The effects of mouse strain and age on a model of unilateral cervical contusion spinal cord injury

PLOS ONE, 2020 · DOI: https://doi.org/10.1371/journal.pone.0234245 · Published: June 15, 2020

Spinal Cord Injury Neurology Research Methodology & Design

Simple Explanation

This study examines a mouse model of unilateral cervical contusion injury, which mimics incomplete spinal cord injuries commonly seen in humans. The researchers assessed behavioral deficits using tasks like grip strength, cylinder reaching, and gait analysis. The study also investigated how different mouse strains (C57Bl/6, immunodeficient Rag2gamma(c)-/-, and Agouti SCIDxRag2-Gamma(c)-/- hybrid) and age (young vs. aging) affect the outcome of the injury. The findings provide insights into experimental design and analysis for future preclinical studies using this translational model.

Study Duration

13 weeks

Participants

Female C57Bl/6 mice, Rag2gamma(c)-/-, Agouti SCIDxRag2Gamma hybrid mice, young (3-4 months old) and aging (16-17 months old) Rag2gamma(c)-/- mice

Evidence Level

Not specified

Key Findings

1
Sustained behavioral deficits were observed in grip strength, cylinder reaching, horizontal ladderbeam, and CatWalk automated gait analysis tasks following unilateral cervical contusion SCI.
2
Fine differences in post-injury ipsilateral grip strength and total number of rearings on the cylinder task were observed between different mouse strains (C57Bl/6, Rag2gamma(c)-/-, and Agouti SCIDxRag2-Gamma(c)-/- hybrid).
3
Age-related pre-injury differences in strength and rearing were identified in young (3–4 months old) and aging (16–17 months old) Rag2gamma(c)-/- mice, but these were largely masked following cervical contusion injury.

Research Summary

This study profiles a clinically relevant model of unilateral cervical contusion injury in the mouse, demonstrating sustained behavioral deficits and exploring the effect of mouse strain and age on injury outcome. Comparison of different mouse strains revealed fine differences in post-injury ipsilateral grip strength and total number of rearings on the cylinder task, as well as differences in contralateral forepaw duty cycle and regularity index. Assessment of young and aging mice identified age-related pre-injury differences in strength and rearing that were largely masked following cervical contusion injury.

Practical Implications

Improved Preclinical Study Design

The findings offer valuable insights for designing and analyzing future preclinical studies using a translational unilateral cervical contusion injury model.

Targeted Therapeutic Strategies

Understanding the differences in injury outcomes based on mouse strain and age can help in developing targeted therapeutic strategies for spinal cord injury.

Enhanced Translational Research

The study contributes to bridging the gap between bench and bedside by providing a more clinically relevant model for preclinical research.

Study Limitations

1
Increasing dwell time beyond 2ms did not result in additional separation in neuroanatomical and functional deficits.
2
The study focused on female mice, and the results may not be generalizable to male mice.
3
The immunodeficient nature of Rag2gamma(c)-/- mice may mask potential age-related differences in injury pathogenesis.

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