Dendritic spine loss and chronic white matter inflammation in a mouse model of highly repetitive head trauma
Open accessAbstract
Mild traumatic brain injury (mTBI) is an emerging risk for chronic behavioral, cognitive, and neurodegenerative conditions. Athletes absorb several hundred mTBIs each year; however, rodent models of repeat mTBI (rmTBI) are often limited to impacts in the single digits. Herein, we describe the effects of 30 rmTBIs, examining structural and pathological changes in mice up to 365 days after injury. We found that single mTBI causes a brief loss of consciousness and a transient reduction in dendritic spines, reflecting a loss of excitatory synapses. Single mTBI does not cause axonal injury, neuroinflammation, or cell death in the gray or white matter. Thirty rmTBIs with a 1-day interval between each mTBI do not cause dendritic spine loss; however, when the interinjury interval is increased to 7 days, dendritic spine loss is reinstated. Thirty rmTBIs cause white matter pathology characterized by positive silver and Fluoro-Jade B staining, and microglial proliferation and activation. This pathology continues to develop through 60 days, and is still apparent at 365 days, after injury. However, rmTBIs did not increase β-amyloid levels or tau phosphorylation in the 3xTg-AD mouse model of Alzheimer disease. Our data reveal that single mTBI causes a transient loss of synapses, but that rmTBIs habituate to repetitive injury within a short time period. rmTBI causes the development of progressive white matter pathology that continues for months after the final impact.
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A recent report indicates that 30 mild TBI's do not alter Aβ and tau pathology in 18-month-old 3xTg mice.
“Nonetheless, a recent report indicates that 30 mild TBI’s do not alter Aβ and tau pathology in 18-month-old 3xTg mice (59).”
From The Inflammatory Continuum of Traumatic Brain Injury and Alzheimer’s Disease (2018) · cites this paper as [59]
The Effect of rmTBI on Amyloid and Tau Pathology reports no change in Aβ levels or tau phosphorylation in 18-month-old 3xTg-AD mice. But it explicitly says those mice received 20 rmTBIs, not 30; the Figure 8 and 9 captions also specify 20. The claim attributes the correct finding to the wrong injury count. (LLM, conf=0.94)
Experimental — accuracy not yet measuredA recent highly repetitive mouse model of TBI including 30 injuries has been characterized.
“A recent highly repetitive mouse model of TBI including 30 injuries has also been characterized (59).”
From The Inflammatory Continuum of Traumatic Brain Injury and Alzheimer’s Disease (2018) · cites this paper as [59]
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References 63 · Cited by 94
Research works printed but not linked: 6
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- Authors
- Winston, C. N., Noël, A., Neustadtl, A., Parsadanian, M., Barton, D. J., Chellappa, D., Wilkins, T. E., Alikhani, A. D., Zapple, D. N., Villapol, S., Planel, E., & Burns, M. P.
- Affiliations
- Georgetown University Medical Center (US)
- Université Laval (CA)
- Centre hospitalier universitaire de Québec (CA)
- Corresponding author
- Planel, Emmanuel
- Burns, Mark P.
- ORCID
- Venue
- The American Journal of Pathology
- Publisher
- Elsevier BV
- Published
- 2016-03
- Volume
- 186
- Issue
- 3
- Pages
- 552-567
- ISSN
- 0002-9440 (ISSN-L)
- PMC
- PMC4816714
- OpenAlex
- W2256655086
- Cited by
- 94
- References
- 63
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 6 · 2023: 10 · 2022: 8 · 2021: 10 · 2020: 12 · 2019: 8 · 2018: 12 · 2017: 15 · 2016: 6
- FWCI
- 12.82
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- American Journal Of Pathology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Georgetown University (T32NS041218)
- Natural Sciences and Engineering Research Council of Canada (354722)
- National Institute of Neurological Disorders and Stroke (R01 NS067417)
- Canadian Institutes of Health Research (PCN-102993, MOP-106423)
- Alzheimer Society
- National Institutes of Health
- Fonds de Recherche du Québec - Santé (20048, 16205)
- Topics
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Automotive and Human Injury Biomechanics
- Keywords
- mild traumatic brain injury, repetitive head trauma, dendritic spine loss, white matter inflammation, microglial activation, chronic neuroinflammation, 3xTg-AD mice, amyloid-beta, tau phosphorylation
- MeSH terms
- Amyloid, Animals, Behavior, Animal, Brain Concussion, Brain Injuries, Disease Models, Animal, Fluoresceins, Golgi Apparatus, Craniocerebral Trauma, Humans, Inflammation, Male, Mice, Inbred C57BL, Recurrence, Unconsciousness, tau Proteins, Maze Learning, Dendritic Spines, Mice, White Matter
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