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Cited by 163Traumatic Brain Injury and Neurovascular DisturbancesTraumatic Brain Injury ResearchNeuroscience and Neuropharmacology Research

Glutamate neurotransmission in rodent models of traumatic brain injury

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Dorsett, Christopher R., McGuire, Jennifer L., DePasquale, Erica A. K., Gardner, Amanda E., Floyd, Candace L., McCullumsmith, Robert E.·2017·Journal of Neurotrauma
DOI 10.1089/neu.2015.4373PMC PMC5220558
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Abstract

Traumatic brain injury (TBI) is a leading cause of death and disability in people younger than 45 and is a significant public health concern. In addition to primary mechanical damage to cells and tissue, TBI involves additional molecular mechanisms of injury, termed secondary injury, that continue to evolve over hours, days, weeks, and beyond. The trajectory of recovery after TBI is highly unpredictable and in many cases results in chronic cognitive and behavioral changes. Acutely after TBI, there is an unregulated release of glutamate that cannot be buffered or cleared effectively, resulting in damaging levels of glutamate in the extracellular space. This initial loss of glutamate homeostasis may initiate additional changes in glutamate regulation. The excitatory amino acid transporters (EAATs) are expressed on both neurons and glia and are the principal mechanism for maintaining extracellular glutamate levels. Diffusion of glutamate outside the synapse due to impaired uptake may lead to increased extrasynaptic glutamate signaling, secondary injury through activation of cell death pathways, and loss of fidelity and specificity of synaptic transmission. Coordination of glutamate release and uptake is critical to regulating synaptic strength, long-term potentiation and depression, and cognitive processes. In this review, we will discuss dysregulation of extracellular glutamate and glutamate uptake in the acute stage of TBI and how failure to resolve acute disruptions in glutamate homeostatic mechanisms may play a causal role in chronic cognitive symptoms after TBI.

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Authors
Dorsett, C. R., McGuire, J. L., DePasquale, E. A. K., Gardner, A. E., Floyd, C. L., & McCullumsmith, R. E.
Affiliations
  • University of North Carolina at Chapel Hill (US)
  • University of Cincinnati (US)
  • University of Alabama at Birmingham (US)
Corresponding author
McCullumsmith, Robert E.
ORCID
Venue
Journal of Neurotrauma
Publisher
SAGE Publications
Published
2017-01
Volume
34
Issue
2
Pages
263-272
ISSN
  • 0897-7151 (ISSN-L)
  • 1557-9042
DOI
10.1089/neu.2015.4373
PMC
PMC5220558
OpenAlex
W2494112084
Cited by
163
References
0
Citations by year
2026: 15 · 2025: 11 · 2024: 26 · 2023: 16 · 2022: 22 · 2021: 22 · 2020: 16 · 2019: 15 · 2018: 12 · 2017: 6 · 2016: 1
FWCI
1.57
Type
journal article
Language
en
Open access
Licence
journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
Locations
  • Journal of Neurotrauma (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
  • UNC Libraries
Funders
  • National Institute of Mental Health (R01MH094445, R01MH107487)
  • National Institute of Neurological Disorders and Stroke (R01NS075162)
Topics
  • Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
  • Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
traumatic brain injury, glutamatergic neurotransmission, glutamate transporters, glutamate homeostasis, secondary injury, excitotoxicity, synaptic transmission, long-term potentiation and depression, rodent models
MeSH terms
Brain Injuries, Traumatic, Animals, Disease Models, Animal, Humans, Synaptic Transmission, Neuroglia, Rodentia, Synapses, Signal Transduction, Glutamic Acid, Glutamate Plasma Membrane Transport Proteins, Mice, Rats

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