Mitchell's influence on European studies of peripheral nerve injuries during World War I.

Science.gov (United States)

Koehler, Peter J; Lanska, Douglas J

2004-12-01

Describe the influence of S. Weir Mitchell's (1829-1914) work, and in particular his ideas on causalgia, on European physicians who treated peripheral nerve injuries during World War I (WWI). During the American Civil War (1861-1865), Mitchell studied peripheral nerve injuries with colleagues George Read Morehouse and William Williams Keen. Three monographs resulted from this work. All were important landmarks in the evolution of knowledge of peripheral nerve injuries. A subsequent occasion to improve knowledge came in WWI. The most important European monographs or series on peripheral nerve injuries from WWI were studied with special interest in references to causalgia and Mitchell's works on peripheral nerve injuries. We included works by Tinel, Athanassio-Benisty, Purves-Stewart & Evans and Carter, Foerster and Oppenheim. Tinel and Athanassio-Benisty provided the most detailed information on peripheral nerve injuries and causalgia and often referred to Mitchell. Both mentioned a possible sympathetic origin. Athanassio-Benisty described tremor and other movement disorders in relation to causalgia. Purves-Stewart and Evans mentioned Mitchell and causalgia in the second edition of their book. They advocated the term "thermalgia." Carter, who had access to data of many cases, concentrated his work on causalgia, referring to Mitchell. Foerster provided data of a great number of peripheral nerve injuries, but did not refer to Mitchell. However, he described the symptoms of causalgia cursorily, applying the term Reflexschmerz (reflexpain). Oppenheim was particularly interested in muscle innervation and referred to Mitchell with respect to hypertrichosis and glossy skin. Oppenheim did not use the term causalgia, although he described the syndrome in some of his patients. It wasn't until around 1920 that German physicians devoted significant attention to causalgia and began using the term. Knowledge of peripheral nerve injuries was greatly advanced during and after WWI

Late radiation injury to muscle and peripheral nerves

International Nuclear Information System (INIS)

Gillette, E. L.; Mahler, P. A.; Powers, B. E.; Gillette, S. M.; Vujaskovic, Z.

1995-01-01

Late radiation injury to muscles and peripheral nerves is infrequently observed. However, the success of radiation oncology has led to longer patient survival, providing a greater opportunity for late effects to develop, increase in severity and, possibly, impact the quality of life of the patient. In addition, when radiation therapy is combined with surgery and/or chemotherapy, the risk of late complications is likely to increase. It is clear that the incidence of complications involving muscles and nerves increases with time following radiation. The influence of volume has yet to be determined; however, an increased volume is likely to increase the risk of injury to muscles and nerves. Experimental and clinical studies have indicated that the (α(β)) ratio for muscle is approximately 4 Gy and, possibly, 2 Gy for peripheral nerve, indicating the great influence of fractionation on response of these tissues. This is of concern for intraoperative radiation therapy, and for high dose rate brachytherapy. This review of clinical and experimental data discusses the response of muscle and nerves late after radiation therapy. A grading system has been proposed and endpoints suggested

Spinal myoclonus following a peripheral nerve injury: a case report

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Erkol Gokhan

2008-08-01

Full Text Available Abstract Spinal myoclonus is a rare disorder characterized by myoclonic movements in muscles that originate from several segments of the spinal cord and usually associated with laminectomy, spinal cord injury, post-operative, lumbosacral radiculopathy, spinal extradural block, myelopathy due to demyelination, cervical spondylosis and many other diseases. On rare occasions, it can originate from the peripheral nerve lesions and be mistaken for peripheral myoclonus. Careful history taking and electrophysiological evaluation is important in differential diagnosis. The aim of this report is to evaluate the clinical and electrophysiological characteristics and treatment results of a case with spinal myoclonus following a peripheral nerve injury without any structural lesion.

Wallerian degeneration: gaining perspective on inflammatory events after peripheral nerve injury

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Popovich Phillip G

2011-08-01

Full Text Available Abstract In this review, we first provide a brief historical perspective, discussing how peripheral nerve injury (PNI may have caused World War I. We then consider the initiation, progression, and resolution of the cellular inflammatory response after PNI, before comparing the PNI inflammatory response with that induced by spinal cord injury (SCI. In contrast with central nervous system (CNS axons, those in the periphery have the remarkable ability to regenerate after injury. Nevertheless, peripheral nervous system (PNS axon regrowth is hampered by nerve gaps created by injury. In addition, the growth-supportive milieu of PNS axons is not sustained over time, precluding long-distance regeneration. Therefore, studying PNI could be instructive for both improving PNS regeneration and recovery after CNS injury. In addition to requiring a robust regenerative response from the injured neuron itself, successful axon regeneration is dependent on the coordinated efforts of non-neuronal cells which release extracellular matrix molecules, cytokines, and growth factors that support axon regrowth. The inflammatory response is initiated by axonal disintegration in the distal nerve stump: this causes blood-nerve barrier permeabilization and activates nearby Schwann cells and resident macrophages via receptors sensitive to tissue damage. Denervated Schwann cells respond to injury by shedding myelin, proliferating, phagocytosing debris, and releasing cytokines that recruit blood-borne monocytes/macrophages. Macrophages take over the bulk of phagocytosis within days of PNI, before exiting the nerve by the circulation once remyelination has occurred. The efficacy of the PNS inflammatory response (although transient stands in stark contrast with that of the CNS, where the response of nearby cells is associated with inhibitory scar formation, quiescence, and degeneration/apoptosis. Rather than efficiently removing debris before resolving the inflammatory response as

The surgery of peripheral nerves (including tumors)

DEFF Research Database (Denmark)

Fugleholm, Kåre

2013-01-01

Surgical pathology of the peripheral nervous system includes traumatic injury, entrapment syndromes, and tumors. The recent significant advances in the understanding of the pathophysiology and cellular biology of peripheral nerve degeneration and regeneration has yet to be translated into improved...... surgical techniques and better outcome after peripheral nerve injury. Decision making in peripheral nerve surgery continues to be a complex challenge, where the mechanism of injury, repeated clinical evaluation, neuroradiological and neurophysiological examination, and detailed knowledge of the peripheral...... nervous system response to injury are prerequisite to obtain the best possible outcome. Surgery continues to be the primary treatment modality for peripheral nerve tumors and advances in adjuvant oncological treatment has improved outcome after malignant peripheral nerve tumors. The present chapter...

Some questions of the treatment of injuries of extremities peripheral nerves

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Виктор Александрович Вишневский

2015-11-01

Full Text Available Trauma of extremities peripheral nerves is on the one of first places on disability and results in stable invalidism in 28–75 % of cases.Mistakes in nerves surgery lead not only to unsatisfactory results and repeated operations but also cause the numerous complications.Indications and contraindications to surgery and conservative treatment, surgical tactics and methods of operations on peripheral nerves depend on trauma prescription, injury character and previous surgical interventions, tissue scarring degree and also level of injury.Aim of research: to carry out an analysis of nerve trunk injuries at traumas of upper and lower extremities, to ground the differentiated approach to treatment depending on traumatization degree and time elapsed since the moment of trauma.Materials and methods: Author carried out retrospective analysis of medical histories of 70 patients with injury of extremities peripheral nerves and the choice of treating tactics and methods. Research was carried out on the base of traumatology department of Dnepropetrovsk clinical hospital № 16 from 2010 to 2013 year.Injuries were divided on cause in primary (65,7 % and secondary (iatrogenic (34,3 %, and also on the degree of conductivity disorder in: neurotmesis (60,0 %, axonotmesis (27,1 % and neuropraxia (12,9 %.Diagnosis of the nerve trunks trauma in clinic was set on the base of clinically-neurological examination using paraclinical methods of research: electroneuromyography, thermal tomography, intramuscular electromyography, bones and joints radiography.Results: According to the results of clinically-neurological and paraclinical methods of research the choice of surgical or conservative treatment depends on dynamics of nerve trunk conductivity disorders: the loss of motor function, sensory impairments and vegetative-trophic impairments in innervation area.The most often were injuries of radial nerve on the level of the shoulder middle one-third – 29 cases (41

Morphology and nanomechanics of sensory neurons growth cones following peripheral nerve injury.

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Marta Martin

Full Text Available A prior peripheral nerve injury in vivo, promotes a rapid elongated mode of sensory neurons neurite regrowth in vitro. This in vitro model of conditioned axotomy allows analysis of the cellular and molecular mechanisms leading to an improved neurite re-growth. Our differential interference contrast microscopy and immunocytochemistry results show that conditioned axotomy, induced by sciatic nerve injury, did not increase somatic size of adult lumbar sensory neurons from mice dorsal root ganglia sensory neurons but promoted the appearance of larger neurites and growth cones. Using atomic force microscopy on live neurons, we investigated whether membrane mechanical properties of growth cones of axotomized neurons were modified following sciatic nerve injury. Our data revealed that neurons having a regenerative growth were characterized by softer growth cones, compared to control neurons. The increase of the growth cone membrane elasticity suggests a modification in the ratio and the inner framework of the main structural proteins.

Biological conduit small gap sleeve bridging method for peripheral nerve injury: regeneration law of nerve fibers in the conduit

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Pei-xun Zhang

2015-01-01

Full Text Available The clinical effects of 2-mm small gap sleeve bridging of the biological conduit to repair peripheral nerve injury are better than in the traditional epineurium suture, so it is possible to replace the epineurium suture in the treatment of peripheral nerve injury. This study sought to identify the regeneration law of nerve fibers in the biological conduit. A nerve regeneration chamber was constructed in models of sciatic nerve injury using 2-mm small gap sleeve bridging of a biodegradable biological conduit. The results showed that the biological conduit had good histocompatibility. Tissue and cell apoptosis in the conduit apparently lessened, and regenerating nerve fibers were common. The degeneration regeneration law of Schwann cells and axons in the conduit was quite different from that in traditional epineurium suture. During the prime period for nerve fiber regeneration (2-8 weeks, the number of Schwann cells and nerve fibers was higher in both proximal and distal ends, and the effects of the small gap sleeve bridging method were better than those of the traditional epineurium suture. The above results provide an objective and reliable theoretical basis for the clinical application of the biological conduit small gap sleeve bridging method to repair peripheral nerve injury.

[Peripheral facial nerve lesion induced long-term dendritic retraction in pyramidal cortico-facial neurons].

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Urrego, Diana; Múnera, Alejandro; Troncoso, Julieta

2011-01-01

Little evidence is available concerning the morphological modifications of motor cortex neurons associated with peripheral nerve injuries, and the consequences of those injuries on post lesion functional recovery. Dendritic branching of cortico-facial neurons was characterized with respect to the effects of irreversible facial nerve injury. Twenty-four adult male rats were distributed into four groups: sham (no lesion surgery), and dendritic assessment at 1, 3 and 5 weeks post surgery. Eighteen lesion animals underwent surgical transection of the mandibular and buccal branches of the facial nerve. Dendritic branching was examined by contralateral primary motor cortex slices stained with the Golgi-Cox technique. Layer V pyramidal (cortico-facial) neurons from sham and injured animals were reconstructed and their dendritic branching was compared using Sholl analysis. Animals with facial nerve lesions displayed persistent vibrissal paralysis throughout the five week observation period. Compared with control animal neurons, cortico-facial pyramidal neurons of surgically injured animals displayed shrinkage of their dendritic branches at statistically significant levels. This shrinkage persisted for at least five weeks after facial nerve injury. Irreversible facial motoneuron axonal damage induced persistent dendritic arborization shrinkage in contralateral cortico-facial neurons. This morphological reorganization may be the physiological basis of functional sequelae observed in peripheral facial palsy patients.

Differential induction of c-Fos and phosphorylated ERK by a noxious stimulus after peripheral nerve injury.

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Tabata, Mitsuyasu; Terayama, Ryuji; Maruhama, Kotaro; Iida, Seiji; Sugimoto, Tomosada

2018-03-01

In this study, we compared induction of c-Fos and phosphorylated extracellular signal-regulated kinase (p-ERK) in the spinal dorsal horn after peripheral nerve injury. We examined the spinal dorsal horn for noxious heat-induced c-Fos and p-ERK protein-like immunoreactive (c-Fos- and p-ERK-IR) neuron profiles after tibial nerve injury. The effect of administration of a MEK 1/2 inhibitor (PD98059) on noxious heat-induced c-Fos expression was also examined after tibial nerve injury. A large number of c-Fos- and p-ERK-IR neuron profiles were induced by noxious heat stimulation to the hindpaw in sham-operated animals. A marked reduction in the number of c-Fos- and p-ERK-IR neuron profiles was observed in the medial 1/3 (tibial territory) of the dorsal horn at 3 and 7 days after nerve injury. Although c-Fos-IR neuron profiles had reappeared by 14 days after injury, the number of p-ERK-IR neuron profiles remained decreased in the tibial territory of the superficial dorsal horn. Double immunofluorescence labeling for c-Fos and p-ERK induced by noxious heat stimulation to the hindpaw at different time points revealed that a large number of c-Fos-IR, but not p-ERK-IR, neuron profiles were distributed in the tibial territory after injury. Although administration of a MEK 1/2 inhibitor to the spinal cord suppressed noxious heat-induced c-Fos expression in the peroneal territory, this treatment did not alter c-Fos induction in the tibial territory after nerve injury. ERK phosphorylation may be involved in c-Fos induction in normal nociceptive responses, but not in exaggerated c-Fos induction after nerve injury.

Use of antioxidants for the prophylaxis of cold-induced peripheral nerve injury.

Science.gov (United States)

Teixeira, Fernanda; Pollock, Martin; Karim, Alveera; Jiang, Yuying

2002-09-01

"Trench foot" is a particular risk for those involved in adventure tourism, for soldiers in winter mountain training exercises, and for the homeless. Nonfreezing cold nerve injury is characterized by axonal degeneration, which is attributed to free radicals released during cycles of ischemia and reperfusion. This pilot study sought to determine whether the administration of antioxidants might prevent or ameliorate the development of cold nerve injury. Twenty-six rats were divided into two groups. Group 1 animals received, by gavage, a mixture of vitamin C (150 mg/kg/d), vitamin E (100 mg/kg/d), and N-acetyl-L-cysteine (250 mg/kg/d) daily for 4 weeks. Allopurinol (20 mg/kg/d) was added in the last 4 days of treatment. Group 2 animals served as controls and did not receive any antioxidant supplements. After 1 month, two cycles of sciatic nerve cooling (0 degrees C) were induced in 10 controls and 10 experimental animals using circulating water through a nerve cuff. Six additional control animals were subjected to surgery but did not undergo nerve cooling. All animals were killed on the third postoperative day, and their nerves were processed for ultrastructural and quantitative studies. The proportion of degenerated myelinated and unmyelinated axons showed no significant difference between treated and untreated animals. We conclude that the administration of commonly used antioxidants does not prevent cold nerve injury.

Establishment of Peripheral Nerve Injury Data Repository to Monitor and Support Population Health Decisions

Science.gov (United States)

2017-07-01

Military Medical Center (WRNMMC) for Peripheral Nerve Injury (PNI) treatment. A database , the Peripheral Nerve Injury Database (PNIDB), will be established...to catalog and describe the characteristics, mechanisms, management, and outcomes of PNIs using both retrospective chart review and prospective...decisions for patients with PNIs. These outcomes could be used in future study to further characterize PNIs and delineate which management

Magnetic resonance imaging research progress on brain functional reorganization after peripheral nerve injury

International Nuclear Information System (INIS)

Wang Weiwei; Liu Hanqiu

2013-01-01

In the recent years, with the development of functional magnetic resonance imaging technology the brain plasticity and functional reorganization are hot topics in the central nervous system imaging studies. Brain functional reorganization and rehabilitation after peripheral nerve injury may have certain regularity. In this paper, the progress of brain functional magnetic resonance imaging technology and its applications in the world wide clinical and experimental researches of the brain functional reorganization after peripheral nerve injury is are reviewed. (authors)

Role of Schwann cells in the regeneration of penile and peripheral nerves

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Lin Wang

2015-01-01

Full Text Available Schwann cells (SCs are the principal glia of the peripheral nervous system. The end point of SC development is the formation of myelinating and nonmyelinating cells which ensheath large and small diameter axons, respectively. They play an important role in axon regeneration after injury, including cavernous nerve injury that leads to erectile dysfunction (ED. Despite improvement in radical prostatectomy surgical techniques, many patients still suffer from ED postoperatively as surgical trauma causes traction injuries and local inflammatory changes in the neuronal microenvironment of the autonomic fibers innervating the penis resulting in pathophysiological alterations in the end organ. The aim of this review is to summarize contemporary evidence regarding: (1 the origin and development of SCs in the peripheral and penile nerve system; (2 Wallerian degeneration and SC plastic change following peripheral and penile nerve injury; (3 how SCs promote peripheral and penile nerve regeneration by secreting neurotrophic factors; (4 and strategies targeting SCs to accelerate peripheral nerve regeneration. We searched PubMed for articles related to these topics in both animal models and human research and found numerous studies suggesting that SCs could be a novel target for treatment of nerve injury-induced ED.

