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Ketamine disturbs normal neurogenesis in cultured rat cortical neural stem progenitor cells
Author(s) -
Dong Chaoxuan,
Rovnaghi Cynthia S,
Anand K.J.S.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1004.2
Subject(s) - neurogenesis , ketamine , neural stem cell , progenitor cell , nmda receptor , embryonic stem cell , apoptosis , stem cell , biology , pharmacology , microbiology and biotechnology , andrology , chemistry , receptor , neuroscience , medicine , biochemistry , gene
Ketamine, an N‐Methyl‐D‐aspartate (NMDA) receptor antagonist, is widely used for anesthesia, analgesia or sedation in pediatric clinical settings. Fate of neural stem stem/progenitor cells (NSPCs) determines normal development of embryonic brains. Current studies indicate that ketamine damages the development of developing brains through inducing neuronal death. However, effects of ketamine on NSPCs have not been detected systemically. This study explored time‐ and dose‐dependent effects of ketamine on cell death and neurogenesis of cultured rat cortical NSPCs. In this study, NSPCs were isolated from embryos of timed‐pregnant SD rats, were treated by varying concentrations of ketamine (0, 1, 10, 20, 20, 50, and 100 μM) for 24 hours or were exposed to 10 μM of ketamine for different durations (0, 1/2, 1, 2, 4, 6, 8, 10, 12, 18, 24, and 48 hrs). Treated cultures were immunostained to detect apoptosis (anti‐cleaved caspase‐3), proliferation (anti‐BrdU & anti‐Ki67), and neuronal differentiation (anti‐Tuj‐1). Additionally, LDH assay was utilized to detect necrosis in cultures. Results showed that ketamine (<100 μM) did not induce apoptosis and necrosis in NSPCs critically. But, ketamine significantly reduced proliferation and promoted neuronal differentiation in rat cortical NSPCs in dose/time dependent manners. This study suggests that ketamine exposure may result in potential abnormalities of cortical structure and functions in developing rat brains.