| Project/Area Number |
19K09508
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 56010:Neurosurgery-related
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| Research Institution | Okayama University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
平松 匡文 岡山大学, 大学病院, 助教 (50771953)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | くも膜下出血 / 早期脳損傷 / 脳低温療法 / 脱分極 / グルタミン酸 / 低体温 / 脳保護 |
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| Outline of Research at the Start |
くも膜下出血(subarachnoid hemorrhage; SAH)後の遅発性虚血性脳障害は予後不良因子とされており、近年、SAH後の早期脳損傷(early brain injury; EBI)が原因の一つとして注目されている。SAHにおけるEBIのメカニズムを解明するためにラットのSAHモデルにおいて、SAH後超急性期の細胞外電位や頭蓋内圧、脳血流、細胞外グルタミン酸濃度の変化を観察し、神経学的予後と組織学的脳障害との関連を評価する。さらにSAH後超急性期に咽頭冷却による脳低温療法を行い、EBIに対する脳低温療法の脳保護効果を検討する。
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| Outline of Final Research Achievements |
Early brain injury after aneurysmal subarachnoid hemorrhage (SAH) worsens the neurological outcome. Dynamic changes in membrane potentials, intracranial pressure, cerebral perfusion pressure, cerebral blood flow, and extracellular glutamate levels were observed within 30 min after SAH. A prolonged duration of depolarization correlated with peak extracellular glutamate levels, and these two factors worsened the neuronal injury. Under brain hypothermia using pharyngeal cooling after SAH, cerebral perfusion pressure in the hypothermia group recovered earlier than that in the normothermia group. Extracellular glutamate levels in the hypothermia group were significantly lower than those in the normothermia group. The early induction of brain hypothermia could facilitate faster recovery of cerebral perfusion pressure, repolarization, and the inhibition of excessive glutamate release, which would prevent ultra-early brain injury following SAH.
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| Academic Significance and Societal Importance of the Research Achievements |
脳動脈瘤破裂によるくも膜下出血は約半数が後遺症を残し、2割が死に至るいまだ予後不良な疾患である。発症72時間以内に生じる早期脳損傷が予後を悪化させる一因であり、早期脳損傷が起こるメカニズムは解明されつつあるが、これをターゲットとした治療は確立されていない。我々は本研究で早期に脳低温療法を行うことでくも膜下出血後の早期脳損傷を予防し得ることを示し、くも膜下出血患者の予後を改善させる上で意義がある研究と考える。
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