The Effects of Ketamine-Isomers on Neuronal Injury and Regeneration in Rat Hippocampal Neurons

Abstract
There is a difference in the relative anesthetic potency of the isomers of ketamine.Neuroprotective differences may therefore also exist. After an 8-min exposure to 500 micro Meter glutamate or axonal transection, cultured rat hippocampal neurons were maintained untreated or in the presence of ketamine-racemate, S(+)-ketamine, or R(-)-ketamine (10-4 M, 10-5 M, 10-6 M). Cell survival was examined by dye inclusion/esterase activity, morphology by phase contrast and immunofluorescence microscopy, and [(3) H]arachidonic acid (ARA) release by liquid scintillation spectrometry. Seven days after glutamate exposure, survival decreased to 30% in the damaged, untreated group. Extracellular [(3) H]ARA increased fivefold. Dendritic length and branching decreased to a quarter and axonal extensions to the half. Ketamine-racemate 10-4 M increased survival to 65%, and induced longer dendrites (P -4 M increased survival to 80%, reduced [(3) H]ARA threefold, and preserved cytoskeletal arborizations (P 3) H]ARA after 7 days. Survival was 80% after 10-4 M ketamine-racemate and 90% after 10-4 M S(+)-ketamine (P 3) H]ARA (P <or=to 0.05). R(-)-Ketamine was ineffective after both types of injury. Ketamine-racemate and S(+)-ketamine attenuated injury after glutamate exposure or axonal transection in hippocampal neurons in vitro. Neuroregenerative effects were uniquely demonstrated by S(+)-ketamine. (Anesth Analg 1996;83:505-12)