The neuronal toxicity of general anesthetics on the developing rat brain

全身麻醉药对发育中的大鼠大脑的神经元毒性

• 批准号: 18591683
• 负责人: MORIMOTO Yuji
• 金额: $ 2.53万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591683/
• 关键词: Anesthesia; Neurotoxicity

It was recently shown that exposure of commonly used general anesthetics to the developing rat brain during the peak of synaptogenesis can trigger widespread apoptotic neurodegeneration in the brain, especially in the hippocampus. This can cause the persistent learning/memory deficits later on life. This study examined whether pentobarbital, an anesthetic with GABAergic property, administered to neonate rats, can trigger the behavioral and electrophysiological deficits occur later in adulthood. Rats administered pentobarbital (10 and 20 mg/kg, i.p.) on the 7th day after birth (7PD) displayed suppressed the hippocampal long-term potentiation (LTP) at 10-12 weeks old. Paired-pulse facilitation was augmented by pentobarbital, suggesting the presynaptic depression in the hippocampus. The behavioral exploration, tested by the open field test, showed the tendency of suppression. Exploration in the open-field test has shown to correlate to the hippocampal function, i.e. spatial memory and learning. These data suggest that administration of pentobarbital during a critical stage of brain development may result in functional deficits of hippocampus in adulthood. On the other hand, blood gas analysis during the pentobarbital anesthesia at 7PD induced the critical hypoxia and/or systemic acidosis via the respiratory depression. Given that neonatal hypoxia and/or systemic acidosis can cause the hippocampal dysfunction later on life, we have to take that bias into consideration when discussing the functional deficits induced by pentobarbital during a critical stage of neonatal brain development.

最近显示，在突触发生的峰值期间，常用的一般麻醉剂暴露于发育中的大鼠大脑会引发大脑中的广泛凋亡神经变性，尤其是在海马中。这可能会导致以后生活的持续学习/记忆缺陷。这项研究检查了对新生大鼠的pentobarbital（具有GABA能特性的麻醉剂）是否可以触发行为和电生理缺陷，在成年后期发生。大鼠在出生后的第7天（7pd）施用五边形（10 mg/kg，i.p.），在10-12周大时显示出海马长期增强（LTP）。配对的脉冲促进是由五边形的促进性增强的，表明海马的突触前抑郁症。通过开放式测试测试的行为探索显示了抑制的趋势。开放式测试中的探索已显示与海马功能（即空间记忆和学习）相关。这些数据表明，在大脑发育的关键阶段，五仅在脑发育的关键阶段可能会导致海马在成年期的功能缺陷。另一方面，在7pd的戊巴比妥麻醉期间的血液分析通过呼吸道抑郁症诱导了临界缺氧和/或全身性酸中毒。鉴于新生儿缺氧和/或全身性酸中毒会在以后的生活中引起海马功能障碍，因此在讨论新生儿大脑发育的关键阶段，我们必须考虑这种偏见。

项目成果

Low concentration of isoflurane induces paired-pulse facilitation in the hippocampal CA1 field: an in vivo study.

低浓度异氟烷在海马 CA1 区域诱导配对脉冲促进：一项体内研究。

• 发表时间: 2007

低濃度イソフルランはin vivoラット海馬CA1領域で短期シナプス可塑性を増強する

低浓度异氟烷增强体内大鼠海马 CA1 区短期突触可塑性

• 发表时间: 2007
• 作者: 土橋玉枝;田辺瀬良美;山本達郎;西野卓;青江知彦;Kaori Tachibana;Kaori Tachibana;橘 かおり
• 通讯作者: 橘 かおり

Isoflurane Bidirectionally Modulates the Paired-Pulse Responses in the Rat Hippocampal CA1 Field In Vivo

• DOI: 10.1213/01.ane.0000281433.73260.8d
• 发表时间: 2007-10
• 期刊: Anesthesia & Analgesia
• 影响因子: 5.7
• 作者: K. Tachibana;K. Takita;Toshikazu Hashimoto;M. Matsumoto;M. Yoshioka;Y. Morimoto

Isoflurane bidirectionally modulates the hippocampal paired-pulse responses in vivo.

异氟醚双向调节体内海马配对脉冲反应。

• 发表时间: 2007
• 作者: 土橋玉枝;田辺瀬良美;山本達郎;西野卓;青江知彦;Kaori Tachibana;Kaori Tachibana
• 通讯作者: Kaori Tachibana