Factors affecting excitatory amino acid release following severe human head injury

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Object. Recent animal studies demonstrate that excitatory amino acids (EAAs) play a major role in neuronal damage after brain trauma and ischemia. However, the role of EAAs in patients who have suffered severe head injury is not understood. Excess quantities of glutamate in the extracellular space may lead to uncontrolled shifts of sodium, potassium, and calcium, disrupting ionic homeostasis, which may lead to severe cell swelling and cell death. The authors evaluated the role of EEAs in human traumatic brain injury.

Methods. In 80 consecutive severely head injured patients, a microdialysis probe was placed into the gray matter along with a ventriculostomy catheter or an intracranial pressure (ICP) monitor for 4 days. Levels of EAAs and structural amino acids were analyzed using high-performance liquid chromatography. Multifactorial analysis of the amino acid pattern was performed and its correlations with clinical parameters and outcome were tested. The levels of EAAs were increased up to 50 times normal in 30% of the patients and were significantly correlated to levels of structural amino acids both in each patient and across the whole group (p < 0.01). Secondary ischemic brain injury and focal contusions were most strongly associated with high EAA levels (27 ± 22 µmol/L). Sustained high ICP and poor outcome were significantly correlated to high levels of EAAs (glutamate > 20 µmol/L; p < 0.01).

Conclusions. The release of EAAs is closely linked to the release of structural amino acids and may thus reflect nonspecific development of membrane micropores, rather than presynaptic neuronal vesicular exocytosis. The magnitude of EAA release in patients with focal contusions and ischemic events may be sufficient to exacerbate neuronal damage, and these patients may be the best candidates for treatment with glutamate antagonists in the future.

Article Information

Contributor Notes

Address reprint requests to: Ross Bullock, M.D., Ph.D., Division of Neurosurgery, Medical College of Virginia, P. O. Box 980631, Richmond, Virginia 23298.
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References
  • 1.

    Adams JHGraham DIGennarelli TA: Head injury in man and experimental animals: neuropathology. Acta Neurochir (Suppl 32):15301983Adams JH Graham DI Gennarelli TA: Head injury in man and experimental animals: neuropathology. Acta Neurochir (Suppl 32):15–30 1983

    • Search Google Scholar
    • Export Citation
  • 2.

    Becker DPKatayama YTamura Tet al: Excitotoxic ion fluxes and neuronal dysfunction following traumatic brain injury. J Cereb Blood Flow Metab 9 (Suppl 1):S3021989 (Abstract)Becker DP Katayama Y Tamura T et al: Excitotoxic ion fluxes and neuronal dysfunction following traumatic brain injury. J Cereb Blood Flow Metab 9 (Suppl 1):S302 1989 (Abstract)

    • Search Google Scholar
    • Export Citation
  • 3.

    Benveniste HDrejer JSchousboe Aet al: Elevation of the extracellular concentrations of glutamate and aspartate in rat hippocampus during transient cerebral ischemia monitored by intracerebral microdialysis. J Neurochem 43:136913741984Benveniste H Drejer J Schousboe A et al: Elevation of the extracellular concentrations of glutamate and aspartate in rat hippocampus during transient cerebral ischemia monitored by intracerebral microdialysis. J Neurochem 43:1369–1374 1984

    • Search Google Scholar
    • Export Citation
  • 4.

    Bouma GJMuizelaar JPStringer WAet al: Ultra-early evaluation of regional cerebral blood flow in severely head-injured patients using xenon-enhanced computerized tomography. J Neurosurg 77:3603681992Bouma GJ Muizelaar JP Stringer WA et al: Ultra-early evaluation of regional cerebral blood flow in severely head-injured patients using xenon-enhanced computerized tomography. J Neurosurg 77:360–368 1992

    • Search Google Scholar
    • Export Citation
  • 5.

