American Society for Peripheral Nerve

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Enhancing Peripheral Nerve Regeneration after Neurorrhaphy: a Systematic Review of Animal Models
Matthew Wordsworth, MRCS, MA1; Nicholas Robbins, DO2; Warren Breidenbach, MD2; Rory Rickard, FRCS, PhD3; Bijaya Parida, PhD1; Michael R. Davis, MD, FACS1; Andrew Hart, MD, PhD4; Erik K Weitzel, MD1
1United States Army Institute of Surgical Research, San Antonio, TX; 259th Medical Wing, San Antonio, TX; 3Academic Department of Military Surgery and Trauma, Birmingham, United Kingdom; 4University of Glasgow, Glasgow, United Kingdom

Background: Primary neurorraphy of peripheral nerve injuries remains a significant clinical problem. Full functional recovery is usually not achieved particularly in severe or proximal nerve injuries. Attempts to enhance peripheral nerve regeneration have been widely studied in animal models but translation of this research into clinical practice has been limited.

Methods: The authors searched PubMed and Medline database for all animal studies that had primary epineural neurorraphy as the control group and with at least one quantitative outcome measure of nerve regeneration. The methodology, interventions and outcomes were analysed.

Results: 180 published studies were identified. The majority used the rat sciatic nerve model and a technical refinement to the standard epineural microsurgical suture repair was the most commonly studied intervention. Eight studies were in large animal models. 123 (68%) studies demonstrated at least one significant improvement to regeneration in the chosen outcome measure; only 18 (10%) demonstrated significant improvement in an electrophysiological, histomorphological and a functional outcome measure. Tacrolimus (FK506) was the single most studied drug intervention in ten studies. 41 studies measured the rat Sciatic Function Index (SFI) in the control arm of epineural repair with no intervention. The best-measured SFI recovery in these control groups across the studies varied from no improvement (SFI=-127) to near complete improvement (SFI=-14). A Pearson correlation coefficient analysis of this data demonstrated the correlation between all control outcomes of SFI in rats was weak (R=0.038).

Conclusions: The majority of studies investigating single interventions to enhance nerve regeneration report positive outcomes but with a wide variety of outcome measures. Several therapeutic options are highlighted that may be of benefit particularly if used synergistically. This review highlights recent trends in peripheral nerve research and offers insights into the strengths and weaknesses of the traditional animal models.

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