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Am J Pathol. 2016 Mar;186(3):552-67. doi: 10.1016/j.ajpath.2015.11.006. Epub 2016 Feb 5.

Dendritic Spine Loss and Chronic White Matter Inflammation in a Mouse Model of Highly Repetitive Head Trauma.

Author information

1
Laboratory for Brain Injury and Dementia, Department of Neuroscience, Georgetown University Medical Center, Washington, District of Columbia.
2
Department of Psychiatry and Neurosciences, Université Laval, Quebec City, Quebec, Canada.
3
Department of Psychiatry and Neurosciences, Université Laval, Quebec City, Quebec, Canada; Research Center of CHU of Québec, Neurosciences, Quebec, Canada. Electronic address: emmanuel@planel.org.
4
Laboratory for Brain Injury and Dementia, Department of Neuroscience, Georgetown University Medical Center, Washington, District of Columbia. Electronic address: mpb37@georgetown.edu.

Abstract

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.

PMID:
26857506
PMCID:
PMC4816714
[Available on 2017-03-01]
DOI:
10.1016/j.ajpath.2015.11.006
[Indexed for MEDLINE]
Free PMC Article

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