Assessing Peripheral Nerve Functional Recovery: Rethinking A Model For The Rat Common Peroneal Nerve

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Peripheral nerve injury is common, with annual incidence rates of 300,000 in the United States. Not surprisingly, a large volume of research exists regarding nerve injury, repair, and regeneration. However, functional outcomes of repair are typically disappointing. Full recovery rarely occurs in spite of recent advances, representing significant personal and societal burdens, and maintaining the importance of continued research. There are various methodologies for assessing peripheral nerve regeneration. However, relatively few useful clinical tests for determining functional recovery exist that are not either invasive or destructive. The most used animal model for peripheral nerve injury research is the common laboratory rat, with the sciatic nerve most frequently studied. Walking track analysis is the most widely used method of assessment in this model. Walking tracks are created by using ink on the rat's feet to make prints on paper, though many variations of both "ink" and "paper" have been used historically. Measurements of various aspects of the prints (e.g. print length or distances between digits) are calculated into a sciatic function index (SFI) that represents dysfunction on a scale of 0 to -100 (with -100 being absolute dysfunction). This method has also been used in the laboratory rat for the branches of the sciatic, the tibial (TFI) and common peroneal (PFI) nerves. Unfortunately, this method is also plagued with difficulties (in any of these nerve models), including autotomy, contracture of injured limbs, and difficulties in obtaining prints (smearing or contamination). Recently, a new method, called skilled locomotion, has been used successfully in assessing recovery from central nervous system damage. In this method, rats traverse either a ladder with alternately missing rungs or a tapered beam. They are then scored based on the accuracy of their steps. This method has been suggested, but not validated, for use in peripheral nerve recovery studies. The present study used both sciatic nerve and common peroneal nerve transection models to compare SFI and PFI to skilled locomotion. Retrograde labels were also used to detect motor neurons that had successfully regenerated from the proximal to the distal nerve stump in order to provide an anatomic correlation of recovery. Our SFI results were consistent with the literature, iii showing approximately a 20% recovery. However, our analysis of individual factors disagrees with the current literature. Specifically, we show that the distance to the opposite foot is significantly affected by nerve injury and recovery, that there is a lack of significant changes in print length, and an inability to differentiate toe spread and intermediate toe spread among post-surgical groups. The traditional PFI did not work as expected for our data. Analysis of measured components, including distance to the opposite foot and deviation angle of the foot (previously discarded as too variable of inconsequential) allowed us to create new models for common peroneal functional index. Using these models, we also addressed other perceived problems with the historical indices, including the use of contralateral limb data to normalize experimental limb data, and the use of the longest individual measurement for each trial in the final analysis. Skilled locomotion analysis of the surgical limb revealed a higher estimate of recovery (41-43%) than SFI (20%) in the sciatic nerve model. Our data also revealed that Sprague-Dawley rats slow down significantly when presented with either difficult terrain or nerve injury, and that they apparently learn to tread more carefully in all limbs under these conditions. Skilled locomotion analysis revealed that slip rates did not vary significantly for the common peroneal model. Finally, motor neuron counts were shown to correlate well with SFI (p = 0.011) and skilled locomotion (p = 0.010) in the sciatic nerve model. iv
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Peripheral; Nerve; Regeneration
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Flaminio,Maria Julia Bevilaqua Felippe
Hermanson,John W
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Veterinary Medicine
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M.S., Veterinary Medicine
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Master of Science
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