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

Brain Res. 2001 Jun 22;904(2):245-51. doi: 10.1016/s0006-8993(01)02465-9.

Abstract

The non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist ketamine can block the action of excitotoxic amino acids in the central nervous system. S(+) ketamine has a 2-3 times higher anesthetic potency compared with 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 neurohistological outcome in rats treated 15 min after global forebrain ischemia with S(+) ketamine in different dosages compared with R(-) ketamine. Influence of the treatment on regional cerebral blood flow (rCBF) and cortical oxygen saturation (HbO2) was monitored over 1 h after the ischemia using laser doppler flowmetry and microphotospectrometry respectively. Sixty and ninety mg/kg of S(+) ketamine but not R(-) ketamine significantly reduced neuronal cell loss in the cortex compared with the saline treated group. No significant neuroprotection was observed in the hippocampus. Although no significant change in rCBF was found, S(+) ketamine restored the cortical HbO2 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 postischemic tissue.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / metabolism
  • Cell Death / drug effects
  • Cell Death / physiology
  • Dose-Response Relationship, Drug
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Amino Acid Antagonists / therapeutic use
  • Ketamine / pharmacology*
  • Ketamine / therapeutic use*
  • Male
  • Neuroprotective Agents / pharmacology*
  • Neuroprotective Agents / therapeutic use*
  • Oxygen Consumption / drug effects
  • Oxygen Consumption / physiology
  • Prosencephalon / blood supply
  • Prosencephalon / drug effects*
  • Prosencephalon / metabolism
  • Rats
  • Rats, Wistar
  • Stereoisomerism

Substances

  • Excitatory Amino Acid Antagonists
  • Neuroprotective Agents
  • Ketamine