    Bullock R: Opportunities for neuroprotective drugs in clinical management of head injury. J Emerg Med 11 (Suppl 1):23301993Bullock R: Opportunities for neuroprotective drugs in clinical management of head injury. J Emerg Med 11 (Suppl 1):23–30 1993

    • Search Google Scholar
    • Export Citation
  • 6.

    Bullock RButcher SPChen MHet al: Correlation of extracellular glutamate concentration with extent of blood flow reduction after subdural hematoma in the rat. J Neurosurg 74:7948011991Bullock R Butcher SP Chen MH et al: Correlation of extracellular glutamate concentration with extent of blood flow reduction after subdural hematoma in the rat. J Neurosurg 74:794–801 1991

    • Search Google Scholar
    • Export Citation
  • 7.

    Bullock RFujisawa H: The role of glutamate antagonists for the treatment of CNS injury. J Neurotrauma 9 (Suppl 2):544354621992Bullock R Fujisawa H: The role of glutamate antagonists for the treatment of CNS injury. J Neurotrauma 9 (Suppl 2):5443–5462 1992

    • Search Google Scholar
    • Export Citation
  • 8.

    Bullock RInglis FMKuroda Yet al: Transient hippocampal hypermetabolism associated with glutamate release after acute subdural haematoma in the rat: a potentially neurotoxic mechanism. J Cereb Blood Flow Metab 11 (Suppl 2):S1091991 (Abstract)Bullock R Inglis FM Kuroda Y et al: Transient hippocampal hypermetabolism associated with glutamate release after acute subdural haematoma in the rat: a potentially neurotoxic mechanism. J Cereb Blood Flow Metab 11 (Suppl 2):S109 1991 (Abstract)

    • Search Google Scholar
    • Export Citation
  • 9.

    Bullock RZauner ATsuji Oet al: Excitatory amino acid release after severe human head trauma: effect of intracranial pressure and cerebral perfusion pressure changes in Nagai HKamiya KIshii S (eds): Intracranial Pressure IX. Tokyo: Springer-Verlag1994 pp 264267Bullock R Zauner A Tsuji O et al: Excitatory amino acid release after severe human head trauma: effect of intracranial pressure and cerebral perfusion pressure changes in Nagai H Kamiya K Ishii S (eds): Intracranial Pressure IX. Tokyo: Springer-Verlag 1994 pp 264–267

    • Search Google Scholar
    • Export Citation
  • 10.

    Bullock RZauner ATsuji Oet al: Patterns of excitatory amino acid release and ionic flux after severe head trauma in Tsubokawa TMarmarou ARobertson Cet al (eds): Neurochemical Monitoring in the Intensive Care Unit. Tokyo: Springer-Verlag1995 pp 6467Bullock R Zauner A Tsuji O et al: Patterns of excitatory amino acid release and ionic flux after severe head trauma in Tsubokawa T Marmarou A Robertson C et al (eds): Neurochemical Monitoring in the Intensive Care Unit. Tokyo: Springer-Verlag 1995 pp 64–67

    • Search Google Scholar
    • Export Citation
  • 11.

    Butcher SPBullock RGraham DLet al: Correlation between amino acid release and neuropathologic outcome in rat brain following middle cerebral artery occlusion. Stroke 21:172717331990Butcher SP Bullock R Graham DL et al: Correlation between amino acid release and neuropathologic outcome in rat brain following middle cerebral artery occlusion. Stroke 21:1727–1733 1990

    • Search Google Scholar
    • Export Citation
  • 12.

    Chen MHBullock RGraham DIet al: Ischemic neuronal damage after acute subdural hematoma in the rat: effects of pretreatment with a glutamate antagonist. J Neurosurg 74:9449501991Chen MH Bullock R Graham DI et al: Ischemic neuronal damage after acute subdural hematoma in the rat: effects of pretreatment with a glutamate antagonist. J Neurosurg 74:944–950 1991

    • Search Google Scholar
    • Export Citation
  • 13.

