The Role of Excitatory Amino Acids and NMDA Receptors in Traumatic Brain Injury

作者：Alan I. Faden, Paul Demediuk, S. Scott Panter, Robert Vink · 发表于：Science · 年份：1989 · DOI：10.1126/science.2567056 · 被引用次数：1521 · 研究领域：Traumatic Brain Injury and Neurovascular Disturbances、Traumatic Brain Injury Research、Anesthesia and Neurotoxicity Research

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.