Effects of general anesthetics on the neural activity of the immature nervous system.

2012 Fiscal Year Final Research Report

• Project/Area Number: 22591712
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Anesthesiology/Resuscitation studies
• Research Institution: Yokohama City University
• Principal Investigator: ANDOH Tomio 横浜市立大学, 医学研究科, 客員教授 (00193110)
• Co-Investigator(Kenkyū-buntansha): KAMIYA Yoshinori 横浜市立大学, 医学研究科, 客員講師 (90381491)
• Co-Investigator(Renkei-kenkyūsha): ECHIGO Noriyuki 横浜市立大学, 医学研究科, 客員准教授 (00363797)
• Project Period (FY): 2010 – 2012
• Keywords: ブメタニド / NKCC1 / pCREB / Ca イメージング / 鎮静作用

Research Abstract

We intended to test the hypothesis that midazolam may exert excitatory actions on the developing hippocampus and may reduce sedative effects in neonatal rats. We found that midazolam increased intracellular Ca concentration and p CREB expression in the hippocampal CA3 area from neonatal rats but not from young rats. These excitatory effects of midazolam were inhibited by bumetanide, an inhibitor for NKCC1. Midazolam exhibited less sedative actions in neonatal rats compared with in young rats. Bumetanide enhanced sedative effects of midazolam in neonatal but not young rats. These results indicate that GABAA receptor-mediated excitation is dependent on NKCC1 and may underlie the attenuated sedative effects of midazolam in neonatal rats.

Research Products

• [Journal Article] Bumetanide, an inhibitor of cation-chloride co-transporter isoform 1, inhibits GABAergic excitatory actions and enhances sedative actions of midazolam in neonatal rats.
  • Author(s): Yukihide Koyama, Tomio Andoh, Yoshinori Kamiya, Satoshi Morita, Tomoyuki Miyazaki, Kazuhiro Uchimoto, Takahiro Mihara, Takahisa Goto
  • Journal Title: Anesthesiology Volume: (in press)
  • Peer Reviewed
• [Presentation] the inhibitor of NKCC1, cation-chloride co-transporter isoform 1, inhibits the GABAergic excitatory action induced by midazolam in the hippocampus in neonatal rats. (2013)
  • Author(s): Yukihide Koyama, Tomio Andoh, Yoshinori Kamiya, Takahisa GotoBumetanide
  • Organizer: Euroanaesthesia 2013
  • Place of Presentation: Barcelona, Spain
  • Year and Date: 20130601-04
• [Presentation] Na+, K+-2Cl- co-transporter (NKCC1) の選択的阻害薬のブメタニドは新生児ラットの海馬 CA3 領域における GABAA 受容体活性化による興奮性活動を抑制する (2013)
  • Author(s): 小山 行秀、安藤 富男、紙谷 義孝、後藤 隆久
  • Organizer: 日本麻酔科学会総会
  • Place of Presentation: ロイトン札幌他(北海道)
  • Year and Date: 20130523-25
• [Presentation] Bumetanide, the inhibitor of NKCC1 (Cation-Chloride Co-Transporter Isoform 1), inhibited an increase in cytosolic Ca2+ concentration ([Ca2+]i) induced by midazolam in the immature hippocampus (2013)
  • Author(s): Yukihide Koyama, Tomio Andoh, Yoshinori Kamiya, Takahisa Goto
  • Organizer: World Anesthesia Convention
  • Place of Presentation: Bangkok, Thailand
  • Year and Date: 20130423-27