Complement inhibition accelerates regeneration in a model of peripheral nerve injury

NARCIS (Netherlands)

Ramaglia, Valeria; Tannemaat, Martijn Rudolf; de Kok, Maryla; Wolterman, Ruud; Vigar, Miriam Ann; King, Rosalind Helen Mary; Morgan, Bryan Paul; Baas, Frank

2009-01-01

Complement (C) activation is a crucial event in peripheral nerve degeneration but its effect on the subsequent regeneration is unknown. Here we show that genetic deficiency of the sixth C component, C6, accelerates axonal regeneration and recovery in a rat model of sciatic nerve injury. Foot-flick

The use of the rat as a model for studying peripheral nerve regeneration and sprouting after complete and partial nerve injuries.

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Gordon, Tessa; Borschel, Gregory H

2017-01-01

Rat models of complete and partial injuries are the most frequently used models for analysis of the cellular and molecular processes of nerve regeneration and axon sprouting. Studies of nerve regeneration and axon sprouting after complete and partial nerve injuries, respectively, are reviewed. Special consideration is made of the peripheral nerves chosen for the studies and the outcome measures that were utilized in the studies. The studies have made important contributions to our knowledge of the degenerative and regenerative processes that occur after the peripheral nerve injuries, why functional recovery is frequently compromised after delayed surgery, the positive effects of neurotrophic factors on nerve regeneration after delayed nerve repair or after insertion of autografts between transected nerve, and how axon regeneration may be accelerated by brief periods of electrical stimulation and/or by administration of androgens. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of intraneural and perineural injection and concentration of Ropivacaine on nerve injury during peripheral nerve block in Wistar rats

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Ilvana Hasanbegovic

2013-12-01

Full Text Available Introduction: Injury during peripheral nerve blocks is relatively uncommon, but potentially devastating complication. Recent studies emphasized that location of needle insertion in relationship to the fascicles may be the predominant factor that determines the risk for neurologic complications. However, it is wellestablished that concentration of local anesthetic is also associated with the risk for injury. In this study, we examined the effect of location of injection and concentration of Ropivacaine on risk for neurologic complications. Our hypothesis is that location of the injection is more prognostic for occurrence of nerve injury than the concentration of Ropivacaine.Methods: In experimental design of the study fi fty Wistar rats were used and sciatic nerves were randomized to receive: Ropivacaine or 0.9% NaCl, either intraneurally or perineurally. Pressure data during application was acquired by using a manometer and was analyzed using software package BioBench. Neurologic examination was performed thought the following seven days, there after the rats were sacrificed while sciatic nerves were extracted for histological examination.Results: Independently of tested solution intraneural injections in most of cases resulted with high injection pressure, followed by obvious neurologic defi cit and microscopic destruction of peripheral nerves. Also, low injection pressure, applied either in perineural or intraneural extrafascicular area, resulted with transitory neurologic defi cit and without destruction of the nerve normal histological structure.Conclusions: The main mechanism which leads to neurologic injury combined with peripheral nerve blockade is intrafascicular injection. Higher concentrations of Ropivacaine during intrafascicular applications magnify nerve injury.

Peripheral Neuropathy and Nerve Compression Syndromes in Burns.

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Strong, Amy L; Agarwal, Shailesh; Cederna, Paul S; Levi, Benjamin

2017-10-01

Peripheral neuropathy and nerve compression syndromes lead to substantial morbidity following burn injury. Patients present with pain, paresthesias, or weakness along a specific nerve distribution or experience generalized peripheral neuropathy. The symptoms manifest at various times from within one week of hospitalization to many months after wound closure. Peripheral neuropathy may be caused by vascular occlusion of vasa nervorum, inflammation, neurotoxin production leading to apoptosis, and direct destruction of nerves from the burn injury. This article discusses the natural history, diagnosis, current treatments, and future directions for potential interventions for peripheral neuropathy and nerve compression syndromes related to burn injury. Copyright © 2017 Elsevier Inc. All rights reserved.

Accelerating axon growth to overcome limitations in functional recovery after peripheral nerve injury.

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Gordon, Tessa; Chan, K Ming; Sulaiman, Olawale A R; Udina, Esther; Amirjani, Nasim; Brushart, Thomas M

2009-10-01

Injured peripheral nerves regenerate at very slow rates. Therefore, proximal injury sites such as the brachial plexus still present major challenges, and the outcomes of conventional treatments remain poor. This is in part attributable to a progressive decline in the Schwann cells' ability to provide a supportive milieu for the growth cone to extend and to find the appropriate target. These challenges are compounded by the often considerable delay of regeneration across the site of nerve laceration. Recently, low-frequency electrical stimulation (as brief as an hour) has shown promise, as it significantly accelerated regeneration in animal models through speeding of axon growth across the injury site. To test whether this might be a useful clinical tool, we carried out a randomized controlled trial in patients who had experienced substantial axonal loss in the median nerve owing to severe compression in the carpal tunnel. To further elucidate the potential mechanisms, we applied rolipram, a cyclic adenosine monophosphate agonist, to rats after axotomy of the femoral nerve. We demonstrated that effects similar to those observed in animal studies could also be attained in humans. The mechanisms of action of electrical stimulation likely operate through up-regulation of neurotrophic factors and cyclic adenosine monophosphate. Indeed, the application of rolipram significantly accelerated nerve regeneration. With new mechanistic insights into the influencing factors of peripheral nerve regeneration, the novel treatments described above could form part of an armament of synergistic therapies that could make a meaningful difference to patients with peripheral nerve injuries.

Cingulate Alpha-2A Adrenoceptors Mediate the Effects of Clonidine on Spontaneous Pain Induced by Peripheral Nerve Injury

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Yong-Jie Wang

2017-09-01

Full Text Available The anterior cingulate cortex (ACC is an important brain area for the regulation of neuropathic pain. The α2A adrenoceptor is a good target for pain management. However, the role of cingulate α2A adrenoceptors in the regulation of neuropathic pain has been less studied. In this study, we investigated the involvement of cingulate α2A adrenoceptors in the regulation of neuropathic pain at different time points after peripheral nerve injury in mice. The application of clonidine, either systemically (0.5 mg/kg intraperitoneally or specifically to the ACC, increased paw withdrawal thresholds (PWTs and induced conditioned place preference (CPP at day 7 after nerve injury, suggesting that cingulate α2 adrenoceptors are involved in the regulation of pain-like behaviors. Quantitative real-time PCR data showed that α2A adrenoceptors are the dominant α2 adrenoceptors in the ACC. Furthermore, the expression of cingulate α2A adrenoceptors was increased at day 3 and day 7 after nerve injury, but decreased at day 14, while no change was detected in the concentration of adrenaline or noradrenaline. BRL-44408 maleate, a selective antagonist of α2A adrenoceptors, was microinfused into the ACC. This blocking of cingulate α2A adrenoceptors activity abolished the CPP induced by clonidine (0.5 mg/kg intraperitoneally but not the effects on PWTs at day 7. However, clonidine applied systemically or specifically to the ACC at day 14 increased the PWTs but failed to induce CPP; this negative effect was reversed by the overexpression of cingulate α2A adrenoceptors. These results suggest that cingulate α2A adrenoceptors are necessary for the analgesic effects of clonidine on spontaneous pain.

3D printing strategies for peripheral nerve regeneration.

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Petcu, Eugen B; Midha, Rajiv; McColl, Erin; Popa-Wagner, Aurel; Chirila, Traian V; Dalton, Paul D

2018-03-23

After many decades of biomaterials research for peripheral nerve regeneration, a clinical product (the nerve guide), is emerging as a proven alternative for relatively short injury gaps. This review identifies aspects where 3D printing can assist in improving long-distance nerve guide regeneration strategies. These include (1) 3D printing of the customizable nerve guides, (2) fabrication of scaffolds that fill nerve guides, (3) 3D bioprinting of cells within a matrix/bioink into the nerve guide lumen and the (4) establishment of growth factor gradients along the length a nerve guide. The improving resolution of 3D printing technologies will be an important factor for peripheral nerve regeneration, as fascicular-like guiding structures provide one path to improved nerve guidance. The capability of 3D printing to manufacture complex structures from patient data based on existing medical imaging technologies is an exciting aspect that could eventually be applied to treating peripheral nerve injury. Ultimately, the goal of 3D printing in peripheral nerve regeneration is the automated fabrication, potentially customized for the patient, of structures within the nerve guide that significantly outperform the nerve autograft over large gap injuries.

An update-tissue engineered nerve grafts for the repair of peripheral nerve injuries.

Science.gov (United States)

Patel, Nitesh P; Lyon, Kristopher A; Huang, Jason H

2018-05-01

Peripheral nerve injuries (PNI) are caused by a range of etiologies and result in a broad spectrum of disability. While nerve autografts are the current gold standard for the reconstruction of extensive nerve damage, the limited supply of autologous nerve and complications associated with harvesting nerve from a second surgical site has driven groups from multiple disciplines, including biomedical engineering, neurosurgery, plastic surgery, and orthopedic surgery, to develop a suitable or superior alternative to autografting. Over the last couple of decades, various types of scaffolds, such as acellular nerve grafts (ANGs), nerve guidance conduits, and non-nervous tissues, have been filled with Schwann cells, stem cells, and/or neurotrophic factors to develop tissue engineered nerve grafts (TENGs). Although these have shown promising effects on peripheral nerve regeneration in experimental models, the autograft has remained the gold standard for large nerve gaps. This review provides a discussion of recent advances in the development of TENGs and their efficacy in experimental models. Specifically, TENGs have been enhanced via incorporation of genetically engineered cells, methods to improve stem cell survival and differentiation, optimized delivery of neurotrophic factors via drug delivery systems (DDS), co-administration of platelet-rich plasma (PRP), and pretreatment with chondroitinase ABC (Ch-ABC). Other notable advancements include conduits that have been bioengineered to mimic native nerve structure via cell-derived extracellular matrix (ECM) deposition, and the development of transplantable living nervous tissue constructs from rat and human dorsal root ganglia (DRG) neurons. Grafts composed of non-nervous tissues, such as vein, artery, and muscle, will be briefly discussed.

A 2-year follow-up survey of 523 cases with peripheral nerve injuries caused by the earthquake in Wenchuan, China

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Chun-qing He

2015-01-01

Full Text Available We performed a 2-year follow-up survey of 523 patients with peripheral nerve injuries caused by the earthquake in Wenchuan, Sichuan Province, China. Nerve injuries were classified into three types: type I injuries were nerve transection injuries, type II injuries were nerve compression injuries, and type III injuries displayed no direct neurological dysfunction due to trauma. In this study, 31 patients had type I injuries involving 41 nerves, 419 had type II injuries involving 823 nerves, and 73 had type III injuries involving 150 nerves. Twenty-two patients had open transection nerve injury. The restoration of peripheral nerve function after different treatments was evaluated. Surgical decompression favorably affected nerve recovery. Physiotherapy was effective for type I and type II nerve injuries, but not substantially for type III nerve injury. Pharmacotherapy had little effect on type II or type III nerve injuries. Targeted decompression surgery and physiotherapy contributed to the effective treatment of nerve transection and compression injuries. The Louisiana State University Health Sciences Center score for nerve injury severity declined with increasing duration of being trapped. In the first year after treatment, the Louisiana State University Health Sciences Center score for grades 3 to 5 nerve injury increased by 28.2% to 81.8%. If scores were still poor (0 or 1 after a 1-year period of treatment, further treatment was not effective.

Peripheral nerve injury is associated with chronic, reversible changes in global DNA methylation in the mouse prefrontal cortex.

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Maral Tajerian

Full Text Available Changes in brain structure and cortical function are associated with many chronic pain conditions including low back pain and fibromyalgia. The magnitude of these changes correlates with the duration and/or the intensity of chronic pain. Most studies report changes in common areas involved in pain modulation, including the prefrontal cortex (PFC, and pain-related pathological changes in the PFC can be reversed with effective treatment. While the mechanisms underlying these changes are unknown, they must be dynamically regulated. Epigenetic modulation of gene expression in response to experience and environment is reversible and dynamic. Epigenetic modulation by DNA methylation is associated with abnormal behavior and pathological gene expression in the central nervous system. DNA methylation might also be involved in mediating the pathologies associated with chronic pain in the brain. We therefore tested a whether alterations in DNA methylation are found in the brain long after chronic neuropathic pain is induced in the periphery using the spared nerve injury modal and b whether these injury-associated changes are reversible by interventions that reverse the pathologies associated with chronic pain. Six months following peripheral nerve injury, abnormal sensory thresholds and increased anxiety were accompanied by decreased global methylation in the PFC and the amygdala but not in the visual cortex or the thalamus. Environmental enrichment attenuated nerve injury-induced hypersensitivity and reversed the changes in global PFC methylation. Furthermore, global PFC methylation correlated with mechanical and thermal sensitivity in neuropathic mice. In summary, induction of chronic pain by peripheral nerve injury is associated with epigenetic changes in the brain. These changes are detected long after the original injury, at a long distance from the site of injury and are reversible with environmental manipulation. Changes in brain structure and

Major Peripheral Nerve Injuries After Elbow Arthroscopy.

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Desai, Mihir J; Mithani, Suhail K; Lodha, Sameer J; Richard, Marc J; Leversedge, Fraser J; Ruch, David S

2016-06-01

To survey the American Society for Surgery of the Hand membership to determine the nature and distribution of nerve injuries treated after elbow arthroscopy. An online survey was sent to all members of the American Society for Surgery of the Hand under an institutional review board-approved protocol. Collected data included the number of nerve injuries observed over a 5-year period, the nature of treatment required for the injuries, and the outcomes observed after any intervention. Responses were anonymous, and results were securely compiled. We obtained 372 responses. A total of 222 nerve injuries were reported. The most injured nerves reported were ulnar, radial, and posterior interosseous (38%, 22%, and 19%, respectively). Nearly half of all patients with injuries required operative intervention, including nerve graft, tendon transfer, nerve repair, or nerve transfer. Of the patients who sustained major injuries, those requiring intervention, 77% had partial or no motor recovery. All minor injuries resolved completely. Our results suggest that major nerve injuries after elbow arthroscopy are not rare occurrences and the risk of these injuries is likely under-reported in the literature. Furthermore, patients should be counseled on this risk because most nerve injuries show only partial or no functional recovery. With the more widespread practice of elbow arthroscopy, understanding the nature and sequelae of significant complications is critically important in ensuring patient safety and improving outcomes. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

BDNF gene delivery mediated by neuron-targeted nanoparticles is neuroprotective in peripheral nerve injury.

Science.gov (United States)

Lopes, Cátia D F; Gonçalves, Nádia P; Gomes, Carla P; Saraiva, Maria J; Pêgo, Ana P

2017-03-01

Neuron-targeted gene delivery is a promising strategy to treat peripheral neuropathies. Here we propose the use of polymeric nanoparticles based on thiolated trimethyl chitosan (TMCSH) to mediate targeted gene delivery to peripheral neurons upon a peripheral and minimally invasive intramuscular administration. Nanoparticles were grafted with the non-toxic carboxylic fragment of the tetanus neurotoxin (HC) to allow neuron targeting and were explored to deliver a plasmid DNA encoding for the brain-derived neurotrophic factor (BDNF) in a peripheral nerve injury model. The TMCSH-HC/BDNF nanoparticle treatment promoted the release and significant expression of BDNF in neural tissues, which resulted in an enhanced functional recovery after injury as compared to control treatments (vehicle and non-targeted nanoparticles), associated with an improvement in key pro-regenerative events, namely, the increased expression of neurofilament and growth-associated protein GAP-43 in the injured nerves. Moreover, the targeted nanoparticle treatment was correlated with a significantly higher density of myelinated axons in the distal stump of injured nerves, as well as with preservation of unmyelinated axon density as compared with controls and a protective role in injury-denervated muscles, preventing them from denervation. These results highlight the potential of TMCSH-HC nanoparticles as non-viral gene carriers to deliver therapeutic genes into the peripheral neurons and thus, pave the way for their use as an effective therapeutic intervention for peripheral neuropathies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Peripheral Nerve Injuries and Transplantation of Olfactory Ensheathing Cells for Axonal Regeneration and Remyelination: Fact or Fiction?

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Christine Radtke

2012-10-01

Full Text Available Successful nerve regeneration after nerve trauma is not only important for the restoration of motor and sensory functions, but also to reduce the potential for abnormal sensory impulse generation that can occur following neuroma formation. Satisfying functional results after severe lesions are difficult to achieve and the development of interventional methods to achieve optimal functional recovery after peripheral nerve injury is of increasing clinical interest. Olfactory ensheathing cells (OECs have been used to improve axonal regeneration and functional outcome in a number of studies in spinal cord injury models. The rationale is that the OECs may provide trophic support and a permissive environment for axonal regeneration. The experimental transplantation of OECs to support and enhance peripheral nerve regeneration is much more limited. This chapter reviews studies using OECs as an experimental cell therapy to improve peripheral nerve regeneration.

