Dramatic increases in blood glutamate concentrations are closely related to traumatic brain injury-induced acute lung injury

Abstract

Traumatic brain injury-induced acute lung injury (TBI-ALI) is a serious complication after brain injury for which predictive factors are lacking. In this study, we found significantly elevated blood glutamate concentrations in patients with TBI or multiple peripheral trauma (MPT), and patients with more severe injuries showed higher blood glutamate concentrations and longer durations of elevated levels. Although the increase in amplitude was similar between the two groups, the duration was longer in the patients with TBI. There were no significant differences in blood glutamate concentrations in the patients with MPT with regard to ALI status, but the blood glutamate levels were significantly higher in the patients with TBI-ALI than in those without ALI. Moreover, compared to patients without ALI, patients with TBI showed a clearly enhanced inflammatory response that was closely correlated with the blood glutamate levels. The blood glutamate concentration was also found to be a risk factor (adjusted odds ratio, 2.229; 95% CI, 1.082–2.634) and was a better predictor of TBI-ALI than the Glasgow Coma Scale (GCS) score. These results indicated that dramatically increased blood glutamate concentrations were closely related to the occurrence of TBI-ALI and could be used as a predictive marker for “at-risk” patients.

Glutamate triggers the expression of functional ionotropic and metabotropic glutamate receptors in mast cells

“…It is known that the concentration of glutamate in blood is~50-100 µM, whereas the extracellular levels of glutamate in the tissues are considerably lower (<1 µM). [32][33][34] Our data suggest that MC activation was triggered at glutamate concentrations ≥10 µM. It is thus reasonable to assume that the baseline concentration of extracellular glutamate in tissues is below this level.…”

Homeostasis of the Intraparenchymal-Blood Glutamate Concentration Gradient: Maintenance, Imbalance, and Regulation

“…However, the effect of elevated blood glutamate on the concentration of intraparenchymal glutamate and whether it is also an important source of the rapid increase in intraparenchymal glutamate remain poorly understood. Moreover, while there is no direct evidence showing that intraparenchymal glutamate levels influence blood glutamate levels, the results of our recent studies in patients with TBI indicate that the severity of brain injury is positively associated with blood glutamate levels ( Bai et al, 2017 ).…”

“…The glutamate concentration in the blood of healthy adults ranges from 40 to 60 μM ( Bai et al, 2017 ). In some in vitro studies using acute brain slices, extracellular glutamate ranges from 25 to 90 nM ( Cavelier and Attwell, 2005 ; Herman and Jahr, 2007 ; Le Meur et al, 2007 ); however, most in vivo studies using microdialysis, which is an FDA-approved method for clinical application, found much higher glutamate levels in brain, ranging from 0.2 μM to approximately 20 μM ( Dash et al, 2009 ; De Bundel et al, 2011 ).…”

“…Moreover, researchers have also found that an excitotoxic reaction is induced by high levels of blood glutamate in these tissues that is similar to that induced in the CNS ( Skerry and Genever, 2001 ). In addition, our previous clinical results showed that high levels of blood glutamate are closely related to the occurrence of traumatic brain injury-induced acute lung injury (TBI-ALI) ( Bai et al, 2017 ). These data further indicate that blood glutamate plays an important role in peripheral organs.…”

A New Perspective on Using Glycols in Glutamate Biosensor Design: From Stabilizing Agents to a New Containment Net

“…In some studies, glutamate concentrations were measured in blood samples using high-performance liquid chromatography (HPLC) [17,18]. While blood sampling is more invasive than imaging, the approach is still suitable for use in patients, and HPLC is reliable and sensitive enough to measure glutamate concentrations in blood samples, as well as in brain samples [17,19,20].…”