Basic NeuroscienceReviewThe sciatic nerve injury model in pre-clinical research
Introduction
Because of their spread distribution throughout the body, peripheral nerves are particularly subject to injuries mainly due to traumatic, e.g. work accidents, or iatrogenic, e.g. for tumor excision lesion (Evans, 2001, Siemionow and Brzezicki, 2009, Isaacs et al., 2013). Although usually not threatening the patient's life, nerve injuries represent a heavy social burden in terms of both long term disability and economic costs (Asplund et al., 2009, Rosberg et al., 2013). For this reason, growing efforts are dedicated to the development of effective treatment for peripheral nerve injuries which increase tissue regeneration and functional recovery and might be eventually translated to the patients for improving the clinical outcome (Tos et al., 2013, Griffin et al., 2013).
This body of pre-clinical research is mainly carried out in animal models since, so far, in vitro investigation of nerve regeneration is very limited due to the structural complexity of this organ which can hardly be reproduced in vitro (Geuna et al., 2009). The far most used experimental paradigm for the pre-clinical investigation of peripheral nerve regeneration is represented by the sciatic nerve injury (SNI) model (Siironen et al., 1996, Beer et al., 2001, Varejão et al., 2004a, Varejão et al., 2004b, Nichols et al., 2005, Savastano et al., 2014). Among the various reasons that might explain the preponderancy of SNI employment, two are the most important: (i) the large size of the sciatic nerve which facilitates surgery; (ii) the easy surgical access; (iii) the sought for data that can be comparable with previous studies, the very large majority of which have been carried out using the SNI model.
Due to the enormous number of experimental papers reporting data obtained with SNI model, a comprehensive review would be almost impossible and, probably, not so useful for researchers. By contrast, the aim of this paper is to overview a selection of relevant papers with the goal of providing the reader with some useful indications about the potentiality of employment of the SNI model as well as some methodological information that might help researchers in critically interpreting the results in a translational perspective.
Section snippets
Compression lesions
Experimental models based on the mechanical compression of the sciatic nerve have been widely used in experimental research in order to investigate the changes occurring to the nerve, proximal and distal to the lesion, as well as to the other central (e.g. neuronal cell bodies) and distal (e.g. muscles) anatomical structures. Sciatic nerve compression can be obtained by either ligation or crush of the epineurium. While ligation, that can be transiently applied and is used for the study of
Transection lesions
Although the experimental model based on the sciatic nerve crush injury has several advantages in terms of feasibility and reproducibility, its translational potential is limited for two main reasons. First, most surgically relevant nerve lesions in human patients are characterized by at least partial transection/laceration of the nerve. Second, crush lesions in patients have a different clinical history in comparison to experimental crush lesions in laboratory animals, namely spontaneous axon
Considerations about selection of the animal species
The SNI model has been used in number different animal species. The rat is by far the most used species (Angius et al., 2012) as shown by more than 13,000 entries obtainable in a PubMed query up to July 2014. When the same query is carried out for the mouse, the second most used animal species, the number of entries drops to about 3500, while the third most widely used species for SNI model is the rabbit with about 1500 entries. Whereas the rat clearly represent the species of choice for SCI
Surgery
Experimental surgery on the sciatic nerve is relatively easy due to its large size (the largest nerve in mammals). The sciatic nerve is a mixed nerve (Schmalbruch, 1986) which originates from the lumbo-sacral plexus and ends at the knee level with its terminal division that is usually represented by a trifurcation: the tibial nerve (the biggest one) the common peroneal nerve and the sural nerve (Rupp et al., 2007b). However, there is a high anatomical variability in the number and site of
Discussion
The investigation of nerve repair and regeneration has a long history and still today represents, un-doubtfully, the most addressed issue in the study of the peripheral nervous system.
The growing ethical concerns regarding the use of animals in biomedical research and the progressive spread among the scientific community of the “Three Rs” concept (replacement, reduction, and refinement of animal studies) (Russell and Burch, 1992) pushes for an increase in the replacement of in vivo models with
Acknowledgement
This work has been supported by the European Community's Seventh Framework Programme (FP7-HEALTH-2011) under grant agreement no. 278612 (BIOHYBRID).
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