Related Experiment Video
Updated: Oct 5, 2025
Modified Mouse Model of Repetitive Mild Traumatic Brain Injury Incorporating Thinned-Skull Window and Fluid Percussion
Published on: April 19, 2024
Repeated mild traumatic brain injury impairs fracture healing in male mice
Chandrasekhar Kesavan1,2, Charles Rundle1,2, Subburaman Mohan3,4,5
1Musculoskeletal Disease Center, VA Loma Linda Healthcare System, 11201 Benton Street, Loma Linda, CA, 92357, USA.
Objectives:
The goal of this study was to evaluate the long-term impact of repeated (r) mild traumatic brain injury (mTBI) on the healing of fractures in a mouse model. Ten week-old male mice were subjected to r-mTBI once per day for 4 days followed by closed femoral fracture using a three-point bending technique, 1 week post impact and fracture healing phenotype evaluated at 20 weeks of age.
Results:
Micro-CT analysis of the fracture callus region at nine weeks post fracture revealed reduced bone volume (30%, p < 0.05) in the r-mTBI fracture group compared to the control-fracture group. The connectivity density of the fracture callus bone was reduced by 40% (p < 0.01) in the r-mTBI fracture group. Finite element analysis of the fracture callus region showed reduced failure load (p = 0.08) in the r-mTBI group compared to control group. There was no residual cartilage in the fracture callus region of either the r-mTBI or control fracture group. The reduced fracture callus bone volume and mechanical strength of fracture callus in r-mTBI mice 9 weeks post fracture are consistent with negative effects of r-mTBI on fracture healing over a long-term resulting in decreased mechanical strength of the fracture callus.
Insights
Repeated mild traumatic brain injury (mTBI) significantly impairs long-term fracture healing in mice. r-mTBI led to reduced bone volume and mechanical strength in healing fractures, indicating delayed recovery.
Area of Science:
- Orthopedics
- Neuroscience
- Regenerative Medicine
Background:
- Repeated mild traumatic brain injury (r-mTBI) is a growing concern with potential systemic effects.
- Fracture healing is a complex biological process that can be influenced by systemic health.
Purpose of the Study:
- To investigate the long-term consequences of r-mTBI on fracture healing.
- To evaluate the impact of r-mTBI on bone regeneration and mechanical properties of the fracture callus.
Main Methods:
- Male mice underwent daily r-mTBI for four days.
- A closed femoral fracture was induced one week after the final impact.
- Fracture healing was assessed at 20 weeks of age using micro-CT, mechanical testing, and histological analysis.
Main Results:
- Micro-CT revealed a 30% reduction in bone volume and a 40% decrease in connectivity density in the fracture callus of the r-mTBI group compared to controls.
- Finite element analysis indicated a trend towards reduced failure load in the r-mTBI group.
- No residual cartilage was observed in either group, suggesting complete endochondral ossification.
Conclusions:
- r-mTBI negatively impacts long-term fracture healing, leading to decreased bone volume and compromised mechanical strength of the callus.
- These findings highlight a potential link between brain injury and impaired bone regeneration.
