Basic analysis for the mechanisms of septic encephalopathy

• Project/Area Number: 23592266
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Anesthesiology/Resuscitation studies
• Research Institution: Tokyo Medical University
• Principal Investigator: UCHINO Hiroyuki 東京医科大学, 医学部, 教授 (60266476)
• Co-Investigator(Kenkyū-buntansha): HAMADA Ryuta 東京医科大学, 医学部, 助教 (20459572) ; KANEKO Kohki 東京医科大学, 医学部, 助教 (40617536)
• Co-Investigator(Renkei-kenkyūsha): SHIBASAKI Futoshi (財)東京都医学研究機構, 東京都臨床医 学総合研究所, 副参事研究員 (90300954)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
• Keywords: 敗血症性脳症状 / ミトコンドリア / Ca2+ / ＣＲＣ / RCR / swelling / ミトコンドリア呼吸能(ＲＣＲ) / SAEモデル / state3 / state4 / 国際研究者交流 スエーデン / 敗血症 / マウス / ラット / ミトコンドリア機能不全 / 敗血症性脳症

Research Abstract

To investigate the mechanisms of septic Encephalopathy(SE), we focused on the mitochon drial dysfunction. Firts year, The swelling assay suggested that brain has showed significant swelling due to Ca2 + loading comapred to control(control vs 1,6,12,24h, p<0.05). Seccond year, Calcium Retention Capacity. Sepsis significantly inhibited the CRC according to the recovery time(control vs 1,6,12,24h, p<0.05). Last year, we have investigated the mitochondrial respiratory control ratio(RCR) due to Klark elctrode assay. RCR was strongly reduced according to the recovery time. Especially, 12 and 24h after recovery, CLP group showed significant reduction of RCR compare to control(P<0.05).
Septic encephalopathy showed the inhibition of mitochondrial function.

