Traumatic brain injury results in cellular, structural and functional changes resembling motor neuron disease

David K. Wright, Shijie Liu, Chris Van Der Poel, Stuart J. McDonald, Rhys D. Brady, Lily Taylor, Li Yang, Andrew J. Gardner, Roger Ordidge, Terence J. O'Brien, Leigh A. Johnston, Sandy R. Shultz

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Traumatic brain injury (TBI) has been suggested to increase the risk of amyotrophic lateral sclerosis (ALS). However, this link remains controversial and as such, here we performed experimental moderate TBI in rats and assessed for the presence of ALS-like pathological and functional abnormalities at both 1 and 12 weeks post-injury. Serial in-vivo magnetic resonance imaging (MRI) demonstrated that rats given a TBI had progressive atrophy of the motor cortices and degeneration of the corticospinal tracts compared with sham-injured rats. Immunofluorescence analyses revealed a progressive reduction in neurons, as well as increased phosphorylated transactive response DNA-binding protein 43 (TDP-43) and cytoplasmic TDP- 43, in the motor cortex of rats given a TBI. Rats given a TBI also had fewer spinal cord motor neurons, increased expression of muscle atrophy markers, and altered muscle fiber contractile properties compared with sham-injured rats at 12 weeks, but not 1 week, post-injury. All of these changes occurred in the presence of persisting motor deficits. These findings resemble some of the pathological and functional abnormalities common in ALS and support the notion that TBI can result in a progressive neurodegenerative disease process pathologically bearing similarities to a motor neuron disease.

Original languageEnglish
Pages (from-to)4503-4515
Number of pages13
JournalCerebral Cortex
Volume27
Issue number9
DOIs
Publication statusPublished - 2017
Externally publishedYes

Keywords

  • Amyotrophic lateral sclerosis
  • Animal model
  • MRI
  • Neurodegeneration
  • TDP-43

Cite this

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title = "Traumatic brain injury results in cellular, structural and functional changes resembling motor neuron disease",
abstract = "Traumatic brain injury (TBI) has been suggested to increase the risk of amyotrophic lateral sclerosis (ALS). However, this link remains controversial and as such, here we performed experimental moderate TBI in rats and assessed for the presence of ALS-like pathological and functional abnormalities at both 1 and 12 weeks post-injury. Serial in-vivo magnetic resonance imaging (MRI) demonstrated that rats given a TBI had progressive atrophy of the motor cortices and degeneration of the corticospinal tracts compared with sham-injured rats. Immunofluorescence analyses revealed a progressive reduction in neurons, as well as increased phosphorylated transactive response DNA-binding protein 43 (TDP-43) and cytoplasmic TDP- 43, in the motor cortex of rats given a TBI. Rats given a TBI also had fewer spinal cord motor neurons, increased expression of muscle atrophy markers, and altered muscle fiber contractile properties compared with sham-injured rats at 12 weeks, but not 1 week, post-injury. All of these changes occurred in the presence of persisting motor deficits. These findings resemble some of the pathological and functional abnormalities common in ALS and support the notion that TBI can result in a progressive neurodegenerative disease process pathologically bearing similarities to a motor neuron disease.",
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author = "Wright, {David K.} and Shijie Liu and {Van Der Poel}, Chris and McDonald, {Stuart J.} and Brady, {Rhys D.} and Lily Taylor and Li Yang and Gardner, {Andrew J.} and Roger Ordidge and O'Brien, {Terence J.} and Johnston, {Leigh A.} and Shultz, {Sandy R.}",
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Traumatic brain injury results in cellular, structural and functional changes resembling motor neuron disease. / Wright, David K.; Liu, Shijie; Van Der Poel, Chris; McDonald, Stuart J.; Brady, Rhys D.; Taylor, Lily; Yang, Li; Gardner, Andrew J.; Ordidge, Roger; O'Brien, Terence J.; Johnston, Leigh A.; Shultz, Sandy R.

In: Cerebral Cortex, Vol. 27, No. 9, 2017, p. 4503-4515.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Traumatic brain injury results in cellular, structural and functional changes resembling motor neuron disease

AU - Wright, David K.

AU - Liu, Shijie

AU - Van Der Poel, Chris

AU - McDonald, Stuart J.

AU - Brady, Rhys D.

AU - Taylor, Lily

AU - Yang, Li

AU - Gardner, Andrew J.

AU - Ordidge, Roger

AU - O'Brien, Terence J.

AU - Johnston, Leigh A.

AU - Shultz, Sandy R.

PY - 2017

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