Hypoxia-Ischemia-Induced Apoptotic Cell Death Correlates with IGF-I mRNA Decrease in Neonatal Rat Brain

Hypoxia-ischemia induces apoptotic and necrotic cell death, which results partially from persistent alterations in cellular energy homeostasis. Insulin-like growth factor I (IGF-I) is an anabolic pleiotrophic factor required by developing neurons for their optimal proliferation, differentiation, and survival. To determine how cell death and changes in IGF-I gene expression relate to the extent of hypoxia-ischemia, we evaluated the time course of apoptosis in a neonatal hypoxia-ischemia model in relation to the cellular distribution of IGF-I and IGFBP5 mRNA. Severe hypoxia-ischemia results in an immediate decrease in neuronal IGF-I and IGFBP5 mRNA. The decrease in neuronal IGF-I mRNA was concurrent with an increase in the number of apoptotic cells. It is conceivable that the immediate decrease in IGF-I gene expression may contribute to the impending neuronal death and selective vulnerability of myelinogenesis during the perinatal period.