Establishment of new diagnostic methods for PICS.

• Project/Area Number: 16K11425
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Emergency medicine
• Research Institution: Nippon Medical School
• Principal Investigator: YAMADA Marina 日本医科大学, 医学部, 講師 (70508621)
• Co-Investigator(Kenkyū-buntansha): 横堀 将司 日本医科大学, 医学部, 准教授 (70449271) ; 近田 祐介 日本医科大学, 医学部, 助教 (80637827) ; 太田黒 崇伸 日本医科大学, 医学部, 助教 (60786812)
• Research Collaborator: CHIBA Tomohiro ; MIYASHITA Masao ; YOKOTA Hiroyuki
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 敗血症 / PICS / Humanin

Outline of Final Research Achievements

Marked increase in survival after critical conditions such as septic shock have led us to further improve long-term illness described as post-intensive care syndrome (PICS), which covers both physical and psychiatric dysfunction among patients recovered from intensive care. The aim of the study was to establish new diagnostic methods for PICS. We developed murine PICS model by cecal ligation and puncture (CLP). CLP-induced sepsis caused acute increase in serum inflammatory cytokines and induced gliosis in the central nervous system, leading to working memory impairment. Using the model, we measured the HN levels in blood and tissue. As a result, HN levels in blood was decreased after CLP, which was negatively correlated with working memory impairment. Using blood samples of patients recovered from intensive care, we measured HN levels. We, however, could not get same result.

Academic Significance and Societal Importance of the Research Achievements

本研究成果は、将来的に重症疾患患者が慢性期に発症する中枢神経系機能障害の予後予測法および治療薬を開発することにつながる。期間内に予後予測法および治療薬を確立することはできなかったが、その候補因子としてHumaninの有用性は明らかにできた。本研究期間で得られた結果は、最終的には患者 QOLの保持、患者関係者の負担軽減、医療費削減に直結しうるものであり、とても重要な一歩だと考えている。

Research Products

• [Presentation] 全身炎症が脳機能に与える影響の検討から得られた治療シーズ～基礎研究 (2016)
  • Author(s): 山田真吏奈、松田明久、相磯貞和、増野智彦、松本尚、宮下正夫、横田裕行
  • Organizer: 第44回日本救急医学会総会・学術集会
  • Place of Presentation: グランドプリンスホテル新高輪・国際館パミール(東京・港区）
  • Year and Date: 2016-11-17
• [Presentation] 早期の感染コントロールは、敗血症マウスモデルにおけるPICS脳機能障害を抑制させ る (2016)
  • Author(s): 山田真吏奈、増野智彦、松本尚、横田裕行
  • Organizer: 第44回日本救急医学会総会・学術集会
  • Place of Presentation: グランドプリンスホテル新高輪・国際館パミール(東京・港区）
  • Year and Date: 2016-11-17
• [Presentation] The role of atrocytes in the nervous system dysfunction, sepsis induced memory impairment (2016)
  • Author(s): Marina Yamada, Tomohiro Chiba, Akihisa Matsuda, Sadakazu Aiso, Tomohiko Masuno, Hisashi Matsumoto, Hiroyuki Yokota, Masao Miyashita
  • Organizer: the 8th Congress of the International Federation of Shock Societies
  • Place of Presentation: 東京ドームホテル(東京・文京区）
  • Year and Date: 2016-10-03
  • Int'l Joint Research
• [Presentation] S14G-Humanin improves the survival from severe sepsis (2016)
  • Author(s): Kumiko Sekiguchi, Marina Yamada, Tomohiro Chiba, Akihisa Matsuda, Sadakazu Aiso, Tomohiko Masuno, Hisashi Matsumoto, Hiroyuki Yokota, Masao Miyashita
  • Organizer: the 8th Congress of the International Federation of Shock Societies
  • Place of Presentation: 東京ドームホテル(東京・文京区）
  • Year and Date: 2016-10-03
  • Int'l Joint Research
• [Presentation] PICS病態におけるアストロサイトの役割 (2016)
  • Author(s): 山田真吏奈、千葉知宏、松田明久、相磯貞和、増野智彦、松本尚、横田裕行、宮下正夫
  • Organizer: 第23回 外科侵襲とサイトカイン研究会
  • Place of Presentation: 伊藤国際学術研究センター(東京・文京区)
  • Year and Date: 2016-07-09
• [Presentation] The effect of S14G-Humanin on memory impairment induced by severe sepsis (2016)
  • Author(s): Marina Yamada, Akihisa Matsuda, Tomohiro Chiba, Sadakazu Aiso, Tomohiko Masuno, Hisashi Matsumoto, Hiroyuki Yokota, Masao Miyashita
  • Organizer: 39th Annual Conference on Shock
  • Place of Presentation: Texas(USA)
  • Year and Date: 2016-05-11
  • Int'l Joint Research