Choudhury Divya, Autry Anita E, Tolias Kimberley F, Krishnan Vaishnav
Department of BioSciences, Rice University, Houston, TX, United States.
Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY, United States.
Front Neurosci. 2021 Sep 10;15:672526. doi: 10.3389/fnins.2021.672526. eCollection 2021.
Ketamine, a non-competitive 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.
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年代以来一直作为静脉麻醉剂用于临床。最近，氯胺酮因其快速的抗抑郁作用而受到关注，并正在积极探索其作为多种神经精神综合征的治疗方法。在模型系统中，氯胺酮似乎表现出神经毒性和神经保护特性的组合，这取决于具体情况。在神经发育窗口期应用麻醉剂量时，氯胺酮会导致炎症、自噬、凋亡，并提高活性氧水平。同时，亚麻醉剂量的氯胺酮是多种平行神经营养信号级联的强大激活剂，具有神经保护作用，且并不总是依赖于NMDAR。在此，我们总结了一系列临床前研究的结果，这些结果突出了氯胺酮调节的细胞内信号通路的复杂情况，并将这种药物的神经保护和神经毒性特征进行了对比。