Scaffoldless tissue-engineered nerve conduit promotes peripheral nerve regeneration and functional recovery after tibial nerve injury in rats

Institute of Scientific and Technical Information of China (English)

Aaron M. Adams; Keith W. VanDusen; Tatiana Y. Kostrominova; Jacob P. Mertens; Lisa M. Larkin

2017-01-01

Damage to peripheral nerve tissue may cause loss of function in both the nerve and the targeted muscles it innervates. This study compared the repair capability of engineered nerve conduit (ENC), engineered fibroblast conduit (EFC), and autograft in a 10-mm tibial nerve gap. ENCs were fabricated utilizing primary fibroblasts and the nerve cells of rats on embryonic day 15 (E15). EFCs were fabricated utilizing primary fi-broblasts only. Following a 12-week recovery, nerve repair was assessed by measuring contractile properties in the medial gastrocnemius muscle, distal motor nerve conduction velocity in the lateral gastrocnemius, and histology of muscle and nerve. The autografts, ENCs and EFCs reestablished 96%, 87% and 84% of native distal motor nerve conduction velocity in the lateral gastrocnemius, 100%, 44% and 44% of native specific force of medical gastrocnemius, and 63%, 61% and 67% of native medial gastrocnemius mass, re-spectively. Histology of the repaired nerve revealed large axons in the autograft, larger but fewer axons in the ENC repair, and many smaller axons in the EFC repair. Muscle histology revealed similar muscle fiber cross-sectional areas among autograft, ENC and EFC repairs. In conclusion, both ENCs and EFCs promot-ed nerve regeneration in a 10-mm tibial nerve gap repair, suggesting that the E15 rat nerve cells may not be necessary for nerve regeneration, and EFC alone can suffice for peripheral nerve injury repair.

Histopathology of cryoballoon ablation-induced phrenic nerve injury.

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Andrade, Jason G; Dubuc, Marc; Ferreira, Jose; Guerra, Peter G; Landry, Evelyn; Coulombe, Nicolas; Rivard, Lena; Macle, Laurent; Thibault, Bernard; Talajic, Mario; Roy, Denis; Khairy, Paul

2014-02-01

Hemi-diaphragmatic paralysis is the most common complication associated with cryoballoon ablation for atrial fibrillation, yet the histopathology of phrenic nerve injury has not been well described. A preclinical randomized study was conducted to characterize the histopathology of phrenic nerve injury induced by cryoballoon ablation and assess the potential for electromyographic (EMG) monitoring to limit phrenic nerve damage. Thirty-two dogs underwent cryoballoon ablation of the right superior pulmonary vein with the objective of inducing phrenic nerve injury. Animals were randomized 1:1 to standard monitoring (i.e., interruption of ablation upon reduction in diaphragmatic motion) versus EMG guidance (i.e., cessation of ablation upon a 30% reduction in the diaphragmatic compound motor action potential [CMAP] amplitude). The acute procedural endpoint was achieved in all dogs. Phrenic nerve injury was characterized by Wallerian degeneration, with subperineural injury to large myelinated axons and evidence of axonal regeneration. The degree of phrenic nerve injury paralleled the reduction in CMAP amplitude (P = 0.007). Animals randomized to EMG guidance had a lower incidence of acute hemi-diaphragmatic paralysis (50% vs 100%; P = 0.001), persistent paralysis at 30 days (21% vs 75%; multivariate odds ratio 0.12, 95% confidence interval [0.02, 0.69], P = 0.017), and a lesser severity of histologic injury (P = 0.001). Mature pulmonary vein ablation lesion characteristics, including circumferentiality and transmurality, were similar in both groups. Phrenic nerve injury induced by cryoballoon ablation is axonal in nature and characterized by Wallerian degeneration, with potential for recovery. An EMG-guided approach is superior to standard monitoring in limiting phrenic nerve damage. © 2013 Wiley Periodicals, Inc.

APP overexpression prevents neuropathic pain and motoneuron death after peripheral nerve injury in mice.

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Kotulska, Katarzyna; Larysz-Brysz, Magdalena; LePecheur, Marie; Marcol, Wiesław; Lewin-Kowalik, Joanna; Paly, Evelyn; London, Jacqueline

2010-03-16

Despite general capacity of peripheral nervous system to regenerate, peripheral nerve injury is often followed by incomplete recovery of function and sometimes burdened by neuropathic pain. Amyloid precursor protein (APP) was suggested to play a role in neuronal growth, however, its role in peripheral nerve repair was not studied. The aim of this study was to examine the role of APP overexpression in peripheral nerve regeneration and neuropathic pain-related behavior in mice. Sciatic nerves of APP overexpressing and FVB/N wild-type mice were transected and immediately resutured. Evaluation of motor and sensory function and autotomy was carried out during 4-week follow up. We found no autotomy behavior as well as less significant atrophy of denervated muscles in APP overexpressing animals when compared to wild-type ones. Sciatic nerve function index outcome did not differ between groups. Histological evaluation revealed that the intensity of regeneration features, including GAP-43-positive growth cones and Schwann cells number in the distal stump of the transected nerve, was also similar in both groups. However, the regenerating fibers were organized more chaotically in wild-type mice and neuromas were much more often seen in this group. The number of macrophages infiltrating the injury site was significantly higher in control group. The number of surviving motoneurons was higher in transgenic mice than in control animals. Taken together, our findings suggest that APP overexpression is beneficial for nerve regeneration processes due to better organization of regenerating fibers, increased survival of motoneurons after autotomy and prevention of neuropathic pain. Copyright 2009 Elsevier Inc. All rights reserved.

Evidence for a systemic regulation of neurotrophin synthesis in response to peripheral nerve injury.

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Shakhbazau, Antos; Martinez, Jose A; Xu, Qing-Gui; Kawasoe, Jean; van Minnen, Jan; Midha, Rajiv

2012-08-01

Up-regulation of neurotrophin synthesis is an important mechanism of peripheral nerve regeneration after injury. Neurotrophin expression is regulated by a complex series of events including cell interactions and multiple molecular stimuli. We have studied neurotrophin synthesis at 2 weeks time-point in a transvertebral model of unilateral or bilateral transection of sciatic nerve in rats. We have found that unilateral sciatic nerve transection results in the elevation of nerve growth factor (NGF) and NT-3, but not glial cell-line derived neurotrophic factor or brain-derived neural factor, in the uninjured nerve on the contralateral side, commonly considered as a control. Bilateral transection further increased NGF but not other neurotrophins in the nerve segment distal to the transection site, as compared to the unilateral injury. To further investigate the distinct role of NGF in regeneration and its potential for peripheral nerve repair, we transduced isogeneic Schwann cells with NGF-encoding lentivirus and transplanted the over-expressing cells into the distal segment of a transected nerve. Axonal regeneration was studied at 2 weeks time-point using pan-neuronal marker NF-200 and found to directly correlate with NGF levels in the regenerating nerve. © 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry.

[Postoperative rehabilitation in patients with peripheral nerve lesions].

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Petronić, I; Marsavelski, A; Nikolić, G; Cirović, D

2003-01-01

Injuries of extremities can be followed by various neuromuscular complications. Injury of peripheral nerves directly depended on the topographic localization of injury (fractures, cuts, contusions). The neuromuscular complications were diagnosed and under follow-up, based on clinical, x-ray, neurologic and neurophysiological findings. The timing of physical treatment and assessment of the necessary neurosurgical intervention depended on the obtained findings. After surgeries, we continued to apply physical treatment and rehabilitation. The aim of the paper was to assess the significance of proper timing for surgery and adequate postoperative rehabilitation, as well as treatment results, depending on the extent of peripheral nerve injury. Based on the study condocted in the period from 2000-2002, most surgeries were done on the ulnar nerve (4 pts), median nerve (4 pts), radial nerve (3 pts), peroneal nerve (2 pts) and plexus brachialis (3 pts). Paresis and peripheral nerve paralysis, associated with sensibility disorders, predominated in clinical features. In most patients surgery was done during the first 3-6 months after injury. In early postoperative Postoperative rehabilitation in patients with peripherial treatment positioning of extremities with electrotherapy were most often used in early postoperative treatment, Bioptron and dosed kinesitherapy. Depending on the neurophysiological findings, in later treatment stage we included electrostimulation, thermotherapy, kinesitherapy and working therapy, with the necessary application of static and dynamic orthroses. Study results showed that the success of treatment depended on the extent of injury, i.e. whether suture of liberalization of the nerve had been done, on the adequate timing of surgery, as well as on the adequate timing and application of physical therapy and rehabilitation. More rapid and complete functional recovery was achieved if the interval between injury and surgery was shorter, as well as

Interleukin-1β overproduction is a common cause for neuropathic pain, memory deficit, and depression following peripheral nerve injury in rodents.

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Gui, Wen-Shan; Wei, Xiao; Mai, Chun-Lin; Murugan, Madhuvika; Wu, Long-Jun; Xin, Wen-Jun; Zhou, Li-Jun; Liu, Xian-Guo

2016-01-01

Chronic pain is often accompanied by short-term memory deficit and depression. Currently, it is believed that short-term memory deficit and depression are consequences of chronic pain. Here, we test the hypothesis that the symptoms might be caused by overproduction of interleukin-1beta (IL-1β) in the injured nerve independent of neuropathic pain following spared nerve injury in rats and mice. Mechanical allodynia, a behavioral sign of neuropathic pain, was not correlated with short-term memory deficit and depressive behavior in spared nerve injury rats. Spared nerve injury upregulated IL-1β in the injured sciatic nerve, plasma, and the regions in central nervous system closely associated with pain, memory and emotion, including spinal dorsal horn, hippocampus, prefrontal cortex, nucleus accumbens, and amygdala. Importantly, the spared nerve injury-induced memory deficits, depressive, and pain behaviors were substantially prevented by peri-sciatic administration of IL-1β neutralizing antibody in rats or deletion of IL-1 receptor type 1 in mice. Furthermore, the behavioral abnormalities induced by spared nerve injury were mimicked in naïve rats by repetitive intravenous injection of re combinant rat IL-1β (rrIL-1β) at a pathological concentration as determined from spared nerve injury rats. In addition, microglia were activated by both spared nerve injury and intravenous injection of rrIL-1β and the effect of spared nerve injury was substantially reversed by peri-sciatic administration of anti-IL-1β. Neuropathic pain was not necessary for the development of cognitive and emotional disorders, while the overproduction of IL-1β in the injured sciatic nerve following peripheral nerve injury may be a common mechanism underlying the generation of neuropathic pain, memory deficit, and depression. © The Author(s) 2016.

Peripheral nerve conduits: technology update

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Arslantunali, D; Dursun, T; Yucel, D; Hasirci, N; Hasirci, V

2014-01-01

Peripheral nerve injury is a worldwide clinical problem which could lead to loss of neuronal communication along sensory and motor nerves between the central nervous system (CNS) and the peripheral organs and impairs the quality of life of a patient. The primary requirement for the treatment of complete lesions is a tension-free, end-to-end repair. When end-to-end repair is not possible, peripheral nerve grafts or nerve conduits are used. The limited availability of autografts, and drawbacks of the allografts and xenografts like immunological reactions, forced the researchers to investigate and develop alternative approaches, mainly nerve conduits. In this review, recent information on the various types of conduit materials (made of biological and synthetic polymers) and designs (tubular, fibrous, and matrix type) are being presented. PMID:25489251

End-to-side nerve suture – a technique to repair peripheral nerve ...

African Journals Online (AJOL)

Lateral sprouting from an intact nerve into an attached nerve does occur, and functional recovery (sensory and motor) has been demonstrated. We have demonstrated conclusively that ETSNS in the human is a viable option in treating peripheral nerve injuries, including injuries to the brachial plexus. Among the many ...

Neuron-Derived ADAM10 Production Stimulates Peripheral Nerve Injury-Induced Neuropathic Pain by Cleavage of E-Cadherin in Satellite Glial Cells.

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Li, Jian; Ouyang, Qing; Chen, Cheng-Wen; Chen, Qian-Bo; Li, Xiang-Nan; Xiang, Zheng-Hua; Yuan, Hong-Bin

2017-09-01

Increasing evidence suggests the potential involvement of metalloproteinase family proteins in the pathogenesis of neuropathic pain, although the underlying mechanisms remain elusive. Using the spinal nerve ligation model, we investigated whether ADAM10 proteins participate in pain regulation. By implementing invitro methods, we produced a purified culture of satellite glial cells to study the underlying mechanisms of ADAM10 in regulating neuropathic pain. Results showed that the ADAM10 protein was expressed in calcitonin gene-related peptide (CGRP)-containing neurons of the dorsal root ganglia, and expression was upregulated following spinal nerve ligation surgery invivo. Intrathecal administration of GI254023X, an ADAM10 selective inhibitor, to the rats one to three days after spinal nerve ligation surgery attenuated the spinal nerve ligation-induced mechanical allodynia and thermal hyperalgesia. Intrathecal injection of ADAM10 recombinant protein simulated pain behavior in normal rats to a similar extent as those treated by spinal nerve ligation surgery. These results raised a question about the relative contribution of ADAM10 in pain regulation. Further results showed that ADAM10 might act by cleaving E-cadherin, which is mainly expressed in satellite glial cells. GI254023X reversed spinal nerve ligation-induced downregulation of E-cadherin and activation of cyclooxygenase 2 after spinal nerve ligation. β-catenin, which creates a complex with E-cadherin in the membranes of satellite glial cells, was also downregulated by spinal nerve ligation surgery in satellite glial cells. Finally, knockdown expression of β-catenin by lentiviral infection in purified satellite glial cells increased expression of inducible nitric oxide synthase and cyclooxygenase 2. Our findings indicate that neuron-derived ADAM10 production stimulates peripheral nerve injury-induced neuropathic pain by cleaving E-cadherin in satellite glial cells. © 2017 American Academy of Pain Medicine

Spinal Microgliosis Due to Resident Microglial Proliferation Is Required for Pain Hypersensitivity after Peripheral Nerve Injury

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Nan Gu

2016-07-01

Full Text Available Peripheral nerve injury causes neuropathic pain accompanied by remarkable microgliosis in the spinal cord dorsal horn. However, it is still debated whether infiltrated monocytes contribute to injury-induced expansion of the microglial population. Here, we found that spinal microgliosis predominantly results from local proliferation of resident microglia but not from infiltrating monocytes after spinal nerve transection (SNT by using two genetic mouse models (CCR2RFP/+:CX3CR1GFP/+ and CX3CR1creER/+:R26tdTomato/+ mice as well as specific staining of microglia and macrophages. Pharmacological inhibition of SNT-induced microglial proliferation correlated with attenuated neuropathic pain hypersensitivities. Microglial proliferation is partially controlled by purinergic and fractalkine signaling, as CX3CR1−/− and P2Y12−/− mice show reduced spinal microglial proliferation and neuropathic pain. These results suggest that local microglial proliferation is the sole source of spinal microgliosis, which represents a potential therapeutic target for neuropathic pain management.

Rehabilitation program for children with brachial plexus and peripheral nerve injury.

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Ramos, L E; Zell, J P

2000-03-01

An aggressive and integrated physical and occupational therapy program is essential in the treatment of congenital brachial plexus injuries and other severe upper extremity nerve injuries. This article addresses the evaluation, identification of needs, establishment of goals, and the approaches to rehabilitation treatment for patients with brachial plexus palsy and other peripheral nerve injuries. Rehabilitative therapy can preserve and build on gains made possible by medical or surgical interventions; however, therapy is vital to these children regardless of whether surgery is indicated. The therapist uses a problem-solving approach to evaluate the patient and select appropriate occupational and physical therapy treatment modalities. Therapy is continually adjusted based on each child's unique needs. An understanding of the therapy principles aids in making appropriate referrals and prescriptions, and helps to coordinate care between the therapist, pediatrician, neurologist, and surgeon.

Intravenous Transplantation of Mesenchymal Stromal Cells to Enhance Peripheral Nerve Regeneration

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Stella M. Matthes

2013-01-01

Full Text Available Peripheral nerve injury is a common and devastating complication after trauma and can cause irreversible impairment or even complete functional loss of the affected limb. While peripheral nerve repair results in some axonal regeneration and functional recovery, the clinical outcome is not optimal and research continues to optimize functional recovery after nerve repair. Cell transplantation approaches are being used experimentally to enhance regeneration. Intravenous infusion of mesenchymal stromal cells (MSCs into spinal cord injury and stroke was shown to improve functional outcome. However, the repair potential of intravenously transplanted MSCs in peripheral nerve injury has not been addressed yet. Here we describe the impact of intravenously infused MSCs on functional outcome in a peripheral nerve injury model. Rat sciatic nerves were transected followed, by intravenous MSCs transplantation. Footprint analysis was carried out and 21 days after transplantation, the nerves were removed for histology. Labelled MSCs were found in the sciatic nerve lesion site after intravenous injection and regeneration was improved. Intravenously infused MSCs after acute peripheral nerve target the lesion site and survive within the nerve and the MSC treated group showed greater functional improvement. The results of study suggest that nerve repair with cell transplantation could lead to greater functional outcome.

