碩士 / 國立臺灣師範大學 / 生命科學研究所 / 99 / Traumatic brain injury (TBI) is one of the most prevalent causes of mortality and morbidity all over the world and represents an enormous economical and social cost. Our previous studies have evidenced that Na+-K+-2Cl- co-transporter (NKCC) played an important role in TBI-induced brain edema via mitogen-activated protein kinases (MAPK) cascade. Transient receptor potential vanilloid type 4 (TRPV4) channel is suggested to correlate with neurogenic inflammation, pain transmission and osmosis regulation. In this study, we want to investigate the role of hippocampal TRPV4 in TBI-induced neuronal damage and the signaling pathways. TBI was induced by the calibrated weight-drop device. Sprague-Dawley rats were divided into sham and experimental group for time course studies of TBI. Hippocampal TRPV4, NKCC1, MAPK cascade and Akt expression were analyzed by Western blot. We also measured the level of brain edema among sham, TBI and TBI combined with TRPV4 antagonist or NKCC1 antagonist treatment. In the present study, we found that expression of hippoccampal TRPV4 peaked at 8 hours after TBI-treatment. The phosphorylation of extracellular signal regulated kinase (ERK), mitogen-activated protein kinase (MEK) and Akt were significantly elevated after TBI. Administration of either TRPV4 antagonist, ruthenium red or NKCC1 antagonist, bumetanide significantly attenuated the TBI-induced brain edema through decreasing the phosphorylation of MEK, ERK and Akt proteins. We also found administration of bumetanide could inhibit TRPV4 expression in hippocampus. However, administration of ruthenium red could not inhibit NKCC1 expression. This study showed that hippocampal NKCC1 activation could increase TRPV4 expression after TBI and induce severe brain edema and neuronal damage through phosphorylation of MAPK cascade and Akt.
| Identifer | oai:union.ndltd.org:TW/099NTNU5112126 |
| Date | January 2011 |
| Creators | Ya-Hsin Tsai, 蔡亞欣 |
| Contributors | Kwok-Tung Lu, Yi-Ling Yang, 呂國棟, 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 | 95 |
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