EXCITO-TOXICITY  [ back to Glossary Index ]
Excito-toxicity refers to the process by which brain cells release toxins into their own micro-environment following localized trauma from a blow to the head or a stroke. The most studied and best understood excito-toxic response to head trauma involves the sudden, massive release of the neurotransmitter glutamate at 10s of 1000s its normal quantity. This jams open NMDA receptors on downstream neurons and allows unrestricted entry of toxic quantities of calcium, which poisons and kills the nerve cell. This chemical event is accompanied by abnormal electrical discharge of the affected brain cells, which fire constantly rather than in on-off fashion during the event. This process has been studied almost exclusively in rats. The sudden massive build up of glutamate has been measured directly in the rat brain (after the rat brain was struck with a metal pendulum weight or a high pressure jet of water) with microdialysis probes, and the abnormal nerve cell firing patterns have been directly measured with electrode probes at preselected time intervals. Neuroscientists have repeated the experiments with "neuro-protective" chemical agents to see if the excito-toxic cascade can be inhibited or its damage limited.  They check the "neuro-protective" effect of the various chemicals by killing the rat, slicing up its brain and counting the number of killed cells vs. surviving cells. The good news is that they have found some highly effective agents in the rat. The bad news is that giving these same chemicals to head trauma patients in hospital studies has not worked. This may be due to the huge size difference between human and rat brains or a myriad of other reasons.

Some scientists question whether excito-toxicity even occurs in the human brain.  The failure of chemical agents to stop spreading brain damage in human patients does not mean humans does rule in or rule out the possibility that humans suffer the same kind of excito-toxic glutamate release as rats. We just don't know right now. The studies continue. A recent paper in the 10/15/99 edition of the Journal of Neuroscience found that hyperglycemia (high glucose content) in the micro-environment of cultured brain cells enhanced their rate of survival following trauma. This occurred because the extra supply of glucose kept the mitochondria in the brain cells operating at peak level to furnish the energy needed to flush the sudden toxic influx of calcium ions back out of the cell. Brain cells in a hypo-glycemic environment died in part because their mitochondria shut down and there was insufficient energy to repel the influx of calcium ions.