Inciting Excitotoxic Cytocide Among Central Neurons

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Abstract
One of my major research goals in recent years has been to answer a simple question: ‘Can one CNS neuron excite another CNS neuron to death?’ I suspect that the answer is yes, although admittedly the evidence is not all in. As a prime example, it seems likely that for millions of years, neurons in the brains of temporal lobe epileptics have been hyper-exciting their fellow neurons to death. In a series of animal studies, we have shown that regardless of the method used to stimulate limbic seizure activity, if such activity persists long enough (>1 hour), it results in a type of acute brain damage which ultrastructurally resembles that induced by the excitotoxic transmitters, glutamate (Glu) and aspartate (Asp). Moreover, in some of our experiments the seizure activity was induced specifically in pathways thought to use Glu or Asp as transmitter and the brain damage observed was selectively localized to postsynaptic neurons innervated by such pathways. Thus, when I refer to ‘inciting excitotoxic cytocide among central neurons’, I am suggesting that one can, by appropriately stimulating seizure circuits in animal brain, cause certain neurons--those that use Glu or Asp as transmitter--to excite other central neurons to death. Here I will review evidence from animal research favoring an excitotoxic explanation for seizure-related brain damage (SRBD) and will also discuss recent evidence shedding new light on the mechanism(s) underlying excitotoxic phenomena.