Injured mice at the gym: review, results and considerations for combining chondroitinase and locomotor exercise to enhance recovery after spinal cord injury

Brain Res Bull, 2011 · DOI: 10.1016/j.brainresbull.2010.06.002 · Published: March 10, 2011

Spinal Cord Injury Neuroplasticity Rehabilitation

Simple Explanation

Exercise has benefits after spinal cord injury, but improvements in walking are limited. The extracellular matrix, with CSPGs, might inhibit exercise-induced changes. Chondroitinase ABC (ChABC) can enhance plasticity by breaking down CSPGs. This article reviews locomotor training and CSPG degradation with ChABC, proposing their combination for better recovery after spinal cord injury. A preliminary study tested combining ChABC injection with voluntary wheel running in mice after spinal cord injury. The study's negative results highlight limitations in understanding effective combination protocols. Further research aims to identify optimal timing, type, and amount of exercise and drugs to maximize functional improvements.

Study Duration

Not specified

Participants

Adult female C57BL/6 mice (n=6–10/group)

Evidence Level

Animal study

Key Findings

1
Neither exercise alone, ChABC alone, nor the combination of both treatments resulted in a significant improvement in locomotor function compared with mice that had no wheels and intraparenchymal vehicle injections.
2
There were also no effects of the experimental conditions on any of the sensory outcome measures.
3
Voluntary wheel running offers advantages including motivation and low stress on the subjects, but does not allow standardization or maximal stepping of injured animals.

Research Summary

This review discusses the potential of combining exercise and chondroitinase ABC (ChABC) to enhance recovery after spinal cord injury (SCI). While exercise alone has limited efficacy, ChABC can promote plasticity by cleaving glycosaminoglycan sidechains from chondroitin sulfate proteoglycans (CSPGs). A preliminary study involving mice with spinal contusion injuries tested the combination of a single ChABC injection with voluntary wheel running. The results were negative, suggesting that this simple approach is insufficient for improving locomotor function. The authors emphasize the need for further research to optimize the timing, type, and intensity of both exercise and pharmacological interventions to maximize functional improvements after SCI.

Practical Implications

Optimizing Combination Therapies

Future research should focus on identifying the ideal combination of exercise type, intensity, and timing with ChABC administration to maximize recovery outcomes.

Refining ChABC Administration

Further investigation is needed to determine the optimal timing, route, and dosing of ChABC to effectively reduce the inhibitory influence of the ECM and permit rehabilitation-dependent plasticity.

Personalized Rehabilitation Strategies

Treatment strategies should consider individual injury severity, motivational state, and potential for both forced and voluntary exercise to tailor rehabilitation plans for optimal recovery.

Study Limitations

1
Single lumbar injection of ChABC may be insufficient.
2
Natural plasticity in mice following a moderate injury might mask effects of ChABC and running.
3
Intensity of training may have been insufficient.

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