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Ketamine exposure during embryogenesis inhibits cellular proliferation in rat fetal cortical neurogenic regions
Author(s) -
Dong C.,
Rovnaghi C. R.,
Anand K. J. S.
Publication year - 2016
Publication title -
acta anaesthesiologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.738
H-Index - 107
eISSN - 1399-6576
pISSN - 0001-5172
DOI - 10.1111/aas.12689
Subject(s) - ketamine , neurogenesis , fetus , medicine , cortex (anatomy) , subventricular zone , neurotoxicity , immunostaining , pharmacology , endocrinology , anesthesia , neural stem cell , neuroscience , biology , immunohistochemistry , toxicity , microbiology and biotechnology , stem cell , pregnancy , genetics
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.