Neuroprotective mechanisms of hydrogen sulfide on ischemic spinal cord injury
| Project/Area Number |
17K16755
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Anesthesiology
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| Research Institution | Juntendo University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 虚血 / ATP感受性Kチャネル / 再灌流障害 / 吸入麻酔薬 / NMDA受容体 / モノカルボン酸トランスポーター / プレコンディショニング / 虚血耐性 / KATPチャネル / 硫化水素 / 遅発性対麻痺 / 一酸化窒素 |
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| Outline of Final Research Achievements |
Sevoflurane has drawn attention because of its preconditioning effects in hypoxic conditions. In our brain slice experiments, deprivation of oxygen and glucose depolarized neurons to subthreshold potentials, and the pre-administration of sevoflurane prolonged the time to depolarization. A KATP channel inhibitor reversed the prolonged time to depolarization and the prevention of the pathological potentiation of excitatory responses, indicating that the short exposure to sevoflurane likely participates in neuroprotection against hypoxia via activation of KATP channels. A monocarboxylate transporter blocker also depolarized striatal neurons. Interestingly, the blockade of monocarboxylate transporters that supply lactate to neurons caused the pathological potentiation, even in the presence of enough oxygen and glucose. In this case, sevoflurane could not prevent the pathological potentiation, suggesting the involvement of monocarboxylate transporters in the sevoflurane-mediated effects.
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| Academic Significance and Societal Importance of the Research Achievements |
周術期合併症として低酸素血症や臓器虚血があるが、手術症例が高齢化する日本において脳虚血が危惧される症例は今後増加していくことが予想される。脳血管障害の予防のために術中の厳密な血圧管理や脳組織酸素化モニターなどが臨床の現場では行われているが、その迅速な発見や予防は現状では難しい。本研究では臨床現場で頻用される吸入麻酔薬セボフルランの脳に対する臓器保護作用について検討し、セボフルランの脳保護効果がKATPチャネルを介した作用機序であることが示された。さらに、セボフルランの効果にモノカルボン酸トランスポーターの関与が考えられた。セボフルランは全身麻酔での手術中に中枢神経保護作用を示す可能性がある。
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Report
(6 results)
Research Products
(22 results)
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[Journal Article] Prevalence of chronic postsurgical pain after thoracotomy and total knee arthroplasty: a retrospective multicenter study in Japan (Japanese Study Group of Subacute Postoperative Pain)2018
Author(s)
Yoko Sugiyama, Hiroki Iida, Fumimasa Amaya, Kanako Matsuo, Yutaka Matsuoka, Keiko Kojima, Fumitaka Matsuno, Takayuki Hamaguchi, Masako Iseki, Keisuke Yamaguchi, Yoshika Takahashi, Atsuko Hara, Yusuke Sugasawa, Mikito Kawamata, Satoshi Tanaka, Yoshimi Inagaki, Akihiro Otsuki, Mitsuaki Yamazaki, Hisakatsu Ito
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Journal Title
Journal of Anesthesia
Volume: -
Issue: 3
Pages: 434-438
DOI
Related Report
Peer Reviewed / Open Access
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