Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 19 May 1989:
Vol. 244. no. 4906, pp. 798 - 800
DOI: 10.1126/science.2567056
Prev | Table of Contents | Next

Articles

Science, Vol 244, Issue 4906, 798-800
Copyright © 1989 by American Association for the Advancement of Science

articles

The role of excitatory amino acids and NMDA receptors in traumatic brain injury

AI Faden, P Demediuk, SS Panter, and R Vink

Department of Neurology, University of California, San Francisco.

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.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
A nonfibrin macromolecular cofactor for tPA-mediated plasmin generation following cellular injury.
A. L. Samson, R. J. Borg, B. Niego, C. H. Y. Wong, P. J. Crack, T. Yongqing, and R. L. Medcalf (2009)
Blood 114, 1937-1946
   Abstract »    Full Text »    PDF »
Altered Prefrontal Glutamate-Glutamine-{gamma}-Aminobutyric Acid Levels and Relation to Low Cognitive Performance and Depressive Symptoms in Type 1 Diabetes Mellitus.
I. K. Lyoo, S. J. Yoon, G. Musen, D. C. Simonson, K. Weinger, N. Bolo, C. M. Ryan, J. E. Kim, P. F. Renshaw, and A. M. Jacobson (2009)
Arch Gen Psychiatry 66, 878-887
   Abstract »    Full Text »    PDF »
Cortical Lesion-Induced Visual Hemineglect Is Prevented by NMDA Antagonist Pretreatment.
H. Jiang, B. E. Stein, and J. G. McHaffie (2009)
J. Neurosci. 29, 6917-6925
   Abstract »    Full Text »    PDF »
Acute Injury to Superficial Cortex Leads to a Decrease in Synaptic Inhibition and Increase in Excitation in Neocortical Layer V Pyramidal Cells.
L. Yang, L. S. Benardo, H. Valsamis, and D. S. F. Ling (2007)
J Neurophysiol 97, 178-187
   Abstract »    Full Text »    PDF »
Detection of glutamate release from neurons by genetically encoded surface-displayed FRET nanosensors.
S. Okumoto, L. L. Looger, K. D. Micheva, R. J. Reimer, S. J Smith, and W. B. Frommer (2005)
PNAS 102, 8740-8745
   Abstract »    Full Text »    PDF »
Diffusion-Weighted Imaging of Acute Excitotoxic Brain Injury.
T. Moritani, W. R. K. Smoker, Y. Sato, Y. Numaguchi, and P.-L. A. Westesson (2005)
AJNR Am. J. Neuroradiol. 26, 216-228
   Full Text »    PDF »
Vulnerability of Central Neurons to Secondary Insults after In Vitro Mechanical Stretch.
M. Arundine, M. Aarts, A. Lau, and M. Tymianski (2004)
J. Neurosci. 24, 8106-8123
   Abstract »    Full Text »    PDF »
Formation of Molecular Complexes by N-Methyl-D-aspartate Receptor Subunit NR2B and Ryanodine Receptor 2 in Neonatal Rat Myocard.
S. Seeber, A. Humeny, M. Herkert, T. Rau, T. Eschenhagen, and C.-M. Becker (2004)
J. Biol. Chem. 279, 21062-21068
   Abstract »    Full Text »    PDF »
Dynamic changes in N-methyl-D-aspartate receptors after closed head injury in mice: Implications for treatment of neurological and cognitive deficits.
A. Biegon, P. A. Fry, C. M. Paden, A. Alexandrovich, J. Tsenter, and E. Shohami (2004)
PNAS 101, 5117-5122
   Abstract »    Full Text »    PDF »
Expression of the Prodynorphin Gene after Experimental Brain Injury and Its Role in Behavioral Dysfunction.
J. B. Redell, A. N. Moore, and P. K. Dash (2003)
Experimental Biology and Medicine 228, 261-269
   Abstract »    Full Text »    PDF »
Antioxidant Therapy in Acute Central Nervous System Injury: Current State.
Y. Gilgun-Sherki, Z. Rosenbaum, E. Melamed, and D. Offen (2002)
Pharmacol. Rev. 54, 271-284
   Abstract »    Full Text »    PDF »
Upregulation of the Fas Receptor Death-Inducing Signaling Complex after Traumatic Brain Injury in Mice and Humans.
J. Qiu, M. J. Whalen, P. Lowenstein, G. Fiskum, B. Fahy, R. Darwish, B. Aarabi, J. Yuan, and M. A. Moskowitz (2002)
