3, IGFBP -5 and IGFBP-6 mRNA all displayed distinct expression patterns in the brain but no significant changes were observed following injury. In co ntrast, IGF-1 mRNA levels were very low prior to contusion, but increa sed markedly at the site of injury with a peak at day 3. We were unabl e to detect any changes in the type 1 IGF-receptor or IGF-2 mRNA follo wing contusion. The neuropeptide cholecystokinin (CCK) mRNA was clearl y up-regulated following contusion, with an even distribution over the ipsilateral cortex. The expression pattern of molecules in the IGF sy stem post-contusion differs in part to changes observed following hypo xic-ischemia or ischemia alone, perhaps reflecting different regulator y mechanisms depending on the type of injury.