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Open Access Ketamine and propofol in combination induce neuroapoptosis and down-regulate the expression of N-methyl-D-aspartate glutamate receptor NR2B subunit in rat forebrain culture

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Background and objective: Ketamine has always been used in combination with propofol in paediatric patients. Ketamine interacts with N-methyl-D-aspartate glutamate receptor to exert its biologic actions. The NMDA receptor NR2B subunit is expressed at nearly adult level during forebrain development in the cortex and considered as the major type of functional NMDA receptor in the central nervous system. This study aimed to investigate whether ketamine or ketamine in combination with propofol induces apoptosis and regulates the expression level of NMDA receptor NR2B subunit in rat forebrain culture. Methods: Rat primary forebrain cultures were exposed to different concentrations of ketamine (1 μM, 10 μM, 20 μM) or 20 μM ketamine plus 5 μM propofol on the 6th day for 12 h. Cell viability was examined by 3-(4,5-dimethylthiazol2-yl)-2,5-diphenyltetrazolium bromide assay. Caspase-3 activity was measured and apoptotic morphology was examined by Hoechst dye staining. The expression of NMDA receptor NR2B subunit at mRNA and protein level was determined by qPCR and Western blot, respectively. Results: Ketamine (10 μM and 20 μM) or 20 μM ketamine plus 5 μM propofol resulted in a significant decrease in cell viability, and a significant increase in caspase-3 activity and apoptosis of primary rat forebrain culture. The expression of NMDA receptor NR2B subunit at both mRNA and protein levels were down-regulated by administration of ketamine (1 μM, 10 μM and 20 μM) and 20 μM ketamine plus 5 μM propofol. Conclusion: Ketamine (10 μM or 20 μM) alone or in combination with propofol (20 μM ketamine plus 5 μM propofol) induces neuroapoptosis and down-regulates of NMDA receptor NR2B subunit in rat forebrain culture.

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Document Type: Research Article

Publication date: October 1, 2011

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  • Pharmazie is a leading journal in the field of pharmaceutical sciences. As a peer-reviewed scientific journal, Pharmazie is regularly indexed in the relevant databases like Web of science, Journal Citation Reports and many others. The journal is open for submissions from the whole spectrum of pharnaceutical sciences including Pharmaceutical Chemistry, Experimental and Clinical Pharmacology, Drug Analysis, Pharmaceutics, Pharmaceutical Biology, Clinical Pharmacy etc.
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