    Choi DWMaulucci-Gedde MKriegstein AR: Glutamate neurotoxicity in cortical cell culture. J Neurosci 7:3573681987Choi DW Maulucci-Gedde M Kriegstein AR: Glutamate neurotoxicity in cortical cell culture. J Neurosci 7:357–368 1987

    • Search Google Scholar
    • Export Citation
  • 14.

    Choi SCChinchilli VM: Analysis of within- and across-subject correlations in Bozdogan HGupta AK (eds):Multivariate Statistical Modeling and Data Analysis. Dordrecht: Reidel1989 pp 7794Choi SC Chinchilli VM: Analysis of within- and across-subject correlations in Bozdogan H Gupta AK (eds): Multivariate Statistical Modeling and Data Analysis. Dordrecht: Reidel 1989 pp 77–94

    • Search Google Scholar
    • Export Citation
  • 15.

    During MJSpencer DD: Extracellular hippocampal glutamate and spontaneous seizure in the conscious human brain. Lancet 341:160716101993During MJ Spencer DD: Extracellular hippocampal glutamate and spontaneous seizure in the conscious human brain. Lancet 341:1607–1610 1993

    • Search Google Scholar
    • Export Citation
  • 16.

    Erb DEPovlishock JT: Axonal damage in severe traumatic brain injury: an experimental study in the cat. Acta Neuropathol 76:3473581988Erb DE Povlishock JT: Axonal damage in severe traumatic brain injury: an experimental study in the cat. Acta Neuropathol 76:347–358 1988

    • Search Google Scholar
    • Export Citation
  • 17.

    Faden AIDemediuk PPanter SSet al: The role of excitatory amino acids and NMDA receptors in traumatic brain injury. Science 244:7988001989Faden AI Demediuk P Panter SS et al: The role of excitatory amino acids and NMDA receptors in traumatic brain injury. Science 244:798–800 1989

    • Search Google Scholar
    • Export Citation
  • 18.

    Gentleman DJennett B: Hazards of inter-hospital transfer of comatose head injured patients. Lancet 2:8538551981Gentleman D Jennett B: Hazards of inter-hospital transfer of comatose head injured patients. Lancet 2:853–855 1981

    • Search Google Scholar
    • Export Citation
  • 19.

    Graham DILawrence AEAdams JHet al: Brain damage in fatal non-missile head injury without high intracranial pressure. J Clin Pathol 41:34371988Graham DI Lawrence AE Adams JH et al: Brain damage in fatal non-missile head injury without high intracranial pressure. J Clin Pathol 41:34–37 1988

    • Search Google Scholar
    • Export Citation
  • 20.

    Hayes RLJenkins LWLyeth BGet al: Pretreatment with phencyclidine, an N-methyl-D-aspartate antagonist, attenuates long-term behavioral deficits in the rat produced by traumatic brain injury. J Neurotrauma 5:2592741988Hayes RL Jenkins LW Lyeth BG et al: Pretreatment with phencyclidine an N-methyl-D-aspartate antagonist attenuates long-term behavioral deficits in the rat produced by traumatic brain injury. J Neurotrauma 5:259–274 1988

    • Search Google Scholar
    • Export Citation
  • 21.

    Heiss WDHayakawa TWaltz AG: Cortical neuronal function during ischemia. Effects of occlusion of one middle cerebral artery on single-unit activity in cats. Arch Neurol 33:8138201976Heiss WD Hayakawa T Waltz AG: Cortical neuronal function during ischemia. Effects of occlusion of one middle cerebral artery on single-unit activity in cats. Arch Neurol 33:813–820 1976

    • Search Google Scholar
    • Export Citation
  • 22.

    Hillered LHallström ASegersvärd Set al: Dynamics of extracellular metabolites in the striatum after middle cerebral artery occlusion in the rat monitored by intracerebral microdialysis. J Cereb Blood Flow Metab 9:6076161989Hillered L Hallström A Segersvärd S et al: Dynamics of extracellular metabolites in the striatum after middle cerebral artery occlusion in the rat monitored by intracerebral microdialysis. J Cereb Blood Flow Metab 9:607–616 1989

    • Search Google Scholar
    • Export Citation
  • 23.

