Open Access

Effects of ketamine on neurogenesis, extracellular matrix homeostasis and proliferation in hypoxia‑exposed HT22 murine hippocampal neurons

  • Authors:
    • Thomas Pichl
    • Titus Keller
    • Christoph Hünseler
    • Bernhard Roth
    • Ruth Janoschek
    • Sarah Appel
    • Eva Hucklenbruch‑Rother
  • View Affiliations

  • Published online on: July 17, 2020     https://doi.org/10.3892/br.2020.1330
  • Article Number: 23
  • Copyright: © Pichl et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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 vitro 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 (neuronal growth factor and syndecan 1), extracellular matrix homeostasis (matrix‑metalloproteinase 2 and 9, tenascin C and tenascin R) or proliferation markers (Ki67 and proliferating cell nuclear antigen) 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 in vitro 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.
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October-2020
Volume 13 Issue 4

Print ISSN: 2049-9434
Online ISSN:2049-9442

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Spandidos Publications style
Pichl T, Keller T, Hünseler C, Roth B, Janoschek R, Appel S and Hucklenbruch‑Rother E: Effects of ketamine on neurogenesis, extracellular matrix homeostasis and proliferation in hypoxia‑exposed HT22 murine hippocampal neurons. Biomed Rep 13: 23, 2020
APA
Pichl, T., Keller, T., Hünseler, C., Roth, B., Janoschek, R., Appel, S., & Hucklenbruch‑Rother, E. (2020). Effects of ketamine on neurogenesis, extracellular matrix homeostasis and proliferation in hypoxia‑exposed HT22 murine hippocampal neurons. Biomedical Reports, 13, 23. https://doi.org/10.3892/br.2020.1330
MLA
Pichl, T., Keller, T., Hünseler, C., Roth, B., Janoschek, R., Appel, S., Hucklenbruch‑Rother, E."Effects of ketamine on neurogenesis, extracellular matrix homeostasis and proliferation in hypoxia‑exposed HT22 murine hippocampal neurons". Biomedical Reports 13.4 (2020): 23.
Chicago
Pichl, T., Keller, T., Hünseler, C., Roth, B., Janoschek, R., Appel, S., Hucklenbruch‑Rother, E."Effects of ketamine on neurogenesis, extracellular matrix homeostasis and proliferation in hypoxia‑exposed HT22 murine hippocampal neurons". Biomedical Reports 13, no. 4 (2020): 23. https://doi.org/10.3892/br.2020.1330