The neuronal toxicity of general anesthetics on the developing rat brain

最近的研究表明，在突触形成的高峰期，将常用的全身麻醉药暴露于发育中的大鼠大脑中，可以在大脑中引发广泛的神经细胞凋亡性变性，尤其是在海马区。这会导致在以后的生活中持续的学习/记忆缺陷。这项研究检测了戊巴比妥，一种具有GABA能特性的麻醉剂，给新生大鼠服用是否会引发成年后发生的行为和电生理缺陷。大鼠腹腔注射戊巴比妥钠(10和20 mg/kg)出生后第7天(7PD)表现出对10-12周龄大鼠海马长时程增强(LTP)的抑制。戊巴比妥可增强双脉冲易化作用，提示海马区存在突触前抑制。旷场实验测试的行为探索显示出抑制的趋势。旷场测试中的探索已被证明与海马体功能相关，即空间记忆和学习。这些数据表明，在大脑发育的关键阶段服用戊巴比妥可能会导致成年后海马体的功能缺陷。另一方面，7PD时戊巴比妥钠麻醉时的血气分析通过呼吸抑制导致严重缺氧和/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命中导致海马区功能障碍，我们在讨论戊巴比妥在新生儿大脑发育的关键阶段导致的功能障碍时，必须考虑到这一偏见。

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.