Influencing factors and repair advancements in rodent models of peripheral nerve regeneration.

Management of peripheral nerve injury

Review question / Objective: It has been the gold standard for decades to reconstruct a large peripheral nerve injury with a nerve autograft, and this remains true today as well. In addition to nerve autografts, biological conduits and vessels can also be applied. A fair amount of studies have examined the benefits of adding stem cells to the lumen of a nerve conduit. The aim of this meta-analysis was to summarize animal experiments related to the utilization of stem cells as a luminal additive when rebuilding a peripheral nerve injury using nerve grafts. Eligibility criteria: The inclusion criteria were as following: 1.Reconstruction of peripheral nerve injury; 2.Complete nerve transection with gap defect created; 3.Animal in-vivo models; 4.Experimental comparisons between nerve conduits containing and not containing one type of stem cell; 5.Functional testing and electrophysiology evaluations are performed. The exclusion criteria were as following: 1.Repair of central nervous system; 2.Nerve repair is accomplished by end-to-end anastomosis; 3.Animal models of entrapment injuries, frostbite, traction injuries and electric injuries; 4.Nerve conduits made from autologous epineurium; 5.Clinical trials, reviews, letters, conference papers, meta-analyses or commentaries; 6.Same studies have been published in different journals under the same or a different title.

Technologies for repairing peripheral nerve injury*: Progress in domestic and foreign investigations

Objective. Guiding Regeneration Gel (GRG) was developed in response to the clinical need of improving treatment for peripheral nerve injuries and helping patients regenerate massive regional losses in peripheral nerves. The efficacy of GRG based on tissue engineering technology for the treatment of complete peripheral nerve injury with significant loss defect was investigated. Background. Many severe peripheral nerve injuries can only be treated through surgical reconstructive procedures. Such procedures are challenging, since functional recovery is slow and can be unsatisfactory. One of the most promising solutions already in clinical practice is synthetic nerve conduits connecting the ends of damaged nerve supporting nerve regeneration. However, this solution still does not enable recovery of massive nerve loss defect. The proposed technology is a biocompatible and biodegradable gel enhancing axonal growth and nerve regeneration. It is composed of a complex of substances comprising transparent, highly viscous gel resembling the extracellular matrix that is almost impermeable to liquids and gasses, flexible, elastic, malleable, and adaptable to various shapes and formats. Preclinical study on rat model of peripheral nerve injury showed that GRG enhanced nerve regeneration when placed in nerve conduits, enabling recovery of massive nerve loss, previously unbridgeable, and enabled nerve regeneration at least as good as with autologous nerve graft “gold standard” treatment.

A Comparison of Polyglycolic Acid Versus Type 1 Collagen Bioabsorbable Nerve Conduits in a Rat Model: An Alternative to Autografting

Peripheral nerve injury is a common complication of accidents and diseases. The traditional autologous nerve graft approach remains the gold standard for the treatment of nerve injuries. While sources of autologous nerve grafts are very limited and difficult to obtain. Nerve guidance conduits have been widely used in the treatment of peripheral nerve injuries as an alternative to nerve autografts and allografts. However, the development of nerve conduits does not meet the needs of large gap peripheral nerve injury. Functional nerve conduits can provide a good microenvironment for axon elongation and myelin regeneration. In this review, we summarize the manufacturing methods and different design types of functional bridging nerve conduits for nerve conduits combined with electrical or magnetic stimulation and loaded with Schwann cells, etc. It summarizes the literature and finds that the technical solutions of functional nerve conduits with electrical stimulation, magnetic stimulation and nerve conduits combined with Schwann cells can be used as effective strategies for bridging large gap nerve injury and provide an effective way for the study of large gap nerve injury repair. In addition, functional nerve conduits provide a new way to construct delivery systems for drugs and growth factors in vivo. This article is protected by copyright. All rights reserved.

