Excitatory amino acids in cerebrospinal fluid following traumatic brain injury in humans

Abstract

Evidence from models of traumatic brain injury implicates excitotoxicity as an integral process in the ultimate neuronal damage that follows. Concentrations of the excitatory amino acid glutamate were serially measured in the cerebrospinal fluid (CSF) of patients with traumatic brain injuries and in control patients for comparison. The purpose of the study was to determine whether glutamate concentrations were significantly elevated following traumatic brain injury and, if so, whether they were elevated in a time frame that would allow the use of antagonist therapy. Cerebrospinal fluid was sampled fresh from ventricular drains every 12 hours and analyzed using high-performance liquid chromatography for the excitatory amino acids. The peak concentrations of glutamate in the CSF of the 12 brain-injured patients ranged from 14 to 474 microM and were significantly higher than those in the three control patients, 4.9 to 17 microM (Mann-Whitney U-test, p < 0.02). Glutamate concentrations in five of the eight patients who were still being sampled on Day 3 were beyond the control group range. The implication of this study is that severely head-injured patients are exposed to high concentrations of a neurotoxic amino acid for days following injury and thus may benefit from antagonist intervention.

The Effect of Blood Glutamate Scavengers Oxaloacetate and Pyruvate on Neurological Outcome in a Rat Model of Subarachnoid Hemorrhage

“…Thus, one can predict that scavengers will be effective in removing excess brain glutamate only when it is administered before the brain injury or during a specific time window of glutamate elevation. However, previous studies have shown that the elevation of glutamate in the ECF of the brain in rats after TBI and stroke is usually short-lasting, rarely extending to 120 minutes [71][72][73][74], whereas in humans it continues for several hours and even days [75][76][77]. Considering that the elevation of glutamate lasts longer in humans than in rats, blood glutamate scavengers may theoretically be effective, even if given later in the course of the condition.…”

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“…The progression to infarction despite adequate CPP may be explained by altered autoregulation, direct toxicity from blood, or neurochemical alterations. For example, experimental models of traumatic hematoma [6] or diffuse axonal injury [13] and clinical studies [1] demonstrate that levels of excitatory amino acids, such as glutamate, which in high concentrations appear integral to the pathophysiological mechanism of neuron injury and death in cerebral ischemia, [27] are increased after head injury and may alter membrane permeability through activation of ligand-gated channels. Similarly, following injury, direct mechanical stimulation can cause ionic fluxes and neuron firing.…”

“…[24,33,50] This discrepancy may result, in part, from other factors not reflected in either ICP or CPP, such as disturbed autoregulation, [2,14,34] traumatic vasospasm, [29] or neurochemical changes such as elevated excitatory amino acids, [1] which may adversely influence cerebral blood flow (CBF) or tissue oxygenation and contribute to infarction.…”

Determination of Glycine Based on Fluorimetric Enhancement of Eu(III)-TTA Complex

“…[1][2][3][4][5] It is also used as a dietary supplement in pharmaceutical formulation. 6 Therefore, reliable measurements of glycine in trace amounts are an important tool.…”