From the Department of Anesthesiology (L.G.A.), Department of Neuroscience (M.L.S.), Departments of Neuroscience, Anesthesiology, and Geriatrics and Palliative Medicine (M.G.B.), the Icahn School of Medicine at Mount Sinai, New York, New York; and the Department of Biomedical Services, University of Oxford, Oxford, United Kingdom (K.L.M.).
Anesthesiology. 2015 Jan;122(1):87-95. doi: 10.1097/ALN.0000000000000477.
Neonatal exposure to general anesthetics may pose significant neurocognitive risk. Human epidemiological studies demonstrate higher rates of learning disability among children with multiple, but not single, exposures to anesthesia. The authors employ a rat model to provide a histological correlate for these population-based observations. The authors examined long-term differences in hippocampal synaptic density, mitochondrial density, and dendritic spine morphology.
Twenty male rat pups (n = 5/condition) were exposed to 2.5% sevoflurane under one of four conditions: single 2-h exposure on postnatal day 7 (P7); single 6-h exposure on P7; repeated 2-h exposures on P7, P10, and P13 for a cumulative 6 h of general anesthetics; or control exposure to 30% oxygen on P7, P10, and P13.
Repeated exposure to general anesthetics resulted in greater synaptic loss relative to a single 2-h exposure (P < 0.001). The magnitude of synaptic loss induced by three 2-h exposures (1.977 ± 0.040 μm [mean ± SEM]) was more profound than that of a single 6-h exposure (2.280 ± 0.045 μm, P = 0.022). Repeated exposures did not alter the distribution of postsynaptic density length, indicating a uniform pattern of loss across spine types. In contrast, mitochondrial toxicity was best predicted by the cumulative duration of exposure. Relative to control (0.595 ± 0.017), both repeated 2-h exposures (0.479 ± 0.015) and a single 6-h exposure (0.488 ± 0.013) were associated with equivalent reductions in the fraction of presynaptic terminals containing mitochondria (P < 0.001).
This suggests a "threshold effect" for general anesthetic-induced neurotoxicity, whereby even brief exposures induce long-lasting alterations in neuronal circuitry and sensitize surviving synapses to subsequent loss.
新生儿接触全身麻醉可能会带来显著的神经认知风险。人类流行病学研究表明，多次而非单次接触麻醉的儿童学习障碍发生率更高。作者采用大鼠模型为这些基于人群的观察结果提供组织学相关性。作者检查了海马突触密度、线粒体密度和树突棘形态的长期差异。
20 只雄性幼鼠（n = 5/条件）在以下四种条件之一中暴露于 2.5%七氟醚下：第 7 天（P7）单次 2 小时暴露；P7 单次 6 小时暴露；P7、P10 和 P13 重复 2 小时暴露，总共 6 小时全身麻醉；或 P7、P10 和 P13 暴露于 30%氧气。
重复接触全身麻醉导致的突触丢失比单次 2 小时暴露更为严重（P < 0.001）。三次 2 小时暴露（1.977 ± 0.040 μm [平均值 ± 标准误]）引起的突触丢失程度比单次 6 小时暴露（2.280 ± 0.045 μm，P = 0.022）更严重。重复暴露并未改变突触后密度长度的分布，表明棘突类型的丢失具有均匀的模式。相比之下，线粒体毒性最好由暴露的累积持续时间来预测。与对照（0.595 ± 0.017）相比，重复 2 小时暴露（0.479 ± 0.015）和单次 6 小时暴露（0.488 ± 0.013）均与包含线粒体的突触前末端分数相等的减少相关（P < 0.001）。
这表明全身麻醉诱导的神经毒性存在“阈值效应”，即即使是短暂的暴露也会导致神经元回路的持久改变，并使存活的突触对随后的丢失敏感。
