Coordinate IGF-I and IGFBP5 gene expression in perinatal rat brain after hypoxia-ischemia

Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism
W H LeeS J Vannucci

Abstract

Insulin-like growth factor I (IGF-I) is an anabolic pleiotrophic factor essential for postnatal rat brain development, especially during the first 21 days, the "critical growth period." Cerebral hypoxic-ischemic insults occurring during the perinatal period can result in neuronal necrosis and permanent brain damage. To understand the regulation of the action of IGF-I in response to such a metabolic insult, we investigated the gene expression of IGF-I, type I IGF receptor, IGF binding protein (IGFBP)2, and IGFBP5 during the first 72 h after hypoxia-ischemia in the immature rat. At 1 h of recovery, messenger RNA (mRNA) levels of all IGF system components were decreased throughout the hemisphere ipsilateral to the carotid artery ligation. This decrease is more pronounced at 24 h of recovery, especially in areas vulnerable to hypoxic-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 rats, the transcriptional levels of all IGF system components are extremely sensitive to metabolic perturbations associated with cer...Continue Reading

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