COORDINATE IGF-I AND IGFBP5 GENE-EXPRESSION IN PERINATAL RAT-BRAIN AFTER HYPOXIA-ISCHEMIA

Insulin-like growth factor I (IGF-I) is an anabolic pleiotrophic facto r essential for postnatal rat brain development, especially during the first 21 days, the ''critical growth period.'' Cerebral hypoxic-ische mic insults occurring during the perinatal period can result in neuron al necrosis and permanent brain damage. To understand the regulation o f the action of IGF-I in response to such a metabolic insult, we inves tigated the gene expression of IGF-I, type I IGF receptor, IGF binding protein (IGFBP) 2, and IGFBP5 during the first 72 h after hypoxia-isc hemia in the immature rat. At 1 h of recovery, messenger RNA (mRNA) le vels of all IGF system components were decreased throughout the hemisp here ipsilateral to the carotid artery ligation. This decrease is more pronounced at 24 h of recovery, especially in areas vulnerable to hyp oxic-ischemic injury, such as the thalamus and hippocampus. At 72 h of recovery, although IGFBP2 and type 1 IGF receptor mRNA levels remain suppressed, gene expression of both IGF-I and IGFBP5 was activated in reactive astrocytes. Therefore, during the critical growth period in r ats, the transcriptional levels of all IGF system components are extre mely sensitive to metabolic perturbations associated with cerebral hyp oxia-ischemia. The immediate decrease in IGF-I gene expression may be partially responsible for the impending neuronal death and selective v ulnerability of myelinogenesis during the perinatal period.