| Project/Area Number |
10557111
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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 | 展開研究 |
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| Research Field |
General surgery
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| Research Institution | Osaka University |
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Principal Investigator |
SUGIMOTO Hisashi Graduate School of Medicine, Osaka University, Professor, 医学研究科, 教授 (90127241)
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| Co-Investigator(Kenkyū-buntansha) |
KUWAGATA Yasuyuki Graduate School of Medicine, Osaka University, Research Assistant, 医学研究科, 助手 (50273678)
TANAKA Hiroshi Graduate School of Medicine, Osaka University, Associate Professor, 医学研究科, 助教授 (90252676)
SHIMAZU Takeshi Graduate School of Medicine, Osaka University, Associate Professor, 医学研究科, 助教授 (50196474)
SHIOZAKI Tadahiko Graduate School of Medicine, Osaka University, Research Assistant, 医学研究科, 助手 (60278687)
OGURA Hiroshi Graduate School of Medicine, Osaka University, Research Assistant, 医学研究科, 助手 (70301265)
平出 敦 大阪大学, 医学部, 講師 (20199037)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥11,700,000 (Direct Cost: ¥11,700,000)
Fiscal Year 2000: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1999: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1998: ¥4,600,000 (Direct Cost: ¥4,600,000)
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| Keywords | central nervous system / endocrine system / immune system / insult / neutrophil function / cytokine / NF-κB / ADH / 頭部外傷 / ADH分泌 / 白血球機能 / NF-κB / サイトカインバランス / 脳死 / 臓器障害 / ナイトカイン / NF-KB / グルココルチコイドレセプター |
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| Research Abstract |
The central nervous system (CNS), endocrine system and immune system closely affect each other in the organismal response to insult and injury, however, the main role is known to be taken by the CNS. In this study, we focus on the following four areas : (1) the alteration in endogeneous cytokine balance and neutrophil function in response to insults ; (2) the balance between pro- and anti-inflammatory responses ; (3) the role of peripheral leucocytes on ectopic antidiuretic hormone (ADH) in brain-dead patients ; and (4) the effect of mildhypothermia in patients with severely brain injury.
(1) In patients with CNS injury, acute pathologies such as increased blood levels of pro-inflammatory cytokines, enhanced leukocyte function, and apoptosis suppression were observed, suggesting that inflammatory responses are predominant in living organisms in such events. In contrast, in patients without CNS injury, the increase in blood levels of anti-inflammatory cytokines and inflammatory cytokine
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inhibitors revealed an organismal response to physical insult that was shifted towards an anti-inflammatory state, suggesting reduced immunocompetence or increased susceptibility to infection at the time of CNS injury. However, for brain-dead patients, the organismal CNS regulation disappeared, indicating an activation of inflammatory response.
(2) In an acute pathological condition, the nuclear NF-κB level in neutrophils increased significantly, indicating a predominantly pro-inflammatory state in which the leucocytes were activated. In patients with trauma and sepsis, the heat shock protein (HSP) expression level was enhanced, suggesting a crucial role for HSPs in functional changes of leucocytes. In contrast, the increased susceptibility to infection at the time of CNS injury suggests a role for the reduction in HSP60 in functional alteration.
(3) We examined ADH secretion in the blood of patients after brain-death using PCR to measure gene expression in peripheral leucocytes and confirmed that ADH gene expression is induced within leucocytes. This result suggests that the leucocytes which govern the immune functions may also play a role in hormonal secretion disorders in organs.
(4) We induced mildhypothermia to the patients with severe head injury. The results demonstrate that mildhypothermia is effective for decreasing problematic elevated intracranial pressure. In contrast, in patients with severe head injury who did not have higher intracranial pressure (<25 mmHg), mildhypothermia increased the complication rates, without showing any favorable effect on prognosis. Less
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