The role of excitatory amino acids and NMDA receptors in traumatic brain injury.
Brain injury induced by fluid percussion in rats caused a marked elevation in extracellular glutamate and aspartate adjacent to the trauma site. This increase in excitatory amino acids was related to the severity of the injury and was associated with a reduction in cellular bioenergetic state and intracellular free magnesium. Treatment with the noncompetitive N-methyl-D-aspartate (NMDA) antagonist dextrophan or the competitive antagonist 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid limited the resultant neurological dysfunction; dextrorphan treatment also improved the bioenergetic state after trauma and increased the intracellular free magnesium. Thus, excitatory amino acids contribute to delayed tissue damage after brain trauma; NMDA antagonists may be of benefit in treating acute head injury.
Faden
A I
AI
Department of Neurology, University of California, San Francisco.
Demediuk
P
P
Panter
S S
SS
Vink
R
R
D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001667:Binding, Competitive; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D001930:Brain Injuries / Q000188:drug therapy / Q000378:metabolism*; D003917:Dextrorphan / Q000494:pharmacology / Q000627:therapeutic use; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D008274:Magnesium / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D016202:N-Methylaspartate; D010710:Phosphates / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*
D005971:Glutamates; D010710:Phosphates; D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D010725:Phosphocreatine; D003917:Dextrorphan; D001224:Aspartic Acid; D018698:Glutamic Acid; D016202:N-Methylaspartate; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; D008274:Magnesium