    Hillered LPersson LCarlson Het al: Studies on excitatory amino acid receptor-linked brain disorders in rat and man using in vivo microdialysis. Clin Neuropharmacol 15 (Suppl 1Part A):695A696A1992Hillered L Persson L Carlson H et al: Studies on excitatory amino acid receptor-linked brain disorders in rat and man using in vivo microdialysis. Clin Neuropharmacol 15 (Suppl 1 Part A):695A–696A 1992

    • Search Google Scholar
    • Export Citation
  • 24.

    Inglis FKuroda YBullock R: Glucose hypermetabolism after acute subdural hematoma is ameliorated by a competitive NMDA antagonist. J Neurotrauma 9:75841992Inglis F Kuroda Y Bullock R: Glucose hypermetabolism after acute subdural hematoma is ameliorated by a competitive NMDA antagonist. J Neurotrauma 9:75–84 1992

    • Search Google Scholar
    • Export Citation
  • 25.

    Jenkins LWLyeth BGLewelt Wet al: Combined pretrauma scopolamine and phencyclidine attenuates posttraumatic increased sensitivity to delayed secondary ischemia. J Neurotrauma 5:2752871988Jenkins LW Lyeth BG Lewelt W et al: Combined pretrauma scopolamine and phencyclidine attenuates posttraumatic increased sensitivity to delayed secondary ischemia. J Neurotrauma 5:275–287 1988

    • Search Google Scholar
    • Export Citation
  • 26.

    Jenkins LWMoszynski KLyeth BGet al: Increased vulnerability of the mildly traumatized rat brain to cerebral ischemia: the use of controlled secondary ischemia as a research tool to identify common or different mechanisms contributing to mechanical and ischemic brain injury. Brain Res 477:2112241989Jenkins LW Moszynski K Lyeth BG et al: Increased vulnerability of the mildly traumatized rat brain to cerebral ischemia: the use of controlled secondary ischemia as a research tool to identify common or different mechanisms contributing to mechanical and ischemic brain injury. Brain Res 477:211–224 1989

    • Search Google Scholar
    • Export Citation
  • 27.

    Jones THMorawetz RBCrowell RMet al: Thresholds of focal cerebral ischemia in awake monkeys. J Neurosurg 54:7737821981Jones TH Morawetz RB Crowell RM et al: Thresholds of focal cerebral ischemia in awake monkeys. J Neurosurg 54:773–782 1981

    • Search Google Scholar
    • Export Citation
  • 28.

    Katayama YBecker DPTamura Tet al: Massive increases in extracellular potassium and the indiscriminate release of glutamate following concussive brain injury. J Neurosurg 73:8899001990Katayama Y Becker DP Tamura T et al: Massive increases in extracellular potassium and the indiscriminate release of glutamate following concussive brain injury. J Neurosurg 73:889–900 1990

    • Search Google Scholar
    • Export Citation
  • 29.

    Kawamata TKatayama YHovda Det al: Administration of excitatory amino acid antagonists via microdialysis attenuates the increase in glucose utilization seen following concussive brain injury. J Cereb Blood Flow Metab 12:12241992Kawamata T Katayama Y Hovda D et al: Administration of excitatory amino acid antagonists via microdialysis attenuates the increase in glucose utilization seen following concussive brain injury. J Cereb Blood Flow Metab 12:12–24 1992

    • Search Google Scholar
    • Export Citation
  • 30.

    Kirino TTamura ASano K: Delayed neuronal death in the rat hippocampus following transient forebrain ischemia. Acta Neuropathol 64:1391471984Kirino T Tamura A Sano K: Delayed neuronal death in the rat hippocampus following transient forebrain ischemia. Acta Neuropathol 64:139–147 1984

    • Search Google Scholar
    • Export Citation
  • 31.

