The new approach to treating cerebral edema following cardiac arrest

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K11564
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Emergency medicine
• Research Institution: University of Tsukuba
• Principal Investigator: Nakayama shin 筑波大学, 医学医療系, 講師 (60596443)
• Co-Investigator(Kenkyū-buntansha): 田口 典子 筑波大学, 医学医療系, 准教授 (90569774)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 脳浮腫 / 心肺蘇生

Outline of Final Research Achievements

A various new drug treatment for cerebral edema was tested using a mouse model of cardiopulmonary resuscitation. (1) Na-K-Cl co-transporter 1 (NKCC1), which increases in the brain early after ischemia, draws water into the brain. Treatment with the antagonist bumetanide reduced cerebral edema, however, dehydration was severe that resulted in poor survival rate. (2) Sulfonylurea receptors expressed after ischemia draw water into the brain. Glibenclamide, an antagonist, reduced cerebral edema. (3) NKCC1 is driven by the Na-K-ATPase; β-blockers inhibit this pathway and may therefore inhibit NKCC1. Continuous administration of β-blocker for 4 hours after resuscitation reduced cerebral edema. Treatment of drugs that inhibit various Na channels expressed in the brain after cardiac arrest reduced cerebral edema.

Free Research Field

麻酔・蘇生学

Academic Significance and Societal Importance of the Research Achievements

心肺蘇生後に起こる脳浮腫は致命的であり根本的な治療法は確立されていない。マウス心肺蘇生モデルを用いて脳浮腫に対する新しい薬物治療を検証した。脳の血流が途絶えると細胞を保護するべく各種ナトリウムチャネルが発現するがナトリウムと同時に水を脳細胞内に引き込んでしまう。これらを阻害する薬物、糖尿病治療薬であるグリベンクラミド、利尿薬であるブメタニド、抗不整脈薬のランジオロールが脳浮腫を軽減した。