Ultrastructural evidence of axonal shearing as a result of lateral acceleration of the head in non-human primates
Abstract
The concept of shearing of axons at the time of non-impact injury to the head was first suggested in the middle of this century. However, no experimental model of diffuse axonal injury (DAI) has provided morphological confirmation of this concept. Evidence from experiments on invertebrate axons suggests that membrane resealing after axonal transection occurs between 5 and 30 min after injury. Thus, ultrastructural evidence in support of axonal shearing will probably only be obtained by examination of very short-term survival animal models. We have examined serial thin sections from the corpus callosum of non-human primates exposed to lateral acceleration of the head under conditions which induce DAI. Tearing or shearing of axons was obtained 20 and 35 min after injury, but not at 60 min. Axonal fragmentation occurred more frequently at the node/paranode but also in the internodal regions of axons. Fragmentation occurred most frequently in small axons. Axonal shearing was associated with dissolution of the cytoskeleton and the occurrence of individual, morphologically abnormal membranous organelles. There was no aggregation of membranous organelles at 20 and 35 min but small groups did occur in some axons at 60 minutes. We suggest that two different mechanisms of injury may be occurring in non-impact injury to the head. The first is shearing of axons and sealing of fragmented axonal membranes within 60 min. A second mechanism occurs in other fibres where perturbation of the ax…
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Traumatic axonal injury is an additional source of accumulating APP.
“Traumatic axonal injury (TAI) is an additional source of accumulating APP (127, 128).”
From The Inflammatory Continuum of Traumatic Brain Injury and Alzheimer’s Disease (2018) · cites this paper as [128]
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“DAI is sustained when the inertial force, generated by forced rotational movement, is applied to the head at the time of the impact (Maxwell et al., 1993; Gennarelli et al., 1998).”
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Yue, Y.-X., Li, Q., Bu, W.-P., Liu, X.-P., Wang, L.-Z., & Fan, Y.-B. (2026) · Medicine in Novel Technology and Devices · doi:10.1016/j.medntd.2026.100463
Microglial process convergence onto injured axonal swellings, a human postmortem brain tissue study
Logan-Wesley, A. L., Gorse, K., & Lafrenaye, A. D. (2024) · Research Square · doi:10.21203/rs.3.rs-4713316/v1
“Secondary axonal injury involves accumulation of the cytoskeleton and organelles within the axons[37–39].”
Powell, M. A. (2016) · doi:10.25772/s1cq-ce32
“occurs primarily in severe injuries (Maxwell et al., 1993), and is likely not a major contributor of axon damage in moderate and mild TBIs.”
BackgroundFatal Pediatric Craniocerebral and Spinal Trauma
Case, M., Collins, K., & Byard, R. (2014) · Springer eBooks · doi:10.1007/978-1-61779-403-2_8
Harris, J. L. (2008) · VCU Scholars Compass (Virginia Commonwealth University) · doi:10.25772/0dqa-d954
“…of axons due to mechanical shear at the moment of impact, this view has been expanded to include the occurrence of both immediate “primary axotomy”, as well as “secondary axotomy” which 6 develops progressively over the course of hours to days after the initial injury (Maxwell et al., 1993).”
BackgroundSun, F.-X. (2003) · doi:10.1007/978-3-540-35280-8_760
- Authors
- Maxwell, W. L., Watt, C., Graham, D. I., & Gennarelli, T. A.
- Affiliations
- University of Glasgow (GB)
- University of Pennsylvania (US)
- Venue
- Acta Neuropathologica
- Published
- 1993-07
- Volume
- 86
- Issue
- 2
- Pages
- 136-144
- ISSN
- 0001-6322 (ISSN-L)
- 1432-0533
- OpenAlex
- W2088301798
- Cited by
- 161
- References
- 0
- Citations by year
- 2026: 2 · 2024: 5 · 2023: 2 · 2022: 2 · 2021: 1 · 2020: 2 · 2019: 2 · 2018: 6 · 2017: 5 · 2016: 3 · 2015: 9 · 2014: 2 · 2013: 4 · 2012: 9
- FWCI
- 4.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Acta Neuropathologica (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (NS-08803-21)
- Topics
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Automotive and Human Injury Biomechanics
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Keywords
- axonal shearing, diffuse axonal injury, lateral acceleration, corpus callosum, axonal swellings, membranous organelles, non-human primates, ultrastructure
- MeSH terms
- Acceleration, Animals, Haplorhini, Axons, Axonal Transport, Brain, Corpus Callosum, Craniocerebral Trauma, Microscopy, Electron, Nerve Fibers, Ranvier's Nodes, Time Factors
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