Cited by 112Traumatic Brain Injury and Neurovascular DisturbancesNeuroscience and Neuropharmacology ResearchTraumatic Brain Injury Research

Calcium-Permeable AMPA Receptors Appear in Cortical Neurons after Traumatic Mechanical Injury and Contribute to Neuronal Fate

Open access
Spaethling, Jennifer M., Klein, Donna M., Singh, Pallab, Meaney, David F.·2008·Journal of Neurotrauma

Abstract

Traumatic brain injury (TBI) is one of the most disabling injuries in the population, with 1.5 million Americans new cases each year and 5.3 million Americans overall requiring long-term daily care as a result of their injuries. One critical aspect in developing effective treatments for TBI is determining if new, specific receptor populations emerge in the early phase after injury that can subsequently be targeted to reduce neuronal death after injury. One specific glutamate receptor subtype, the calcium-permeable AMPA receptor (CP-AMPAR), is becoming increasingly recognized for its role in physiological and pathophysiological processes. Although present in relatively low levels in the mature brain, recent studies show that CP-AMPARs can appear following ischemic brain injury or status epilepticus, and the mechanisms that regulate the appearance of these receptors include alterations in transcription, RNA editing, and receptor trafficking. In this report, we use an in vitro model of TBI to show a gradual appearance of CP-AMPARs four hours following injury to cortical neurons. Moreover, the appearance of these receptors is mediated by the phosphorylation of CaMKIIalpha following injury. Selectively blocking CP-AMPARs after mechanical injury leads to a significant reduction in the cell death that occurs 24 h following injury in untreated controls, and is similar in protection offered by broad-spectrum NMDA and AMPA receptor antagonists. These data point to a potentially new and more targeted therapeutic approach for treating TBI.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1089/neu.2008.0532

Cites

60 of 60 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Blocking calcium-permeable AMPA receptors reduces cortical neuron death in an in vitro traumatic brain injury model, hippocampal pyramidal neuron loss in an oxygen-glucose deprivation slice model, and retinal ganglion cell loss in a glaucoma rat model.

    “Consistent with the notion that the presence of Ca 2+ -permeable AMPA receptors contributes to the vulnerability of PV-INs, blocking of these receptors attenuates cortical neuron death in an in vitro model of traumatic brain injury; attenuates hippocampal pyramidal neuron loss in a mouse hippocampal slice model of oxygen-glucose deprivation; and attenuates retinal ganglion cells loss in a rat”

    From Parvalbumin interneuron vulnerability and brain disorders (2021) · cites this paper as [117]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 3

  1. Jia Y Jeng J-M Sensi SL Weiss JH Zn2+ currents are mediated by calcium-permeable AMPA/kainate channels in cultured murine hippocampal neurons J. Physiol 2002 543 35 48 12181280 PMC2290471
  2. Laplaca MC Thibault LE Dynamic mechanical deformation of neurons triggers an acute calcium response and cell injury involving the N-methyl-d-aspartate glutamate receptor J. Neurosci. Res 1998 52 220 229 9579412
  3. Thurman D Alverson C Dunn K Guerrero J Sniezek J Traumatic brain injury in the United States: a public health perspective J. Head Trauma Rehabil 1999 14 602 615 10671706

Cited by

Sorted by citations

Authors
Spaethling, J. M., Klein, D. M., Singh, P., & Meaney, D. F.
Affiliations
University of Pennsylvania (US)
Corresponding author
Meaney, David F.
Venue
Journal of Neurotrauma
Published
2008-10
Volume
25
Issue
10
Pages
1207-1216
ISSN
  • 0897-7151 (ISSN-L)
  • 1557-9042
OpenAlex
W2096887290
Cited by
112
References
60
Citations by year
2026: 3 · 2025: 5 · 2024: 5 · 2023: 5 · 2022: 6 · 2021: 11 · 2020: 7 · 2019: 4 · 2018: 4 · 2017: 5 · 2016: 6 · 2015: 10 · 2014: 3 · 2013: 6 · 2012: 8
FWCI
5.04
Type
journal article
Language
en
Open access
Locations
  • Journal of Neurotrauma (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Institute of Neurological Disorders and Stroke (NS35712, R01NS035712)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD041699)
Topics
  • Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
Keywords
calcium-permeable AMPA receptors, traumatic brain injury, cortical neurons, neuronal cell death, receptor trafficking, AMPA receptor antagonists, NMDA receptor antagonists, glutamate receptors
MeSH terms
Animals, Brain Injuries, Calcium, Cells, Cultured, Cerebral Cortex, Cytosol, Nerve Degeneration, Neurons, Stress, Mechanical, Time Factors, Up-Regulation, Cell Death, RNA Editing, Receptors, AMPA, Patch-Clamp Techniques, Excitatory Amino Acid Antagonists, Neuroprotective Agents, Cytoprotection, Calcium Signaling, Protein Transport, Rats, Calcium-Calmodulin-Dependent Protein Kinase Type 2

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review