Effect of propofol on ketamine-induced cognitive dysfunction in aged rats

Abstract

Objective To investigate the effect of propofol on ketamine-induced cognitive dysfunction and neuronal apoptosis in hippocampus in aged rats. Methods Thirty-two male SD rats aged 18-24 months weighing 380-470 g were randomly divided into 4 groups ( n = 8 each) :control group (group C);propofol group (group P);ketamine group (group K) and propofol + ketamine group (group PK). Propofol 30 mg·kg-1·h-1 or/and ketamine 40 mg· kg-1·h-1 were infused for 2 h once a day for 7 consecutive days. After the last day of drug administration cognitive function was assessed using Morris water maze (escape latency and the number of animals' swimming across the platform). The animals were sncrificed after water naze test and their hippocampi were removed for determination of neuronal apoptosis (by TUNEL) and caspase-3 expression (by immuno-histochemistry) in hippocampal CA1 region. Results There was no significant difference in escape latency and the number of the animals,swimming across the platform, the neuronal apoptotic rate (the number of apoptotic neurons/the number of total neurons) and caspase-3 expression between group C and P. In group K and PK the escape latency was prolonged,the number of animals' swimming across the platform was decreased, neuronal apoptotic rate increased and the caspase-3 expression up-regulated as compared with group C. The ketamine-induced changes were significantly attenuated by coadministration of propofol in group PK. Conclusion Coadministration of propofol can ameliorate ketamine-induced cognitive dysfunction and hippocampal neuronal apoptosis. Key words: Propofol; Ketamine; Cognition disorders; Aged