Jiang Sufang, Li Xuze, Jin Wei, Duan Xiaofeng, Bo Lijun, Wu Jiangli, Zhang Rui, Wang Ying, Kang Rongtian, Huang Lining
Department of Anesthesiology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China.
Department of Neurology, Hebei General Hospital, Shijiazhuang, Hebei Province, China.
Neurosci Lett. 2018 Apr 23;673:122-131. doi: 10.1016/j.neulet.2018.02.051. Epub 2018 Mar 1.
Ketamine, a non-competitive N-methyl d-aspartate (NMDA) receptor antagonist, is widely used in pediatric clinical practice. However, prolonged exposure to ketamine results in widespread anesthetic neurotoxicity and long-term neurocognitive deficits. The molecular mechanisms that underlie this important event are poorly understood. We investigated effects of anesthetic ketamine on neuroapoptosis and further explored role of NMDA receptors in ketamine-induced neurotoxicity. Here we demonstrate that ketamine induces activation of cell cycle entry, resulting in cycle-related neuronal apoptosis. On the other hand, ketamine administration alters early and late apoptosis of cultured hippocampus neurons by inhibiting PKC/ERK pathway, whereas excitatory NMDA receptor activation reverses these effects. Ketamine-induced neurotoxicity blocked by NMDA is mediated through activation of PKC/ERK pathway in developing hippocampal neurons.
氯胺酮是一种非竞争性N-甲基-D-天冬氨酸（NMDA）受体拮抗剂，在儿科临床实践中被广泛使用。然而，长期接触氯胺酮会导致广泛的麻醉性神经毒性和长期的神经认知缺陷。导致这一重要现象的分子机制尚不清楚。我们研究了麻醉剂氯胺酮对神经细胞凋亡的影响，并进一步探讨了NMDA受体在氯胺酮诱导的神经毒性中的作用。在此我们证明，氯胺酮诱导细胞周期进入的激活，导致与周期相关的神经元凋亡。另一方面，给予氯胺酮通过抑制PKC/ERK通路改变培养海马神经元的早期和晚期凋亡，而兴奋性NMDA受体激活可逆转这些效应。NMDA阻断的氯胺酮诱导的神经毒性是通过发育中的海马神经元中PKC/ERK通路的激活介导的。
