Abstract:

Objective    To explore the effect of long-term administration of ketamine on cerebrovascular(communicating branches of the cerebral arterial circle) pathology and nicotinamide adenine dinucleotide phosphate(NADPH) oxidase activation in cynomolgus monkeys. Methods    Twelve male monkeys were randomly divided into the experimental group  and the control group, six in each group. Monkeys in the experimental group were injected with ketamine at 1mg/ kg, while the control group received normal saline. 6 months later, the monkeys were sacrificed. Cerebrovascular pathology was observed by HE staining. Reactive oxygen species (ROS) level was expressed as the decrement of H2O2 with the biochemical method.  NADPH oxidase activation was observed by immunohistochemistry and Western blot. Results    The experimental group showed a significant increase in NADPH oxidase activation and ROS level compared with the control group. Thrombus and inflammatory cells infiltration were observed in the cerebrovascular tissue of the experimental group. Conclusion    Long-term administration of ketamine up-regulate NADPH oxidase level  leading to cerebrovascular pathological changes.

Key words: Ketamine; Macaca fascicularis; NADPH oxidase; Reactive oxygen species