The effects of ketamine-isomers on neuronal injury and regeneration in rat hippocampal neurons.
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 microM 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 [3H]arachidonic acid (ARA) release by liquid scintillation spectrometry. Seven days after glutamate exposure, survival decreased to 30% in the damaged, untreated group. Extracellular [3H]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 < or = 0.05). S(+)-Ketamine 10(-4) M increased survival to 80%, reduced [3H]ARA threefold, and preserved cytoskeletal arborizations (P < or = 0.05). Axotomy decreased survival to 60% and caused a minor increase in [3H]ARA after 7 days. Survival was 80% after 10(-4) M ketamine-racemate and 90% after 10(-4) M S(+)-ketamine (P < or = 0.05). Only S(+)-ketamine supported axonal reoutgrowth and decreased [3H]ARA (P < or = 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.
Himmelseher
S
S
University Clinic of Anesthesiology, Ulm, Germany. sabine.himmelseher@medizin.uni-ulm.de
Pfenninger
E
E
Georgieff
M
M
D000778:Anesthetics, Dissociative / Q000494:pharmacology*; D000818:Animals; D001369:Axons / Q000502:physiology; D002470:Cell Survival; D002478:Cells, Cultured; D003712:Dendrites / Q000502:physiology; D018698:Glutamic Acid; D006624:Hippocampus / Q000187:drug effects / Q000293:injuries / Q000502:physiology*; D007536:Isomerism; D007649:Ketamine / Q000494:pharmacology*; D009410:Nerve Degeneration; D009416:Nerve Regeneration / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000778:Anesthetics, Dissociative; D018698:Glutamic Acid; D007649:Ketamine