Factors affecting excitatory amino acid release following severe human head injury

J Neurosurg. 1998 Oct;89(4):507-18. doi: 10.3171/jns.1998.89.4.0507.


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 micromol/L). Sustained high ICP and poor outcome were significantly correlated to high levels of EAAs (glutamate > 20 micromol/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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acids / analysis
  • Brain Concussion / drug therapy
  • Brain Concussion / metabolism
  • Brain Injuries / drug therapy
  • Brain Injuries / metabolism*
  • Brain Ischemia / drug therapy
  • Brain Ischemia / metabolism
  • Cell Death
  • Cell Size
  • Chromatography, High Pressure Liquid
  • Craniocerebral Trauma / drug therapy
  • Craniocerebral Trauma / metabolism*
  • Excitatory Amino Acid Antagonists / therapeutic use
  • Excitatory Amino Acids / analysis
  • Excitatory Amino Acids / metabolism*
  • Exocytosis / physiology
  • Extracellular Space / metabolism
  • Female
  • Glutamic Acid / metabolism
  • Homeostasis
  • Humans
  • Intracranial Hypertension / drug therapy
  • Intracranial Hypertension / metabolism
  • Intracranial Pressure
  • Male
  • Microdialysis / instrumentation
  • Presynaptic Terminals / metabolism
  • Treatment Outcome
  • Ventriculostomy / instrumentation


  • Amino Acids
  • Excitatory Amino Acid Antagonists
  • Excitatory Amino Acids
  • Glutamic Acid