The individual and combined neuroprotective effects of propofol and ketamine on rat mixed cortical cultures exposed to oxygen-glucose deprivation-reperfusion injury

Abstract

Propofol and ketamine are have been known to have neuroprotective effects. However, the effect of combined therapy with these 2 drugs is not well known with in vitro model. This study was conducted to determine whether combined administration of propofol and ketamine could have additive effects in protecting cortical neurons from the oxygen-glucose deprivation (ischemia) - reoxygenation (reperfusion) injury. Methods: Thirteen-day-old primary mixed cortical cultures were exposed to a 5-min combined oxygen-glucose deprivation (OGD, in vitro ischemia model), followed by 2 hr of reperfusion. Propofol (1, 10, 25, 50, 100μM) and ketamine (1, 2.5, 5, 10, 50μM) were added as alone or combination from the initiation of the OGD injury to the end of the reperfusion periods. The survived cells were counted using trypan-blue staining. The data were converted to the cell death rate. Statistical analysis was done by oneway-ANOVA tests and Bonferroni's test. P ＜ 0.05 was considered as statistically significant. Results: OGD-reperfusion demonstrated about a 70% cell death rate. 5−50μM of ketamine decreased the cell death rate compared with the no drug treated group (P ＜ 0.05). 10−100μM of propofol decreased the cell death rate compared with the no drug treated group (P ＜ 0.05). Combined administration of ketamine 2.5μM + propofol 50, 100μM, ketamine 10μM + propofol 100μM and propofol 1, 10μM + ketamine 5, 10μM decreased cell death rate compared with the same dosage of propofol or ketamine alone treated group (P ＜ 0.05). Conclusions: Propofol or ketamine demonstrated neuroprotective effects. And, combined administration ofpropofol and ketamine demonstrated additive neuroprotective effects against OGD-reperfusion injury.