Department of Anesthesiology, University of Virginia Health System, Charlottesville, Virginia 22908, USA.
Curr Opin Anaesthesiol. 2011 Aug;24(4):395-9. doi: 10.1097/ACO.0b013e3283487247.
Due to increased frequency of surgical interventions, infants and young children are exposed to anesthesia, often repeatedly, during an extremely delicate period of brain development. We review new evidence that continues to challenge the safety of this practice.
In animal models, anesthesia impairs normal synapse development and sculpting, which are crucial elements of developmental synaptogenesis. This age-dependent phenomenon is caused in part by actin cytoskeleton disorganization and impaired dendritic branching. Recent evidence also suggests that developing glia are sensitive to anesthesia-induced toxicity, which is manifested as stunted growth, delayed maturation, and disturbed process formation. Newly published findings in nonhuman primates, which report long-lasting cognitive impairment, stress the potential seriousness of anesthesia-induced developmental neurotoxicity.
Although clinical importance remains to be substantiated, results to date do indicate that exposure of animals to general anesthesia during active synaptogenesis is most detrimental. Accordingly, it is essential to determine when synaptogenesis begins and ends in developing humans. It is also imperative that effective preventive techniques be developed so that existing anesthetics can be used with minimum risk of neurotoxic side-effects of anesthesia.
由于手术干预的频率增加,婴儿和幼儿在大脑发育极其脆弱的时期经常反复接受麻醉。我们回顾了新的证据,这些证据继续对这种做法的安全性提出挑战。
在动物模型中,麻醉会损害正常的突触发育和重塑,而突触发育和重塑是发育性突触发生的关键因素。这种年龄依赖性现象部分是由肌动蛋白细胞骨架的紊乱和树突分支受损引起的。最近的证据还表明,发育中的神经胶质细胞对麻醉诱导的毒性敏感,其表现为生长迟缓、成熟延迟和过程形成紊乱。新发表的在非人类灵长类动物中的研究结果报告了长期的认知障碍,强调了麻醉诱导的发育性神经毒性的潜在严重性。
尽管临床重要性仍有待证实,但迄今为止的结果确实表明,在活跃的突触发生期间,动物暴露于全身麻醉的影响最为不利。因此,确定人类发育中突触发生开始和结束的时间至关重要。此外,开发有效的预防技术也是至关重要的,以便在使用现有麻醉剂时,可以将神经毒性副作用的风险降到最低。