Perinatal hypoxia-ischemia remains the leading cause of severe brain damage in newborns. Hypoxic-ischemic brain injury includes apoptotic and necrotic cell death resulting from persistent alterations in cellular energy homeostasis. Insulin-like growth factor I (IGF-I) is an anabolic pleiotrophic factor required by all cell types in the developing brain for optimal proliferation, differentiation, and survival. To determine how cell death and changes in IGF-I gene expression relate to the events of varying times of hypoxia-ischemia, we evaluated the time course of apoptosis in a neonatal hypoxic-ischemic injury model in relationship to IGF-I mRNA levels. One hour after an hypoxic-ischemic insult to the newborn rat brain mRNA levels of IGF-I decreased in the whole hemisphere ipsilateral to the ligated carotid artery. This decrease is more pronounced at 24 hours, especially in areas vulnerable to hypoxic-ischemic injury, such as the thalamus and hippocampus. At 72 hours post-injury, gene expression of IGF-I was activated in reactive astrocytes. The decrease in IGF-I mRNA was concurrent with an increase in apoptosis. The immediate decrease in IGF-I gene expression may be partially responsible for the impending neuronal death and selective vulnerability of myelinogenesis during the perinatal period. The temporal relationship between the decrease in IGF-I and apoptosis may provide clues of prognostic or therapeutic value, especially as it relates to delineation of a “therapeutic window,” where IGF-I gene therapy could theoretically prevent devastating neuronal injury.
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(Spon. by Mervin C. Yoder).
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Clawson, T., Wang, GM., Vannucci, S. et al. DECREASE IN IGF-I mRNA CORRELATES WITH INCREASED APOPTOTIC CELL DEATH IN NEONATAL HYPOXIA-ISCHEMIA. ▴ 1196. Pediatr Res 39 (Suppl 4), 202 (1996). https://doi.org/10.1203/00006450-199604001-01218
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DOI: https://doi.org/10.1203/00006450-199604001-01218