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Microstructural and microglial changes after repetitive mild traumatic brain injury in mice
Shenandoah Robinson1,2, Jacqueline B Berglass3, Jesse L Denson4
1Departments of Neurosurgery and Neurology, Boston Children's Hospital, Kirby Center for Neurobiology, Harvard Medical School, Boston, Massachusetts.
Journal of Neuroscience Research
|July 26, 2016
Summary
Repetitive mild traumatic brain injury (TBI) in mice caused microhemorrhages and altered brain microstructure. These changes, visible with MRI, were linked to increased microglia and inflammation, suggesting potential biomarkers for TBI outcomes.
Area of Science:
- Neuroscience
- Radiology
- Pathology
Background:
- Traumatic brain injury (TBI) is a significant public health concern.
- Repetitive mild TBI (rmTBI) poses risks for long-term neurological damage.
- Objective diagnostic tools for TBI are lacking, hindering outcome prediction and mechanistic understanding.
Purpose of the Study:
- To investigate if acute and subacute pathological changes from rmTBI are detectable via advanced MRI techniques.
- To correlate microstructural abnormalities with cellular and molecular responses, specifically microgliosis and inflammation.
- To establish a clinically relevant animal model for studying rmTBI pathophysiology.
Main Methods:
- Male mice underwent seven consecutive mild closed head injuries over 9 days.
- High-resolution magnetic resonance imaging (MRI), including susceptibility-weighted and diffusion-tensor imaging, was employed.
- Stereology and quantitative PCR were used to assess microglial activation and inflammatory markers (TNF-α receptor mRNA).
Main Results:
- rmTBI induced focal cortical microhemorrhages and impaired axial diffusivity at 1 week post-injury.
- These imaging abnormalities correlated with a significant increase in microglia (microgliosis).
- Microgliosis was associated with altered inflammatory signaling, indicated by changes in TNF-α receptor mRNA.
Conclusions:
- Subacute microstructural abnormalities detected by MRI reflect underlying pathology in rmTBI.
- Microgliosis and inflammatory changes are key components of the brain's response to repeated mild injury.
- These findings suggest potential MRI-based biomarkers for diagnosing TBI and guiding therapeutic interventions.
