Inciting excitotoxic cytocide among central neurons.
Here I have reviewed evidence from electron microscopic studies showing that each of several sustained limbic seizure syndromes is associated with a type of acute brain damage which is ultrastructurally indistinguishable from the brain damage induced by Glu and other excitotoxins. In addition, I have presented evidence that persistent stimulation of specific axonal tracts that use Glu as transmitter results in Glu-like excitotoxic degeneration of postsynaptic neurons innervated by such tracts. Phencyclidine and ketamine, which powerfully block the neurotoxicity of the Glu analog NMA, protect against seizure-related brain damage. This may be explained by either an anticonvulsant or antiexcitotoxic mechanism, or both. Recent evidence suggests that an excitotoxic mechanism (excessive activation of Glu/Asp receptors) may underlie both seizure-mediated and anoxic brain damage. The acute fulminating type of neuronal degeneration induced by Glu is a Na+ and Cl- but not Ca2+ dependent phenomenon. According to a recent study, however, Glu may induce neuronal necrosis not only by an acute Ca2+ independent process but by a more slowly evolving Ca2+ dependent process. If, as these data suggest, an excitotoxic mechanism underlies brain damage associated with anoxia and epilepsy, a better understanding of excitotoxic mechanisms may lead eventually to prophylactic approaches for preventing such forms of brain damage.
D000200:Action Potentials; D000818:Animals; D001921:Brain / Q000473:pathology* / Q000503:physiopathology; D002470:Cell Survival; D002642:Chick Embryo; D002799:Cholinergic Fibers / Q000503:physiopathology; D004195:Disease Models, Animal; D004487:Edema / Q000473:pathology; D004828:Epilepsies, Partial / Q000503:physiopathology; D005492:Folic Acid / Q000633:toxicity; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology; D000860:Hypoxia / Q000473:pathology / Q000503:physiopathology; D007608:Kainic Acid / Q000633:toxicity; D007649:Ketamine / Q000494:pharmacology; D008854:Microscopy, Electron; D010277:Parasympathomimetics / Q000494:pharmacology; D010622:Phencyclidine / Q000494:pharmacology; D010880:Piperidines / Q000633:toxicity; D012640:Seizures / Q000139:chemically induced / Q000473:pathology*; D009435:Synaptic Transmission; D013788:Thalamus / Q000503:physiopathology
D010277:Parasympathomimetics; D010880:Piperidines; C023791:dipiperidinoethane; D007649:Ketamine; D005492:Folic Acid; D010622:Phencyclidine; D007608:Kainic Acid