Distinctive pathophysiological features of Carbon monoxide poisoning-induced delayed encephalopathy compared with hypoxemia-induced brain damage

• Project/Area Number: 17K11576
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Emergency medicine
• Research Institution: Ehime University
• Principal Investigator: Yorozuya Toshihiro 愛媛大学, 医学系研究科, 教授 (10230848)
• Co-Investigator(Kenkyū-buntansha): 西原 佑 愛媛大学, 医学部附属病院, 講師 (50568912)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: microglia / neurotrophic factor / carbon monoxide / delayed encephalopathy / マイクログリア / 一酸化炭素 / 神経保護因子 / 遅発性脳症 / アポトーシス / 一酸化炭素中毒 / 神経細胞 / ミエリン / 脳・神経

Outline of Final Research Achievements

Carbon monoxide (CO) causes a delayed neurologic syndrome called delayed encephalopathy (DE). Rats were randomly assigned to three groups; the air group, the CO group (exposed to CO), and the low O2 group (exposed to low concentration of O2). The impairment of memory function was observed only in the CO group. The demyelination in the CO group was more severe and continued longer than that in the low O2 group. Moreover, decrease in microglial cells were observed in the CO group, however, on the other hand, microglial cells were activated in the low O2 group. mRNAs of several neurotrophic factors expressed by microglia were decreased in the CO group but increased in the low O2 group. Conclusively, CO-induced DE displayed distinctive pathological features from simple hypoxic insults; prolonged demyelination accompanying a significant decrease in microglial cells. The decreased neurotrophic factor expression in microglial cells may be one of causes of CO-induced DE.

Academic Significance and Societal Importance of the Research Achievements

我々の行った研究で得られた知見は、これまでの報告とは全く異なる新しいものであった。特に、マイクログリアの活性化によって脱髄が引き起こされることが問題の一つとされていたこれまでの報告と比べ、マイクログリアは活性化するどころか、逆に減少し、おそらくはそれに伴うと考えれらる神経保護因子の減少は、今後の治療方法が大きく変わる可能性がある。例えば、マイクログリアの活性化を抑制することを目的とする治療方針から、マイクログリアの生存を助けることを目的とする、もしくは、減少した神経保護因子を補う事を目的とする治療方針への転換などが考えられ、社会的に大きな意義を持つものと考えられる。

Research Products

• [Journal Article] Chronic constriction injury of the sciatic nerve in rats causes different activation modes of microglia between the anterior and posterior horns of the spinal cord (2020)
  • Author(s): Nishihara T, Tanaka J, Sekiya K, Nishikawa Y, Abe N, Hamada T, Kitamura S, Ikemune K, Ochi S, Choudhury ME, Yano H, Yorozuya T
  • Journal Title: Neurochemistry International Volume: 134 Pages: 104672-104672
  • DOI: 10.1016/j.neuint.2020.104672
  • Peer Reviewed / Open Access
• [Journal Article] Carbon monoxide poisoning-induced delayed encephalopathy accompanies decreased microglial cell numbers: Distinctive pathophysiological features from hypoxemia-induced brain damage (2019)
  • Author(s): Sekiya K, Nishihara T, Abe N, Konishi A, Nandate H, Hamada T, Ikemune K, Takasaki Y, Tanaka J, Asano M, Yorozuya T
  • Journal Title: Brain Research Volume: 1710 Pages: 22-32
  • DOI: 10.1016/j.brainres.2018.12.027
  • Peer Reviewed / Open Access
• [Journal Article] Hemolytic reaction in the washed salvaged blood of a patient with paroxysmal nocturnal hemoglobinuria (2019)
  • Author(s): Kawamoto Y, Nishihara T, Watanabe A, Nakanishi K, Hamada T, Konishi A, Abe N, Kitamura S, Ikemune K, Toda Y, Yorozuya T
  • Journal Title: BMC Anesthesiology Volume: 19(1) Issue: 1 Pages: 83-83
  • DOI: 10.1186/s12871-019-0752-4
  • Peer Reviewed / Open Access
• [Journal Article] Comparison of the detrimental features of microglia and infiltrated macrophages in traumatic brain injury: a study using a hypnotic bromovalerylurea (2018)
  • Author(s): Abe N, Choudhury ME, Watanabe M, Kawasaki S, Nishihara T, Yano H, Matsumoto S, Kunieda T, Kumon Y, Yorozuya T, Tanaka J
  • Journal Title: Glia Volume: 66(10) Issue: 10 Pages: 2158-2173
  • DOI: 10.1002/glia.23469
  • Peer Reviewed / Open Access
• [Journal Article] Effect of dexmedetomidine on intraocular pressure in patients undergoing robot-assisted laparoscopic radical prostatectomy under total intravenous anesthesia: A randomized, double blinded placebo controlled clinical trial (2018)
  • Author(s): Kitamura S, Takechi K, Nishihara T, Konishi A, Takasaki Y, Yorozuya T
  • Journal Title: Journal of Clinical Anesthesia Volume: 49 Pages: 30-35
  • DOI: 10.1016/j.jclinane.2018.10.001
  • Peer Reviewed
• [Journal Article] Lower limb perfusion during robotic-assisted laparoscopic radical prostatectomy evaluated by near-infrared spectroscopy: an observational prospective study. (2018)
  • Author(s): Takechi K, Kitamura S, Shimizu I, Yorozuya T.
  • Journal Title: BMC Anesthesiology Volume: 18(1) Issue: 1 Pages: 114-114
  • DOI: 10.1186/s12871-018-0567-8
  • Peer Reviewed / Open Access
• [Presentation] The comparison of microglial phagocytosis between carbon monoxide poisoning and hypoxemic hypoxia (2018)
  • Author(s): Keisuke Sekiya, Tasuku Nishihara, Naoki Abe, Toshihiro Yorozuya
  • Organizer: Society for Neuroscience Annual Meeting 2018