A Clinically Relevant Mouse Model of Concussion Incorporating High Rotational Forces

Elizabeth M Teasell ^1,2, Emilie Potts ³, Nicole Geremia ¹

⁰Robarts Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Canada.

Neurotrauma Reports +

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March 25, 2025

View abstract on PubMed

Summary

This study introduces a new mouse model for concussion, replicating human mild traumatic brain injuries (mTBIs) with realistic biomechanics. The model shows key pathological changes, offering a valuable tool for concussion research.

Area Of Science

Neuroscience
Traumatic Brain Injury Research
Animal Models

Background

Concussion research requires clinically relevant animal models that mimic human mild traumatic brain injuries (mTBIs).
Existing models often lack the specific biomechanical properties of human concussions, limiting their translational value.
Bridging the gap between preclinical and clinical studies necessitates models with high construct validity.

Purpose Of The Study

To develop and validate a mouse model of concussion that accurately replicates the biomechanical and pathological features of human concussions.
To assess the construct validity by comparing biomechanical parameters to human football impacts.
To evaluate the face validity through histopathological analysis of injury-induced changes.

Main Methods

A closed-head mild traumatic brain injury (mTBI) model was created using a cortical impactor in mice.
Mice were placed on a break-away platform allowing unrestrained head and body motion during impact.
Over 100 mice, including those with humanized amyloid precursor protein and tau genes, were used; histopathology assessed injury outcomes.

Main Results

The model consistently produced peak angular velocities in mice that, when scaled, approximated those in human football impacts.
Histopathology revealed diffuse axonal injury, astrogliosis, and microglial activation one week after three impacts.
Persistent axonal degeneration was observed up to six months post-injury, particularly in white matter tracts.

Conclusions

This mouse model effectively captures key biomechanical and pathological features of human concussions.
The model demonstrates high construct and face validity, making it suitable for studying concussion pathophysiology and long-term outcomes.
This tool advances preclinical research by providing a more accurate representation of concussive injuries.

Keywords:

closed-head impact animal model of concussion with high rotational forces concussion diffuse axonal injury mild traumatic brain injury (mTBI) mouse model of concussion