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Background: Less is known about the role of Netrin-1 in the peripheral nervous system. In this study, we evaluated the role of Netrin-1 using the mouse median nerve model for assessment of peripheral nerve regeneration., Methods: Using real-time PCR and western blot analysis, we examined expression changes of netrin-1 mRNA and Netrin-1 protein after transection and repair of the mouse median nerve in Wild-type animals. We further evaluated histomorphometrical changes as well as the functional recovery of the grasping force after median nerve transection and repair in WT mice and Netrin-1(+/-) heterozygous mice., Results: RT-PCR revealed a 1, 9 fold increase of Netrin-1 mRNA two weeks after nerve transection and repair in the nerve segment distal to the injury site. In Western blot analysis, we could show a high increase of Netrin-1 in the nerve segment distal to the injury site at day 14. Histomorphometrical analysis showed significantly higher cross sectional area and a lower fibre density in heterozygous Netrin-1(+/-) mice. Using the functional grasping test, we could show that peripheral nerve regeneration is significantly diminished in heterozygous Netrin-1(+/-) mice., Conclusions: Employing the mouse median nerve model in transgenic animals, we demonstrate that Netrin-1 plays an important role during peripheral nerve regeneration.

While in the central nervous system plasticity (in response to stimulus) and regeneration (in response to injury) are mainly based on adaptive changes in neural circuitries and synaptic reorganization, in the peripheral nervous system they are predominantly based on axonal (re)growth and neuron addition. In this paper, we will briefly overview the main investigation lines on plasticity and regeneration in the peripheral nervous system that have been carried out at the Laboratory of Human Anatomy of the Department of Clinical and Biological Sciences at the "San Luigi Gonzaga" Medical Faculty of the University of Turin. This body of research was mainly focused on the identification of the adaptive changes occurring to the sensory and autonomic neurons as a consequence of exceptional stimuli and/or damage at their periphery, as well as on the identification of effective new strategies for improving post-traumatic peripheral nerve fiber regeneration. These studies are in line with the long standing tradition on peripheral nervous system investigation carried out by the Anatomical School at the University of Turin since the times of Giuseppe Levi and we are honoured to have the occasion to present the results of our research on occasion of the appointment of Giovanni Orlandini as Emeritus Professor of the University of Florence.

The issue of postnatal neurogenesis has gained great importance over the last few years and the recent amazing scientific advancements, changing our viewpoint on the long-lasting "no new neurons" dogma, have opened promising new perspectives on the treatment of the damaged nervous system. While most of the researchers have focused on the central nervous system, the peripheral nervous system has received little attention so far with respect to postnatal histogenesis. To attract scientific attention on this issue, the present article was written with the aim of reviewing the body of literature on postnatal histogenesis in the various districts of the peripheral nervous system, from the historical roots to the most recent reports.

Cell secretome has been explored as a cell-free technique with high scientific and medical interest for Regenerative Medicine. In this work, the secretome produced and collected from Olfactory Mucosa Mesenchymal Stem Cells and Olfactory Ensheating Cells was analyzed and therapeutically applied to promote peripheral nerve regeneration. The analysis of the conditioned medium revealed the production and secretion of several factors with immunomodulatory functions, capable of intervening beneficially in the phases of nerve regeneration. Subsequently, the conditioned medium was applied to sciatic nerves of rats after neurotmesis, using Reaxon® as tube-guides. Over 20 weeks, the animals were subjected to periodic functional assessments, and after this period, the sciatic nerves and cranial tibial muscles were evaluated stereologically and histomorphometrically, respectively. The results obtained allowed to confirm the beneficial effects resulting from the application of this therapeutic combination. The administration of conditioned medium from Olfactory Mucosal Mesenchymal Stem Cells led to the best results in motor performance, sensory recovery, and gait patterns. Stereological and histomorphometric evaluation also revealed the ability of this therapeutic combination to promote nervous and muscular histologic reorganization during the regenerative process. The therapeutic combination discussed in this work shows promising results and should be further explored to clarify irregularities found in the outcomes and to allow establishing the use of cell secretome as a new therapeutic field applied in the treatment of peripheral nerves after injury. [ABSTRACT FROM AUTHOR]

