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

• Published in: Anesthesia and analgesia Vol. 83; no. 3; pp. 505 - 512
• Main Authors: Himmelseher, Sabine, Pfenninger, Ernst, Georgieff, Michael
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD International Anesthesia Research Society 01.09.1996; Lippincott
• Subjects: Anesthetics, Dissociative - pharmacology; Animals; Axons - physiology; Biological and medical sciences; Cell Survival; Cells, Cultured; Dendrites - physiology; Glutamic Acid; Hippocampus - drug effects; Hippocampus - injuries; Hippocampus - physiology; Isomerism; Ketamine - pharmacology; Medical sciences; Nerve Degeneration; Nerve Regeneration - drug effects; Neuropharmacology; Neuroprotective agent; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Nervous system diseases; Rat; Rodentia; Neuroprotective agent; In vitro; Isomer; Stereoselectivity; Vertebrata; Axotomy; Mammalia; Neuron; Animal; Central nervous system disease; Hippocampus; Brain (vertebrata)
• ISSN: 0003-2999; 1526-7598
• DOI: 10.1097/00000539-199609000-00011

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 M, 10 M, 10 M). Cell survival was examined by dye inclusion/esterase activity, morphology by phase contrast and immunofluorescence microscopy, and [() H]arachidonic acid (ARA) release by liquid scintillation spectrometry. Seven days after glutamate exposure, survival decreased to 30% in the damaged, untreated group. Extracellular [() H]ARA increased fivefold. Dendritic length and branching decreased to a quarter and axonal extensions to the half. Ketamine-racemate 10 M increased survival to 65%, and induced longer dendrites (P <or=to 0.05). S(+)-Ketamine 10 M increased survival to 80%, reduced [() H]ARA threefold, and preserved cytoskeletal arborizations (P <or=to 0.05). Axotomy decreased survival to 60% and caused a minor increase in [() H]ARA after 7 days. Survival was 80% after 10 M ketamine-racemate and 90% after 10 M S(+)-ketamine (P <or=to 0.05). Only S(+)-ketamine supported axonal reoutgrowth and decreased [() 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)