Restoration of sensory dysfunction following peripheral nerve injury by the polysaccharide from culinary and medicinal mushroom, Hericium erinaceus (Bull.: Fr. Pers. through its neuroregenerative action

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Kah-Hui WONG

2015-01-01

Full Text Available Abstract Peripheral nerves have the unique capability to regenerate after injury. Insights into regeneration of peripheral nerves after injury may have implications for neurodegenerative diseases of the nervous system. We investigated the ability of polysaccharide from Hericium erinaceus mushroom in the treatment of nerve injury following peroneal nerve crush in Sprague-Dawley rats by daily oral administration. In sensory functional recovery test, the time taken for the rats to withdraw its hind limb from contact with the hot plate was measured. The test revealed acceleration of sensory recovery in the polysaccharide group compared to negative controls. Further, peripheral nerve injury leads to changes at the remotely located DRG containing cell bodies of sensory neurons. Immunofluorescence studies showed that Akt and p38 MAPK were expressed in DRG and strongly upregulated in polysaccharide group after peripheral nerve injury. The intensity of endothelial cells antigen-1 that recognized endothelial cells in the blood vessels of distal segments in crushed nerves was significantly higher in the treated groups than in the negative control group. Our findings suggest that H. erinaceus is capable of accelerating sensory functional recovery after peripheral nerve injury and the effect involves the activation of protein kinase signaling pathways and restoration of blood-nerve barrier.

Thermometric diagnosis of peripheral nerve injuries. Assessment of the diagnostic accuracy of a new practical technique.

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Ya'ish, F M M; Cooper, J P; Craigen, M A C

2007-07-01

The diagnosis of nerve injury using thermotropic liquid crystal temperature strips was compared blindly and prospectively against operative findings in 36 patients requiring surgical exploration for unilateral upper limb lacerations with suspected nerve injury. Thermotropic liquid crystal strips were applied to affected and non-affected segments in both hands in all subjects. A pilot study showed that a simple unilateral laceration without nerve injury results in a cutaneous temperature difference between limbs, but not within each limb. Thus, for detection of a nerve injury, comparison was made against the unaffected nerve distribution in the same hand. Receiver operating characteristic curve analysis showed that an absolute temperature difference > or = 1.0 degrees C was diagnostic of a nerve injury (area under the curve = 0.985, sensitivity = 100%, specificity = 93.8%). Thermotropic liquid crystal strip assessment is a new, reliable and objective method for the diagnosis of traumatic peripheral nerve injuries. If implemented in the acute setting, it could improve the reliability of clinical assessment and reduce the number of negative surgical explorations.

Delayed peripheral nerve repair: methods, including surgical 'cross-bridging' to promote nerve regeneration.

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Gordon, Tessa; Eva, Placheta; Borschel, Gregory H

2015-10-01

Despite the capacity of Schwann cells to support peripheral nerve regeneration, functional recovery after nerve injuries is frequently poor, especially for proximal injuries that require regenerating axons to grow over long distances to reinnervate distal targets. Nerve transfers, where small fascicles from an adjacent intact nerve are coapted to the nerve stump of a nearby denervated muscle, allow for functional return but at the expense of reduced numbers of innervating nerves. A 1-hour period of 20 Hz electrical nerve stimulation via electrodes proximal to an injury site accelerates axon outgrowth to hasten target reinnervation in rats and humans, even after delayed surgery. A novel strategy of enticing donor axons from an otherwise intact nerve to grow through small nerve grafts (cross-bridges) into a denervated nerve stump, promotes improved axon regeneration after delayed nerve repair. The efficacy of this technique has been demonstrated in a rat model and is now in clinical use in patients undergoing cross-face nerve grafting for facial paralysis. In conclusion, brief electrical stimulation, combined with the surgical technique of promoting the regeneration of some donor axons to 'protect' chronically denervated Schwann cells, improves nerve regeneration and, in turn, functional outcomes in the management of peripheral nerve injuries.

Neuroprotective effects of agmatine in experimental peripheral nerve injury in rats: a prospective randomized and placebo-controlled trial.

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Sezer, Aykut; Guclu, Bulent; Kazanci, Burak; Cakir, Murteza; Coban, Mustafa Kemal

2014-01-01

The purpose of this study was to demonstrate the activity of agmatine, an inducible nitric oxide synthase (iNOS) inhibitor and selective N-methyl-D-aspartate receptor (NMDAR) antagonist, on reducing tissue damage in distal part of traumatic nerve in an experimental rat peripheral nerve injury model. Sciatic nerves of 30 Sprague Dawley male rats were used. Rats were divided into 5 groups; group 1 (n=6), control group; group 2 (n=6), axonotmesis + placebo group; group 3 (n=6), axonotmesis + 50 mg/kg agmatine treatment group; group 4 (n=6), neurotmesis + placebo group; group 5 (n=6), neurotmesis + 50 mg/kg agmatine treatment group. Axonolysis, axon degeneration, edema, hemorrhage, and inflammation were evaluated in histopathologic examinations of all the groups. When group 2 was compared with group 3 in histopathologic sections, axonolysis was less in group 3 (p=0.007), as was axon degeneration (p=0.022) and edema (p=0.018). When group 4 was compared with group 5, axonolysis was less in group 5 (p=0.009), as was axon degeneration (p=0.006) and edema (p=0.021). This study demonstrated agmatine to have antioxidant and antineurotoxic effects in an experimental rat peripheral nerve injury model.

Neuroprotective effects of ultrasound-guided nerve growth factor injections after sciatic nerve injury

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Hong-fei Li

2015-01-01

Full Text Available Nerve growth factor (NGF plays an important role in promoting neuroregeneration after peripheral nerve injury. However, its effects are limited by its short half-life; it is therefore important to identify an effective mode of administration. High-frequency ultrasound (HFU is increasingly used in the clinic for high-resolution visualization of tissues, and has been proposed as a method for identifying and evaluating peripheral nerve damage after injury. In addition, HFU is widely used for guiding needle placement when administering drugs to a specific site. We hypothesized that HFU guiding would optimize the neuroprotective effects of NGF on sciatic nerve injury in the rabbit. We performed behavioral, ultrasound, electrophysiological, histological, and immunohistochemical evaluation of HFU-guided NGF injections administered immediately after injury, or 14 days later, and compared this mode of administration with intramuscular NGF injections. Across all assessments, HFU-guided NGF injections gave consistently better outcomes than intramuscular NGF injections administered immediately or 14 days after injury, with immediate treatment also yielding better structural and functional results than when the treatment was delayed by 14 days. Our findings indicate that NGF should be administered as early as possible after peripheral nerve injury, and highlight the striking neuroprotective effects of HFU-guided NGF injections on peripheral nerve injury compared with intramuscular administration.

Adult Stem Cell Based Enhancement of Nerve Conduit for Peripheral Nerve Repair

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2016-10-01

accompanied by injuries to peripheral nerves; if not repaired, the trauma can lead to significant dysfunction and disability . While nerves have the ability to...recovery, minimized disability , and increased quality of life for our wounded warriors. 2. KEYWORDS: Stem Cell, Nerve Conduit, Peripheral Nerve...would be a paradigm shift away from ordering X-rays at 10-12 weeks and only ordering a CT scan. It has the potential to change the standard of care

Nerve Regeneration in the Peripheral Nervous System versus the Central Nervous System and the Relevance to Speech and Hearing after Nerve Injuries

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Gordon, Tessa; Gordon, Karen

2010-01-01

Schwann cells normally form myelin sheaths around axons in the peripheral nervous system (PNS) and support nerve regeneration after nerve injury. In contrast, nerve regeneration in the central nervous system (CNS) is not supported by the myelinating cells known as oligodendrocytes. We have found that: 1) low frequency electrical stimulation can be…

Peripheral nerve conduits: technology update

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Arslantunali D

2014-12-01

Full Text Available D Arslantunali,1–3,* T Dursun,1,2,* D Yucel,1,4,5 N Hasirci,1,2,6 V Hasirci,1,2,7 1BIOMATEN, Center of Excellence in Biomaterials and Tissue Engineering, Middle East Technical University (METU, Ankara, Turkey; 2Department of Biotechnology, METU, Ankara, Turkey; 3Department of Bioengineering, Gumushane University, Gumushane, Turkey; 4Faculty of Engineering, Department of Medical Engineering, Acibadem University, Istanbul, Turkey; 5School of Medicine, Department of Histology and Embryology, Acibadem University, Istanbul, Turkey; 6Department of Chemistry, Faculty of Arts and Sciences, METU, Ankara, Turkey; 7Department of Biological Sciences, Faculty of Arts and Sciences, METU, Ankara, Turkey *These authors have contributed equally to this work Abstract: Peripheral nerve injury is a worldwide clinical problem which could lead to loss of neuronal communication along sensory and motor nerves between the central nervous system (CNS and the peripheral organs and impairs the quality of life of a patient. The primary requirement for the treatment of complete lesions is a tension-free, end-to-end repair. When end-to-end repair is not possible, peripheral nerve grafts or nerve conduits are used. The limited availability of autografts, and drawbacks of the allografts and xenografts like immunological reactions, forced the researchers to investigate and develop alternative approaches, mainly nerve conduits. In this review, recent information on the various types of conduit materials (made of biological and synthetic polymers and designs (tubular, fibrous, and matrix type are being presented. Keywords: peripheral nerve injury, natural biomaterials, synthetic biomaterials

Ultrasound assessment of selected peripheral nerve pathologies. Part III: Injuries and postoperative evaluation

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Berta Kowalska

2013-03-01

Full Text Available The previous articles of the series devoted to ultrasound diagnostics of peripheral nerves concerned the most common nerve pathologies, i.e. entrapment neuropathies. The aim of the last part of the series is to present ultrasound possibilities in the postoperative control of the peripheral nerves as well as in the diagnostics of the second most common neuropathies of peripheral nerves, i.e. posttraumatic lesions. Early diagnostics of posttraumatic changes is of fundamental importance for the course of treatment and its long-term effects. It aids surgeons in making treatment decisions (whether surgical or conservative. When surgical treatment is necessary, the surgeon, based on US findings, is able to plan a given type of operative method. In certain cases, may even abandon the corrective or reconstructive surgery of the nerve trunk (when there are extensive defects of the nerve trunks and instead, proceed with muscle transfers. Medical literature proposes a range of divisions of the kinds of peripheral nerve injuries depending on, among others, the mechanism or degree of damage. However, the most important issue in the surgeon-diagnostician communication is a detailed description of stumps of the nerve trunks, their distance and location. In the postoperative period, ultrasound is used for monitoring the operative or conservative treatment effects including the determination of the causes of a persistent or recurrent neuropathy. It facilitates decision-making concerning a repeated surgical procedure or assuming a wait-and-see attitude. It is a difficult task for a diagnostician and it requires experience, close cooperation with a clinician and knowledge concerning surgical techniques. Apart from a static assessment, a dynamic assessment of possible adhesions constitutes a crucial element of postoperative examination. This feature distinguishes ultrasound scanning from other methods used in the diagnostics of peripheral neuropathies.

Dietary supplement with fermented soybeans, natto, improved the neurobehavioral deficits after sciatic nerve injury in rats.

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Pan, Hung-Chuan; Cheng, Fu-Chou; Chen, Chun-Jung; Lai, Shu-Zhen; Liu, Mu-Jung; Chang, Ming-Hong; Wang, Yeou-Chih; Yang, Dar-Yu; Ho, Shu-Peng

2009-06-01

Clearance of fibrin and associated inflammatory cytokines by tissue-type plasminogen activator (t-PA) is related to improved regeneration in neurological disorder. The biological activity of fermented soybean (natto) is very similar to that of t-PA. We investigated the effect of the dietary supplement of natto on peripheral nerve regeneration. The peripheral nerve injury was produced by crushing the left sciatic nerve with a vessel clamp in Sprague-Dawley rats. The injured animals were fed orally either with saline or natto (16 mg/day) for seven consecutive days after injury. Increased functional outcome such as sciatic nerve functional index, angle of ankle, compound muscle action potential and conduction latency were observed in natto-treated group. Histological examination demonstrated that natto treatment improved injury-induced vacuole formation, S-100 and vessel immunoreactivities and axon loss. Oral intake of natto prolonged prothrombin time and reduced fibrinogen but did not change activated partial thromboplastin time and bleeding time. Furthermore, natto decreased injury-induced fibrin deposition, indicating a tolerant fibrinolytic activity. The treatment of natto significantly improved injury-induced disruption of blood-nerve barrier and loss of matrix component such as laminin and fibronectin. Sciatic nerve crush injury induced elevation of tumor necrosis factor alpha (TNF-alpha) production and caused apoptosis. The increased production of TNF-alpha and apoptosis were attenuated by natto treatment. These findings indicate that oral intake of natto has the potential to augment regeneration in peripheral nerve injury, possibly mediated by the clearance of fibrin and decreased production of TNF-alpha.

Delayed peripheral nerve repair: methods, including surgical ?cross-bridging? to promote nerve regeneration

OpenAIRE

Gordon, Tessa; Eva, Placheta; Borschel, Gregory H.

2015-01-01

Despite the capacity of Schwann cells to support peripheral nerve regeneration, functional recovery after nerve injuries is frequently poor, especially for proximal injuries that require regenerating axons to grow over long distances to reinnervate distal targets. Nerve transfers, where small fascicles from an adjacent intact nerve are coapted to the nerve stump of a nearby denervated muscle, allow for functional return but at the expense of reduced numbers of innervating nerves. A 1-hour per...

The challenges and beauty of peripheral nerve regrowth.

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Zochodne, Douglas W

2012-03-01

This review provides an overview of selected aspects of peripheral nerve regeneration and potential avenues to explore therapeutically. The overall coordinated and orchestrated pattern of recovery from peripheral nerve injury has a beauty of execution and progress that rivals all other forms of neurobiology. It involves changes at the level of the perikaryon, coordination with important peripheral glial partners, the Schwann cells, a controlled inflammatory response, and growth that overcomes surprising intrinsic roadblocks. Both regenerative axon growth and collateral sprouting encompass fascinating aspects of this story. Better understanding of peripheral nerve regeneration may also lead to enhanced central nervous system recovery. © 2012 Peripheral Nerve Society.

The role of exosomes in peripheral nerve regeneration

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Rosanna C Ching

2015-01-01

Full Text Available Peripheral nerve injuries remain problematic to treat, with poor functional recovery commonly observed. Injuries resulting in a nerve gap create specific difficulties for axonal regeneration. Approaches to address these difficulties include autologous nerve grafts (which are currently the gold standard treatment and synthetic conduits, with the latter option being able to be impregnated with Schwann cells or stem cells which provide an appropriate micro-environment for neuronal regeneration to occur. Transplanting stem cells, however, infers additional risk of malignant transformation as well as manufacturing difficulties and ethical concerns, and the use of autologous nerve grafts and Schwann cells requires the sacrifice of a functioning nerve. A new approach utilizing exosomes, secreted extracellular vesicles, could avoid these complications. In this review, we summarize the current literature on exosomes, and suggest how they could help to improve axonal regeneration following peripheral nerve injury.

End-to-side neurorrhaphy repairs peripheral nerve injury: sensory nerve induces motor nerve regeneration.

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Yu, Qing; Zhang, She-Hong; Wang, Tao; Peng, Feng; Han, Dong; Gu, Yu-Dong

2017-10-01

End-to-side neurorrhaphy is an option in the treatment of the long segment defects of a nerve. It involves suturing the distal stump of the disconnected nerve (recipient nerve) to the side of the intimate adjacent nerve (donor nerve). However, the motor-sensory specificity after end-to-side neurorrhaphy remains unclear. This study sought to evaluate whether cutaneous sensory nerve regeneration induces motor nerves after end-to-side neurorrhaphy. Thirty rats were randomized into three groups: (1) end-to-side neurorrhaphy using the ulnar nerve (mixed sensory and motor) as the donor nerve and the cutaneous antebrachii medialis nerve as the recipient nerve; (2) the sham group: ulnar nerve and cutaneous antebrachii medialis nerve were just exposed; and (3) the transected nerve group: cutaneous antebrachii medialis nerve was transected and the stumps were turned over and tied. At 5 months, acetylcholinesterase staining results showed that 34% ± 16% of the myelinated axons were stained in the end-to-side group, and none of the myelinated axons were stained in either the sham or transected nerve groups. Retrograde fluorescent tracing of spinal motor neurons and dorsal root ganglion showed the proportion of motor neurons from the cutaneous antebrachii medialis nerve of the end-to-side group was 21% ± 5%. In contrast, no motor neurons from the cutaneous antebrachii medialis nerve of the sham group and transected nerve group were found in the spinal cord segment. These results confirmed that motor neuron regeneration occurred after cutaneous nerve end-to-side neurorrhaphy.

Trigeminal nerve injury-induced thrombospondin-4 up-regulation contributes to orofacial neuropathic pain states in a rat model.

