Department of Anesthesiology and Critical Care Medicine, University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany.
J Neurosurg Anesthesiol. 2010 Apr;22(2):144-54. doi: 10.1097/ANA.0b013e3181cb7cb8.
Postoperative cognitive dysfunction (POCD) is a known phenomenon occurring after anesthesia with volatile anesthetics (VA), such as isoflurane. Recent reports suggest that VA interact with neurodegenerative disease-associated proteins including compounds with pathogenic relevance in Alzheimer disease (AD) and induce processes that may be linked to AD neuropathology. Unfortunately, our present understanding of the exact anesthetics' molecular mechanisms of action, their side effects on the brain, and their catenation with AD pathology is still limited. The present study analyzes the differential proteome of the hippocampus immediately after and 3 days after a 3-hour 1 minimal alveolar concentration isoflurane anesthesia in rats. Differential 2-dimensional electrophoresis, mass spectrometry, and functional network mapping were used to identify and functionally classify 12 different hippocampal proteins, which were significantly regulated after isoflurane anesthesia (6 up-regulated, 11 down-regulated with P<0.01). Induction of differential expression ranged from 0.05 (25-fold down-regulation) to 4.4 (4.4-fold up-regulation). Ten proteins were regulated immediately after and 7 proteins 3 days after isoflurane exposure. The proteome displays isoflurane-responsive protein candidates, which have also been shown to play a role in AD. They were grouped according to their key biologic activities, which showed that isoflurane affects selected biologic processes including synaptic plasticity, stress response, detoxification, and cytoskeleton in early and late recovery phases after anesthesia. These processes are also affected in AD. Results are discussed in view of AD, the toxicity mechanisms of isoflurane as well as the implications for our present understanding and conduction of clinical anesthesia.
术后认知功能障碍（POCD）是一种已知的现象，发生在挥发性麻醉剂（VA），如异氟烷麻醉后。最近的报告表明，VA 与神经退行性疾病相关蛋白相互作用，包括在阿尔茨海默病（AD）中具有致病相关性的化合物，并诱导可能与 AD 神经病理学相关的过程。不幸的是，我们目前对确切的麻醉剂作用机制、它们对大脑的副作用以及它们与 AD 病理学的连锁反应的理解仍然有限。本研究分析了大鼠海马体在 3 小时 1 最小肺泡浓度异氟烷麻醉后立即和 3 天后的差异蛋白质组。差异 2-维电泳、质谱和功能网络映射用于鉴定和功能分类 12 种不同的海马体蛋白，这些蛋白在异氟烷麻醉后显著调节（6 个上调，11 个下调，P<0.01）。诱导差异表达的范围从 0.05（25 倍下调）到 4.4（4.4 倍上调）。10 种蛋白质在异氟烷暴露后立即和 7 种蛋白质 3 天后调节。蛋白质组显示异氟烷反应性蛋白候选物，这些蛋白也被证明在 AD 中发挥作用。根据其关键的生物活性进行分组，结果表明异氟烷影响包括突触可塑性、应激反应、解毒和细胞骨架在内的选定生物过程，这些过程在 AD 中也受到影响。结果从 AD、异氟烷的毒性机制以及对我们目前对临床麻醉的理解和实施的影响进行了讨论。
