Pichl Thomas, Keller Titus, Hünseler Christoph, Roth Bernhard, Janoschek Ruth, Appel Sarah, Hucklenbruch-Rother Eva
Department of Pediatrics and Adolescent Medicine, University of Cologne, Faculty of Medicine and University Hospital, D-50931 Cologne, Germany.
Biomed Rep. 2020 Oct;13(4):23. doi: 10.3892/br.2020.1330. Epub 2020 Jul 17.
Ketamine is a widely used drug in pediatric anesthesia, and both neurotoxic and neuroprotective effects have been associated with its use. There are only a few studies to date which have examined the effects of ketamine on neurons under hypoxic conditions, which may lead to severe brain damage and poor neurocognitive outcomes in neonates. In the present study, the effects of ketamine on cellular pathways associated with neurogenesis, extracellular matrix homeostasis and proliferation were examined in hypoxia-exposed neurons. Differentiated HT22 murine hippocampal neurons were treated with 1, 10 and 20 µM ketamine and cultured under hypoxic or normoxic conditions for 24 h followed by quantitative PCR analysis of relevant candidate genes. Ketamine treatment did not exert any notable effects on the mRNA expression levels of markers of neurogenesis ( and ), extracellular matrix homeostasis ( and 9, and ) or proliferation markers ( and ) compared with the respective untreated controls. However, there was a tendency towards downregulation of multiple cellular markers under hypoxic conditions and simultaneous ketamine treatment. No dose-dependent association was found in the ketamine treated groups for genetic markers of neurogenesis, extracellular matrix homeostasis or proliferation. Based on the results, ketamine may have increased the vulnerability of hippocampal neurons to hypoxia, independent of the dose. The results of the present study contribute to the ongoing discussion on the safety concerns around ketamine use in pediatric clinical practice from a laboratory perspective.
氯胺酮是儿科麻醉中广泛使用的药物，其使用既与神经毒性有关，也与神经保护作用有关。迄今为止，只有少数研究探讨了氯胺酮在缺氧条件下对神经元的影响，而缺氧可能导致新生儿严重脑损伤和不良神经认知结果。在本研究中，研究了氯胺酮对缺氧暴露神经元中与神经发生、细胞外基质稳态和增殖相关的细胞途径的影响。将分化的HT22小鼠海马神经元用1、10和20 μM氯胺酮处理，并在缺氧或常氧条件下培养24小时，随后对相关候选基因进行定量PCR分析。与各自未处理的对照相比，氯胺酮处理对神经发生标志物（和）、细胞外基质稳态标志物（和9、和）或增殖标志物（和）的mRNA表达水平没有产生任何显著影响。然而，在缺氧条件下同时进行氯胺酮处理时，多种细胞标志物有下调的趋势。在氯胺酮处理组中，未发现神经发生、细胞外基质稳态或增殖的遗传标志物存在剂量依赖性关联。根据结果，氯胺酮可能增加了海马神经元对缺氧的易感性，与剂量无关。本研究结果从实验室角度为儿科临床实践中氯胺酮使用的安全性问题的持续讨论做出了贡献。
