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Proceedings Paper

A review of glutamate's role in traumatic brain injury mechanisms
Author(s): Cameron H. Good
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Paper Abstract

Glutamate is the primary excitatory neurotransmitter used by the central nervous system (CNS) for synaptic communication, and its extracellular concentration is tightly regulated by glutamate transporters located on nearby astrocytes. Both animal models and human clinical studies have demonstrated elevated glutamate levels immediately following a traumatic brain event, with the duration and severity of the rise corresponding to prognosis. This rise in extracellular glutamate likely results from a combination of excessive neurotransmitter release from damaged neurons and down regulation of uptake mechanisms in local astrocytes. The immediate results of a traumatic event can lead to necrotic tissue in severely injured regions, while prolonged increases in excitatory transmission can cause secondary excitotoxic injury through activation of delayed apoptotic pathways. Initial TBI animal studies utilized a variety of broad glutamate receptor antagonists to successfully combat secondary injury mechanisms, but unfortunately this same strategy has proven inconclusive in subsequent human trials due to deleterious side effects and heterogeneity of injuries. More recent treatment strategies have utilized specific glutamate receptor subunit antagonists in an effort to minimize side effects and have shown promising results. Future challenges will be detecting the concentration and kinetics of the glutamate rise following injury, determining which patient populations could benefit from antagonist treatment based on their extracellular glutamate concentrations and when drugs should be administered to maximize efficacy.

Paper Details

Date Published: 29 May 2013
PDF: 8 pages
Proc. SPIE 8723, Sensing Technologies for Global Health, Military Medicine, and Environmental Monitoring III, 87230Q (29 May 2013); doi: 10.1117/12.2021764
Show Author Affiliations
Cameron H. Good, U.S. Army Research Lab. (United States)

Published in SPIE Proceedings Vol. 8723:
Sensing Technologies for Global Health, Military Medicine, and Environmental Monitoring III
Šárka O. Southern, Editor(s)

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