Raper Jessica, Alvarado Maria C, Murphy Kathy L, Baxter Mark G
From the Division of Developmental and Cognitive Neuroscience, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia (J.R., M.C.A.); Department of Experimental Psychology, Oxford University, Oxford, United Kingdom (K.L.M.); and Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York (M.G.B.).
Anesthesiology. 2015 Nov;123(5):1084-92. doi: 10.1097/ALN.0000000000000851.
Retrospective studies in humans have shown a higher prevalence of learning disabilities in children that received multiple exposures to general anesthesia before the age of 4 yr. Animal studies, primarily in rodents, have found that postnatal anesthetic exposure causes neurotoxicity and neurocognitive deficits in adulthood. The authors addressed the question of whether repeated postnatal anesthetic exposure was sufficient to cause long-term behavioral changes in a highly translationally relevant rhesus monkey model, allowing study of these variables against a background of protracted nervous system and behavioral development.
Rhesus monkeys of both sexes underwent either three 4-h exposures to sevoflurane anesthesia (anesthesia group n = 10) or brief maternal separations (control group n = 10) on postnatal day 6 to 10 that were repeated 14 and 28 days later. Monkeys remained with their mothers in large social groups at all times except for overnight observation after each anesthetic/control procedure. At 6 months of age, each monkey was tested on the human intruder paradigm, a common test for emotional reactivity in nonhuman primates.
The frequency of anxiety-related behaviors was significantly higher in monkeys that were exposed to anesthesia as neonates as compared with controls: anesthesia 11.04 ± 1.68, controls 4.79 ± 0.77, mean ± SEM across all stimulus conditions.
Increased emotional behavior in monkeys after anesthesia exposure in infancy may reflect long-term adverse effects of anesthesia.
对人类的回顾性研究表明，4岁前多次接受全身麻醉的儿童中学习障碍的患病率较高。主要以啮齿动物为对象的动物研究发现，出生后接触麻醉剂会导致成年期神经毒性和神经认知缺陷。作者探讨了在高度具有转化相关性的恒河猴模型中，出生后反复接触麻醉剂是否足以导致长期行为改变的问题，从而能够在长期神经系统和行为发育的背景下研究这些变量。
在出生后第6至10天，雌雄恒河猴接受三次4小时的七氟醚麻醉暴露（麻醉组n = 10）或短暂的母婴分离（对照组n = 10），并在14天和28天后重复进行。除了每次麻醉/对照程序后的过夜观察外，猴子始终与它们的母亲一起生活在大型社会群体中。在6个月大时，对每只猴子进行人类入侵者范式测试，这是一种对非人类灵长类动物情绪反应性的常见测试。
与对照组相比，新生儿期接受麻醉暴露的猴子中与焦虑相关行为的频率显著更高：在所有刺激条件下，麻醉组为11.04±1.68，对照组为4.79±0.77，均值±标准误。
婴儿期麻醉暴露后猴子情绪行为增加可能反映了麻醉的长期不良影响。
