Oxygen or glucose deprivation-induced neuronal injury in cortical cell cultures is reduced by tetanus toxin.
We examined glutamate-mediated neurotoxicity in cortical cell cultures pretreated with 1-5 micrograms/ml tetanus toxin to attenuate the Ca(2+)-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 Ca(2+)-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.
Monyer
H
H
Department of Neurology and Neurological Sciences, Stanford University Medical Center, California 94305.
Giffard
R G
RG
Hartley
D M
DM
Dugan
L L
LL
Goldberg
M P
MP
Choi
D W
DW
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004594:Electrophysiology; D005947:Glucose / Q000008:administration & dosage*; D005971:Glutamates / Q000378:metabolism / Q000494:pharmacology; D018698:Glutamic Acid; D008274:Magnesium / Q000008:administration & dosage; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000378:metabolism; D010100:Oxygen / Q000008:administration & dosage*; D011188:Potassium / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D013744:Tetanus Toxin / Q000494:pharmacology*
D005971:Glutamates; D018377:Neurotransmitter Agents; D011810:Quinoxalines; D013744:Tetanus Toxin; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D008274:Magnesium; D005947:Glucose; D011188:Potassium; D010100:Oxygen; D002118:Calcium