    Kotapka MJGraham DIAdams JHet al: Hippocampal pathology in fatal non-missile human head injury. Acta Neuropathol 83:5305341992Kotapka MJ Graham DI Adams JH et al: Hippocampal pathology in fatal non-missile human head injury. Acta Neuropathol 83:530–534 1992

    • Search Google Scholar
    • Export Citation
  • 32.

    Kuroda YFujisawa HStrebel Set al: Effect of neuroprotective N-methyl-D-aspartate antagonists on increased intracranial pressure: studies in the rat acute subdural hematoma model. Neurosurgery 35:1061121994Kuroda Y Fujisawa H Strebel S et al: Effect of neuroprotective N-methyl-D-aspartate antagonists on increased intracranial pressure: studies in the rat acute subdural hematoma model. Neurosurgery 35:106–112 1994

    • Search Google Scholar
    • Export Citation
  • 33.

    Lindroth PMopper K: High performance liquid chromatographic determination of sub-picomole amounts of amino acids by precolumn fluorescence derivatization with o-pthaldialdehyde. Anal Chem 51:166716741979Lindroth P Mopper K: High performance liquid chromatographic determination of sub-picomole amounts of amino acids by precolumn fluorescence derivatization with o-pthaldialdehyde. Anal Chem 51:1667–1674 1979

    • Search Google Scholar
    • Export Citation
  • 34.

    Lyeth BGJenkins LWHamm RJet al: Pretreatment with MK-801 reduces behavioral deficits following traumatic brain injury in rats. Soc Neurosci 15:11131989 (Abstract)Lyeth BG Jenkins LW Hamm RJ et al: Pretreatment with MK-801 reduces behavioral deficits following traumatic brain injury in rats. Soc Neurosci 15:1113 1989 (Abstract)

    • Search Google Scholar
    • Export Citation
  • 35.

    McIntosh TKVink RSoares Het al: Effect of noncompetitive blockade of N-methyl-D-aspartate receptors on the neurochemical sequelae of experimental brain injury. J Neurochem 55:117011791990McIntosh TK Vink R Soares H et al: Effect of noncompetitive blockade of N-methyl-D-aspartate receptors on the neurochemical sequelae of experimental brain injury. J Neurochem 55:1170–1179 1990

    • Search Google Scholar
    • Export Citation
  • 36.

    McIntosh TKVink RSoares Het al: Effects of the N-methyl-D-aspartate receptor blocker MK-801 on neurologic function after experimental brain injury. J Neurotrauma 6:2472591989McIntosh TK Vink R Soares H et al: Effects of the N-methyl-D-aspartate receptor blocker MK-801 on neurologic function after experimental brain injury. J Neurotrauma 6:247–259 1989

    • Search Google Scholar
    • Export Citation
  • 37.

    Meldrum B: Protection against ischaemic neuronal damage by drugs acting on excitatory neurotransmission. Cerebrovasc Brain Metabol Rev 2:27571990Meldrum B: Protection against ischaemic neuronal damage by drugs acting on excitatory neurotransmission. Cerebrovasc Brain Metabol Rev 2:27–57 1990

    • Search Google Scholar
    • Export Citation
  • 38.

    Meyer JSHayman LAYamamoto Met al: Local cerebral blood flow measured by CT after stable xenon inhalation. AJR 135:2392511980Meyer JS Hayman LA Yamamoto M et al: Local cerebral blood flow measured by CT after stable xenon inhalation. AJR 135:239–251 1980

    • Search Google Scholar
    • Export Citation
  • 39.

    Muizelaar JPSchröder ML: Overview of monitoring of cerebral blood flow and metabolism after severe head injury. Can J Neurol Sci 21 (Suppl):161994Muizelaar JP Schröder ML: Overview of monitoring of cerebral blood flow and metabolism after severe head injury. Can J Neurol Sci 21 (Suppl):1–6 1994

    • Search Google Scholar
    • Export Citation
  • 40.

