Prophylactic effects of hypothermia and general anesthetics against anoxia in rat hippocampal slices in vitro

低温联合全身麻醉对体外大鼠海马切片缺氧的预防作用

• 批准号: 11671485
• 负责人: HIROTA Koki
• 金额: $ 2.18万
• 依托单位: TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671485/
• 关键词: Rat; Hippocampus; Cerebral ischemia; General anesthetics; Hypothermia; Prophylaxis; 全身麻酔

Although previous clinical reports suggested the prophylactic effects of hypothermia and/or general anesthetics against cerebral ischemia, the cellular mechanisms by which hypothermia and/or anesthetics protect brain tissue against hypoxia remain unknown. In the present study, we have employed the rat hippocampal slice preparations in vitro, and studied the effects of hypothermia and general anesthetics against anoxia using electrophysiological techniques.Extracellular recordings were used to record field potentials in CA1 pyramidal neurons of rat hippocampal slices. Slices were placed on a liquid/gas interface, and were perfused with 95%O_2/5%CO_2 and artificial cerebrospinal fluid (37℃). Anoxia (0% oxygen) was applied to slices by switching the gas mixture from 95%O_2/5%CO_2 to 95%N_2/5%CO_2 in the absence and presence of hypothermia (27℃) and/or general anesthetics (thiopental, propofol, volatile anesthetics).The 180-sec anoxia induced anoxic depolarization (AD) in hippocampal slices at 37℃ in the absence of general anesthetics. Since combination of the NMDA, non-NMDA, and GABA receptor antagonists failed to prevent AD, synaptic transmission is not responsible for elicitation of AD. The treatment with thiopental, but not propofol and volatile anesthetics, significantly reduced the incidence of AD. The hypothermia alone reduced the incidence of AD, and accelerated the reduction in the presence of thiopental.The present study clearly demonstrated that the treatment with hypothermia and/or thiopental prevent AD, and produce prophylactic actions against ischemia in hippocampal slice preparations in vitro.

尽管先前的临床报告表明低温和/或全身麻醉剂对脑缺血的预防作用，但低温和/或麻醉剂保护脑组织免受缺氧的细胞机制仍然未知。本研究采用体外培养的大鼠海马脑片，采用细胞外记录法记录海马脑片CA 1区锥体神经元的场电位，研究了低温和全身麻醉药对大鼠海马脑片缺氧的影响。将脑片置于液/气界面上，用95%O_2/5%CO_2和人工脑脊液（37℃）灌注。在低温（27℃）和/或全身麻醉药（硫喷妥钠、异丙酚、挥发性麻醉药）存在下，通过将混合气体从95%O_2/5%CO_2切换到95%N_2/5%CO_2，对脑片施加缺氧（0%氧），在37℃无全身麻醉药的情况下，缺氧180秒诱导海马脑片缺氧去极化（AD）。由于NMDA、非NMDA和GABA受体拮抗剂的组合未能预防AD，因此突触传递不负责AD的诱发。硫喷妥钠治疗显著降低了AD的发生率，而丙泊酚和挥发性麻醉药则无此作用。单纯低温可降低AD的发生率，而硫喷妥钠可加速其降低，本研究清楚地表明低温和/或硫喷妥钠对AD的预防作用，并对体外海马脑片缺血有预防作用。

项目成果

K Hirota, T Asahi, R Sasaki, M Yamazaki, SH Roth: "The agent-and pathway-specific actions of general anesthetics in hippocampus in vitro (Molecular and Basic Mechanisms of Anesthesia)"Urban BW (ed.) Pabst Science Publishers, Lengerich, Germany. 370-375 (2

K Hirota、T Asahi、R Sasaki、M Yamazaki、SH Roth：“体外海马体中全身麻醉剂的药剂和通路特异性作用（麻醉的分子和基本机制）”Urban BW（编辑）Pabst Science 出版社，

K Takahana, K Hirota, SH Roth, A Masuda, Y Ito: "The effects of n-alcohols on evoked synaptic potentials in rat hippocampal slices: Hill coefficients account for the cutoff phenomenon"Toxicology Letters. (in press). (2000)

K Takahana、K Hirota、SH Roth、A Masuda、Y Ito：“n-醇对大鼠海马切片诱发突触电位的影响：希尔系数解释截止现象”毒理学快报。

K Hirota, A Masuda, Y. Ito: "Volatile anesthetics reduce calcium current in parasympathetic neurons from bullfrog hearts"Anesthesia & Analgesia. 89. 225-229 (1999)

K Hirota、A Masuda、Y. Ito：“挥发性麻醉剂可减少牛蛙心脏副交感神经元中的钙电流”麻醉

廣田弘毅: "富山の麻酔-黎明期,現在,そして21世紀へ-"伊藤祐輔編(桂書房). 185 (2000)

广田弘树：“富山的麻醉——早期、现在和21世纪——”伊藤佑介编辑（桂书房）185（2000）。

Hirota K, et al.: "Intravenous anesthetics produce use-dependent changes of paired-pulse facilitation in rat in vitro hippocampal preparations"Progress in Anesthetic Mechanisms. 6. 56-62 (2000)

Hirota K 等人：“静脉麻醉药在大鼠体外海马制剂中产生依赖于使用的配对脉冲促进变化”麻醉机制进展。