American Society for Peripheral Nerve

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Selective Nerve Root Transection Produces a Permanent, Partial Nerve Injury Model
Louis H. Poppler, MD; Matthew D. Wood, PhD; Daniel A. Hunter; Lauren Prange; Susan E. Mackinnon, MD; Amy M. Moore, MD
Department of Surgery, Division of Plastic and Reconstructive Surgery, Washington University School of Medicine, St. Louis, MO

Introduction: This study's goal was to develop a partial, non-regenerative nerve injury model that results in permanently reduced muscle force to allow the study of therapeutics to improve motor function. Reduction of the motorneuron pool to 20% normal values is required to produce a measureable loss of muscle force in rats. We hypothesized that transection of one or more of the L4-6 nerve roots would cause a permanent measurable reduction in muscle force.

Methods: Eighty rats were randomized into four groups (n=20) that underwent variations of nerve root transections. Group I and II had the L4 or L5 nerve root transected respectively, and a silicone cap placed proximally to prevent regeneration. Group III had both L4&5 roots and group IV had the L4&6 roots transected and capped. Retrograde labeling of the tibial and peroneal nerves (n=12 per group) was performed at 3 weeks. Normal values were established in a sham surgery group. Tibial and peroneal nerves were harvested for histomorphometry at 3 and 12 weeks to evaluate the presence of myelinated axons. Muscle force testing (n=8 per group) was conducted to provide functional data corroborating the reduced counts. Neurman-Keuls post-hoc analysis was performed.

Results: In group III (L4&5-cut), the tibial mean motoneuron count was 6% of control, and peroneal nerve had no motoneurons. In group IV (L4&6-cut) mean motoneuron counts in the tibial and peroneal were 20% and 8% respectively (Figure 1). Large myelinated axon counts confirmed these results. In group III, the muscle mass of gastrocnemeus and extensor digitorum longus (EDL) were significantly reduced v. sham (p<0.05). In group III, mean gastrocnemeus force was to 1.1N (9.6% of sham), a statistically significant reduction. EDL force was 0.0 N in group III, confirming motoneuron and myelinated axon counts (Figure 2). No significant reduction in muscle force was observed in other nerve injury groups.

Summary Points:
This partial nerve injury model produces reproducible and stable decrease in muscle force.
Unlike previously described partial nerve injury models, this novel model avoids the rat's innate neuroregenerative capability and produces a stable platform from which to evaluate therapeutics to increase motor function.

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