Ketamine: Neuroprotective or Neurotoxic?
Ketamine: Neuroprotective or Neurotoxic?
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DOI：
10.3389/fnins.2021.672526
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发表时间：
2021
影响因子：
4.3
通讯作者：
Krishnan V
中科院分区：
文献类型：
--
作者：
Choudhury D;Autry AE;Tolias KF;Krishnan V
氯胺酮是一种非竞争性N-甲基-D-天冬氨酸受体（NMDAR）拮抗剂，自20世纪70年代以来一直被临床用作静脉麻醉剂。最近，氯胺酮因其快速的抗抑郁作用而受到关注，并正在积极探索作为广泛的神经精神综合征的治疗方法。在模型系统中，氯胺酮似乎显示出环境依赖性的神经毒性和神经保护特性的组合。在神经发育窗口期间应用的麻醉剂量下，氯胺酮有助于炎症、自噬、细胞凋亡，并提高活性氧水平。同时，亚麻醉剂量氯胺酮是多个平行神经营养信号级联的强有力激活剂，具有不总是NMDAR依赖性的神经保护作用。在这里，我们总结了一系列临床前研究的结果，这些研究突出了氯胺酮调节的细胞内信号通路的复杂景观，并将这种药物的神经保护和神经毒性特征进行了对比。
Ketamine, a non-competitive N-methyl-D-aspartate receptor (NMDAR) antagonist, has been employed clinically as an intravenous anesthetic since the 1970s. More recently, ketamine has received attention for its rapid antidepressant effects and is actively being explored as a treatment for a wide range of neuropsychiatric syndromes. In model systems, ketamine appears to display a combination of neurotoxic and neuroprotective properties that are context dependent. At anesthetic doses applied during neurodevelopmental windows, ketamine contributes to inflammation, autophagy, apoptosis, and enhances levels of reactive oxygen species. At the same time, subanesthetic dose ketamine is a powerful activator of multiple parallel neurotrophic signaling cascades with neuroprotective actions that are not always NMDAR-dependent. Here, we summarize results from an array of preclinical studies that highlight a complex landscape of intracellular signaling pathways modulated by ketamine and juxtapose the somewhat contrasting neuroprotective and neurotoxic features of this drug.
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