Science.gov (United States)

Li, K-W; Kim, D-S; Zaucke, F; Luo, Z D

2014-04-01

Injury to the trigeminal nerve often results in the development of chronic pain states including tactile allodynia, or hypersensitivity to light touch, in orofacial area, but its underlying mechanisms are poorly understood. Peripheral nerve injury has been shown to cause up-regulation of thrombospondin-4 (TSP4) in dorsal spinal cord that correlates with neuropathic pain development. In this study, we examined whether injury-induced TSP4 is critical in mediating orofacial pain development in a rat model of chronic constriction injury to the infraorbital nerve. Orofacial sensitivity to mechanical stimulation was examined in a unilateral infraorbital nerve ligation rat model. The levels of TSP4 in trigeminal ganglia and associated spinal subnucleus caudalis and C1/C2 spinal cord (Vc/C2) from injured rats were examined at time points correlating with the initiation and peak orofacial hypersensitivity. TSP4 antisense and mismatch oligodeoxynucleotides were intrathecally injected into injured rats to see if antisense oligodeoxynucleotide treatment could reverse injury-induced TSP4 up-regulation and orofacial behavioural hypersensitivity. Our data indicated that trigeminal nerve injury induced TSP4 up-regulation in Vc/C2 at a time point correlated with orofacial tactile allodynia. In addition, intrathecal treatment with TSP4 antisense, but not mismatch, oligodeoxynucleotides blocked both injury-induced TSP4 up-regulation in Vc/C2 and behavioural hypersensitivity. Our data support that infraorbital nerve injury leads to TSP4 up-regulation in trigeminal spinal complex that contributes to orofacial neuropathic pain states. Blocking this pathway may provide an alternative approach in management of orofacial neuropathic pain states. © 2013 European Pain Federation - EFIC®

Delayed peripheral nerve repair: methods, including surgical ′cross-bridging′ to promote nerve regeneration

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Tessa Gordon

2015-01-01

Full Text Available Despite the capacity of Schwann cells to support peripheral nerve regeneration, functional recovery after nerve injuries is frequently poor, especially for proximal injuries that require regenerating axons to grow over long distances to reinnervate distal targets. Nerve transfers, where small fascicles from an adjacent intact nerve are coapted to the nerve stump of a nearby denervated muscle, allow for functional return but at the expense of reduced numbers of innervating nerves. A 1-hour period of 20 Hz electrical nerve stimulation via electrodes proximal to an injury site accelerates axon outgrowth to hasten target reinnervation in rats and humans, even after delayed surgery. A novel strategy of enticing donor axons from an otherwise intact nerve to grow through small nerve grafts (cross-bridges into a denervated nerve stump, promotes improved axon regeneration after delayed nerve repair. The efficacy of this technique has been demonstrated in a rat model and is now in clinical use in patients undergoing cross-face nerve grafting for facial paralysis. In conclusion, brief electrical stimulation, combined with the surgical technique of promoting the regeneration of some donor axons to ′protect′ chronically denervated Schwann cells, improves nerve regeneration and, in turn, functional outcomes in the management of peripheral nerve injuries.

Studies of peripheral sensory nerves in paclitaxel-induced painful peripheral neuropathy: Evidence for mitochondrial dysfunction

OpenAIRE

Flatters, Sarah J.L.; Bennett, Gary J.

2006-01-01

Paclitaxel chemotherapy frequently induces neuropathic pain during and often persisting after therapy. The mechanisms responsible for this pain are unknown. Using a rat model of paclitaxel-induced painful peripheral neuropathy, we have performed studies to search for peripheral nerve pathology. Paclitaxel-induced mechano-allodynia and mechano-hyperalgesia were evident after a short delay, peaked at day 27 and finally resolved on day 155. Paclitaxel- and vehicle-treated rats were perfused on d...

Desert hedgehog promotes ischemia-induced angiogenesis by ensuring peripheral nerve survival.

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Renault, Marie-Ange; Chapouly, Candice; Yao, Qinyu; Larrieu-Lahargue, Frédéric; Vandierdonck, Soizic; Reynaud, Annabel; Petit, Myriam; Jaspard-Vinassa, Béatrice; Belloc, Isabelle; Traiffort, Elisabeth; Ruat, Martial; Duplàa, Cécile; Couffinhal, Thierry; Desgranges, Claude; Gadeau, Alain-Pierre

2013-03-01

Blood vessel growth and patterning have been shown to be regulated by nerve-derived signals. Desert hedgehog (Dhh), one of the Hedgehog family members, is expressed by Schwann cells of peripheral nerves. The purpose of this study was to investigate the contribution of Dhh to angiogenesis in the setting of ischemia. We induced hindlimb ischemia in wild-type and Dhh(-/-) mice. First, we found that limb perfusion is significantly impaired in the absence of Dhh. This effect is associated with a significant decrease in capillary and artery density in Dhh(-/-). By using mice in which the Hedgehog signaling pathway effector Smoothened was specifically invalidated in endothelial cells, we demonstrated that Dhh does not promote angiogenesis by a direct activation of endothelial cells. On the contrary, we found that Dhh promotes peripheral nerve survival in the ischemic muscle and, by doing so, maintains the pool of nerve-derived proangiogenic factors. Consistently, we found that denervation of the leg, immediately after the onset of ischemia, severely impairs ischemia-induced angiogenesis and decreases expression of vascular endothelial growth factor A, angiopoietin 1, and neurotrophin 3 in the ischemic muscle. This study demonstrates the crucial roles of nerves and factors regulating nerve physiology in the setting of ischemia-induced angiogenesis.

Cytidine 5’-diphosphocholine administration prevents peripheral neuropathic pain after sciatic nerve crush injury in rats

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Emril DR

2016-05-01

Full Text Available Dessy R Emril,1 Samekto Wibowo,2 Lucas Meliala,2 Rina Susilowati3 1Department of Neurology, Faculty of Medicine, Syiah Kuala University, Banda Aceh, 2Department of Neurology, 3Department of Histology and Cell Biology, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, IndonesiaBackground: Cytidine 5’-diphosphocholine (citicoline has been shown to have beneficial effects in central nervous system injury as well as in motoric functional recovery after peripheral nerve injury. This study aimed to examine the effect of citicoline on prevention of neuropathic pain in a rat model of sciatic nerve crush injury.Methods: Forty experimental rats were divided into four groups. In three groups, the right sciatic nerves were crushed in the mid-thigh region, and a gelatin sponge moistened with 0.4 or 0.8 mL of 100 µmol/L citicoline, or saline 0.4 mL in the control group, was applied. The fourth group of rats was sham-operated, ie the sciatic nerve was exposed with no crush. Functional assessments were performed 4 weeks after crush injury. von Frey filaments (100 g threshold were used to assess neuropathic pain. In addition, the sciatic functional index and extensor postural thrust (EPT tests were used to assess motoric function.Results: The crush/citicoline 0.4 mL group had a lower percentage of pain (23.53%, n=17 compared with the crush/saline group (53.33%, n=15, P<0.005. The crush/citicoline 0.4 mL group also showed better motoric recovery, as seen in stronger EPT results (P<0.001. However, the sciatic functional index analysis did not show significant differences between groups (P=0.35. The crush/citicoline 0.8 mL group showed a higher percentage of pain (66.67%, n=18 and less EPT recovery. These results may be explained by more severe nerve injury due to compression with a larger administered volume.Conclusion: In situ administration of 0.4 mL of 100 μmol/L citicoline prevents the occurrence of neuropathic pain and induces motoric recovery

Fabrication of nerve guidance conduit with luminal filler as scaffold for peripheral nerve repair

International Nuclear Information System (INIS)

Aranilla, Charito T.; Wach, Rodoslaw; Ulanski, Piotr

2015-01-01

Peripheral nerve injury is a serious health concern for society, affecting trauma patients, many of whom acquire life-long disability. The gold standard of treatment for peripheral nerve injury is the use of nerve grafts, wherein nerve autograft or allograft is used to bridge the gap in the damaged nerve. Nerve guidance conduits (NGCs) are an attractive alternative to nerve autografts for aiding in the regeneration of peripheral nerve tissue. NGCs are small cylinders or tubes composed of either natural or synthetic biomaterials that are used to axon regeneration. The ends of the damaged nerve are inserted into either end of the cylinder and the NGC acts both as a connecting bridge for the severed nerve ends as well as a protective shelter for the regenerating nerve. This study aims at fabricating nerve guidance conduits with luminal structure based on synthetic biodegradable and biocompatible polymers such as poly (trimethylene carbonate ) (PTMC), poly (lactic acid) (PLA) and poly (caprolactone) (PCL). Initial base materials for fabrication were PLA acid tubes compared to PCL tubes when prepared by spray and dip-coating methods. The morphology of the tubes where examined by SEM and results showed better porosity of PLA acid tubes compared to PCL tubes when prepared by spraying technique. Poly(lactic acid) was then blended with poly(trimethylene carbonate) at a ratio of 1:4 (5% total polymer content) for further fabrication. Electron beam radiation (25 and 50 kGy) was employed for sterilization and the changes in properties induced by irradiation in comprising polymers were evaluated. The wettability, mechanical thermal properties were not significantly changed by irradiation.In a separate experiment, synthesis of carboxymethyl chitosan hydrogel crosslinked by electron beam radiation was studied to create a luminal filler for PTMC-PLA tubes. Based on proper viscosity of solution before crosslinking, sufficient gel fraction and swelling, 10% w/v concentration of

Acceleration of Regeneration of Large Gap Peripheral Nerve Injuries Using Acellular Nerve Allografts plus amniotic Fluid Derived Stem Cells (AFS)

Science.gov (United States)

2016-09-01

AWARD NUMBER: W811XWH-13-1-0310 TITLE: Acceleration of Regeneration of Large-Gap Peripheral Nerve Injuries Using Acellular Nerve Allografts...plus amniotic Fluid Derived Stem Cells (AFS). PRINCIPAL INVESTIGATOR: Zhongyu Li, MD, PhD RECIPIENT: Wake Forest University Health Sciences...REPORT DATE September 2016 2. REPORT TYPE Annual 3. DATES COVERED 1Sep2015 - 31Aug2016 4. TITLE AND SUBTITLE Acceleration of Regeneration of Large

Peripheral nerve stimulator-induced electrostimulation at the P6 ...

African Journals Online (AJOL)

2012-12-03

Dec 3, 2012 ... Original Research: Peripheral nerve stimulator-induced electrostimulation. 216. 2013;19(4). South Afr J Anaesth Analg. Introduction. Spinal anaesthesia is often associated with hypotension and bradycardia.1 Strategies to manage post-spinal hypotension include the use of vasopressors or fluids, or a ...

Progress of nerve bridges in the treatment of peripheral nerve disruptions

OpenAIRE

Ao,Qiang

2016-01-01

Qiang Ao Department of Tissue Engineering, School of Fundamental Science, China Medical University, Shenyang, Liaoning, Peoples’ Republic of China Abstract: Clinical repair of a nerve defect is one of the most challenging surgical problems. Autologous nerve grafting remains the gold standard treatment in addressing peripheral nerve injuries that cannot be bridged by direct epineural suturing. However, the autologous nerve graft is not readily available, and the process of harvesting...

Resveratrol Promotes Nerve Regeneration via Activation of p300 Acetyltransferase-Mediated VEGF Signaling in a Rat Model of Sciatic Nerve Crush Injury.

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Ding, Zhuofeng; Cao, Jiawei; Shen, Yu; Zou, Yu; Yang, Xin; Zhou, Wen; Guo, Qulian; Huang, Changsheng

2018-01-01

Peripheral nerve injuries are generally associated with incomplete restoration of motor function. The slow rate of nerve regeneration after injury may account for this. Although many benefits of resveratrol have been shown in the nervous system, it is not clear whether resveratrol could promote fast nerve regeneration and motor repair after peripheral nerve injury. This study showed that the motor deficits caused by sciatic nerve crush injury were alleviated by daily systematic resveratrol treatment within 10 days. Resveratrol increased the number of axons in the distal part of the injured nerve, indicating enhanced nerve regeneration. In the affected ventral spinal cord, resveratrol enhanced the expression of several vascular endothelial growth factor family proteins (VEGFs) and increased the phosphorylation of p300 through Akt signaling, indicating activation of p300 acetyltransferase. Inactivation of p300 acetyltransferase reversed the resveratrol-induced expression of VEGFs and motor repair in rats that had undergone sciatic nerve crush injury. The above results indicated that daily systematic resveratrol treatment promoted nerve regeneration and led to rapid motor repair. Resveratrol activated p300 acetyltransferase-mediated VEGF signaling in the affected ventral spinal cord, which may have thus contributed to the acceleration of nerve regeneration and motor repair.

Electrical Stimulation to Enhance Axon Regeneration After Peripheral Nerve Injuries in Animal Models and Humans

OpenAIRE

Gordon, Tessa

2016-01-01

Injured peripheral nerves regenerate their lost axons but functional recovery in humans is frequently disappointing. This is so particularly when injuries require regeneration over long distances and/or over long time periods. Fat replacement of chronically denervated muscles, a commonly accepted explanation, does not account for poor functional recovery. Rather, the basis for the poor nerve regeneration is the transient expression of growth-associated genes that accounts for declining regene...

(--Epigallocatechin gallate attenuates NADPH-d/nNOS expression in motor neurons of rats following peripheral nerve injury

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Tseng Chi-Yu

2011-06-01

Full Text Available Abstract Background Oxidative stress and large amounts of nitric oxide (NO have been implicated in the pathophysiology of neuronal injury and neurodegenerative disease. Recent studies have shown that (--epigallocatechin gallate (EGCG, one of the green tea polyphenols, has potent antioxidant effects against free radical-mediated lipid peroxidation in ischemia-induced neuronal damage. The purpose of this study was to examine whether EGCG would attenuate neuronal expression of NADPH-d/nNOS in the motor neurons of the lower brainstem following peripheral nerve crush. Thus, young adult rats were treated with EGCG (10, 25, or 50 mg/kg, i.p. 30 min prior to crushing their hypoglossal and vagus nerves for 30 seconds (left side, at the cervical level. The treatment (pre-crush doses of EGCG was continued from day 1 to day 6, and the animals were sacrificed on days 3, 7, 14 and 28. Nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d histochemistry and neuronal nitric oxide synthase (nNOS immunohistochemistry were used to assess neuronal NADPH-d/nNOS expression in the hypoglossal nucleus and dorsal motor nucleus of the vagus. Results In rats treated with high dosages of EGCG (25 or 50 mg/kg, NADPH-d/nNOS reactivity and cell death of the motor neurons were significantly decreased. Conclusions The present evidence indicated that EGCG can reduce NADPH-d/nNOS reactivity and thus may enhance motor neuron survival time following peripheral nerve injury.

The longitudinal epineural incision and complete nerve transection method for modeling sciatic nerve injury

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Xing-long Cheng

2015-01-01

Full Text Available Injury severity, operative technique and nerve regeneration are important factors to consider when constructing a model of peripheral nerve injury. Here, we present a novel peripheral nerve injury model and compare it with the complete sciatic nerve transection method. In the experimental group, under a microscope, a 3-mm longitudinal incision was made in the epineurium of the sciatic nerve to reveal the nerve fibers, which were then transected. The small, longitudinal incision in the epineurium was then sutured closed, requiring no stump anastomosis. In the control group, the sciatic nerve was completely transected, and the epineurium was repaired by anastomosis. At 2 and 4 weeks after surgery, Wallerian degeneration was observed in both groups. In the experimental group, at 8 and 12 weeks after surgery, distinct medullary nerve fibers and axons were observed in the injured sciatic nerve. Regular, dense myelin sheaths were visible, as well as some scarring. By 12 weeks, the myelin sheaths were normal and intact, and a tight lamellar structure was observed. Functionally, limb movement and nerve conduction recovered in the injured region between 4 and 12 weeks. The present results demonstrate that longitudinal epineural incision with nerve transection can stably replicate a model of Sunderland grade IV peripheral nerve injury. Compared with the complete sciatic nerve transection model, our method reduced the difficulties of micromanipulation and surgery time, and resulted in good stump restoration, nerve regeneration, and functional recovery.

Peripheral nerve repair: a hot spot analysis on treatment methods from 2010 to 2014

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Guang-yao Liu

2015-01-01

Full Text Available Therapeutic strategies for neurological deficits and for promoting nerve regeneration after peripheral nerve injuries have received much focus in clinical research. Advances in basic research in recent years have increased our understanding of the anatomy of peripheral nerves and the importance of the microenvironment. Various new intervention methods have been developed, but with varying effectiveness. In the present study, we selected 911 papers on different repair methods for peripheral nerve injury from the Web of Science and indexed in the Science Citation Index from 2010 to 2014. We quantitatively examine new repair methods and strategies using bibliometrics, and we discuss the present state of knowledge and the problems and prospects of various repair methods, including nerve transfer, neural transplantation, tissue engineering and genetic engineering. Our findings should help in the study and development of repair methods for peripheral nerve injury.

Electrical Stimulation to Enhance Axon Regeneration After Peripheral Nerve Injuries in Animal Models and Humans.

