Protective effects of endogenous carbon monoxide on cerebral energy metabolism during acute focal brain ischemia

• Project/Area Number: 15K10315
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurosurgery
• Research Institution: National Center for Global Health and Medicine (2016-2017); Keio University (2015)
• Principal Investigator: Takayuki Morikawa 国立研究開発法人国立国際医療研究センター, その他部局等, 研究員 (80465012)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 一酸化炭素 / 脳血流代謝

Outline of Final Research Achievements

Brain generates a micromolar order of carbon monoxide (CO) via heme oxygenase (HO) reactions. In this study, we examined the hypothesis that the deletion of HO-2 exacerbates cerebral energy metabolism during acute focal brain ischemia. We conducted quantitative imaging mass spectrometry (Q-IMS) analysis for adenylates and lactate to decipher local cerebral responses of energy metabolism from wild-type (WT) and HO-2-null mice that underwent a 60-min occlusion of the left middle cerebral artery. Striking differences were found in the contralateral hemispheres, where the levels of ADP, AMP and lactate in HO-2-null mice were higher than those in WT mice. These results suggest that the HO-2/CO system plays roles in protecting against ischemia not only at the ischemic core where the severe reduction of blood flow occurs, but it also protects even more effectively in the trans-hemispheric regions where only a subtle reduction of blood flow takes place.

Research Products

• [Journal Article] Gold-nanofève surface-enhanced Raman spectroscopy visualizes hypotaurine as a robust anti-oxidant consumed in cancer survival (2018)
  • Author(s): Shiota M, Naya M, Yamamoto T, Hishiki T, Tani T, Takahashi H, Kubo A, Koike D, Itoh M, Ohmura M, Kabe Y, Sugiura Y, Hiraoka N, Morikawa T, Takubo K, Suina K, Nagashima H, Sampetrean O, Nagano O, Saya H, Yamazoe S, Watanabe H, Suematsu M
  • Journal Title: Nature Communications Volume: 9 Issue: 1 Pages: 1561-1561
  • DOI: 10.1038/s41467-018-03899-1
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Quantitative imaging mass spectroscopy reveals roles of heme oxygenase-2 for protecting against transhemispheric diaschisis in the brain ischemia (2018)
  • Author(s): 1.Shinichi Goto, Takayuki Morikawa, Akiko Kubo, Keiyo Takubo, Keiichi Fukuda, Mayumi Kajimura, Makoto Suematsu
  • Journal Title: Journal of Clinical Biochemistry and Nutrition Volume: 63 Issue: 1 Pages: 70-79
  • DOI: 10.3164/jcbn.17-136
  • NAID: 130007387127
  • ISSN: 0912-0009, 1880-5086
  • Peer Reviewed / Open Access
• [Journal Article] Abnormal hematopoiesis and hematopoietic stem cell niche (2017)
  • Author(s): 田久保 圭誉、森川 隆之、小林 央
  • Journal Title: Rinsho Ketsueki Volume: 58 Issue: 10 Pages: 1844-1850
  • DOI: 10.11406/rinketsu.58.1844
  • NAID: 130006132651
  • ISSN: 0485-1439, 1882-0824
  • Peer Reviewed
• [Journal Article] Karigane D, Kobayashi H, Morikawa T, Ootomo Y, Sakai M, Nagamatsu G, Kubota Y, Goda N, Matsumoto M, Nishimura EK, Soga T, Otsu K, Suematsu M, Okamoto S, Suda T, Takubo K. (2016)
  • Author(s): Karigane D, Kobayashi H, Morikawa T, Ootomo Y, Sakai M, Nagamatsu G, Kubota Y, Goda N, Matsumoto M, Nishimura EK, Soga T, Otsu K, Suematsu M, Okamoto S, Suda T, Takubo K.
  • Journal Title: Cell Stem Cell Volume: 19 Issue: 2 Pages: 192-204
  • DOI: 10.1016/j.stem.2016.05.013
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Leukocyte plugging and cortical capillary flow after subarachnoid hemorrhage (2016)
  • Author(s): Ishikawa M., Kajimura M., Morikawa T., Tsukada K., Tsuji T., Kusaka G., Tanaka Y., Suematsu M.
  • Journal Title: Acta Neurochirurgica Volume: - Issue: 6 Pages: 1057-1067
  • DOI: 10.1007/s00701-016-2792-6
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The EGF receptor promotes the malignant potential of glioma by regulating amino acid transport system xc(-) (2016)
  • Author(s): Tsuchihashi K, Okazaki S, Ohmura M, Ishikawa M, Sampetrean O, Onishi N, Wakimoto H, Yoshikawa M, Seishima R, Iwasaki Y, Morikawa T, Abe S, Takao A, Shimizu M, Masuko T, Nagane M, Furnari FB, Akiyama T, Suematsu M, Baba E, Akashi K, Saya H, Nagano O.
  • Journal Title: Cancer Research Volume: in press Issue: 10 Pages: 2954-2963
  • DOI: 10.1158/0008-5472.can-15-2121
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Hypoxia regulates the hematopoietic stem cell niche. (2016)
  • Author(s): Morikawa T, Takubo K.
  • Journal Title: Pflugers Arch. Volume: 468 Issue: 1 Pages: 13-22
  • DOI: 10.1007/s00424-015-1743-z
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Deletion of heme oxygenase-2 exacerbates cerebral energy metabolism during acute focal brain ischemia (2015)
  • Author(s): 森川隆之、梶村眞弓、後藤信一、星野岳郎、善岡尊文、久保亜紀子、杉浦八十男、菱木貴子、末松誠
  • Organizer: The 10th World Congress for Microcirculation
  • Place of Presentation: 国立京都国際会館(京都府左京区）
  • Year and Date: 2015-09-25
  • Int'l Joint Research