DIFFERENTIAL EXPRESSION OF INSULIN-LIKE GROWTH-FACTOR BINDING-PROTEINS (IGFBP) 4 AND 5 MESSENGER-RNA IN THE RAT-BRAIN AFTER TRANSIENT HYPOXIC-ISCHEMIC INJURY

Recent studies suggest a role for the insulin-like growth factor (IGF) system in the repair of damaged tissue following hypoxic-ischemic inj ury in the infant rat brain. We have used a unilateral model of hypoxi c-ischemic injury to assess the possible involvement of two IGF bindin g proteins (IGFBPs), IGFBP-4 and IGFBP-5, in the post-asphyxial respon se. Ligation of the right carotid artery of 21-day-old rats was follow ed by either 15 min or 60 min exposure to 8% oxygen to produce moderat e and severe damage respectively. Using in situ hybridization, the dis tribution of IGFBP-4 and IGFBP-5 mRNA was determined in brains collect ed over 10 days following the insult. In the control brains (no damage ), both IGFBPs were expressed in distinct regions. IGFBP-4 mRNA was de tected in limited areas of the hippocampus and in several cortical lay ers, while IGFBP-5 mRNA was found primarily in the thalamus. In respon se to hypoxic-ischemic injury, IGFBP-4 mRNA expression was reduced in regions of neuronal loss, suggesting a neuronal origin for IGFBP-4. Th e expression of IGFBP-5 mRNA was not altered by the 15 min insult, but was heavily induced from 3 days following the 60 min insult, particul arly in the subependymal layer and adjacent white matter on the ligate d hemisphere. This suggests that IGFBP-5 may be involved in recovery f rom severe hypoxic-ischemic injury and may be important in the regener ation of oligodendrocytes.