Aim of this study is to investigate effects of stem cells derived from the peripheral nerve and adipose tissues following the nerve crush injury in control and obese rats. For this aim, 41 Wistar Albino female rats were separated into eight equal groups; non-obese control (NOC) obese control (OC), non-obese injury (NOH), obese injury (OH), non-obese adipose (NOY), obese adipose (OY), non-obese nerve (NOPS), obese nerve (OPS). At the end of 8 weeks, all experimental animals without control groups were subjected to nerve crush procedure and sciatic nerve or fat stem cell homogenates were injected on the treatment group rats, and then, recovery process has been observed and histopathological, stereological, electrophysiological analyses and bioinformatic evaluation were made on removed sciatic nerves. Stereological results showed that adipose homogenate gave more successful results than peripheral nerve homogenates in the NOY group in comparison to the NOPS group in terms of myelinated axon number. Peripheral nerve homogenate has shown more successful results in the OPS group in comparison to the OY group. The number of unmyelinated axons was increased following treatment with adipose tissue homogenate in NOY and OY groups. In terms of myelin sheath thickness; we detected that treatments by peripheral nerve and especially adipose tissue homogenates lead to increase in the thickness of the axons of the peripheral nerves belong to the control and obese injury groups. All results showed that mesenchymal stem cell treatment by fresh tissue homogenates is successful in peripheral nerve regeneration and fat tissue is a considerable source of the stem cells for clinical applications. [ABSTRACT FROM AUTHOR]

Nerve guidance conduits (NGCs) are used as an alternative to the "gold standard" nerve autografting, preventing the need for surgical intervention required to harvest autologous nerves. However, the regeneration outcomes achieved with the current NGCs are only comparable with autografting when the gap is short (less than 10 mm). In the present study, we have developed NGCs made from a blend of polyhydroxyalkanoates, a family of natural resorbable polymers. Hollow NGCs made from a 75:25 poly(3‐hydroxyoctanoate)/poly(3‐hydroxybutyrate) blend (PHA‐NGCs) were manufactured using dip‐molding. These PHA‐NGCs showed appropriate flexibility for peripheral nerve regeneration. In vitro cell studies performed using RT4‐D6P2T rat Schwann cell line confirmed that the material is capable of sustaining cell proliferation and adhesion. PHA‐NGCs were then implanted in vivo to repair 10 mm gaps of the median nerve of female Wistar rats for 12 weeks. Functional evaluation of the regenerated nerve using the grasping test showed that PHA‐NGCs displayed similar motor recovery as the autograft, starting from week 7. Additionally, nerve cross‐sectional area, density and number of myelinated cells, as well as axon diameter, fiber diameter, myelin thickness and g‐ratio obtained using the PHA‐NGCs were found comparable to an autograft. This preclinical data confirmed that the PHA‐NGCs are indeed highly promising candidates for peripheral nerve regeneration. [ABSTRACT FROM AUTHOR]

