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Axonal pathology in traumatic brain injury
Open accessAbstract
Over the past 70 years, diffuse axonal injury (DAI) has emerged as one of the most common and important pathological features of traumatic brain injury (TBI). Axons in the white matter appear to be especially vulnerable to injury due to the mechanical loading of the brain during TBI. As such, DAI has been found in all severities of TBI and may represent a key pathologic substrate of mild TBI (concussion). Pathologically, DAI encompasses a spectrum of effects from primary mechanical breaking of the axonal cytoskeleton, to transport interruption, swelling and proteolysis, through secondary physiological changes. Depending on the severity and extent of injury, these changes can manifest acutely as immediate loss of consciousness or confusion and persist as coma and/or cognitive dysfunction. In addition, recent evidence suggests that TBI may induce long-term neurodegenerative processes, such as insidiously progressive axonal pathology. Indeed, axonal degeneration has been found to continue even years after injury in humans, and appears to play a role in the development of Alzheimer’s disease-like pathological changes. Here we review the current understanding of DAI as a uniquely mechanical injury, its histopathological identification, and its acute and chronic pathogenesis following TBI.
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“As a neuropathological definition, concussion is thought to be a type of DAI because axons may be injured due to stretching (104, 105).”
From Pituitary Dysfunction After Traumatic Brain Injury: A Clinical and Pathophysiological Approach (2015) · cites this paper as [105]
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“DAI is the primary neuropathology of TBI that is caused by the shearing of fragile axons (disruption of axonal fibers and myelin sheaths) by acceleration/deceleration forces from the head trauma (105, 106).”
From Pituitary Dysfunction After Traumatic Brain Injury: A Clinical and Pathophysiological Approach (2015) · cites this paper as [105]
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“By using histopathological techniques, DAI can be identified within hours after head trauma and is characterized by sequential changes with an initial shearing of axons that causes disrupted axonal transport, secondary axonal disconnection, and eventually, Wallerian degeneration (105, 110).”
From Pituitary Dysfunction After Traumatic Brain Injury: A Clinical and Pathophysiological Approach (2015) · cites this paper as [105]
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“As we discussed above, concussion is the most frequent type of acute TBI in sports-related head trauma, and DAI, which is caused by the shearing of fragile axons, is the primary pathophysiology of TBI (105).”
From Pituitary Dysfunction After Traumatic Brain Injury: A Clinical and Pathophysiological Approach (2015) · cites this paper as [105]
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Localized Axolemma Deformations Suggest Mechanoporation as Axonal Injury Trigger
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Mild Traumatic Brain Injury Results in Significant and Lasting Cortical Demyelination
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Physical Biology of Axonal Damage
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Toward a Comprehensive Delineation of White Matter Tract-Related Deformation
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Paclitaxel improves outcome from traumatic brain injury
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Bidirectional Changes in Anisotropy Are Associated with Outcomes in Mild Traumatic Brain Injury
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Axonal injury is a targetable driver of glioblastoma progression
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Mechanisms of Local Stress Amplification in Axons near the Gray-White Matter Interface
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Modelling the slight compressibility of anisotropic soft tissue
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Metadata
- Authors
- Johnson, V. E., Stewart, W., & Smith, D. H.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Smith, Douglas H.
- Venue
- Experimental Neurology
- Publisher
- Elsevier BV
- Published
- 2013-08
- Volume
- 246
- Pages
- 35-43
- ISSN
- 0014-4886 (ISSN-L)
- PMC
- PMC3979341
- OpenAlex
- W2170921124
- Semantic Scholar
- 6fdff07fcccb6429453f06a8aae43cdaad508837
- Cited by
- 1,273
- References
- 162
- Citations by year
- 2026: 82 · 2025: 88 · 2024: 86 · 2023: 106 · 2022: 105 · 2021: 123 · 2020: 102 · 2019: 98 · 2018: 93 · 2017: 113 · 2016: 92 · 2015: 89 · 2014: 37 · 2013: 44
- FWCI
- 8.26
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (R03AG038911)
- National Institute of Neurological Disorders and Stroke (NS-038104, R01NS038104, P01NS056202, NS 056202)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury Research
- Physical Sciences › Engineering › Biomedical Engineering › Automotive and Human Injury Biomechanics
- Keywords
- diffuse axonal injury, traumatic brain injury, axonal pathology, white matter, mild traumatic brain injury, concussion, axonal cytoskeleton, axonal transport, axonal swellings, proteolysis, secondary injury, Alzheimer's disease, histopathology, pathogenesis
- MeSH terms
- Animals, Axons, Brain Injuries, Coma, Humans, Nerve Degeneration, Nerve Fibers, Myelinated, Diffuse Axonal Injury
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