Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits
Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits
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DOI：
10.1523/jneurosci.23-03-00876.2003
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发表时间：
2003-02-01
影响因子：
5.3
通讯作者：
Wozniak, DF
中科院分区：
文献类型：
--
作者：
Jevtovic-Todorovic, V;Hartman, RE;Wozniak, DF
最近，研究表明，在突触发生期间，发育中的大脑暴露于阻断NMDA谷氨酸受体的药物或增强GABA（A）受体的药物可引发广泛的凋亡性神经变性。目前使用的所有全身麻醉剂都具有NMDA受体阻断或GABA（A）受体增强特性。为了诱导或维持手术麻醉平面，儿科或产科医学中的常见做法是联合使用这两类药物。因此，问题是这种做法是否会在发育中的人脑中引起凋亡性神经变性的重大风险。为了开始解决这个问题，我们给7-d龄的幼鼠联合使用儿科麻醉常用的药物（咪达唑仑、一氧化二氮和异氟烷），剂量足以维持手术麻醉平面6小时，并观察到这会导致发育中的大脑中广泛的凋亡性神经变性、海马突触功能缺陷和持续的记忆/学习障碍。
Recently it was demonstrated that exposure of the developing brain during the period of synaptogenesis to drugs that block NMDA glutamate receptors or drugs that potentiate GABA(A) receptors can trigger widespread apoptotic neurodegeneration. All currently used general anesthetic agents have either NMDA receptor-blocking or GABA(A) receptor-enhancing properties. To induce or maintain a surgical plane of anesthesia, it is common practice in pediatric or obstetrical medicine to use agents from these two classes in combination. Therefore, the question arises whether this practice entails significant risk of inducing apoptotic neurodegeneration in the developing human brain. To begin to address this problem, we have administered to 7-d-old infant rats a combination of drugs commonly used in pediatric anesthesia (midazolam, nitrous oxide, and isoflurane) in doses sufficient to maintain a surgical plane of anesthesia for 6 hr, and have observed that this causes widespread apoptotic neurodegeneration in the developing brain, deficits in hippocampal synaptic function, and persistent memory/learning impairments.