Peripheral nerve injury remains a clinical challenge with severe physiological and functional consequences. Despite the existence of multiple possible therapeutic approaches, until now, there is no consensus regarding the advantages of each option or the best methodology in promoting nerve regeneration. Regenerative medicine is a promise to overcome this medical limitation, and in this work, chitosan nerve guide conduits and olfactory mucosa mesenchymal stem/stromal cells were applied in different therapeutic combinations to promote regeneration in sciatic nerves after neurotmesis injury. Over 20 weeks, the intervened animals were subjected to a regular functional assessment (determination of motor performance, nociception, and sciatic indexes), and after this period, they were evaluated kinematically and the sciatic nerves and cranial tibial muscles were evaluated stereologically and histomorphometrically, respectively. The results obtained allowed confirming the beneficial effects of using these therapeutic approaches. The use of chitosan NGCs and cells resulted in better motor performance, better sciatic indexes, and lower gait dysfunction after 20 weeks. The use of only NGGs demonstrated better nociceptive recoveries. The stereological evaluation of the sciatic nerve revealed identical values in the different parameters for all therapeutic groups. In the muscle histomorphometric evaluation, the groups treated with NGCs and cells showed results close to those of the group that received traditional sutures, the one with the best final values. The therapeutic combinations studied show promising outcomes and should be the target of new future works to overcome some irregularities found in the results and establish the combination of nerve guidance conduits and olfactory mucosa mesenchymal stem/stromal cells as viable options in the treatment of peripheral nerves after injury. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate: (i) the neuro‐regenerative potential of chitosan membrane (CS‐Me) on acutely axotomised autonomic neurones in vitro; (ii) to exclude the possibility that a pro‐regenerative biomaterial could interfere with the proliferation activity of prostate cancer cell lines; (iii) to provide an in vivo proof of the biocompatibility and regeneration promoting effect of CS‐Me in a standardised rat model of peripheral nerve injury and repair; (iv) finally, to evaluate the tissue reaction induced by the degrading material; as previous studies have shown promising effects of CS‐Me for protection of the neurovascular bundles for potency recovery in patients that undergo nerve‐sparing radical prostatectomy (RP). Materials and Methods: Addressing aim (i), the neuro‐regenerative potential, organotypic cultures derived from primary sympathetic ganglia were cultured on CS‐Me over 3 days and neurite extension and axonal sprouting were evaluated. Addressing aim (ii), effects of CS on cancer cells, different human prostate cancer cell lines (PC3, DU‐145, LN‐Cap) were seeded on CS‐coated plates or cultured in the presence of CS‐Me dissolution products. Addressing aims (iii) and (iv), functional recovery of peripheral nerve fibres and tissue reaction with the biomaterial, CS‐Me and CS nerve guides were used to repair a median nerve injury in the rat. Functional recovery was evaluated during the post‐recovery time by the behavioural grasping test. Results: CS‐Me significantly stimulated axon elongation from autonomic ganglia in comparison to control conditions in organotypic three‐dimensional cultures. CS coating, as well as the dissolution products of CS‐Me, led to a significantly lower proliferation rate of prostate cancer cell lines in vitro. Tissue reaction towards CS‐Me and standard CS nerve guides was similar in the rat median nerve model, as was the outcome of nerve fibre regeneration and functional recovery. Conclusion: The results of this study provide the first experimental evidence in support of the clinical safety of CS‐Me and of their postulated effectiveness for improving functional recovery after RP. The presented results are coherent in demonstrating that acutely axotomised autonomic neurones show increased neurite outgrowth on CS‐Me substrate, whilst the same substrate reduces prostate cancer cell line proliferation in vitro. Furthermore, CS‐Me do not demonstrate any disadvantage for peripheral nerve repair in a standard animal model. [ABSTRACT FROM AUTHOR]

The successful introduction of innovative treatment strategies into clinical practise strongly depends on the availability of effective experimental models and their reliable pre-clinical assessment. Considering pre-clinical research for peripheral nerve repair and reconstruction, the far most used nerve regeneration model in the last decades is the sciatic nerve injury and repair model. More recently, the use of the median nerve injury and repair model has gained increasing attention due to some significant advantages it provides compared to sciatic nerve injury. Outstanding advantages are the availability of reliable behavioural tests for assessing posttraumatic voluntary motor recovery and a much lower impact on the animal wellbeing. In this article, the potential application of the median nerve injury and repair model in pre-clinical research is reviewed. In addition, we provide a synthetic overview of a variety of methods that can be applied in this model for nerve regeneration assessment. This article is aimed at helping researchers in adequately adopting this in vivo model for pre-clinical evaluation of peripheral nerve reconstruction as well as for interpreting the results in a translational perspective. [ABSTRACT FROM AUTHOR]

