Factors affecting excitatory amino acid release following severe human head injury

Ross Bullock, Alois Zauner, John J. Woodward, John Myseros, Sung C. Choi, John D. Ward, Anthony Marmarou, Harold F. Young

Research output: Contribution to journalArticlepeer-review

407 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)507-518
Number of pages12
JournalJournal of neurosurgery
Issue number4
StatePublished - Oct 1998


  • Glutamate
  • Glutamate antagonist
  • Intracranial pressure
  • Microdialysis
  • Outcome
  • Severe head injury

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)


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