Myelinated and unmyelinated axons of the corpus callosum differ in vulnerability and functional recovery following traumatic brain injury
Abstract
Traumatic axonal injury (TAI), a common feature of traumatic brain injury, is associated with postinjury morbidity and mortality. However, TAI is not uniformly expressed in all axonal populations, with fiber caliber and anatomical location influencing specific TAI pathology. To study differential axonal vulnerability to brain injury, axonal excitability and integrity were assessed in the corpus callosum following fluid percussion injury in the rat. In brain slice electrophysiological recordings, compound action potentials (CAPs) were evoked in the corpus callosum, and injury effects were quantified separately for CAP waveform components generated by myelinated axons (N1 wave) and by unmyelinated axons (N2 wave). Ultrastructural analyses were also conducted of TAI-induced morphological changes in these axonal populations. The two populations of axons differed in response to brain injury, and in their functional recovery, during the first week postinjury. Amplitudes of N1 and N2 were significantly depressed at 3 h, 1 day, and 3 days survival. N1 amplitudes exhibited a recovery to control levels by 7 days postinjury. In contrast, N2 amplitudes were persistently suppressed through 7 days postinjury. Strength-duration properties of evoked CAPs further differentiated the effects of injury in these axonal populations, with N2 exhibiting an elevated strength-duration time constant postinjury. Ultrastructural observations revealed degeneration of myelinated axons consistent with diffuse injury sequelae, as well as previously undocumented pathology within the unmyelinated fiber population. Collectively, these findings demonstrate differential vulnerabilities of axons to brain injury and suggest that damage to unmyelinated fibers may play a significant role in morbidity associated with brain injury.
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Traumatic axonal injury does not uniformly affect all axonal populations; smaller, unmyelinated axons may be more susceptible to damage from concussive forces than larger myelinated axons.
“Traumatic axonal injury (TAI) does not uniformly affect all axonal populations; smaller, unmyelinated axons may be more susceptible to damage from concussive forces than larger myelinated axons [158].”
From The neuropathology of sport (2014) · cites this paper as [158]
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- Authors
- REEVES, T., PHILLIPS, L., & POVLISHOCK, J.
- Affiliations
- Virginia Commonwealth University (US)
- Corresponding author
- REEVES, T
- Venue
- Experimental Neurology
- Publisher
- Elsevier BV
- Published
- 2005-11
- Volume
- 196
- Issue
- 1
- Pages
- 126-137
- ISSN
- 0014-4886 (ISSN-L)
- OpenAlex
- W1994314634
- Cited by
- 270
- References
- 40
- Citations by year
- 2026: 7 · 2025: 9 · 2024: 9 · 2023: 12 · 2022: 18 · 2021: 11 · 2020: 15 · 2019: 16 · 2018: 11 · 2017: 20 · 2016: 18 · 2015: 26 · 2014: 13 · 2013: 16 · 2012: 20
- FWCI
- 3.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS020193, NS-20193)
- Topics
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Keywords
- traumatic axonal injury, traumatic brain injury, corpus callosum, myelinated axons, unmyelinated axons, functional recovery, compound action potential, fluid percussion injury, axonal excitability, axon ultrastructure, axonal degeneration
- MeSH terms
- Action Potentials, Animals, Brain Injuries, Corpus Callosum, Electrophysiology, Male, Nerve Fibers, Myelinated, Nerve Regeneration, Organ Culture Techniques, Nerve Fibers, Unmyelinated, Microscopy, Electron, Transmission, Rats
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