Research Products

• [Journal Article] Cyclophilin-D inhibition in neuroprotection: dawn of a new era of mitochondrial medicine. (2013)
  • Author(s): Uchino H1, Hatakeyama K, Morota S, Tanoue T, Nishiyama T, Usui D, Taguchi C, Suzuki M, Hansson MJ, Elmér E.
  • Journal Title: Acta Neurochir Suppl. Volume: 118 Pages: 311-315
  • DOI: 10.1007/978-3-7091-1434-6_61
  • ISBN: 9783709114339, 9783709114346
  • Peer Reviewed
• [Journal Article] Mitochondrial respiration in human viable platelets--methodology and influence of gender, age and storage (2013)
  • Author(s): Sjövall F, Ehinger JK, Marelsson SE, Morota S, Frostner EA, Uchino H, Lundgren J Arnbjörnsson E, Hansson MJ, Fellman V, Elmér E
  • Journal Title: Mitochondrion Volume: 13(1) Issue: 1 Pages: 7-14
  • DOI: 10.1016/j.mito.2012.11.001
  • Peer Reviewed
• [Journal Article] Cytokine marker measurement in human neuroblastoma cells with supersensitive and multiplex assay: MUSTag technology. (2013)
  • Author(s): Miyashita R1, Chen L, Morizane Y, Takeshita Y, Fukui H, Ishizaki T, Hatakeyama K, Ohseto K, Shibasaki F, Uchino H.
  • Journal Title: Acta Neurochir Suppl. Volume: 118 Pages: 317-320
  • DOI: 10.1007/978-3-7091-1434-6_62
  • ISBN: 9783709114339, 9783709114346
  • Peer Reviewed
• [Journal Article] 虚血性脳障害のメカニズム (2013)
  • Author(s): 内野 博之, 福井 秀公, 宮下 亮一, 屋良 美紀, 原 直美, 斉木 巌, 三浦 仁, 畑山 聖
  • Journal Title: 蘇生 Volume: 32 Pages: 94-105
  • NAID: 10024169094
  • Peer Reviewed
• [Journal Article] Mitochondrial respiration in human viable platelets--methodology and influence of gender, age and storage. (2013)
  • Author(s): Sjövall F, Ehinger JK, Marelsson SE, Morota S, Frostner EA, Uchino H, Lundgren J, Arnbjörnsson E, Hansson MJ, Fellman V, Elmér E.
  • Journal Title: Mitochondrion. Volume: 13 Pages: 7-14
  • Peer Reviewed
• [Journal Article] Int6 silencing causes induction of angiogenic factors in neuronal cells via accumulation of hypoxia-inducible factor 2αand decreases br ain damage in rats (2012)
  • Author(s): Miyashita R, Chen L, Oshiro H, Uchino H, Shibasaki F
  • Journal Title: Neurosci Lett Volume: 528(1) Issue: 1 Pages: 83-8
  • DOI: 10.1016/j.neulet.2012.08.033
  • Peer Reviewed
• [Journal Article] Organ protective effects of volatile anesthetics and perioperative outcomes] (2012)
  • Author(s): Uchino H, Suzuki M, Okita A, Yuhnaiyama Y, Shibuya M, Usui D, Miyashita R, Hatakeyama K. Masui
  • Journal Title: Review. Japanese Volume: 61(5) Pages: 478-95
  • NAID: 40019314239
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/22702090
  • Peer Reviewed
• [Journal Article] Evaluation of the protective effects of cyclosporin a and FK506 on abnormal cytosolic and mitochondrial Ca²⁺ dynamics during ischemia and exposure to high glutamate concentration in mouse brain slice preparations. (2012)
  • Author(s): Yokoyama T, Tanoue T, Hasegawa E, Ikeda Y, Ohta S, Omi A, Kudo Y, Uchino H.
  • Journal Title: J Pharmacol Sci. Volume: 120 Pages: 228-240
  • NAID: 10031147569
  • Peer Reviewed
• [Journal Article] Int6 silencing causes induction of angiogenic factors in neuronal cells via accumulation of hypoxia-inducible factor 2α and decreases brain damage in rats. (2012)
  • Author(s): Miyashita R, Chen L, Oshiro H, Uchino H, Shibasaki F.
  • Journal Title: Neurosci Lett. Volume: 528 Pages: 83-88
  • Peer Reviewed
