ABSTRACT
PURPOSE: To investigate the role of growth factors in the compensatory response to radiation injury during development of the brain. Levels of gene expression in the embryonic rat brain were assessed for IGF-I, IGF-II, BDNF and NT-3. MATERIALS AND METHODS: Pregnant Wistar rats were exposed to a single dose of 10, 20 or 40 cGy X-rays on day 15 or 17 of gestation. Animals were sacrificed 4 or 24 h after exposure. IGF-I, BDNF and NT-3 proteins were detected by immunocytochemistry, while IGF-I and IGF-II mRNA by in situ hybridization, and Northern analysis respectively. RESULTS: In utero low dose X-irradiation led to a decrease in IGF-I gene expression and a compensatory increase in the expression of IGF-II, BDNF and NT-3 in the developing rat brain. IGF-I, BDNF and NT-3 immunopositive cells were detected among proliferating, migratory and post-mitotic neurones in the developing neuroepithelium. CONCLUSIONS: Low dose prenatal irradiation of the developing brain results in down-regulation of IGF-I, which could lead to cell death by apoptosis. On the other hand, IGF-II, BDNF and NT-3 gene expression is increased following irradiation, possibly as a compensatory mechanism.
Subject(s)
Brain/embryology , Brain/radiation effects , Growth Substances/biosynthesis , Pregnancy, Animal/radiation effects , X-Rays/adverse effects , Animals , Apoptosis , Blotting, Northern , Brain/metabolism , Brain-Derived Neurotrophic Factor/biosynthesis , Dose-Response Relationship, Radiation , Down-Regulation , Epithelium/metabolism , Female , Immunohistochemistry , In Situ Hybridization , Insulin-Like Growth Factor I/biosynthesis , Insulin-Like Growth Factor II/biosynthesis , Neurotrophin 3/biosynthesis , Pregnancy , RNA, Messenger/metabolism , Rats , Rats, Wistar , Time FactorsABSTRACT
This study was undertaken in order to investigate the role of insulin-like growth factor (IGF)-II, c-fos, N-methyl-D-aspartate (NMDA) receptors, and nNOS in the cellular processes following a penetrating brain injury. IGF-II mRNA levels, as determined by Northern analysis, were decreased at 4, 8, and 24 h after brain injury, in the lesioned, compared to the contralateral intact hemisphere. Forty-eight and 72 h after the injury, there was no difference between the lesioned and the contralateral intact hemisphere in IGF-II mRNA levels. c-fos mRNA levels followed a parallel, but opposite course: They were increased at 4, 8 and 24 h after the injury, while at 48 and 72 h c-fos mRNA levels in the lesioned hemisphere did not differ from those in the intact. Administration of MK-801 reversed the injury-induced decrease in IGF-II mRNA levels. Administration of MK-801 resulted in an increase in IGF-II mRNA in both the intact and the lesioned hemispheres. Brain injury resulted in an increase in nNOS immunopositive cells in the hippocampal formation, which was detectable at 4 and 12, but not 48 h after the injury. These results suggest that IGF-II, c-fos, NMDA receptors and nNOS are involved in the cellular responses to brain injury.
