1. DECREASE IN IGF-I mRNA CORRELATES WITH INCREASED APOPTOTIC CELL DEATH IN NEONATAL HYPOXIA-ISCHEMIA. ▴ 1196
- Author
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Wei Hua Lee, Teresa F. Clawson, Susan P Vannucci, and Guo-Ming Wang
- Subjects
Cell type ,Programmed cell death ,medicine.medical_specialty ,Growth factor ,medicine.medical_treatment ,Ischemia ,Biology ,medicine.disease ,medicine.anatomical_structure ,Endocrinology ,Apoptosis ,Internal medicine ,Pediatrics, Perinatology and Child Health ,Immunology ,Gene expression ,medicine ,Myelinogenesis ,Homeostasis - Abstract
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. more...
- Published
- 1996
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