Neuron
Volume 8, Issue 5, May 1992, Pages 967-973
Journal home page for Neuron

Article
Oxygen or glucose deprivation-induced neuronal injury in cortical cell cultures is reduced by tetanus toxin

https://doi.org/10.1016/0896-6273(92)90211-UGet rights and content

Abstract

We examined glutamate-mediated neurotoxicity in cortical cell cultures pretreated with 1–5 μg/ml tetanus toxin to attenuate the Ca2+-dependent release of neurotransmitters. Efficacy of the tetanus toxin pretreatment was suggested by blockade of electrical burst activity induced by Mg2+ removal and by reduction of glutamate efflux induced by high K+. Tetanus toxin reduced neuronal injury produced by brief exposure to elevated extracellular K+ or to glutamate, situations in which release of endogenous excitatory neurotransmitter is likely to play a role. Furthermore, although glutamate efflux evoked by anoxic conditions may occur largely via Ca2+-independent transport, tetanus toxin attenuated both glutamate efflux and neuronal injury following combined oxygen and glucose deprivation. With prolonged exposure periods, the neuroprotective efficacy of tetanus toxin was comparable to that of NMDA receptor antagonists. Presynaptic inhibition of Ca 2+-dependent glutamate release may be a valuable approach to attenuating hypoxic-ischemic brain injury.

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    Present address: Department of Molecular Neuroendocrinology, Center for Molecular Biology, Heidelberg, INF 282, 6900 Heidelberg, Germany.

    Present address: Department of Anesthesia, Stanford University Medical Center, Stanford, California 94305.

    §

    Present address: Department of Neurology, Washington University School of Medicine, St. Louis, Missouri 63110.

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