Science.gov (United States)

Gordon, Tessa

2016-04-01

Injured peripheral nerves regenerate their lost axons but functional recovery in humans is frequently disappointing. This is so particularly when injuries require regeneration over long distances and/or over long time periods. Fat replacement of chronically denervated muscles, a commonly accepted explanation, does not account for poor functional recovery. Rather, the basis for the poor nerve regeneration is the transient expression of growth-associated genes that accounts for declining regenerative capacity of neurons and the regenerative support of Schwann cells over time. Brief low-frequency electrical stimulation accelerates motor and sensory axon outgrowth across injury sites that, even after delayed surgical repair of injured nerves in animal models and patients, enhances nerve regeneration and target reinnervation. The stimulation elevates neuronal cyclic adenosine monophosphate and, in turn, the expression of neurotrophic factors and other growth-associated genes, including cytoskeletal proteins. Electrical stimulation of denervated muscles immediately after nerve transection and surgical repair also accelerates muscle reinnervation but, at this time, how the daily requirement of long-duration electrical pulses can be delivered to muscles remains a practical issue prior to translation to patients. Finally, the technique of inserting autologous nerve grafts that bridge between a donor nerve and an adjacent recipient denervated nerve stump significantly improves nerve regeneration after delayed nerve repair, the donor nerves sustaining the capacity of the denervated Schwann cells to support nerve regeneration. These reviewed methods to promote nerve regeneration and, in turn, to enhance functional recovery after nerve injury and surgical repair are sufficiently promising for early translation to the clinic.

Acute injury in the peripheral nervous system triggers an alternative macrophage response

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Ydens Elke

2012-07-01

Full Text Available Abstract Background The activation of the immune system in neurodegeneration has detrimental as well as beneficial effects. Which aspects of this immune response aggravate the neurodegenerative breakdown and which stimulate regeneration remains an open question. To unravel the neuroprotective aspects of the immune system we focused on a model of acute peripheral nerve injury, in which the immune system was shown to be protective. Methods To determine the type of immune response triggered after axotomy of the sciatic nerve, a model for Wallerian degeneration in the peripheral nervous system, we evaluated markers representing the two extremes of a type I and type II immune response (classical vs. alternative using real-time quantitative polymerase chain reaction (RT-qPCR, western blot, and immunohistochemistry. Results Our results showed that acute peripheral nerve injury triggers an anti-inflammatory and immunosuppressive response, rather than a pro-inflammatory response. This was reflected by the complete absence of classical macrophage markers (iNOS, IFNγ, and IL12p40, and the strong up-regulation of tissue repair markers (arginase-1, Ym1, and Trem2. The signal favoring the alternative macrophage environment was induced immediately after nerve damage and appeared to be established within the nerve, well before the infiltration of macrophages. In addition, negative regulators of the innate immune response, as well as the anti-inflammatory cytokine IL-10 were induced. The strict regulation of the immune system dampens the potential tissue damaging effects of an over-activated response. Conclusions We here demonstrate that acute peripheral nerve injury triggers an inherent protective environment by inducing the M2 phenotype of macrophages and the expression of arginase-1. We believe that the M2 phenotype, associated with a sterile inflammatory response and tissue repair, might explain their neuroprotective capacity. As such, shifting the

17β-Estradiol Promotes Schwann Cell Proliferation and Differentiation, Accelerating Early Remyelination in a Mouse Peripheral Nerve Injury Model

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Yan Chen

2016-01-01

Full Text Available Estrogen induces oligodendrocyte remyelination in response to demyelination in the central nervous system. Our objective was to determine the effects of 17β-estradiol (E2 on Schwann cell function and peripheral nerve remyelination after injury. Adult male C57BL/6J mice were used to prepare the sciatic nerve transection injury model and were randomly categorized into control and E2 groups. To study myelination in vitro, dorsal root ganglion (DRG explant culture was prepared using 13.5-day-old mouse embryos. Primary Schwann cells were isolated from the sciatic nerves of 1- to 3-day-old Sprague–Dawley rats. Immunostaining for myelin basic protein (MBP expression and toluidine blue staining for myelin sheaths demonstrated that E2 treatment accelerates early remyelination in the “nerve bridge” region between the proximal and distal stumps of the transection injury site in the mouse sciatic nerve. The 5-bromo-2′-deoxyuridine incorporation assay revealed that E2 promotes Schwann cell proliferation in the bridge region and in the primary culture, which is blocked using AKT inhibitor MK2206. The in vitro myelination in the DRG explant culture determined showed that the MBP expression in the E2-treated group is higher than that in the control group. These results show that E2 promotes Schwann cell proliferation and myelination depending on AKT activation.

17β-Estradiol Promotes Schwann Cell Proliferation and Differentiation, Accelerating Early Remyelination in a Mouse Peripheral Nerve Injury Model

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Chen, Yan; Guo, Wenjie; Li, Wenjuan; Cheng, Meng; Hu, Ying; Xu, Wenming

2016-01-01

Estrogen induces oligodendrocyte remyelination in response to demyelination in the central nervous system. Our objective was to determine the effects of 17β-estradiol (E2) on Schwann cell function and peripheral nerve remyelination after injury. Adult male C57BL/6J mice were used to prepare the sciatic nerve transection injury model and were randomly categorized into control and E2 groups. To study myelination in vitro, dorsal root ganglion (DRG) explant culture was prepared using 13.5-day-old mouse embryos. Primary Schwann cells were isolated from the sciatic nerves of 1- to 3-day-old Sprague–Dawley rats. Immunostaining for myelin basic protein (MBP) expression and toluidine blue staining for myelin sheaths demonstrated that E2 treatment accelerates early remyelination in the “nerve bridge” region between the proximal and distal stumps of the transection injury site in the mouse sciatic nerve. The 5-bromo-2′-deoxyuridine incorporation assay revealed that E2 promotes Schwann cell proliferation in the bridge region and in the primary culture, which is blocked using AKT inhibitor MK2206. The in vitro myelination in the DRG explant culture determined showed that the MBP expression in the E2-treated group is higher than that in the control group. These results show that E2 promotes Schwann cell proliferation and myelination depending on AKT activation. PMID:27872858

A standardized method to create peripheral nerve injury in dogs using an automatic non-serrated forceps

Institute of Scientific and Technical Information of China (English)

Xuhui Wang; Shiting Li; Liang Wan; Xinyuan Li; Youqiang Meng; Ningxi Zhu; Min Yang; Baohui Feng; Wenchuan Zhang; Shugan Zhu

2012-01-01

This study describes a method that not only generates an automatic and standardized crush injury in the skull base, but also provides investigators with the option to choose from a range of varying pressure levels. We designed an automatic, non-serrated forceps that exerts a varying force of 0 to 100 g and lasts for a defined period of 0 to 60 seconds. This device was then used to generate a crush injury to the right oculomotor nerve of dogs with a force of 10 g for 15 seconds, resulting in a deficit in the pupil-light reflex and ptosis. Further testing of our model with Toluidine-blue staining demonstrated that, at 2 weeks post-surgery disordered oculomotor nerve fibers, axonal loss, and a thinner than normal myelin sheath were visible. Electrophysiological examination showed occasional spontaneous potentials. Together, these data verified that the model for oculomotor nerve injury was successful, and that the forceps we designed can be used to establish standard mechanical injury models of peripheral nerves.

A preconditioning nerve lesion inhibits mechanical pain hypersensitivity following subsequent neuropathic injury

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Wu Ann

2011-01-01

Full Text Available Abstract Background A preconditioning stimulus can trigger a neuroprotective phenotype in the nervous system - a preconditioning nerve lesion causes a significant increase in axonal regeneration, and cerebral preconditioning protects against subsequent ischemia. We hypothesized that a preconditioning nerve lesion induces gene/protein modifications, neuronal changes, and immune activation that may affect pain sensation following subsequent nerve injury. We examined whether a preconditioning lesion affects neuropathic pain and neuroinflammation after peripheral nerve injury. Results We found that a preconditioning crush injury to a terminal branch of the sciatic nerve seven days before partial ligation of the sciatic nerve (PSNL; a model of neuropathic pain induced a significant attenuation of pain hypersensitivity, particularly mechanical allodynia. A preconditioning lesion of the tibial nerve induced a long-term significant increase in paw-withdrawal threshold to mechanical stimuli and paw-withdrawal latency to thermal stimuli, after PSNL. A preconditioning lesion of the common peroneal induced a smaller but significant short-term increase in paw-withdrawal threshold to mechanical stimuli, after PSNL. There was no difference between preconditioned and unconditioned animals in neuronal damage and macrophage and T-cell infiltration into the dorsal root ganglia (DRGs or in astrocyte and microglia activation in the spinal dorsal and ventral horns. Conclusions These results suggest that prior exposure to a mild nerve lesion protects against adverse effects of subsequent neuropathic injury, and that this conditioning-induced inhibition of pain hypersensitivity is not dependent on neuroinflammation in DRGs and spinal cord. Identifying the underlying mechanisms may have important implications for the understanding of neuropathic pain due to nerve injury.

Distribution of elements and water in peripheral nerve of streptozocin-induced diabetic rats

International Nuclear Information System (INIS)

Lowery, J.M.; Eichberg, J.; Saubermann, A.J.; LoPachin, R.M. Jr.

1990-01-01

Accumulating evidence suggests that alterations in Na, Ca, K, and other biologically relevant elements play a role in the mechanism of cell injury. The pathogenesis of experimental diabetic neuropathy is unknown but might include changes in the distribution of these elements in morphological compartments. In this study, this possibility was examined via electron-probe X-ray microanalysis to measure both concentrations of elements (millimoles of element per kilogram dry or wet weight) and cell water content (percent water) in frozen, unfixed, unstained sections of peripheral nerve from control and streptozocin-induced diabetic rats. Our results indicate that after 20 wk of experimental diabetes, mitochondria and axoplasm from myelinated axons of proximal sciatic nerve displayed diminished K and Cl content, whereas in tibial nerve, the intraaxonal levels of these elements increased. In distal sciatic nerve, mitochondrial and axoplasmic levels of Ca were increased, whereas other elemental alterations were not observed. These regional changes resulted in a reversal of the decreasing proximodistal concentration gradients for K and Cl, which exist in nondiabetic rat sciatic nerve. Our results cannot be explained on the basis of altered water. Highly distinctive changes in elemental distribution observed might be a critical component of the neurotoxic mechanism underlying diabetic neuropathy

Progranulin promotes peripheral nerve regeneration and reinnervation: role of notch signaling.

Science.gov (United States)

Altmann, Christine; Vasic, Verica; Hardt, Stefanie; Heidler, Juliana; Häussler, Annett; Wittig, Ilka; Schmidt, Mirko H H; Tegeder, Irmgard

2016-10-22

Peripheral nerve injury is a frequent cause of lasting motor deficits and chronic pain. Although peripheral nerves are capable of regrowth they often fail to re-innervate target tissues. Using newly generated transgenic mice with inducible neuronal progranulin overexpression we show that progranulin accelerates axonal regrowth, restoration of neuromuscular synapses and recovery of sensory and motor functions after injury of the sciatic nerve. Oppositely, progranulin deficient mice have long-lasting deficits in motor function tests after nerve injury due to enhanced losses of motor neurons and stronger microglia activation in the ventral horn of the spinal cord. Deep proteome and gene ontology (GO) enrichment analysis revealed that the proteins upregulated in progranulin overexpressing mice were involved in 'regulation of transcription' and 'response to insulin' (GO terms). Transcription factor prediction pointed to activation of Notch signaling and indeed, co-immunoprecipitation studies revealed that progranulin bound to the extracellular domain of Notch receptors, and this was functionally associated with higher expression of Notch target genes in the dorsal root ganglia of transgenic mice with neuronal progranulin overexpression. Functionally, these transgenic mice recovered normal gait and running, which was not achieved by controls and was stronger impaired in progranulin deficient mice. We infer that progranulin activates Notch signaling pathways, enhancing thereby the regenerative capacity of partially injured neurons, which leads to improved motor function recovery.

Miconazole enhances nerve regeneration and functional recovery after sciatic nerve crush injury.

Science.gov (United States)

Lin, Tao; Qiu, Shuai; Yan, Liwei; Zhu, Shuang; Zheng, Canbin; Zhu, Qingtang; Liu, Xiaolin

2018-05-01

Improving axonal outgrowth and remyelination is crucial for peripheral nerve regeneration. Miconazole appears to enhance remyelination in the central nervous system. In this study we assess the effect of miconazole on axonal regeneration using a sciatic nerve crush injury model in rats. Fifty Sprague-Dawley rats were divided into control and miconazole groups. Nerve regeneration and myelination were determined using histological and electrophysiological assessment. Evaluation of sensory and motor recovery was performed using the pinprick assay and sciatic functional index. The Cell Counting Kit-8 assay and Western blotting were used to assess the proliferation and neurotrophic expression of RSC 96 Schwann cells. Miconazole promoted axonal regrowth, increased myelinated nerve fibers, improved sensory recovery and walking behavior, enhanced stimulated amplitude and nerve conduction velocity, and elevated proliferation and neurotrophic expression of RSC 96 Schwann cells. Miconazole was beneficial for nerve regeneration and functional recovery after peripheral nerve injury. Muscle Nerve 57: 821-828, 2018. © 2017 Wiley Periodicals, Inc.

Large Extremity Peripheral Nerve Repair

Science.gov (United States)

2016-12-01

LM, de Crombrugghe B. Some recent advances in the chemistry and biology of trans- forming growth factor-beta. J Cell Biol 1987;105:1039e45. 12. Hao Y...SUPPLEMENTARY NOTES 14. ABSTRACT In current war trauma, 20-30% of all extremity injuries and >80% of penetrating injuries being associated with peripheral nerve...through both axonal advance and in revascularization of the graft following placement. We are confident that this technology may allow us to

Tissue-engineered spiral nerve guidance conduit for peripheral nerve regeneration.

Science.gov (United States)

Chang, Wei; Shah, Munish B; Lee, Paul; Yu, Xiaojun

2018-06-01

Recently in peripheral nerve regeneration, preclinical studies have shown that the use of nerve guidance conduits (NGCs) with multiple longitudinally channels and intra-luminal topography enhance the functional outcomes when bridging a nerve gap caused by traumatic injury. These features not only provide guidance cues for regenerating nerve, but also become the essential approaches for developing a novel NGC. In this study, a novel spiral NGC with aligned nanofibers and wrapped with an outer nanofibrous tube was first developed and investigated. Using the common rat sciatic 10-mm nerve defect model, the in vivo study showed that a novel spiral NGC (with and without inner nanofibers) increased the successful rate of nerve regeneration after 6 weeks recovery. Substantial improvements in nerve regeneration were achieved by combining the spiral NGC with inner nanofibers and outer nanofibrous tube, based on the results of walking track analysis, electrophysiology, nerve histological assessment, and gastrocnemius muscle measurement. This demonstrated that the novel spiral NGC with inner aligned nanofibers and wrapped with an outer nanofibrous tube provided a better environment for peripheral nerve regeneration than standard tubular NGCs. Results from this study will benefit for future NGC design to optimize tissue-engineering strategies for peripheral nerve regeneration. We developed a novel spiral nerve guidance conduit (NGC) with coated aligned nanofibers. The spiral structure increases surface area by 4.5 fold relative to a tubular NGC. Furthermore, the aligned nanofibers was coated on the spiral walls, providing cues for guiding neurite extension. Finally, the outside of spiral NGC was wrapped with randomly nanofibers to enhance mechanical strength that can stabilize the spiral NGC. Our nerve histological data have shown that the spiral NGC had 50% more myelinated axons than a tubular structure for nerve regeneration across a 10 mm gap in a rat sciatic nerve

Lentiviral-mediated transfer of CDNF promotes nerve regeneration and functional recovery after sciatic nerve injury in adult rats

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Cheng, Lei; Liu, Yi; Zhao, Hua; Zhang, Wen; Guo, Ying-Jun; Nie, Lin, E-mail: chengleiyx@126.com

2013-10-18

Highlights: •CDNF was successfully transfected by a lentiviral vector into the distal sciatic nerve. •CDNF improved S-100, NF200 expression and nerve regeneration after sciatic injury. •CDNF improved the remyelination and thickness of the regenerated sciatic nerve. •CDNF improved gastrocnemius muscle weight and sciatic functional recovery. -- Abstract: Peripheral nerve injury is often followed by incomplete and unsatisfactory functional recovery and may be associated with sensory and motor impairment of the affected limb. Therefore, a novel method is needed to improve the speed of recovery and the final functional outcome after peripheral nerve injuries. This report investigates the effect of lentiviral-mediated transfer of conserved dopamine neurotrophic factor (CDNF) on regeneration of the rat peripheral nerve in a transection model in vivo. We observed notable overexpression of CDNF protein in the distal sciatic nerve after recombinant CDNF lentiviral vector application. We evaluated sciatic nerve regeneration after surgery using light and electron microscopy and the functional recovery using the sciatic functional index and target muscle weight. HE staining revealed better ordered structured in the CDNF-treated group at 8 weeks post-surgery. Quantitative analysis of immunohistochemistry of NF200 and S-100 in the CDNF group revealed significant improvement of axonal and Schwann cell regeneration compared with the control groups at 4 weeks and 8 weeks after injury. The thickness of the myelination around the axons in the CDNF group was significantly higher than in the control groups at 8 weeks post-surgery. The CDNF group displayed higher muscle weights and significantly increased sciatic nerve index values. Our findings suggest that CDNF gene therapy could provide durable and stable CDNF protein concentration and has the potential to enhance peripheral nerve regeneration, morphological and functional recovery following nerve injury, which suggests a

Lentiviral-mediated transfer of CDNF promotes nerve regeneration and functional recovery after sciatic nerve injury in adult rats

International Nuclear Information System (INIS)

Cheng, Lei; Liu, Yi; Zhao, Hua; Zhang, Wen; Guo, Ying-Jun; Nie, Lin

2013-01-01

Highlights: •CDNF was successfully transfected by a lentiviral vector into the distal sciatic nerve. •CDNF improved S-100, NF200 expression and nerve regeneration after sciatic injury. •CDNF improved the remyelination and thickness of the regenerated sciatic nerve. •CDNF improved gastrocnemius muscle weight and sciatic functional recovery. -- Abstract: Peripheral nerve injury is often followed by incomplete and unsatisfactory functional recovery and may be associated with sensory and motor impairment of the affected limb. Therefore, a novel method is needed to improve the speed of recovery and the final functional outcome after peripheral nerve injuries. This report investigates the effect of lentiviral-mediated transfer of conserved dopamine neurotrophic factor (CDNF) on regeneration of the rat peripheral nerve in a transection model in vivo. We observed notable overexpression of CDNF protein in the distal sciatic nerve after recombinant CDNF lentiviral vector application. We evaluated sciatic nerve regeneration after surgery using light and electron microscopy and the functional recovery using the sciatic functional index and target muscle weight. HE staining revealed better ordered structured in the CDNF-treated group at 8 weeks post-surgery. Quantitative analysis of immunohistochemistry of NF200 and S-100 in the CDNF group revealed significant improvement of axonal and Schwann cell regeneration compared with the control groups at 4 weeks and 8 weeks after injury. The thickness of the myelination around the axons in the CDNF group was significantly higher than in the control groups at 8 weeks post-surgery. The CDNF group displayed higher muscle weights and significantly increased sciatic nerve index values. Our findings suggest that CDNF gene therapy could provide durable and stable CDNF protein concentration and has the potential to enhance peripheral nerve regeneration, morphological and functional recovery following nerve injury, which suggests a

Peripheral Nerve Injury in Developing Rats Reorganizes Representation Pattern in Motor Cortex

Science.gov (United States)

Donoghue, John P.; Sanes, Jerome N.

