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Acta Anaesthesiol Scand. 2016 May;60(5):579-87. doi: 10.1111/aas.12689. Epub 2016 Jan 29.

Ketamine exposure during embryogenesis inhibits cellular proliferation in rat fetal cortical neurogenic regions.

Dong C1,2,3, Rovnaghi CR2,3, Anand KJ2,3,4.

Author information

1
Department of Anesthesiology, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
2
Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN, USA.
3
Department of Anatomy and Neurobiology, Neuroscience Institute, University of Tennessee Health Science Center, Memphis, TN, USA.
4
Department of Pediatrics, Stanford University School of Medicine, Palo Alto, CA, USA.

Abstract

BACKGROUND:

Developmental neurotoxicity of ketamine, an N-methyl-D-aspartate receptor antagonist, must be considered due to its widespread uses for sedation/analgesia/anesthesia in pediatric and obstetric settings. Dose-dependent effects of ketamine on cellular proliferation in the neurogenic regions of rat fetal cortex [ventricular zone (VZ) and subventricular zone (SVZ)] were investigated in this in vivo study.

METHODS:

Timed-pregnant Sprague-Dawley rats at embryonic day 17 (E17) were given with different doses of ketamine intraperitoneally (0, 1, 2, 10, 20, 40, and 100 mg/kg). Proliferating cells in the rat fetal brains were labeled by injecting 100 mg/kg of 5-bromo-2'-deoxyuridine (BrdU) intraperitoneally. BrdU-labeled cells were detected by immunostaining methods. The numbers of BrdU-positive cells in VZ and SVZ of rat fetal cortex were employed to quantify proliferation in the developing rat cortex.

RESULTS:

Ketamine dose-dependently reduced the number of BrdU-positive cells in VZ (P < 0.001) and SVZ (P < 0.001) of the rat fetal cortex. SVZ showed greater susceptibility to ketamine-induced reduction of proliferation in rat fetal cortex, occurring even at clinically relevant doses (2 mg/kg).

CONCLUSION:

These data suggest that exposure to ketamine during embryogenesis can dose-dependently inhibit the cellular proliferation in neurogenic regions of the rat fetal cortex.

PMID:
26822861
PMCID:
PMC4821784
DOI:
10.1111/aas.12689
[Indexed for MEDLINE]
Free PMC Article

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