Neuroprotection of S(+) ketamine isomer in global forebrain ischemia

dThe non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist ketami ne can block the action of excitotoxic amino acids in the central nervous s ystem. S(+) ketamine has a 2-3 times higher anesthetic potency compared wit h the ketamine-racemate and also shows a higher neuroprotective efficacy in vitro. To determine the neuroprotective activity of S(+) ketamine compared with its R(-) stereoisomer in vivo, we examined the functional and neurohi stological outcome in rats treated 15 min after global forebrain ischemia w ith S(+) ketamine in different dosages compared with R(-) ketamine. Influen ce of the treatment on regional cerebral blood flow (rCBF) and cortical oxy gen saturation (HbO(2)) was monitored over 1 h after the ischemia using las er doppler flowmetry and microphotospectrometry respectively. Sixty and nin ety mg/kg of S(+) ketamine but not R(-) ketamine significantly reduced neur onal cell loss in the cortex compared with the saline treated group. No sig nificant neuroprotection was observed in the hippocampus. Although no signi ficant change in rCBF was found, S(S) ketamine restored the cortical HbO(2) to preischemic values. These results indicate that S(+) ketamine in higher dosages can reduce neuronal damage in the cortex after cerebral ischemia, possibly by improving the ratio of oxygen supply to consumption in the post ischemic tissue. (C) 2001 Elsevier Science B.V. All rights reserved.