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Updated: Apr 1, 2026
Intravital Imaging of Axonal Interactions with Microglia and Macrophages in a Mouse Dorsal Column Crush Injury
Published on: November 23, 2014
Microglia processes associate with diffusely injured axons following mild traumatic brain injury in the micro pig
Audrey D Lafrenaye1, Masaki Todani2,3, Susan A Walker4
1Department of Anatomy and Neurobiology, Virginia Commonwealth University Medical Center, P.O. Box 980709, Richmond, VA, 23298, USA. forrestad@vcu.edu.
Background:
Mild traumatic brain injury (mTBI) is an all too common occurrence that exacts significant personal and societal costs. The pathophysiology of mTBI is complex, with reports routinely correlating diffuse axonal injury (DAI) with prolonged morbidity. Progressive chronic neuroinflammation has also recently been correlated to morbidity, however, the potential association between neuroinflammatory microglia and DAI is not well understood. The majority of studies exploring neuroinflammatory responses to TBI have focused on more chronic phases of injury involving phagocytosis associated with Wallerian change. Little, however, is known regarding the neuroinflammatory response seen acutely following diffuse mTBI and its potential relationship to early DAI. Additionally, while inflammation is drastically different in rodents compared to humans, pigs and humans share very similar inflammatory profiles and responses.
Methods:
In the current study, we employed a modified central fluid percussion model in micro pigs. Using this model of diffuse mTBI, paired with various immunohistological endpoints, we assessed the potential association between acute thalamic DAI and neuroinflammation 6 h following injury.
Results:
Injured micro pigs displayed substantial axonal damage reflected in the presence of APP+ proximal axonal swellings, which were particularly prominent in the thalamus. In companion, the same thalamic sites displayed extensive neuroinflammation, which was observed using Iba-1 immunohistochemistry. The physical relationship between microglia and DAI, assessed via confocal 3D analysis, revealed a dramatic increase in the number of Iba-1+ microglial processes that contacted APP+ proximal axonal swellings compared to uninjured myelinated thalamic axons in sham animals.
Conclusions:
In aggregate, these studies reveal acute microglial process convergence on proximal axonal swellings undergoing DAI, an interaction not previously recognized in the literature. These findings transform our understanding of acute neuroinflammation following mTBI and may suggest its potential as a diagnostic and/or a therapeutic target.
Insights
Acute mild traumatic brain injury (mTBI) causes axonal damage and neuroinflammation. Microglia rapidly interact with damaged axons, suggesting a new diagnostic and therapeutic target for mTBI.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Mild traumatic brain injury (mTBI) is a common injury with significant costs.
- Diffuse axonal injury (DAI) and chronic neuroinflammation are linked to prolonged morbidity.
- The acute relationship between microglia and DAI post-mTBI is poorly understood.
Purpose of the Study:
- To investigate the association between acute thalamic DAI and neuroinflammation 6 hours after diffuse mTBI.
- To explore the role of microglia in the early stages of DAI.
Main Methods:
- Utilized a modified central fluid percussion model in micro pigs to induce diffuse mTBI.
- Employed immunohistochemistry (Iba-1) and APP staining to assess neuroinflammation and axonal damage.
- Conducted confocal 3D analysis to examine the physical interaction between microglia and DAI.
Main Results:
- Significant axonal damage (APP+ swellings) was observed in the thalamus of injured pigs.
- Extensive neuroinflammation (Iba-1+ microglia) was present in the same thalamic regions.
- Microglial processes showed increased contact with acutely swollen axons undergoing DAI.
Conclusions:
- Demonstrated acute microglial process convergence on DAI sites, a novel finding.
- These results offer new insights into acute neuroinflammation following mTBI.
- Identified a potential diagnostic and therapeutic target for mTBI.