    Nehls DGPark CKMacCormack AGet al: The effects of N-methyl-D-aspartate receptor blockade with MK-801 upon the relationship between cerebral blood flow and glucose utilization. Brain Res 511:2712791990Nehls DG Park CK MacCormack AG et al: The effects of N-methyl-D-aspartate receptor blockade with MK-801 upon the relationship between cerebral blood flow and glucose utilization. Brain Res 511:271–279 1990

    • Search Google Scholar
    • Export Citation
  • 41.

    Nicholls DAttwell D: The release and uptake of excitatory amino acids. Trends Pharmacol Sci 11:4624681990Nicholls D Attwell D: The release and uptake of excitatory amino acids. Trends Pharmacol Sci 11:462–468 1990

    • Search Google Scholar
    • Export Citation
  • 42.

    Nilsson PHillered LOlsson Yet al: Regional changes in interstitial K+ and Ca2+ levels following cortical compression contusion trauma in rats. J Cereb Blood Flow Metab 13:1831921993Nilsson P Hillered L Olsson Y et al: Regional changes in interstitial K+ and Ca2+ levels following cortical compression contusion trauma in rats. J Cereb Blood Flow Metab 13:183–192 1993

    • Search Google Scholar
    • Export Citation
  • 43.

    Nilsson PHillered LPontén Uet al: Changes in cortical extracellular levels of energy-related metabolites and amino acids following concussive brain injury in rats. J Cereb Blood Flow Metab 10:6316371990Nilsson P Hillered L Pontén U et al: Changes in cortical extracellular levels of energy-related metabolites and amino acids following concussive brain injury in rats. J Cereb Blood Flow Metab 10:631–637 1990

    • Search Google Scholar
    • Export Citation
  • 44.

    Persson LHillered L: Chemical monitoring of neurosurgical intensive care patients using intracerebral microdialysis. J Neurosurg 76:72801992Persson L Hillered L: Chemical monitoring of neurosurgical intensive care patients using intracerebral microdialysis. J Neurosurg 76:72–80 1992

    • Search Google Scholar
    • Export Citation
  • 45.

    Ronne-Engström EHillered LFlink Ret al: Intracerebral microdialysis of extracellular amino acids in the human epileptic focus. J Cereb Blood Flow Metab 12:8738761992Ronne-Engström E Hillered L Flink R et al: Intracerebral microdialysis of extracellular amino acids in the human epileptic focus. J Cereb Blood Flow Metab 12:873–876 1992

    • Search Google Scholar
    • Export Citation
  • 46.

    Rothman SMOlney JW: Excitotoxicity and the NMDA receptor. Trends Neurosci 10:2993021987Rothman SM Olney JW: Excitotoxicity and the NMDA receptor. Trends Neurosci 10:299–302 1987

    • Search Google Scholar
    • Export Citation
  • 47.

    Schröder MLMuizelaar JPKuta AJ: Documented reversal of global ischemia immediately after removal of acute subdural hematoma. Report of two cases. J Neurosurg 80:3243271994Schröder ML Muizelaar JP Kuta AJ: Documented reversal of global ischemia immediately after removal of acute subdural hematoma. Report of two cases. J Neurosurg 80:324–327 1994

    • Search Google Scholar
    • Export Citation
  • 48.

    Shapira YYadid GCotev Set al: Protective effect of MK801 in experimental brain injury. J Neurotrauma 7:1311391990Shapira Y Yadid G Cotev S et al: Protective effect of MK801 in experimental brain injury. J Neurotrauma 7:131–139 1990

    • Search Google Scholar
    • Export Citation
  • 49.

    Shimada NGraf RRosner Get al: Differences in ischemia-induced accumulation of amino acids in the cat cortex. Stroke 21:144514511990Shimada N Graf R Rosner G et al: Differences in ischemia-induced accumulation of amino acids in the cat cortex. Stroke 21:1445–1451 1990

    • Search Google Scholar
    • Export Citation
  • 50.