The peripheral nerve injuries, representing some of the most common types of traumatic lesions affecting the nervous system, are highly invalidating for the patients besides being a huge social burden. Although peripheral nervous system owns a higher regenerative capacity than does central nervous system, mostly depending on Schwann cells intervention in injury repair, several factors determine the extent of functional outcome after healing. Based on the injury type, different therapeutic approaches have been investigated so far. Nerve grafting and Schwann cell transplantation have represented the gold standard treatment for peripheral nerve injuries, however these approaches own limitations, such as scarce donor nerve availability and donor site morbidity. Cell based therapies might provide a suitable tool for peripheral nerve regeneration, in fact, the ability of different stem cell types to differentiate towards Schwann cells in combination with the use of different scaffolds have been widely investigated in animal models of peripheral nerve injuries in the last decade. Dental pulp is a promising cell source for regenerative medicine, because of the ease of isolation procedures, stem cell proliferation and multipotency abilities, which are due to the embryological origin from neural crest. In this article we review the literature concerning the application of tooth derived stem cell populations combined with different conduits to peripheral nerve injuries animal models, highlighting their regenerative contribution exerted through either glial differentiation and neuroprotective/neurotrophic effects on the host tissue.

Approach to management of nerve gaps in peripheral nerve injuries

Peripheral nerve injuries commonly occur due to trauma, like a traffic accident. Peripheral nerves get severed, causing motor neuron death and potential muscle atrophy. The current golden standard to treat peripheral nerve lesions, especially lesions with large (≥ 3 cm) nerve gaps, is the use of a nerve autograft or reimplantation in cases where nerve root avulsions occur. If not tended early, degeneration of motor neurons and loss of axon regeneration can occur, leading to loss of function. Although surgical procedures exist, patients often do not fully recover, and quality of life deteriorates. Peripheral nerves have limited regeneration, and it is usually mediated by Schwann cells and neurotrophic factors, like glial cell line-derived neurotrophic factor, as seen in Wallerian degeneration. Glial cell line-derived neurotrophic factor is a neurotrophic factor known to promote motor neuron survival and neurite outgrowth. Glial cell line-derived neurotrophic factor is upregulated in different forms of nerve injuries like axotomy, sciatic nerve crush, and compression, thus creating great interest to explore this protein as a potential treatment for peripheral nerve injuries. Exogenous glial cell line-derived neurotrophic factor has shown positive effects in regeneration and functional recovery when applied in experimental models of peripheral nerve injuries. In this review, we discuss the mechanism of repair provided by Schwann cells and upregulation of glial cell line-derived neurotrophic factor, the latest findings on the effects of glial cell line-derived neurotrophic factor in different types of peripheral nerve injuries, delivery systems, and complementary treatments (electrical muscle stimulation and exercise). Understanding and overcoming the challenges of proper timing and glial cell line-derived neurotrophic factor delivery is paramount to creating novel treatments to tend to peripheral nerve injuries to improve patients’ quality of life.

The facial nerve stimulates the muscles of facial expression and the parasympathetic nerves of the face. Consequently, facial nerve paralysis can lead to facial asymmetry, deformation, and functional impairment. Facial nerve palsy is most commonly idiopathic, as with Bell palsy, but it can also result from a tumor or trauma. In this article, we discuss traumatic facial nerve injury. To identify the cause of the injury, it is important to first determine its location. The location and extent of the damage inform the treatment method, with options including primary repair, nerve graft, cross-face nerve graft, nerve crossover, and muscle transfer. Intracranial proximal facial nerve injuries present a challenge to surgical approaches due to the complexity of the temporal bone. Surgical intervention in these cases requires a collaborative approach between neurosurgery and otolaryngology, and nerve repair or grafting is difficult. This article describes the treatment of peripheral facial nerve injury. Primary repair generally offers the best prognosis. If primary repair is not feasible within 6 months of injury, nerve grafting should be attempted, and if more than 12 months have elapsed, functional muscle transfer should be performed. If the affected nerve cannot be utilized at that time, the contralateral facial nerve, ipsilateral masseter nerve, or hypoglossal nerve can serve as the donor nerve. Other accompanying symptoms, such as lagophthalmos or midface ptosis, must also be considered for the successful treatment of facial nerve injury.

