ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2004
Traumatic axonal injury induces proteolytic cleavage of the voltage-gated sodium channels modulated by tetrodotoxin and protease inhibitors.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers.
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Who cites it
106 citing papers in PubMed, 217 citations in OpenAlex.
- A statistical damage model for coupled mechano-electrophysiological axonal injury.PLoS computational biology · 2026Article
- Differences in the Subcortical White Matter Integrity Based on the Disorder of Consciousness at the Chronic Stage of Diffuse Axonal Injury: A Tract-Based Spatial Statistics Study.Medicina (Kaunas, Lithuania) · 2026Article
- The Role of MRI in Debunking the Fallacy of "Mild" Traumatic Brain Injury.Journal of magnetic resonance imaging : JMRI · 2026Review
- Synaptic Pathology in Traumatic Brain Injury and Therapeutic Insights.International journal of molecular sciences · 2025Review
- Review
- Mechanisms of Traumatic Spinal Cord Injury AIS Grade Conversion.Neurotrauma reports · 2025Review
- Article
- The neuropathological basis of elevated serum neurofilament light following experimental concussion.Acta neuropathologica communications · 2024Article
- Sex differences in the extent of acute axonal pathologies after experimental concussion.Acta neuropathologica · 2024Article
- Longitudinal changes in sodium concentration and in clinical outcome in mild traumatic brain injury.Brain communications · 2024Article
- Voluntary running wheel exercise induces cognitive improvement post traumatic brain injury in mouse model through redressing aberrant excitation regulated by voltage-gated sodium channels 1.1, 1.3, and 1.6.Experimental brain research · 2024Article
- Identifying the Phenotypes of Diffuse Axonal Injury Following Traumatic Brain Injury.Brain sciences · 2023Review
- Hippocampal interneuronal dysfunction and hyperexcitability in a porcine model of concussion.Communications biology · 2023Article
- Military-related mild traumatic brain injury: clinical characteristics, advanced neuroimaging, and molecular mechanisms.Translational psychiatry · 2023Review
- The Node of Ranvier as an Interface for Axo-Glial Interactions: Perturbation of Axo-Glial Interactions in Various Neurological Disorders.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2023Review
- Dorsal root ganglion neurons recapitulate the traumatic axonal injury of CNS neurons in response to a rapid stretchFrontiers in cellular neuroscience · 2023Article
- Traumatic axonal injury: neuropathological features, postmortem diagnostic methods, and strategies.Forensic science, medicine, and pathology · 2022Review
- Concussion leads to widespread axonal sodium channel loss and disruption of the node of Ranvier.Acta neuropathologica · 2022Article
- A multilayer network model of neuron-astrocyte populations in vitro reveals mGluRNetwork neuroscience (Cambridge, Mass.) · 2022Article
- Military traumatic brain injury: a challenge straddling neurology and psychiatry.Military Medical Research · 2022Review
46 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
We demonstrated previously that dynamic stretch injury of cultured axons induces structural changes and Ca2+ influx modulated by tetrodotoxin (TTX)-sensitive voltage-gated sodium channels (NaChs). In the present study, we evaluated potential damage to the NaCh alpha-subunit, which can cause noninactivation of NaChs. In addition, we explored the effects of pre-injury and post-injury treatment with TTX and protease inhibition on proteolysis of the NaCh alpha-subunit and intra-axonal calcium levels ([Ca2+]i) over 60 min after trauma. After stretch injury, we found that [Ca2+]i continued to increase in untreated axons for at least 60 min. We also observed that the III-IV intra-axonal loop of the NaCh alpha-subunit was proteolyzed between 5 and 20 min after trauma. Pre-injury treatment of the axons with TTX completely abolished the posttraumatic increase in [Ca2+]i and proteolysis of the NaCh alpha-subunit. In addition, both pre-injury and post-injury inhibition of protease activity attenuated long-term increases in [Ca2+]i as well as mitigating degradation of the NaCh alpha-subunit. These results suggest a unique "feed-forward" deleterious process initiated by mechanical trauma of axons. Na+ influx through NaChs resulting from axonal deformation triggers initial increases in [Ca2+]i and subsequent proteolysis of the NaCh-subunit. In turn, degradation of the alpha-subunit promotes persistent elevations in [Ca2+]i, fueling additional pathologic changes. These observations may have important implications for developing therapeutic strategies for axonal trauma.
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