    Shimada NGraf RRosner Get al: Ischemia-induced accumulation of extracellular amino acids in cerebral cortex, white matter, and cerebrospinal fluid. J Neurochem 60:66711993Shimada N Graf R Rosner G et al: Ischemia-induced accumulation of extracellular amino acids in cerebral cortex white matter and cerebrospinal fluid. J Neurochem 60:66–71 1993

    • Search Google Scholar
    • Export Citation
  • 51.

    Shiraishi KSharp FRSimon RP: Sequential metabolic changes in rat brain following middle cerebral artery occlusion: a 2-deoxyglucose study. J Cereb Blood Flow Metab 9:7657731989Shiraishi K Sharp FR Simon RP: Sequential metabolic changes in rat brain following middle cerebral artery occlusion: a 2-deoxyglucose study. J Cereb Blood Flow Metab 9:765–773 1989

    • Search Google Scholar
    • Export Citation
  • 52.

    Smith DHOkiyama KMcIntosh T: Ketamine and magnesium attenuates memory loss after experimental brain injury. Soc Neurosci 17:1671991 (Abstract)Smith DH Okiyama K McIntosh T: Ketamine and magnesium attenuates memory loss after experimental brain injury. Soc Neurosci 17:167 1991 (Abstract)

    • Search Google Scholar
    • Export Citation
  • 53.

    Smith DHOkiyama KThomas Met al: The effects of two novel NMDA antagonists on regional cation concentration and edema formation following experimental brain injury. J Cereb Blood Flow Metab 11 (Suppl 2):S3001991 (Abstract)Smith DH Okiyama K Thomas M et al: The effects of two novel NMDA antagonists on regional cation concentration and edema formation following experimental brain injury. J Cereb Blood Flow Metab 11 (Suppl 2):S300 1991 (Abstract)

    • Search Google Scholar
    • Export Citation
  • 54.

    Smith DHOkiyama KThomas Met al: An NMDA receptor-associated glycine site antagonist attenuates memory loss after experimental brain injury. Soc Neurosci 2:7791990 (Abstract)Smith DH Okiyama K Thomas M et al: An NMDA receptor-associated glycine site antagonist attenuates memory loss after experimental brain injury. Soc Neurosci 2:779 1990 (Abstract)

    • Search Google Scholar
    • Export Citation
  • 55.

    Smith DHThomas MSoares Het al: Differential effects of competitive and non-competitive N-methyl-D-aspartate (NMDA) antagonists following experimental brain injury. J FASEB 4:4001990 (Abstract)Smith DH Thomas M Soares H et al: Differential effects of competitive and non-competitive N-methyl-D-aspartate (NMDA) antagonists following experimental brain injury. J FASEB 4:400 1990 (Abstract)

    • Search Google Scholar
    • Export Citation
  • 56.

    Takizawa SHogan MHakim AM: The effects of a competitive NMDA receptor antagonist (CGS-19755) on cerebral blood flow and pH in focal ischemia. J Cereb Blood Flow Metab 11:7867931991Takizawa S Hogan M Hakim AM: The effects of a competitive NMDA receptor antagonist (CGS-19755) on cerebral blood flow and pH in focal ischemia. J Cereb Blood Flow Metab 11:786–793 1991

    • Search Google Scholar
    • Export Citation
  • 57.

    Zauner ABullock RKuta AJet al: Glutamate release and cerebral blood flow after severe human head injury. Acta Neurochir Suppl 67:40441996Zauner A Bullock R Kuta AJ et al: Glutamate release and cerebral blood flow after severe human head injury. Acta Neurochir Suppl 67:40–44 1996

    • Search Google Scholar
    • Export Citation
  • 58.

    Zauner ADoppenberg EMRWoodward JJet al: Continuous monitoring of cerebral substrate delivery and clearance: initial experience in 24 patients with severe acute brain injuries. Neurosurgery 41:108210931997Zauner A Doppenberg EMR Woodward JJ et al: Continuous monitoring of cerebral substrate delivery and clearance: initial experience in 24 patients with severe acute brain injuries. Neurosurgery 41:1082–1093 1997

    • Search Google Scholar
    • Export Citation
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