Background: In this study, we evaluate the role of RGMa (Repulsive Guidance Molecule a) during peripheral nerve regeneration using the mouse median nerve model. Methods: By real-time PCR and Western Blot analysis, we examined expression changes of RGMa mRNA and RGMa protein in neural tissue after transection and microsurgical repair of the mouse median nerve distal to the transection site. We evaluated histomorphometrical changes in neural tissue distal to the injury site and functional recovery of the grasping force after median nerve transection and repair in wild-type mice and RGMa+/– heterozygous mice. Results: RT-PCR revealed a 1,8 fold increase of RGMa mRNA two weeks and a 4,4 fold increase of RGMa mRNA 3 weeks after nerve transection and repair in the nerve segment distal to the injury site. In Western blot analysis, we could show a high increase of RGMa in the nerve segment distal to the injury site at day 14. Histomorphometrical analysis showed significant differences between wild-type animals and heterozygous animals. The absolute number of myelinated fibres was significantly higher in operated heterozygous RGMa+/– animals compared to operated wildtye animals. Using the functional grasping test, we could demonstrate that peripheral nerve regeneration is significantly diminished in heterozygous RGMa+/– mice. Conclusions: Employing the mouse median nerve model in transgenic animals, we demonstrate that RGMa plays an important role during peripheral nerve regeneration. [ABSTRACT FROM AUTHOR]

Neuregulin 1 (NRG1) is a growth factor produced by both peripheral nerves and skeletal muscle. In muscle, it regulates neuromuscular junction gene expression, acetylcholine receptor number, muscle homeostasis and satellite cell survival. NRG1 signalling is mediated by the tyrosine kinase receptors ErbB3 and ErbB4 and their co-receptors ErbB1 and ErbB2. The NRG1/ErbB system is well studied in nerve tissue after injury, but little is known about this system in skeletal muscle after denervation/ reinnervation processes. Here, we performed a detailed time-course expression analysis of several NRG1 isoforms and ErbB receptors in the rat superficial digitorum flexor muscle after three types of median nerve injuries of different severities. We found that ErbB receptor expression was correlated with the innervated state of the muscle, with upregulation of ErbB2 clearly associated with the denervation state. Interestingly, the NRG1 isoforms were differently regulated depending on the nerve injury type, leading to the hypothesis that both the NRG1α and NRG1β isoforms play a key role in the muscle reaction to injury. Indeed, in vitro experiments with C2C12 atrophic myotubes revealed that both NRG1α and NRG1β treatment influences the best-known atrophic pathways, suggesting that NRG1 might play an anti-atrophic role. [ABSTRACT FROM AUTHOR]

Background: Delayed reconstruction of transection or laceration injuries of peripheral nerves is inflicted by a reduced regeneration capacity. Diabetic conditions, more frequently encountered in clinical practice, are known to further impair regeneration in peripheral nerves. Chitosan nerve guides (CNGs) have recently been introduced as a new generation of medical devices for immediate peripheral nerve reconstruction. Here, CNGs were used for 45 days delayed reconstruction of critical length 15 mm rat sciatic nerve defects in either healthy Wistar rats or diabetic Goto-Kakizaki rats; the latter resembling type 2 diabetes. In short and long-term investigations, we comprehensively analyzed the performance of one-chambered hollow CNGs (hCNGs) and two-chambered CNGs (CFeCNGs) in which a chitosan film has been longitudinally introduced. Additionally, we investigated in vitro the immunomodulatory effect provided by the chitosan film.Results: Both types of nerve guides, i.e. hCNGs and CFeCNGs, enabled moderate morphological and functional nerve regeneration after reconstruction that was delayed for 45 days. These positive findings were detectable in generally healthy as well as in diabetic Goto-Kakizaki rats (for the latter only in short-term studies). The regenerative outcome did not reach the degree as recently demonstrated after immediate reconstruction using hCNGs and CFeCNGs. CFeCNG-treatment, however, enabled tissue regrowth in all animals (hCNGs: only in 80% of animals). CFeCNGs did further support with an increased vascularization of the regenerated tissue and an enhanced regrowth of motor axons. One mechanism by which the CFeCNGs potentially support successful regeneration is an immunomodulatory effect induced by the chitosan film itself. Our in vitro results suggest that the pro-regenerative effect of chitosan is related to the differentiation of chitosan-adherent monocytes into pro-healing M2 macrophages.Conclusions: No considerable differences appear for the delayed nerve regeneration process related to healthy and diabetic conditions. Currently available chitosan nerve grafts do not support delayed nerve regeneration to the same extent as they do after immediate nerve reconstruction. The immunomodulatory characteristics of the biomaterial may, however, be crucial for their regeneration supportive effects. [ABSTRACT FROM AUTHOR]