Background:Direct neurorrhaphy, nerve grafting interposition and neurotization are the options for nerve repair in children, whereas few reports about using nerve conduits (tubulization) are referred to pediatrics in the literature. The authors present their experience about nerve repairing by means of nerve tubes during the developmental age when the harvesting of nerve grafts and also vein grafts of adequate caliber for bridging nerve defects is difficult. A critical review of their case series offers indications for using nerve conduits in pediatrics.Materials and Methods:Fifteen patients were treated using the nerve tubulization; nine patients were affected by obstetrical brachial plexus palsy (OBPP) while six were suffering from peripheral nerve injuries (PNIs).Results:In patients suffering from OBPP, we observed 1 good, 3 fair and 5 bad results. In the PNI group, we observed 4 patients who had good results while only 2 had a bad outcome. No fair results were observed.Conclusions:In peripheral nerve repairing in children by using nerve conduits, the outcome has been widely effective even when dealing with mixed and motor nerve, thus nerve tubulization might be considered as an alternative to nerve grafting. Conversely, considering the uncertain result obtained in brachial plexus repairing, the conduits cannot be considered as a first choice of treatment in brachial plexus reconstruction.

Tacrolimus (FK506) is a widely used immunosuppressant in organ transplantation. However, it also has neurotrophic activity that occurs independently of its immunosuppressive effects. Other neurotrophic immunophilin ligands that do not exhibit immunosuppression have subsequently been developed and studied in various models of nerve injury. This article reviews the literature on the use of tacrolimus and other immunophilin ligands in peripheral nerve, cranial nerve and spinal cord injuries. The most convincing evidence of enhanced nerve regeneration is seen with systemic administration of tacrolimus in peripheral nerve injury, although clinical use is limited due to its immunosuppressive side effects. Local tacrolimus delivery to the site of nerve repair in peripheral and cranial nerve injury is less effective but requires further investigation. Tacrolimus can enhance outcomes in nerve allograft reconstruction and accelerates reinnervation of complex functional allograft transplants. Other non-immunosuppressive immunophilins ligands such as V-10367 and FK1706 demonstrate enhanced neuroregeneration in the peripheral nervous system and CNS. Mixed results are found in the application of immunophilin ligands to treat spinal cord injury. Immunophilin ligands have great potential in the treatment of nerve injury, but further preclinical studies are necessary to permit translation into clinical trials.

Peripheral nerve injuries can have devastating functional consequences. Particularly in the pediatric population, nerve injuries may have negative implications on growth, mobility, and quality of life of children. Historically, treatment of peripheral nerve injuries had limited application and suboptimal results. While the advancement of microsurgical technique as well as our understanding of nerve injury and regeneration has led to improved technical ability to repair nerve pathology, the slow rate of neuroregeneration has limited the results of treatment of proximal nerve injury. Previous decades of work have helped shape the novel concept of treating proximal peripheral nerve injuries with a distal reconstruction via nerve transfers. Injuries that are far from the end target can be managed more efficaciously by converting them to a distal reconstruction, by borrowing expendable nerves to reestablish critical function. This not only speeds reinnervation, thereby preserving motor end plates and improving function, but also allows reconstruction of previously untreatable lesions or those that have a delayed presentation. This chapter reviews special considerations specific to nerve injury in the pediatric population, the mechanisms of neuroregeneration, obstacles in muscular reinnervation after injury, and modern approaches to the treatment of peripheral nerve injuries in children.

In vivo evaluation of rabbit sciatic nerve regeneration with diffusion tensor imaging (DTI): correlations with histology and behavior

Hybrid construction of tissue-engineered nerve graft using skin derived precursors induced neurons and Schwann cells to enhance peripheral neuroregeneration