Ketamine fails to protect against ischaemic neuronal necrosis in the rat

Ketamine is a dissociative anaesthetic known to be an N-methyl-D-aspartate receptor blocker. Since the NMDA excitatory receptor on neurones is implicated in ischaemic neuronal necrosis, ketamine might be expected to have a beneficial effect in cerebral hypoxia-ischaemia. Ketamine was tested in a rat model of forebrain ischaemia allowing 7 days recovery. Ketamine 6 mg kg-1 i.v. was administered 5-10 min before ischaemia in one group of rats, and ketamine 60 mg kg-1 day-1 i.m. for 3 days and 7 continuous days after ischaemia in two other groups. An additional group received ketamine 24 mg kg-1 i.v. before ischaemia and 120 mg kg-1 day-1 i.m. after ischaemia for 7 days continuously. Control rats received ischaemia but no treatment. The results were compared with untreated controls by neuropathological examination of the entire brain, sectioned subserially. There was no significant difference in necrosis between treated and untreated groups after any of the ketamine regimens. The findings demonstrate that systemically administered ketamine fails to protect the brain against hypoxic-ischaemic injury in the rat.