Quantitative estimation of myelinated nerve fiber number, together with fiber size parameters, is one of the most important tools for nerve regeneration research. In this study we used a design-based stereological method to evaluate the regenerative process in two experimental paradigms: crush injury and autograft repair. Samples were embedded in resin and morphometric counting and measurements were performed using both light and electron microscopes. Results show a significant difference in myelinated fiber number estimation between light and electron microscopes, especially after autograft repair; light microscope significantly underestimates the number of fibers because of the large number of very small axons that can be detected only in electron microscope. The analysis of the size parameters also shows a higher number of small fibers in electron microscopic analysis, especially in regenerated nerves. This comparative study shows that the integration of data obtained in light microscope with those obtained in electron microscope is necessary in revealing very small myelinated fibers that cannot be detected otherwise. Moreover, the difference in the estimation of total number of myelinated fibers between light and electron microscopes must be considered in data analysis to ensure accurate interpretation of the results. [ABSTRACT FROM AUTHOR]

Injury to the peripheral nerve induces dramatic changes in terms of cellular composition that are reflected on RNA quality and quantity, making messenger RNA expression analysis very complex. Several commonly used housekeeping genes are regulated following peripheral nerve injury and are thus not suitable for quantitative real-time PCR normalization; moreover, the presence of pseudogenes in some of them impairs their use. To deal with this problem, we have developed a new method to identify new stable housekeeping genes based on publicly available microarray data on normal and injured nerves. Four new candidate stable genes were identified and validated by quantitative real-time PCR analysis on nerves during the different phases after nerve injury: nerve degeneration, regeneration and remyelination. The stability measure of these genes was calculated with both NormFinder and geNorm algorithms and compared with six commonly used housekeeping genes. This procedure allowed us to identify two new and highly stable genes that can be employed for normalizing injured peripheral nerve data: ANKRD27 and RICTOR. Besides providing a tool for peripheral nerve research, our study also describes a simple and cheap procedure that can be used to identify suitable housekeeping genes in other tissues and organs. [ABSTRACT FROM AUTHOR]

Many surgical techniques are available for bridging peripheral nerve defects. Autologous nerve grafts are the current gold standard for most clinical conditions. In selected cases, alternative types of conduits can be used. Although most efforts are today directed towards the development of artificial synthetic nerve guides, the use of non-nervous autologous tissue-based conduits (biological tubulization) can still be considered a valuable alternative to nerve autografts. In this paper we will overview the advancements in biological tubulization of nerve defects, with either mono-component or multiple-component autotransplants, with a special focus on the use of a vein segment filled with skeletal muscle fibers, a technique that has been widely investigated in our laboratory and that has already been successfully introduced in the clinical practice. [ABSTRACT FROM AUTHOR]

The article offers information on a study that deals with the induced neurogenesis in the peripheral nervous system. The study presents the history of research on adult neurogenesis in the peripheral nervous system. It reveals the evidence on the under estimated potential for generation of new neurons in the peripheral nervous system.

Peripheral nerves possess the capacity of self-regeneration after traumatic injury but the extent of regeneration is often poor and may benefit from exogenous factors that enhance growth. The use of cellular systems is a rational approach for delivering neurotrophic factors at the nerve lesion site, and in the present study we investigated the effects of enwrapping the site of end-to-end rat sciatic nerve repair with an equine type III collagen membrane enriched or not with N1E-115 pre-differentiated neural cells. After neurotmesis, the sciatic nerve was repaired by end-to-end suture (End-to-End group), end-to-end suture enwrapped with an equine collagen type III membrane (End-to-EndMemb group); and end-to-end suture enwrapped with an equine collagen type III membrane previously covered with neural cells pre-differentiated in vitro from N1E-115 cells (End-to-EndMembCell group). Along the postoperative, motor and sensory functional recovery was evaluated using extensor postural thrust (EPT), withdrawal reflex latency (WRL) and ankle kinematics. After 20 weeks animals were sacrificed and the repaired sciatic nerves were processed for histological and stereological analysis. Results showed that enwrapment of the rapair site with a collagen membrane, with or without neural cell enrichment, did not lead to any significant improvement in most of functional and stereological predictors of nerve regeneration that we have assessed, with the exception of EPT which recovered significantly better after neural cell enriched membrane employment. It can thus be concluded that this particular type of nerve tissue engineering approach has very limited effects on nerve regeneration after sciatic end-to-end nerve reconstruction in the rat. [ABSTRACT FROM AUTHOR]

