A functional model system of an hypoxic nerve injury and its evaluation

Abstract

Objective/Hypothesis: Develop an hypoxic peripheral nerve injury model with a controlled injury type and two types of clinically relevant physiological measurements of function during and after recovery. The model, controlling for injury and measurement variables, would have predictable outcomes in function. The functional model could test potential therapeutic interventions with greater sensitivity. Study Design: Twenty-one rats were used in preliminary studies evaluating peroneal nerve injury types and functional model evaluation. Forty-eight rates were used in a controlled and blinded evaluation of the injury model followed by treatment with hyperbaric oxygen (HBO) as a potential therapeutic intervention and evaluated with functional models. Methods: Preliminary studies compared nerve injuries: epineurectomy, epineurectomy with crush and transection with autograft for rate of return of function and final extent of return of function. The gait analysis model was also evaluated and modified to decrease variability. The final study evaluated peroneal epineurectomy and nerve crush injury with serial gait analysis during recovery, final elicited maximum force measurements, and histological analysis. Half of the animals were treated with HBO during recovery (ANOVA or regression statistical analysis were used to determine group differences.) Results: Preliminary studies suggested that the peroneal nerve injury model of an epineurectomy with crush of specified length and a modification of the gait analysis model would yield a useful and predictable injury outcome. The final study resulted in predicted and consistent injury outcomes. In the HBO treatment group, a 12% improvement in function 5 days after HBO treatment was demonstrated (P < .03), but no long- term or histological benefit was seen. Conclusions: A reliable hypoxic nerve injury model has been developed and tested utilizing two functional methods as the primary outcome variables.