2007 Fiscal Year Final Research Report Summary
Protective Effects of Therapeutic Hypothermia in Severe traumatic Brain Injured Patients Evaluated by Large scale Proteome Analyses in Cerebrospinal Fluid
| Project/Area Number |
18390480
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Emergency medicine
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| Research Institution | Yamaguchi University |
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Principal Investigator |
MAEKAWA Tsuyoshi Yamaguchi University, Graduate School of Medicine, Professor (60034972)
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| Co-Investigator(Kenkyū-buntansha) |
IZUMI Tomonori Yamaguchi University, Graduate School of Medicine, Associate Professor (00261694)
KASAOKA Shunji Yamaguchi University, Graduate School of Medicine, Associate Professor (90243667)
TSURUTA Ryosuke Yamaguchi University, University Hospital, Associate Professor (30263768)
ODA Yasutaka Yamaguchi University, University Hospital, Assistant Professor (40397998)
KANEKO Tadashi Yamaguchi University, University Hospital, Assistant Professor (50362372)
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| Project Period (FY) |
2006 – 2007
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| Keywords | severe traumatic brain injury / Cerebrospinal fluid / proteome / high performance liquid chromatography / mass spectrometry / brain protection / therapeutic mild hypothermia / candidate proteins |
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| Research Abstract |
The outcome of severe traumatic brain injury (TBI) patients is poor. We carry out the outcome improvement strategy for severe TBI patients (Glasgow Coma Scale score 4 to 8) by the therapeutic mild hypothermia treatment since 2002. These patients were randomized in two groups, i.e, normothermia group (NT, 35.5-37.0℃) and mild hypothermia group (HT, 32.0-34.0℃). Neurological outocome was evaluated by Glasgow Outcome Scale, 6 months later. The part of the results of intermediate analyses is reported. Among these patients, we measured various cytokine in cerebrospinal fluid (CSF) by beads array method to choose appropriate CSF samples in 2006. In addition, we established large-scale protein identification method in the exhaustive proteome analysis in human CSF.
To identify proteins associated with pathologic states of the acute brain injury and/or the hypothermia treatment, we performed large-scale analyses of CSF proteins using a two dimensional liquid chromatography/tandem mass spectromet
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ry system in fiscal year 2007. A total of 235 proteins, including 167 proteins with quantitative values, were identified in a mixture of CSF samples from a single NT, a single HT, and 13 Ctrl patients. Major subcellular localizations assigned to these proteins were "extracellular (52%)", "plasma membrane (19%)", and "cytoplasm (12%)", and the list of identified proteins were cataloged together with various types of biological information. Typical CSF proteins such as cystatin C did not show quantitative changes among three patient groups, whereas 84 proteins increased and 16 proteins decreased in NT, and 65 proteins increased and 19 proteins decreased in HT. Higher levels of glial fibrillary acidic protein and significantly lower levels of chromogranin A in both NT and HT, higher levels of acute-phase proteins, adhesion molecules, and extracellular matrix proteins in NT, and suppression of these NT-specific changes in HT suggested damages of the central nervous tissue and the up-regulation of inflammatory responses that could be suppressed partially by the hypothermia treatment in the pathologic state of the acute brain injury. Less
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