Thousands of people worldwide suffer from peripheral nerve injuries and must deal daily with the resulting physiological and functional deficits. Recent advances in this field are still insufficient to guarantee adequate outcomes, and the development of new and compelling therapeutic options require the use of valid preclinical models that effectively replicate the characteristics and challenges associated with these injuries in humans. In this study, we established a sheep model for common peroneal nerve injuries that can be applied in preclinical research with the advantages associated with the use of large animal models. The anatomy of the common peroneal nerve and topographically related nerves, the functional consequences of its injury and a neurological examination directed at this nerve have been described. Furthermore, the surgical protocol for accessing the common peroneal nerve, the induction of different types of nerve damage and the application of possible therapeutic options were described. Finally, a preliminary morphological and stereological study was carried out to establish control values for the healthy common peroneal nerves regarding this animal model and to identify preliminary differences between therapeutic methods. This study allowed to define the described lateral incision as the best to access the common peroneal nerve, besides establishing 12 and 24 weeks as the minimum periods to study lesions of axonotmesis and neurotmesis, respectively, in this specie. The post-mortem evaluation of the harvested nerves allowed to register stereological values for healthy common peroneal nerves to be used as controls in future studies, and to establish preliminary values associated with the therapeutic performance of the different applied options, although limited by a small sample size, thus requiring further validation studies. Finally, this study demonstrated that the sheep is a valid model of peripheral nerve injury to be used in pre-clinical and translational works and to evaluate the efficacy and safety of nerve injury therapeutic options before its clinical application in humans and veterinary patients. [ABSTRACT FROM AUTHOR]

Conduits for the repair of peripheral nerve gaps are a good alternative to autografts as they provide a protected environment and a physical guide for axonal re-growth. Conduits require colonization by cells involved in nerve regeneration (Schwann cells, fibroblasts, endothelial cells, macrophages) while in the autograft many cells are resident and just need to be activated. Since it is known that soluble Neuregulin1 (sNRG1) is released after injury and plays an important role activating Schwann cell dedifferentiation, its expression level was investigated in early regeneration steps (7, 14, 28 days) inside a 10 mm chitosan conduit used to repair median nerve gaps in Wistar rats. In vivo data show that sNRG1, mainly the isoform α, is highly expressed in the conduit, together with a fibroblast marker, while Schwann cell markers, including NRG1 receptors, were not. Primary culture analysis shows that nerve fibroblasts, unlike Schwann cells, express high NRG1α levels, while both express NRG1β. These data suggest that sNRG1 might be mainly expressed by fibroblasts colonizing nerve conduit before Schwann cells. Immunohistochemistry analysis confirmed NRG1 and fibroblast marker co-localization. These results suggest that fibroblasts, releasing sNRG1, might promote Schwann cell dedifferentiation to a "repair" phenotype, contributing to peripheral nerve regeneration. [ABSTRACT FROM AUTHOR]