J. Neurosci. 22, 3504-3511
   Abstract »    Full Text »    PDF »
Reduced NR2A expression and prolonged decay of NMDA receptor-mediated synaptic current in rat vagal motoneurons following axotomy.
J. Nabekura, T. Ueno, S. Katsurabayashi, A. Furuta, N. Akaike, and M. Okada (2002)
J. Physiol. 539, 735-741
   Abstract »    Full Text »    PDF »
Differential Expression of Apoptotic Protease-Activating Factor-1 and Caspase-3 Genes and Susceptibility to Apoptosis during Brain Development and after Traumatic Brain Injury.
A. G. Yakovlev, K. Ota, G. Wang, V. Movsesyan, W.-L. Bao, K. Yoshihara, and A. I. Faden (2001)
J. Neurosci. 21, 7439-7446
   Abstract »    Full Text »    PDF »
Neuroprotection and Traumatic Brain Injury: The Search Continues.
A. I. Faden (2001)
Arch Neurol 58, 1553-1555
   Full Text »    PDF »
Excitatory Amino Acids in Cerebrospinal Fluid of Patients with Acute Head Injuries.
Z. Hong, Z. Xinding, Z. Tianlin, and C. Liren (2001)
Clin. Chem. 47, 1458-1462
   Abstract »    Full Text »    PDF »
Vasopressin-Induced Protein Kinase C-Dependent Superoxide Generation Contributes to ATP-Sensitive Potassium Channel but Not Calcium-Sensitive Potassium Channel Function Impairment After Brain Injury.
W. M. Armstead (2001)
Stroke 32, 1408-1414
   Abstract »    Full Text »    PDF »
Hibernation, a Model of Neuroprotection.
F. Zhou, X. Zhu, R. J. Castellani, R. Stimmelmayr, G. Perry, M. A. Smith, and K. L. Drew (2001)
Am. J. Pathol. 158, 2145-2151
   Abstract »    Full Text »    PDF »
mGluR5 Antagonists 2-Methyl-6-(phenylethynyl)-pyridine and (E)-2-Methyl-6-(2-phenylethenyl)-pyridine Reduce Traumatic Neuronal Injury In Vitro and In Vivo by Antagonizing N-Methyl-D-aspartate Receptors.
V. A. Movsesyan, D. M. O'Leary, L. Fan, W. Bao, P. G. M. Mullins, S. M. Knoblach, and A. I. Faden (2001)
J. Pharmacol. Exp. Ther. 296, 41-47
   Abstract »    Full Text »
Fornix and Hippocampal Atrophy in Traumatic Brain Injury.
D. F. Tate and E. D. Bigler (2000)
Learn. Mem. 7, 442-446
   Abstract »    Full Text »
Calcineurin-Mediated BAD Dephosphorylation Activates the Caspase-3 Apoptotic Cascade in Traumatic Spinal Cord Injury.
J. E. Springer, R. D. Azbill, S. A. Nottingham, and S. E. Kennedy (2000)
J. Neurosci. 20, 7246-7251
   Abstract »    Full Text »    PDF »
Effects of Matrix Metalloproteinase-9 Gene Knock-Out on Morphological and Motor Outcomes after Traumatic Brain Injury.
X. Wang, J. Jung, M. Asahi, W. Chwang, L. Russo, M. A. Moskowitz, C. E. Dixon, M. E. Fini, and E. H. Lo (2000)
J. Neurosci. 20, 7037-7042
   Abstract »    Full Text »    PDF »
Agmatine reverses pain induced by inflammation, neuropathy, and spinal cord injury.
C. A. Fairbanks, K. L. Schreiber, K. L. Brewer, C.-G. Yu, L. S. Stone, K. F. Kitto, H. O. Nguyen, B. M. Grocholski, D. W. Shoeman, L. J. Kehl, et al. (2000)
PNAS 97, 10584-10589
   Abstract »    Full Text »    PDF »
Selective Depolarization of Interneurons in the Early Posttraumatic Dentate Gyrus: Involvement of the Na+/K+-ATPase.
S. T. Ross and I. Soltesz (2000)
J Neurophysiol 83, 2916-2930
   Abstract »    Full Text »    PDF »
Platelet-derived Growth Factor Rapidly Increases Activity and Cell Surface Expression of the EAAC1 Subtype of Glutamate Transporter through Activation of Phosphatidylinositol 3-Kinase.
K. D. Sims, D. J. Straff, and M. B. Robinson (2000)
J. Biol. Chem. 275, 5228-5237
   Abstract »    Full Text »    PDF »
Distinct Roles of Synaptic and Extrasynaptic NMDA Receptors in Excitotoxicity.
R. Sattler, Z. Xiong, W.-Y. Lu, J. F. MacDonald, and M. Tymianski (2000)
J. Neurosci. 20, 22-33
   Abstract »    Full Text »    PDF »