1987-02-01

We investigated the effect of neonatal nerve lesions on cerebral motor cortex organization by comparing the cortical motor representation of normal adult rats with adult rats that had one forelimb removed on the day of birth. Mapping of cerebral neocortex with electrical stimulation revealed an altered relationship between the motor cortex and the remaining muscles. Whereas distal forelimb movements are normally elicited at the lowest threshold in the motor cortex forelimb area, the same stimuli activated shoulder and trunk muscles in experimental animals. In addition, an expanded cortical representation of intact body parts was present and there was an absence of a distinct portion of motor cortex. These data demonstrate that representation patterns in motor cortex can be altered by peripheral nerve injury during development.

Thermo-sensitive TRP channels in peripheral nerve injury: a review of their role in cold intolerance

NARCIS (Netherlands)

Kambiz, S.; Duraku, L.S.; Holstege, J.C.; Hovius, S.E.; Ruigrok, T.J.; Walbeehm, E.T.

2014-01-01

One of the sensory complications of traumatic peripheral nerve injury is thermal intolerance, which manifests in humans mainly as cold intolerance. It has a major effect on the quality of life, and adequate therapy is not yet available. In order to better understand the pathophysiological background

Use of early tactile stimulation in rehabilitation of digital nerve injuries.

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Cheng, A S

2000-01-01

Digital nerves are the most frequently injured peripheral nerve. To improve the recovery of functional sensibility of digital nerve injuries, a prospective randomized controlled study was conducted to see the effect of using early tactile stimulation in rehabilitation of digital nerve injuries. Two specific tactile stimulators were made and prescribed for patients with digital nerve-injury. Twenty-four participants with 32 digital nerve injuries received the prescribed tactile stimulators (experimental group), and another 25 participants with 33 digital nerve injuries received only routine conventional therapy (control group). A significant difference (p sensibility in digital nerve injuries without combined nerve, tendon, and bone injuries.

Macrophage polarization in nerve injury: do Schwann cells play a role?

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Jo Anne Stratton

2016-01-01

Full Text Available In response to peripheral nerve injury, the inflammatory response is almost entirely comprised of infiltrating macrophages. Macrophages are a highly plastic, heterogenic immune cell, playing an indispensable role in peripheral nerve injury, clearing debris and regulating the microenvironment to allow for efficient regeneration. There are several cells within the microenvironment that likely interact with macrophages to support their function - most notably the Schwann cell, the glial cell of the peripheral nervous system. Schwann cells express several ligands that are known to interact with receptors expressed by macrophages, yet the effects of Schwann cells in regulating macrophage phenotype remains largely unexplored. This review discusses macrophages in peripheral nerve injury and how Schwann cells may regulate their behavior.

Peripheral injury of pelvic visceral sensory nerves alters GFRa (GDNF family receptor alpha localization in sensory and autonomic pathways of the sacral spinal cord

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Shelley Lynne Forrest

2015-04-01

Full Text Available GDNF (glial cell line-derived neurotrophic factor, neurturin and artemin use their co-receptors (GFRα1, GFRα2 and GFRα3, respectively and the tyrosine kinase Ret for downstream signalling. In rodent dorsal root ganglia (DRG most of the unmyelinated and some myelinated sensory afferents express at least one GFRα. The adult function of these receptors is not completely elucidated but their activity after peripheral nerve injury can facilitate peripheral and central axonal regeneration, recovery of sensation, and sensory hypersensitivity that contributes to pain. Our previous immunohistochemical studies of spinal cord and sciatic nerve injuries in adult rodents have identified characteristic changes in GFRα1, GFRα2 or GFRα3 in central spinal cord axons of sensory neurons located in dorsal root ganglia. Here we extend and contrast this analysis by studying injuries of the pelvic and hypogastric nerves that contain the majority of sensory axons projecting to the pelvic viscera (e.g., bladder and lower bowel. At 7 d, we detected some effects of pelvic but not hypogastric nerve transection on the ipsilateral spinal cord. In sacral (L6-S1 cord ipsilateral to nerve injury, GFRα1-immunoreactivity (IR was increased in medial dorsal horn and CGRP-IR was decreased in lateral dorsal horn. Pelvic nerve injury also upregulated GFRα1- and GFRα3-IR terminals and GFRα1-IR neuronal cell bodies in the sacral parasympathetic nucleus that provides the spinal parasympathetic preganglionic output to the pelvic nerve. This evidence suggests peripheral axotomy has different effects on somatic and visceral sensory input to the spinal cord, and identifies sensory-autonomic interactions as a possible site of post-injury regulation.

Bone marrow-derived cells in the population of spinal microglia after peripheral nerve injury

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Tashima, Ryoichi; Mikuriya, Satsuki; Tomiyama, Daisuke; Shiratori-Hayashi, Miho; Yamashita, Tomohiro; Kohro, Yuta; Tozaki-Saitoh, Hidetoshi; Inoue, Kazuhide; Tsuda, Makoto

2016-01-01

Accumulating evidence indicates that peripheral nerve injury (PNI) activates spinal microglia that are necessary for neuropathic pain. Recent studies using bone marrow (BM) chimeric mice have reported that after PNI, circulating BM-derived cells infiltrate into the spinal cord and differentiate into microglia-like cells. This raises the possibility that the population of spinal microglia after PNI may be heterogeneous. However, the infiltration of BM cells in the spinal cord remains controversial because of experimental adverse effects of strong irradiation used for generating BM chimeric mice. In this study, we evaluated the PNI-induced spinal infiltration of BM-derived cells not only by irradiation-induced myeloablation with various conditioning regimens, but also by parabiosis and mice with genetically labelled microglia, models without irradiation and BM transplantation. Results obtained from these independent approaches provide compelling evidence indicating little contribution of circulating BM-derived cells to the population of spinal microglia after PNI. PMID:27005516

Hericium erinaceus (Bull.: Fr.) Pers., a medicinal mushroom, activates peripheral nerve regeneration.

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Wong, Kah-Hui; Kanagasabapathy, Gowri; Naidu, Murali; David, Pamela; Sabaratnam, Vikineswary

2016-10-01

To study the ability of aqueous extract of Hericium erinaceus mushroom in the treatment of nerve injury following peroneal nerve crush in Sprague-Dawley rats. Aqueous extract of Hericium erinaceus was given by daily oral administration following peroneal nerve crush injury in Sprague-Dawley rats. The expression of protein kinase B (Akt) and mitogen-activated protein kinase (MAPK) signaling pathways; and c-Jun and c-Fos genes were studied in dorsal root ganglia (DRG) whereas the activity of protein synthesis was assessed in peroneal nerves by immunohistochemical method. Peripheral nerve injury leads to changes at the axonal site of injury and remotely located DRG containing cell bodies of sensory afferent neurons. Immunofluorescence studies showed that DRG neurons ipsilateral to the crush injury in rats of treated groups expressed higher immunoreactivities for Akt, MAPK, c-Jun and c-Fos as compared with negative control group (P <0.05). The intensity of nuclear ribonucleoprotein in the distal segments of crushed nerves of treated groups was significantly higher than in the negative control group (P <0.05). H. erinaceus is capable of promoting peripheral nerve regeneration after injury. Potential signaling pathways include Akt, MAPK, c-Jun, and c-Fos, and protein synthesis have been shown to be involved in its action.

Wallerian degeneration: the innate-immune response to traumatic nerve injury

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Rotshenker Shlomo

2011-08-01

Full Text Available Abstract Traumatic injury to peripheral nerves results in the loss of neural functions. Recovery by regeneration depends on the cellular and molecular events of Wallerian degeneration that injury induces distal to the lesion site, the domain through which severed axons regenerate back to their target tissues. Innate-immunity is central to Wallerian degeneration since innate-immune cells, functions and molecules that are produced by immune and non-immune cells are involved. The innate-immune response helps to turn the peripheral nerve tissue into an environment that supports regeneration by removing inhibitory myelin and by upregulating neurotrophic properties. The characteristics of an efficient innate-immune response are rapid onset and conclusion, and the orchestrated interplay between Schwann cells, fibroblasts, macrophages, endothelial cells, and molecules they produce. Wallerian degeneration serves as a prelude for successful repair when these requirements are met. In contrast, functional recovery is poor when injury fails to produce the efficient innate-immune response of Wallerian degeneration.

A study of tapping by the unaffected finger of patients presenting with central and peripheral nerve damage.

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Zhang, Lingli; Han, Xiuying; Li, Peihong; Liu, Yang; Zhu, Yulian; Zou, Jun; Yu, Zhusheng

2015-01-01

Whether the unaffected function of the hand of patients presenting with nerve injury is affected remains inconclusive. We aimed to evaluate whether there are differences in finger tapping following central or peripheral nerve injury compared with the unaffected hand and the ipsilateral hand of a healthy subject. Thirty right brain stroke patients with hemiplegia, 30 left arm peripheral nerve injury cases, and 60 healthy people were selected. We tested finger tapping of the right hands, and each subject performed the test twice. Finger tapping following peripheral nerve injury as compared with the unaffected hand and the dominant hand of a healthy person was markedly higher than was found for central nerve injury (P tapping of the male peripheral group's unaffected hand and the control group's dominant hand was significantly higher than the central group (P tapping of the female control group's dominant hand was significantly higher than the central group's unaffected hand (P < 0.01, P = 0.002), the peripheral group's unaffected hand (P < 0.05, P = 0.034). The unaffected function of the hand of patients with central and peripheral nerve injury was different as compared with the ipsilateral hand of healthy individuals. The rehabilitation therapist should intensify the practice of normal upper limb fine activities and coordination of the patient.

A Study of Tapping by the Unaffected Finger of Patients Presenting with Central and Peripheral Nerve Damage

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Lingli eZhang

2015-05-01

Full Text Available Aim: Whether the unaffected function of the hand of patients presenting with nerve injury is affected remains inconclusive. We aimed to evaluate whether there are differences in finger tapping following central or peripheral nerve injury compared with the unaffected hand and the ipsilateral hand of a healthy subject.Methods: 30 right brain stroke patients with hemiplegia, 30 left arm peripheral nerve injury cases and 60 healthy people were selected. We tested finger tapping of the right hands, and each subject performed the test twice.Results: Finger tapping following peripheral nerve injury as compared with the unaffected hand and the dominant hand of a healthy person was significantly higher than was found for central nerve injury (P<0.05. Finger tapping of the male peripheral group’s unaffected hand and the control group’s dominant hand was significantly higher than the central group (P<0.001. However, finger tapping of the female control group’s dominant hand was markedly higher than the central group’s unaffected hand (P<0.01, P=0.002, the peripheral group’s unaffected hand (P<0.05, P=0.034. Conclusion: The unaffected function of the hand of patients with central and peripheral nerve injury was different as compared with the ipsilateral hand of healthy individuals. The rehabilitation therapist should intensify the practice of normal upper limb fine activities and coordination of the patient.

Acellular Nerve Allografts in Peripheral Nerve Regeneration: A Comparative Study

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Moore, Amy M.; MacEwan, Matthew; Santosa, Katherine B.; Chenard, Kristofer E.; Ray, Wilson Z.; Hunter, Daniel A.; Mackinnon, Susan E.; Johnson, Philip J.

2011-01-01

Background Processed nerve allografts offer a promising alternative to nerve autografts in the surgical management of peripheral nerve injuries where short deficits exist. Methods Three established models of acellular nerve allograft (cold-preserved, detergent-processed, and AxoGen® -processed nerve allografts) were compared to nerve isografts and silicone nerve guidance conduits in a 14 mm rat sciatic nerve defect. Results All acellular nerve grafts were superior to silicone nerve conduits in support of nerve regeneration. Detergent-processed allografts were similar to isografts at 6 weeks post-operatively, while AxoGen®-processed and cold-preserved allografts supported significantly fewer regenerating nerve fibers. Measurement of muscle force confirmed that detergent-processed allografts promoted isograft-equivalent levels of motor recovery 16 weeks post-operatively. All acellular allografts promoted greater amounts of motor recovery compared to silicone conduits. Conclusions These findings provide evidence that differential processing for removal of cellular constituents in preparing acellular nerve allografts affects recovery in vivo. PMID:21660979

Regeneration of long-distance peripheral nerve defects after delayed reconstruction in healthy and diabetic rats is supported by immunomodulatory chitosan nerve guides

OpenAIRE

Stenberg, Lena; Stã¶ãŸel, Maria; Ronchi, Giulia; Geuna, Stefano; Yin, Yaobin; Mommert, Susanne; Mã¥rtensson, Lisa; Metzen, Jennifer; Grothe, Claudia; Dahlin, Lars B.; Haastert-Talini, Kirsten

2017-01-01

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 1...

Ultrasonographic demonstration of intraneural neovascularization after penetrating nerve injury.

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Arányi, Zsuzsanna; Csillik, Anita; Dévay, Katalin; Rosero, Maja

2018-06-01

Hypervascularization of nerves has been shown to be a pathological sign in some peripheral nerve disorders, but has not been investigated in nerve trauma. An observational cohort study was performed of the intraneural blood flow of 30 patients (34 nerves) with penetrating nerve injuries, before or after nerve reconstruction. All patients underwent electrophysiological assessment, and B-mode and color Doppler ultrasonography. Intraneural hypervascularization proximal to the site of injury was found in all nerves, which was typically marked and had a longitudinal extension of several centimeters. In 6 nerves, some blood flow was also present within the injury site or immediately distal to the injury. No correlation was found between the degree of vascularization and age, size of the scar / neuroma, or degree of reinnervation. Neovascularization of nerves proximal to injury sites appears to be an essential element of nerve regeneration after penetrating nerve injuries. Muscle Nerve 57: 994-999, 2018. © 2018 Wiley Periodicals, Inc.

