Department of Anesthesiology, University of Virginia Health System, Charlottesville, 22908, USA.
Curr Pharm Des. 2012;18(38):6225-31. doi: 10.2174/138161212803832380.
Normal cognitive development depends on the timely formation of meaningful neuronal circuitries. These, in turn, depend on the proper formation and functioning of neuronal synapses, which control the flow of information between neurons. The time period when synapse formation is most intense is referred to as synaptogenesis, coinciding with the peak of brain development. The latest animal and human research suggests that general anesthetics, which act by modulating the fine balance in neurotransmission, may disturb the fine homeostasis necessary for neuronal signaling, resulting in morphometric and functional disturbances of developing synapses in synaptogenesis. Anesthesia-induced impairment of synaptogenesis is strongly age-dependant. At a younger stage, neurons respond by decreasing synaptic densities. But in later development, they respond by overly upregulating synapse formation. Although a direct causal link between disturbed synaptogenesis and behavioral development is not yet established, several animal studies have confirmed that cognitive development of rodents and non-human primates could be permanently impaired after a single exposure to clinically-relevant general anesthetics. Clinical evidence is now beginning to emerge suggesting that very young children may be susceptible to anesthesia-induced impairment of behavioral development, cognitive in particular. This review will summarize some of the presently available evidence regarding anesthesia-induced effects on developmental synaptogenesis and intellectual functioning.
正常的认知发展依赖于有意义的神经元回路的及时形成。这些反过来又依赖于神经元突触的正确形成和功能，神经元突触控制着神经元之间的信息流动。突触形成最强烈的时期被称为突触发生，与大脑发育的高峰期相吻合。最新的动物和人类研究表明，全身麻醉通过调节神经递质的精细平衡起作用，可能会干扰神经元信号所需的精细动态平衡，导致突触发生过程中发育中的突触出现形态和功能紊乱。麻醉诱导的突触发生障碍强烈地依赖于年龄。在更年轻的阶段，神经元通过减少突触密度来做出反应。但在后期发育中，它们通过过度上调突触形成来做出反应。尽管干扰突触发生与行为发展之间的直接因果关系尚未建立，但几项动物研究证实，单次接触临床相关的全身麻醉后，啮齿动物和非人类灵长类动物的认知发育可能会受到永久性损害。目前开始出现临床证据表明，非常年幼的儿童可能容易受到麻醉诱导的行为发育障碍的影响，特别是认知方面。这篇综述将总结一些关于麻醉对发育中突触发生和智力功能影响的现有证据。
