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Updated: Mar 26, 2026
A Mouse Model of Single and Repetitive Mild Traumatic Brain Injury
Published on: June 20, 2017
Dendritic Spine Loss and Chronic White Matter Inflammation in a Mouse Model of Highly Repetitive Head Trauma
Charisse N Winston1, Anastasia Noël2, Aidan Neustadtl1
1Laboratory for Brain Injury and Dementia, Department of Neuroscience, Georgetown University Medical Center, Washington, District of Columbia.
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.
Insights
Repetitive mild traumatic brain injuries (rmTBIs) can cause lasting white matter damage in mice. While single injuries are transient, repeated impacts lead to progressive pathology months after the event.
Area of Science:
- Neuroscience
- Pathology
- Traumatic Brain Injury Research
Background:
- Mild traumatic brain injury (mTBI) is linked to chronic neurological issues.
- Current rodent models often use limited numbers of repetitive mTBIs (rmTBIs).
Purpose of the Study:
- To investigate the long-term structural and pathological effects of a high number (30) of rmTBIs in mice.
- To understand how the interval between injuries influences outcomes.
Main Methods:
- Mice were subjected to 30 rmTBIs with varying interinjury intervals (1 or 7 days).
- Structural changes (dendritic spines) and pathological markers (axonal injury, neuroinflammation, cell death, white matter changes, amyloid and tau levels) were assessed up to 365 days post-injury.
Main Results:
- Single mTBI caused transient synapse loss but no lasting damage.
- 30 rmTBIs with a 1-day interval did not cause synapse loss.
- A 7-day interval between 30 rmTBIs reinstated synapse loss.
- 30 rmTBIs induced progressive white matter pathology, including microglial activation, evident up to 365 days post-injury.
- rmTBIs did not alter amyloid or tau levels in an Alzheimer's disease mouse model.
Conclusions:
- Single mTBIs result in transient synaptic changes.
- The brain can habituate to closely spaced rmTBIs, but longer intervals can reinstate injury effects.
- rmTBI induces persistent white matter pathology that develops and lasts for months post-injury.
