Universität zu Köln

Pichl, Thomas, Keller, Titus, Huenseler, Christoph, Roth, Bernhard, Janoschek, Ruth, Appel, Sarah and Hucklenbruch-Rother, Eva (2020). Effects of ketamine on neurogenesis, extracellular matrix homeostasis and proliferation in hypoxia-exposed HT22 murine hippocampal neurons. Biomed. Rep., 13 (4). ATHENS: SPANDIDOS PUBL LTD. ISSN 2049-9442

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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 mu M 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Pichl, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Keller, Titus UNSPECIFIED UNSPECIFIED UNSPECIFIED Huenseler, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Roth, Bernhard UNSPECIFIED UNSPECIFIED UNSPECIFIED Janoschek, Ruth UNSPECIFIED UNSPECIFIED UNSPECIFIED Appel, Sarah UNSPECIFIED UNSPECIFIED UNSPECIFIED Hucklenbruch-Rother, Eva UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-317808
DOI:	10.3892/br.2020.1330
Journal or Publication Title:	Biomed. Rep.
Volume:	13
Number:	4
Date:	2020
Publisher:	SPANDIDOS PUBL LTD
Place of Publication:	ATHENS
ISSN:	2049-9442
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language WHITE-MATTER INJURY; CELL-DEATH; INDUCED TOXICITY; NMDA RECEPTOR; NEURODEGENERATION; NEUROPROTECTION; PCNA; NEUROTOXICITY; DEGENERATION; IMPAIRMENT Multiple languages Medicine, Research & Experimental Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/31780