The osmotic/calcium stress theory of brain damage: are free radicals involved?
This overview presents data showing that glucose use increases and that excitatory amino acids (i.e., glutamate, aspartate), taurine and ascorbate increase in the extracellular fluid during seizures. During the cellular hyperactive state taurine appears to serve as an osmoregulator and ascorbate may serve as either an antioxidant or as a pro-oxidant. Finally, a unifying hypothesis is given for seizure-induced brain damage. This unifying hypothesis states that during seizures there is a release of excitatory amino acids which act on glutamatergic receptors, increasing neuronal activity and thereby increasing glucose use. This hyperactivity of cells causes an influx of calcium (i.e., calcium stress) and water movements (i.e., osmotic stress) into the cells that culminate in brain damage mediated by reactive oxygen species.
Pazdernik
T L
TL
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City 66103.
Layton
M
M
Nelson
S R
SR
Samson
F E
FE
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000503:physiopathology; D001927:Brain Diseases / Q000209:etiology* / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism*; D005609:Free Radicals; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D010100:Oxygen / Q000378:metabolism*; D012640:Seizures / Q000150:complications*; D014882:Water-Electrolyte Balance
D000596:Amino Acids; D005609:Free Radicals; D005947:Glucose; D010100:Oxygen; D002118:Calcium