Novel ischemic therapy targetting post-free radical molecules
| Project/Area Number |
18K08955
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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 | Kurume University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
広畑 優 久留米大学, 医学部, 教授 (40218863)
折戸 公彦 久留米大学, 医学部, 講師 (50597408)
吉富 宗健 久留米大学, 医学部, 助教 (80529462)
青木 孝親 久留米大学, 医学部, 講師 (70330842)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 脳梗塞 / 神経細胞障害 / 活性酸素 / 脳虚血 / フリーラジカル / ヒドロキシノネナール / カルノシンヒドラジド / 神経細胞死 / HSP70 / 海馬 / ichemia / therapy / free radical / hydroxy nonenal |
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| Outline of Final Research Achievements |
4-hydroxy-trans-2-nonenal (4-HNE), a highly cytotoxic aldehyde, which is produced by peroxide lipid oxidation, induces neuronal cell death in the ischemic disease. We synthesized a novel 4-HNE scavenger; a carnosine-hydrazide derivative, L-carnosine hydrazide (CNN). We examined the anti-ischemic effect of CNN in various models. This compound completely inhibited 4-HNE induced cell toxicity in cultured neuronal cells. In animal models, CNN protected hippocampal CA1 pyramidal neuronal cell death after transient forebrain ischemia in Mongorian gerbil. Furthremore, in the rat middle cerebral artery occlusion model, CNN reduced the infarction area. Our novel chemical compound of CNN can be used as neuroprotective medication even after ischemic disease onset.
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| Academic Significance and Societal Importance of the Research Achievements |
脳血管の閉塞／狭窄による脳虚血状態は神経細胞障害／神経細胞死をもたらす。今まではこの脳梗塞の障害が始まった後には止めることができる有効な薬剤が存在しなかった。我々は今回の研究で新しくL-カルノシンノネナール(CNN)を合成した。このCNNは実際の脳梗塞の治療において脳梗塞の障害が始まった後に投与しても細胞障害の進行に中心的な役割をしている分子4-HNEをを抑制することができる。このことは脳梗塞が発症してもその後の投与で神経細胞障害を予防でき後遺症を極力軽くすることができると考えられる。
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Report
(4 results)
Research Products
(13 results)
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[Journal Article] Leptomeningeal carcinomatosis following neoplastic cerebral aneurysm rupture: a case report.2019
Author(s)
Koga M, Aoki T, Negoto T, Makizono T, Sugi K, Fujimori K, Kajiwara S, Komaki S, Yoshitomi M, Sugita Y, Morioka M.
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Journal Title
World Neurosurg.
Volume: pii: S1878-8750(19)30469-3.
Pages: 0469-3
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Leakage sign for acute subdural hematoma in clinical treatment.2019
Author(s)
Yamamoto M, Orito K, Nakamura Y, Takeshige N, Yoshitomi M, Takeuchi Y, Uzu H, Takasu O, Abe T, Tanoue S, Uchiyama Y, Morioka M.
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Journal Title
Acta Neurochir (Wien).
Volume: 161(2)
Issue: 2
Pages: 233-238
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Neuroprotective effects of a novel carnosine-hydrazide derivative on hippocampal CA1 damage after transient cerebral ischemia.2019
Author(s)
Noguchi K, Ali TFS, Miyoshi J, Orito K, Negoto T, Biswas T, Taira N, Koga R, Okamoto Y, Fujita M, Otsuka M, Morioka M.
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Journal Title
Eur J Med Chem.
Volume: 163
Pages: 207-214
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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