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BMC Anesthesiology
Published in: BMC Anesthesiology 1/2018

Open Access 01-12-2018 | Research article

Ketamine exacerbates cortical neuroapoptosis under hyperoxic conditions by upregulating expression of the N-methyl-D-aspartate receptor subunit NR1 in the developing rat brain

Authors: Changyi Wu, Jun Wang, Xiangyang Guo, Ying Zhang

Published in: BMC Anesthesiology | Issue 1/2018

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Abstract

Background

Ketamine and hyperoxia are widely used in obstetric and pediatric settings. Either ketamine or hyperoxia has been reported to cause neuroapoptosis in the developing brain, and ketamine-induced neuronal apoptosis may involve a compensatory upregulation of the N-methyl-D-aspartate (NMDA) receptor NR1 subunit. This study investigated the impact of ketamine administration under hyperoxic conditions on cortical neuroapoptosis and NR1 subunit expression in the infant rat brain.

Methods

Male, 7-day-old rats were randomly allocated to four groups: control, ketamine, hyperoxia, and ketamine + hyperoxia (n = 18 per group). Rats in the control and ketamine groups received subcutaneous injections of either vehicle (saline) or ketamine (50 mg/kg) in room air (21% oxygen). The hyperoxia and ketamine + hyperoxia groups were exposed to 60% oxygen for 2 h after receiving saline or ketamine. Physiological parameters and arterial oxygen saturation were observed. Neuronal apoptosis and the expressions of NR1 mRNA and protein in the frontal cortex were also examined by transferase dUTP nick end labeling (TUNEL) assays, qPCR and Western blot, respectively.

Results

Ketamine alone had no effect on paO2 (P > 0.05), but pups exposed to hyperoxia or hyperoxia + ketamine had significantly greater paO2 values compared to control animals (P < 0.01). Animals exposed to ketamine and ketamine + hyperoxia showed higher apoptotic scores, mRNA and protein expression levels of NR1 than control animals (P < 0.01), and ketamine + hyperoxia caused a significantly greater increase than ketamine alone (P < 0.01).

Conclusions

These data suggest that ketamine administration under hyperoxic conditions exacerbates cortical neuroapoptosis in the developing brain, which may be closely associated with an enhancement in NMDA receptor NR1 subunit expression.
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Metadata
Title
Ketamine exacerbates cortical neuroapoptosis under hyperoxic conditions by upregulating expression of the N-methyl-D-aspartate receptor subunit NR1 in the developing rat brain
Authors
Changyi Wu
Jun Wang
Xiangyang Guo
Ying Zhang
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Anesthesiology / Issue 1/2018
Electronic ISSN: 1471-2253
DOI
https://doi.org/10.1186/s12871-018-0511-y

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