Nerve fiber regeneration and complete functional recovery after peripheral nerve injury do not always occur and can be influenced by patient age, gender, lesion site, injury severity, size of the gap between damaged nerve stumps and time interval that elapses before performing surgical repair. The poor outcome occurring after a long delay can be due to loss of the neuron ability to regenerate, loss of the Schwann cell ability to support regeneration and, of course, progressive muscle atrophy. The aim of this study was to investigate the degenerative processes of the denervated distal nerve stump in order to understand which role they can have during delayed nerve regeneration. Morphological and biomolecular analyses carried out on degenerated nerves showed several collagen fibers and fibroblasts, atrophic Schwann cells and a significant reduction of soluble Neuregulin1 (NRG1, an important factor for the survival and activity of Schwann cells) already after 3 months of degeneration. Moreover, functional, morphological, morphometrical and biomolecular analyses were carried out on regenerated distal nerve stumps 6 months after nerve repair (immediate or 3 and 6 months delayed). A rat surgical model of delayed nerve repair consisting of a cross suture between the chronically degenerated median nerve distal stump and the freshly axotomized ulnar proximal stump was used. Functional recovery analysis shows that only the group repaired immediately and not the two delayed-repaired groups, recovered partially. Moreover, quantitative analysis shows that the delayed groups have fewer and smaller myelinated fibers compared to the immediate repair group. Finally, biomolecular analysis performed on the 6-months delayed group shows that soluble NRG1 maintains a low expression also after 6 months of regeneration. These results demonstrate that, despite a delay of 3 or 6 months, the fibers are still able to regenerate, even if they are fewer and smaller than the immediate repaired group. Moreover, the analysis of the NRG1/ErbB system shows a significant decrease of soluble NRG1 in both degenerating and delayed-repaired nerves. Our results suggest that NRG1 plays an important role in Schwann cell activity after denervation, therefore its manipulation could be a good strategy to improve the outcome after delayed nerve repair. [ABSTRACT FROM AUTHOR]

Biosynthetic nerve grafts are developed in order to complement or replace autologous nerve grafts for peripheral nerve reconstruction. Artificial nerve guides currently approved for clinical use are not widely applied in reconstructive surgery as they still have limitations especially when it comes to critical distance repair. Here we report a comprehensive analysis of fine-tuned chitosan nerve guides (CNGs) enhanced by introduction of a longitudinal chitosan film to reconstruct critical length 15 mm sciatic nerve defects in adult healthy Wistar or diabetic Goto-Kakizaki rats. Short and long term investigations demonstrated that the CNGs enhanced by the guiding structure of the introduced chitosan film significantly improved functional and morphological results of nerve regeneration in comparison to simple hollow CNGs. Importantly, this was detectable both in healthy and in diabetic rats (short term) and the regeneration outcome almost reached the outcome after autologous nerve grafting (long term). Hollow CNGs provide properties likely leading to a wider clinical acceptance than other artificial nerve guides and their performance can be increased by simple introduction of a chitosan film with the same advantageous properties. Therefore, the chitosan film enhanced CNGs represent a new generation medical device for peripheral nerve reconstruction. [ABSTRACT FROM AUTHOR]

The quantitative assessment of motor function is an important requirement for studies on peripheral nerve injury and repair. So far, most studies on peripheral nerves have been performed on the sciatic nerve model using walking track analysis for assessing motor function. Alternatively, the employment of the median nerve model, which allows motor function evaluation by means of a simple behavioural test named grasping test (GT), have been more recently proposed. In this paper, the efficacy of the GT for the quantitative assessment of motor function recovery is re-appraised and a modified device for its carrying out is described. Finally, the rationale for the employment of the median nerve model as an alternative to the sciatic nerve model is critically discussed. [Copyright &y& Elsevier]

Peripheral nerve lesions are frequent occurrences in both human and animal patients, leading to important physiological and labor complications that affect the quality of life of those who suffer the injury. More severe injuries are often associated with poor nerve regeneration and inadequate functional recovery, even with early medical and surgical interventions. Peripheral nerve crush lesions are frequent and, therefore, an experimental lesion paradigm widely used in researches involving nerve injury models and therapies for its resolution. In recent years, many studies have focused on innovative approaches to peripheral nerve treatment after crush injuries with more or less success. This review addresses the theme of peripheral nerve injury, with a special focus on the axonotmesis lesion, its etiology, pathophysiological mechanisms, methods of functional evaluation and regenerative processes, therapeutic options and corresponding recent advances. [ABSTRACT FROM AUTHOR]