• [Journal Article] Cyclophilin D-sensitive mitochondrial permeability transition in adult human brain and liver mitochondria (2011)
  • Author(s): Hansson MJ, Morota S, Chen L, Matsuyama N, Suzuki Y, Nakajima S, Tanoue T, Omi A, Shibasaki F, Shimazu M, Ikeda Y, Uchino H, Elmér E
  • Journal Title: J Neurotrauma Volume: 28(1) Pages: 143-53
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/22702090
  • Peer Reviewed
• [Journal Article] 6.分子生物学的観点から脳蘇生・脳保護を考える (2011)
  • Author(s): 内野博之,田上正,安藤千尋,富野美紀子,岩瀬直人,古川雄一,本間豊彦,近江明文,畑山聖
  • Journal Title: 脳死・脳蘇生 Volume: 123巻2号 Pages: 49-59
  • URL: http://search.jamas.or.jp/index.php?format=detail&pp=30&uid=115&nocert=on&module=Advanced&action=DetailOne&sid=268435459&change_f=on&nocert=on
  • Peer Reviewed
• [Journal Article] 神経救急・集中治療における脳保護法の新たな展開 薬物療法による脳保護 脳保護薬の展望 (2011)
  • Author(s): 室園美智博, 畑山聖, 内野博之
  • Journal Title: 救急・集中治療 Volume: ２３巻 Pages: 1283-1289
  • Peer Reviewed
• [Journal Article] 神経救急・集中治療における周術期の脳脊髄保護戦略 血管外科手術と脊髄保護 (2011)
  • Author(s): 柿沼孝泰, 畑山聖, 内野博之
  • Journal Title: 救急・集中治療 Volume: ２３巻 Pages: 1264-1269
  • Peer Reviewed
• [Journal Article] 神経救急・集中治療における周術期の脳脊髄保護戦略 心臓・血管外科手術と脳保護 (2011)
  • Author(s): 宮田和人, 畑山聖, 内野博之
  • Journal Title: 救急・集中治療 Volume: ２３巻 Pages: 1256-1263
  • Peer Reviewed
• [Journal Article] 神経救急・集中治療の重要性と必要な基礎知識および脳保護・脳蘇生の展望 最先端の脳障害の基礎的メカニズム (2011)
  • Author(s): 宮下亮一, 畑山聖, 内野博之
  • Journal Title: 救急・集中治療 Volume: ２３巻 Pages: 1019-1025
  • Peer Reviewed
• [Journal Article] 分子生物学的観点から脳蘇生・脳保護を考える (2011)
  • Author(s): 内野博之, 田上正, 安藤千尋, 富野美紀子, 岩瀬直人, 古川雄一, 本間豊彦, 近江明文, 畑山聖
  • Journal Title: 脳死・脳蘇生 Volume: ２３巻 Pages: 49-59
  • Peer Reviewed
• [Journal Article] Cyclophilin D-sensitive mitochondrial permeability transition in adult human brain and liver mitochondria. (2011)
  • Author(s): Hansson MJ, Morota S, Chen L, Matsuyama N, Suzuki Y, Nakajima S, Tanoue T, Omi A, Shibasaki F, Shimazu M, Ikeda Y, Uchino H, Elmér E.
  • Journal Title: J Neurotrauma Volume: ２８巻 Pages: 143-153
  • Peer Reviewed
• [Presentation] 教育講演神経集中治療における脳保護を考える (2014)
  • Author(s): 内野博之
  • Organizer: 第41回日本集中治療医学会
  • Place of Presentation: 京都
  • Year and Date: 2014-02-28
• [Presentation] 神経集中治療における脳保護を考える (2014)
  • Author(s): 内野 博之
  • Organizer: 第４１回日本集中治療医学会総会
  • Place of Presentation: 京都
  • Invited
• [Presentation] 教育講演分子生物学的観点からみた脳保護・脳蘇生 (2013)
  • Author(s): 内野博之
  • Organizer: 第40回日本集中治療医学会
  • Place of Presentation: 松本
  • Year and Date: 2013-02-28
• [Presentation] シンポジウム脳低体温療法とその周辺脳虚血のメカニズム (2012)
  • Author(s): 内野博之
  • Organizer: 第31回日本蘇生学会
  • Year and Date: 2012-11-23
• [Presentation] 招請講演麻酔薬の脳虚血に対する保護効果 (2012)
  • Author(s): 内野博之
  • Organizer: 第32回日本臨床麻酔学会
  • Place of Presentation: 福島
  • Year and Date: 2012-11-03
• [Presentation] 分子生物学的観点から脳保護・脳蘇生を考える
  • Author(s): 内野 博之
  • Organizer: 栃木麻酔・集中治療セミナー
  • Place of Presentation: 小山
  • Invited
• [Presentation] 麻酔薬の脳虚血に対する脳保護効果
  • Author(s): 内野 博之
  • Organizer: 第32回日本臨床麻酔学会
  • Place of Presentation: 福島
  • Invited
• [Presentation] 脳虚血のメカニズム
  • Author(s): 内野 博之
  • Organizer: 第31回日本蘇生学会
  • Place of Presentation: 大津
  • Invited
• [Presentation] 分子生物学的観点からみた脳保護・脳蘇生
  • Author(s): 内野 博之
  • Organizer: 第40回日本集中治療医学会
  • Place of Presentation: 松本
  • Invited
• [Book] 【sepsis・SIRS-いま生かす!最新の病態把握に基づく適切な診療へ-】sepsisの急性期治療循環管理の目標とカテコラミンの使い分け(Q&A/特集), 救急・集中治療(1346-0935)24巻9-10 (2012)
  • Author(s): 宮田和人,内野博之
  • Publisher: 総合医学社