Combined mechanical trauma and metabolic impairment in vitro induces NMDA receptor-dependent neuronal cell death and caspase-3-dependent apoptosis.
J. W. ALLEN, S. M. KNOBLACH, and A. I. FADEN (1999)
FASEB J 13, 1875-1882
   Abstract »    Full Text »
N-Methyl-D-aspartate antagonists and apoptotic cell death triggered by head trauma in developing rat brain.
D. Pohl, P. Bittigau, M. J. Ishimaru, D. Stadthaus, C. Hubner, J. W. Olney, L. Turski, and C. Ikonomidou (1999)
PNAS 96, 2508-2513
   Abstract »    Full Text »    PDF »
Axonal Injury Alters Alternative Splicing of the Retinal NR1 Receptor: the Preferential Expression of the NR1b Isoforms Is Crucial for Retinal Ganglion Cell Survival.
M. R. Kreutz, T. M. Bockers, J. Bockmann, C. I. Seidenbecher, B. Kracht, C. K. Vorwerk, J. Weise, and B. A. Sabel (1998)
J. Neurosci. 18, 8278-8291
   Abstract »    Full Text »    PDF »
GR89,696 Is a Kappa-2 Opioid Receptor Agonist and a Kappa-1 Opioid Receptor Antagonist in the Guinea Pig Hippocampus.
R. M. Caudle, A. J. Mannes, and M. J. Iadarola (1997)
J. Pharmacol. Exp. Ther. 283, 1342-1349
   Abstract »    Full Text »
Topical Review: Glutamate in Neurologic Diseases.
P. Bittigau and C. Ikonomidou (1997)
J Child Neurol 12, 471-485
   Abstract »    PDF »
Secondary Activation of a Cation Conductance Is Responsible for NMDA Toxicity in Acutely Isolated Hippocampal Neurons.
Q. X. Chen, K. L. Perkins, D. W. Choi, and R. K. S. Wong (1997)
J. Neurosci. 17, 4032-4036
   Abstract »    Full Text »    PDF »
REVIEW {blacksquare} : Calcium and the Pathogenesis of Traumatic CNS Injury: Cellular and Molecular Mechanisms.
T. K. Mcintosh, K. E. Saatman, and R. Raghupathi (1997)
Neuroscientist 3, 169-175
   Abstract »    PDF »
Inhibition of the Electrogenic Na Pump Underlies Delayed Depolarization of Cortical Neurons After Mechanical Injury or Glutamate.
S. J. Tavalin, E. F. Ellis, and L. S. Satin (1997)
J Neurophysiol 77, 632-638
   Abstract »    Full Text »    PDF »
Elevated Glutamate Levels in the Vitreous Body of Humans and Monkeys With Glaucoma.
E. B. Dreyer, D. Zurakowski, R. A. Schumer, S. M. Podos, and S. A. Lipton (1996)
Arch Ophthalmol 114, 299-305
   Abstract »    PDF »
Review : Recovery from Spinal Cord Injury: New Approaches.
L. Yen and R. G. Kalb (1995)
Neuroscientist 1, 321-327
   Abstract »    PDF »
Secondary Neuronal Injury After Head Trauma: Role of Excitotoxicity.
D. W. Choi (1995)
Neurorehabil Neural Repair 9, 61-64
   PDF »
Excitatory Amino Acids as a Final Common Pathway for Neurologic Disorders.
S. A. Lipton and P. A. Rosenberg (1994)
N. Engl. J. Med. 330, 613-622
   Full Text »
Oxidative stress, glutamate, and neurodegenerative disorders.
J. Coyle and P Puttfarcken (1993)
Science 262, 689-695
   Abstract »    PDF »
Invited Review: Nutrition in the Neurologically Injured Patient.
L. Ott and B. Young (1991)
Nutr Clin Pract 6, 223-229
   Abstract »    PDF »
Pharmacologic Modulation of Recovery After Brain Injury: A Reconsideration of Diaschisis.
D. M. Feeney (1991)
Neurorehabil Neural Repair 5, 113-128
   Abstract »    PDF »
The calcium channel blocker nifedipine attenuates slow excitatory amino acid neurotoxicity.
J. Weiss, D. Hartley, J Koh, and D. Choi (1990)
Science 247, 1474-1477
   Abstract »    PDF »
Neurologic Sequelae of Open-Heart Surgery in Children: An 'Irritating Question'.
P. C. Ferry (1990)
Arch Pediatr Adolesc Med 144, 369-373
   Abstract »    PDF »
Tonic activation of NMDA receptors by ambient glutamate enhances excitability of neurons.
P Sah, S Hestrin, and R. Nicoll (1989)
Science 246, 815-818
   Abstract »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)