碩士 / 國立嘉義大學 / 生化科技學系研究所 / 101 / Traumatic brain injury (TBI) is one of the most prevalent causes of worldwide mortality and morbidity, and its treatment might result in enormous medical and social expenses. TBI causes neurological dysfunction and death through both primary and secondary cellular damages. One of the primary effects is TBI-associated damage to axons, blood vessels, and glial cells in a focal or diffuse pattern. This damage might subsequently be amplified by certain secondary responses including hypoxia, hypotension, ischemia, edema, and intracranial pressure elevation. Our previous studies have suggested that Na+-K+-2Cl- cotransporter (NKCC1) is significantly upregulated after TBI and is critical to TBI-induced brain edema. It is also evidenced that NKCC1 is involved in cell proliferation. Adult neurogenesis occurs mainly in the rostral subventricular zone of the lateral ventricles and the subgranular zone of the hippocampal dentate gyrus. We have evidenced that VEGF mediated the TBI-induced neurogenesis through VEGF receptor 2 and Raf/MEK/ERK cascade. In this study, we would like to elucidate whether the NKCC1 is involved in TBI-induced neurogenesis and its possible mechanism. The expression of NKCC1, VEGF, CREB, HIF-1 and the phosphorylation level of Raf/MEK/ERK were analyzed by Western blot, and TBI-induced neurogenesis was determined by immunofluorescence labeling and confocal microscopic detection. Along with the upregulation of NKCC1, VEGF, and MAPK cascade phosphorylation, neurogenesis in the hippocampus also increased. Administration of the CREB antisense oligonucleotides significantly attenuates the expression of HIF-1, however, there is no significant effect of HIF-1 antisense oligonucleotides (100 M, i.c.v.) administration on CREB phosphorylation. HIF-1antisense oligonucleotides administration significantly attenuated the expression of VEGF and NKCC1. Our ChIP results evidenced that HIF-1 interacts with NKCC1 and VEGF promoter and is important to NKCC1 and VEGF gene expression. Our results indicate that NKCC1 plays an important role in neurogenesis after TBI, and that the process involves the Raf/MEK/ERK cascade and VEGF gene activation.
| Identifer | oai:union.ndltd.org:TW/101NCYU5103001 |
| Creators | Ya-Sheng You, 游亞聖 |
| Contributors | Yi-Ling Yang, 楊奕玲 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 102 |
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