FACTORS AFFECTING EXCITATORY AMINO-ACID RELEASE FOLLOWING SEVERE HUMAN HEAD-INJURY

Recent animal studies demonstrate that excitatory amino acids (EAAs) p lay a major role in neuronal damage after brain trauma and ischemia. H owever, the role of EAAs in patients who have suffered severe head inj ury is not understood. Excess quantities of glutamate in the extracell ular space may lead to uncontrolled shifts of sodium, potassium, and c alcium, disrupting ionic homeostasis, which may lead to severe cell sw elling and cell death. The authors evaluated the role of EEAs in human traumatic brain injury. Methods. In SO consecutive severely head inju red patients, a microdialysis probe was placed into the gray matter al ong with a ventriculostomy catheter or an intracranial pressure (ICP) monitor for 4 days. Levels of EAAs and structural amino acids were ana lyzed using high-performance liquid chromatography. Multifactorial ana lysis of the amino acid pattern was performed and its correlations wit h clinical parameters and outcome were tested. The levels of EAAs were increased up to 50 times normal in 30% of the patients and were signi ficantly correlated to levels of structural amino acids both in each p atient and across the whole group (p < 0.01). Secondary ischemic brain injury and focal contusions were most strongly associated with high E AA levels (27 +/- 22 mu mol/L). Sustained high ICP and poor outcome we re significantly correlated to high levels of EAAs (glutamate > 20 mu mol/L; p < 0.01). Conclusions. The release of EAAs is closely linked t o the release of structural amino acids and may thus reflect nonspecif ic development of membrane micropores, rather than presynaptic neurona l vesicular exocytosis. The magnitude of EAA release in patients with focal contusions and ischemic events may be sufficient to exacerbate n euronal damage, and these patients may be the best candidates for trea tment with glutamate antagonists in the future.