In vivo USPIO magnetic resonance imaging shows that minocycline mitigates macrophage recruitment to a peripheral nerve injury

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Ghanouni Pejman

2012-06-01

Full Text Available Abstract Background Minocycline has proven anti-nociceptive effects, but the mechanism by which minocycline delays the development of allodynia and hyperalgesia after peripheral nerve injury remains unclear. Inflammatory cells, in particular macrophages, are critical components of the response to nerve injury. Using ultrasmall superparamagnetic iron oxide-magnetic resonance imaging (USPIO-MRI to monitor macrophage trafficking, the purpose of this project is to determine whether minocycline modulates macrophage trafficking to the site of nerve injury in vivo and, in turn, results in altered pain thresholds. Results Animal experiments were approved by Stanford IACUC. A model of neuropathic pain was created using the Spared Nerve Injury (SNI model that involves ligation of the left sciatic nerve in the left thigh of adult Sprague–Dawley rats. Animals with SNI and uninjured animals were then injected with/without USPIOs (300 μmol/kg IV and with/without minocycline (50 mg/kg IP. Bilateral sciatic nerves were scanned with a volume coil in a 7 T magnet 7 days after USPIO administration. Fluid-sensitive MR images were obtained, and ROIs were placed on bilateral sciatic nerves to quantify signal intensity. Pain behavior modulation by minocycline was measured using the Von Frey filament test. Sciatic nerves were ultimately harvested at day 7, fixed in 10% buffered formalin and stained for the presence of iron oxide-laden macrophages. Behavioral measurements confirmed the presence of allodynia in the neuropathic pain model while the uninjured and minocycline-treated injured group had significantly higher paw withdrawal thresholds (p  Conclusion Animals with neuropathic pain in the left hindpaw show increased trafficking of USPIO-laden macrophages to the site of sciatic nerve injury. Minocycline to retards the migration of macrophages to the nerve injury site, which may partly explain its anti-nociceptive effects. USPIO-MRI is an effective in

Peripheral nerve regeneration with conduits: use of vein tubes

OpenAIRE

Sabongi, Rodrigo Guerra; Fernandes, Marcela; dos Santos, Jo?o Baptista Gomes

2015-01-01

Treatment of peripheral nerve injuries remains a challenge to modern medicine due to the complexity of the neurobiological nerve regenerating process. There is a greater challenge when the transected nerve ends are not amenable to primary end-to-end tensionless neurorraphy. When facing a segmental nerve defect, great effort has been made to develop an alternative to the autologous nerve graft in order to circumvent morbidity at donor site, such as neuroma formation, scarring and permanent los...

Raman spectroscopic detection of peripheral nerves towards nerve-sparing surgery

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Minamikawa, Takeo; Harada, Yoshinori; Takamatsu, Tetsuro

2017-02-01

The peripheral nervous system plays an important role in motility, sensory, and autonomic functions of the human body. Preservation of peripheral nerves in surgery, namely nerve-sparing surgery, is now promising technique to avoid functional deficits of the limbs and organs following surgery as an aspect of the improvement of quality of life of patients. Detection of peripheral nerves including myelinated and unmyelinated nerves is required for the nerve-sparing surgery; however, conventional nerve identification scheme is sometimes difficult to identify peripheral nerves due to similarity of shape and color to non-nerve tissues or its limited application to only motor peripheral nerves. To overcome these issues, we proposed a label-free detection technique of peripheral nerves by means of Raman spectroscopy. We found several fingerprints of peripheral myelinated and unmyelinated nerves by employing a modified principal component analysis of typical spectra including myelinated nerve, unmyelinated nerve, and adjacent tissues. We finally realized the sensitivity of 94.2% and the selectivity of 92.0% for peripheral nerves including myelinated and unmyelinated nerves against adjacent tissues. Although further development of an intraoperative Raman spectroscopy system is required for clinical use, our proposed approach will serve as a unique and powerful tool for peripheral nerve detection for nerve-sparing surgery in the future.

Effect of neural-induced mesenchymal stem cells and platelet-rich plasma on facial nerve regeneration in an acute nerve injury model.

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Cho, Hyong-Ho; Jang, Sujeong; Lee, Sang-Chul; Jeong, Han-Seong; Park, Jong-Seong; Han, Jae-Young; Lee, Kyung-Hwa; Cho, Yong-Bum

2010-05-01

The purpose of this study was to investigate the effects of platelet-rich plasma (PRP) and neural-induced human mesenchymal stem cells (nMSCs) on axonal regeneration from a facial nerve axotomy injury in a guinea pig model. Prospective, controlled animal study. Experiments involved the transection and repair of the facial nerve in 24 albino guinea pigs. Four groups were created based on the method of repair: suture only (group I, control group); PRP with suture (group II); nMSCs with suture (group III); and PRP and nMSCs with suture (group IV). Each method of repair was applied immediately after nerve transection. The outcomes measured were: 1) functional outcome measurement (vibrissae and eyelid closure movements); 2) electrophysiologic evaluation; 3) neurotrophic factors assay; and 4) histologic evaluation. With respect to the functional outcome measurement, the functional outcomes improved after transection and reanastomosis in all groups. The control group was the slowest to demonstrate recovery of movement after transection and reanastomosis. The other three groups (groups II, III, and IV) had significant improvement in function compared to the control group 4 weeks after surgery (P facial nerve regeneration in an animal model of facial nerve axotomy. The use of nMSCs showed no benefit over the use of PRP in facial nerve regeneration, but the combined use of PRP and nMSCs showed a greater beneficial effect than use of either alone. This study provides evidence for the potential clinical application of PRP and nMSCs in peripheral nerve regeneration of an acute nerve injury. Laryngoscope, 2010.

Direct Conversion of Human Fibroblasts into Schwann Cells that Facilitate Regeneration of Injured Peripheral Nerve In Vivo.

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Sowa, Yoshihiro; Kishida, Tsunao; Tomita, Koichi; Yamamoto, Kenta; Numajiri, Toshiaki; Mazda, Osam

2017-04-01

Schwann cells (SCs) play pivotal roles in the maintenance and regeneration of the peripheral nervous system. Although transplantation of SCs enhances repair of experimentally damaged peripheral and central nerve tissues, it is difficult to prepare a sufficient number of functional SCs for transplantation therapy without causing adverse events for the donor. Here, we generated functional SCs by somatic cell reprogramming procedures and demonstrated their capability to promote peripheral nerve regeneration. Normal human fibroblasts were phenotypically converted into SCs by transducing SOX10 and Krox20 genes followed by culturing for 10 days resulting in approximately 43% directly converted Schwann cells (dSCs). The dSCs expressed SC-specific proteins, secreted neurotrophic factors, and induced neuronal cells to extend neurites. The dSCs also displayed myelin-forming capability both in vitro and in vivo. Moreover, transplantation of the dSCs into the transected sciatic nerve in mice resulted in significantly accelerated regeneration of the nerve and in improved motor function at a level comparable to that with transplantation of the SCs obtained from a peripheral nerve. The dSCs induced by our procedure may be applicable for novel regeneration therapy for not only peripheral nerve injury but also for central nerve damage and for neurodegenerative disorders related to SC dysfunction. Stem Cells Translational Medicine 2017;6:1207-1216. © 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

Nerve conduction and excitability studies in peripheral nerve disorders

DEFF Research Database (Denmark)

Krarup, Christian; Moldovan, Mihai

2009-01-01

counterparts in the peripheral nervous system, in some instances without peripheral nervous system symptoms. Both hereditary and acquired demyelinating neuropathies have been studied and the effects on nerve pathophysiology have been compared with degeneration and regeneration of axons. SUMMARY: Excitability......PURPOSE OF REVIEW: The review is aimed at providing information about the role of nerve excitability studies in peripheral nerve disorders. It has been known for many years that the insight into peripheral nerve pathophysiology provided by conventional nerve conduction studies is limited. Nerve...... excitability studies are relatively novel but are acquiring an increasingly important role in the study of peripheral nerves. RECENT FINDINGS: By measuring responses in nerve that are related to nodal function (strength-duration time constant, rheobase and recovery cycle) and internodal function (threshold...

Origins, actions and dynamic expression patterns of the neuropeptide VGF in rat peripheral and central sensory neurones following peripheral nerve injury

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Costigan Michael

2008-12-01

Full Text Available Abstract Background The role of the neurotrophin regulated polypeptide, VGF, has been investigated in a rat spared injury model of neuropathic pain. This peptide has been shown to be associated with synaptic strengthening and learning in the hippocampus and while it is known that VGFmRNA is upregulated in dorsal root ganglia following peripheral nerve injury, the role of this VGF peptide in neuropathic pain has yet to be investigated. Results Prolonged upregulation of VGF mRNA and protein was observed in injured dorsal root ganglion neurons, central terminals and their target dorsal horn neurons. Intrathecal application of TLQP-62, the C-terminal active portion of VGF (5–50 nmol to naïve rats caused a long-lasting mechanical and cold behavioral allodynia. Direct actions of 50 nM TLQP-62 upon dorsal horn neuron excitability was demonstrated in whole cell patch recordings in spinal cord slices and in receptive field analysis in intact, anesthetized rats where significant actions of VGF were upon spontaneous activity and cold evoked responses. Conclusion VGF expression is therefore highly modulated in nociceptive pathways following peripheral nerve injury and can cause dorsal horn cell excitation and behavioral hypersensitivity in naïve animals. Together the results point to a novel and powerful role for VGF in neuropathic pain.

Engineering a multimodal nerve conduit for repair of injured peripheral nerve

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Quigley, A. F.; Bulluss, K. J.; Kyratzis, I. L. B.; Gilmore, K.; Mysore, T.; Schirmer, K. S. U.; Kennedy, E. L.; O'Shea, M.; Truong, Y. B.; Edwards, S. L.; Peeters, G.; Herwig, P.; Razal, J. M.; Campbell, T. E.; Lowes, K. N.; Higgins, M. J.; Moulton, S. E.; Murphy, M. A.; Cook, M. J.; Clark, G. M.; Wallace, G. G.; Kapsa, R. M. I.

2013-02-01

Injury to nerve tissue in the peripheral nervous system (PNS) results in long-term impairment of limb function, dysaesthesia and pain, often with associated psychological effects. Whilst minor injuries can be left to regenerate without intervention and short gaps up to 2 cm can be sutured, larger or more severe injuries commonly require autogenous nerve grafts harvested from elsewhere in the body (usually sensory nerves). Functional recovery is often suboptimal and associated with loss of sensation from the tissue innervated by the harvested nerve. The challenges that persist with nerve repair have resulted in development of nerve guides or conduits from non-neural biological tissues and various polymers to improve the prognosis for the repair of damaged nerves in the PNS. This study describes the design and fabrication of a multimodal controlled pore size nerve regeneration conduit using polylactic acid (PLA) and (PLA):poly(lactic-co-glycolic) acid (PLGA) fibers within a neurotrophin-enriched alginate hydrogel. The nerve repair conduit design consists of two types of PLGA fibers selected specifically for promotion of axonal outgrowth and Schwann cell growth (75:25 for axons; 85:15 for Schwann cells). These aligned fibers are contained within the lumen of a knitted PLA sheath coated with electrospun PLA nanofibers to control pore size. The PLGA guidance fibers within the nerve repair conduit lumen are supported within an alginate hydrogel impregnated with neurotrophic factors (NT-3 or BDNF with LIF, SMDF and MGF-1) to provide neuroprotection, stimulation of axonal growth and Schwann cell migration. The conduit was used to promote repair of transected sciatic nerve in rats over a period of 4 weeks. Over this period, it was observed that over-grooming and self-mutilation (autotomy) of the limb implanted with the conduit was significantly reduced in rats implanted with the full-configuration conduit compared to rats implanted with conduits containing only an alginate

A Study of Tapping by the Unaffected Finger of Patients Presenting with Central and Peripheral Nerve Damage

OpenAIRE

Zhang, Lingli; Han, Xiuying; Li, Peihong; Liu, Yang; Zhu, Yulian; Zou, Jun; Yu, Zhusheng

2015-01-01

Aim Whether the unaffected function of the hand of patients presenting with nerve injury is affected remains inconclusive. We aimed to evaluate whether there are differences in finger tapping following central or peripheral nerve injury compared with the unaffected hand and the ipsilateral hand of a healthy subject. Methods Thirty right brain stroke patients with hemiplegia, 30 left arm peripheral nerve injury cases, and 60 healthy people were selected. We tested finger tapping of ...

Scaffolds for peripheral nerve repair and reconstruction.

Science.gov (United States)

Yi, Sheng; Xu, Lai; Gu, Xiaosong

2018-06-02

Trauma-associated peripheral nerve defect is a widespread clinical problem. Autologous nerve grafting, the current gold standard technique for the treatment of peripheral nerve injury, has many internal disadvantages. Emerging studies showed that tissue engineered nerve graft is an effective substitute to autologous nerves. Tissue engineered nerve graft is generally composed of neural scaffolds and incorporating cells and molecules. A variety of biomaterials have been used to construct neural scaffolds, the main component of tissue engineered nerve graft. Synthetic polymers (e.g. silicone, polyglycolic acid, and poly(lactic-co-glycolic acid)) and natural materials (e.g. chitosan, silk fibroin, and extracellular matrix components) are commonly used along or together to build neural scaffolds. Many other materials, including the extracellular matrix, glass fabrics, ceramics, and metallic materials, have also been used to construct neural scaffolds. These biomaterials are fabricated to create specific structures and surface features. Seeding supporting cells and/or incorporating neurotrophic factors to neural scaffolds further improve restoration effects. Preliminary studies demonstrate that clinical applications of these neural scaffolds achieve satisfactory functional recovery. Therefore, tissue engineered nerve graft provides a good alternative to autologous nerve graft and represents a promising frontier in neural tissue engineering. Copyright © 2018 Elsevier Inc. All rights reserved.

Safety of intramedullary autologous peripheral nerve grafts for post-rehabilitated complete motor spinal cord injuries: a phase I study.

Directory of Open Access Journals (Sweden)

Nazi Derakhshanrad

2013-12-01

Full Text Available Many experimental studies have reported behavioral improvement after transplantation of peripheral nerve tissue into the contused spinal cord, even in large animals. The safety of this treatment in human remains unknown. In this translational phase 1 study, safety of peripheral nerve grafting for chronic spinal cord injuries and possible outcomes are being reported. Twelve complete motor spinal cord injury patients, who had finished their rehabilitation program, were enrolled. There were 4 thoracic and 8 cervical cases. Patients underwent sural nerve preconditioning in the calf, followed 1 week later, by intramedullary transplantation of the harvested nerve fascicles. The patients were followed up for potential complications periodically, and final assessment by American Spinal Injury association (ASIA and Spinal Cord Independence Measure (SCIM III were reported after 2 years of follow-up. The median duration of the spinal cord injury was 31 months. At two years of follow up, out of 7 cases with ASIA Impairment Scale (AIS A, 4(57.1% cases improved to AIS B and 1 (14.3% case became AIS C. There were 1 patient with transient increased spasm, one case of transient cystitis, 3 patients with transient increased neuropathic pain and 1 case with transient episode of autonomic dysreflexia, all being managed medically. There was no case of donor site infection. The above complications were transient as they responded to temporary medical treatment. It may be deduced that after two years follow-up of patients that the procedure may be safe, however further controlled studies are needed to prove its efficacy.

Iatrogenic nerve injuries during shoulder surgery.

Science.gov (United States)

Carofino, Bradley C; Brogan, David M; Kircher, Michelle F; Elhassan, Bassem T; Spinner, Robert J; Bishop, Allen T; Shin, Alexander Y

2013-09-18

The current literature indicates that neurologic injuries during shoulder surgery occur infrequently and result in little if any morbidity. The purpose of this study was to review one institution's experience treating patients with iatrogenic nerve injuries after shoulder surgery. A retrospective review of the records of patients evaluated in a brachial plexus specialty clinic from 2000 to 2010 identified twenty-six patients with iatrogenic nerve injury secondary to shoulder surgery. The records were reviewed to determine the operative procedure, time to presentation, findings on physical examination, treatment, and outcome. The average age was forty-three years (range, seventeen to seventy-two years), and the average delay prior to referral was 5.4 months (range, one to fifteen months). Seven nerve injuries resulted from open procedures done to treat instability; nine, from arthroscopic surgery; four, from total shoulder arthroplasty; and six, from a combined open and arthroscopic operation. The injury occurred at the level of the brachial plexus in thirteen patients and at a terminal nerve branch in thirteen. Fifteen patients (58%) did not recover nerve function after observation and required surgical management. A structural nerve injury (laceration or suture entrapment) occurred in nine patients (35%), including eight of the thirteen who presented with a terminal nerve branch injury and one of the thirteen who presented with an injury at the level of the brachial plexus. Nerve injuries occurring during shoulder surgery can produce severe morbidity and may require surgical management. Injuries at the level of a peripheral nerve are more likely to be surgically treatable than injuries of the brachial plexus. A high index of suspicion and early referral and evaluation should be considered when evaluating patients with iatrogenic neurologic deficits after shoulder surgery.

Promotion of peripheral nerve regeneration of a peptide compound hydrogel scaffold

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Wei GJ

2013-08-01

Full Text Available Guo-Jun Wei,1 Meng Yao,1 Yan-Song Wang,1 Chang-Wei Zhou,1 De-Yu Wan,1 Peng-Zhen Lei,1 Jian Wen,1 Hong-Wei Lei,2 Da-Ming Dong1 1Department of Orthopaedics, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China; 2Department of Rheumatology, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China Background: Peripheral nerve injury is a common trauma, but presents a significant challenge to the clinic. Silk-based materials have recently become an important biomaterial for tissue engineering applications due to silk’s biocompatibility and impressive mechanical and degradative properties. In the present study, a silk fibroin peptide (SF16 was designed and used as a component of the hydrogel scaffold for the repair of peripheral nerve injury. Methods: The SF16 peptide’s structure was characterized using spectrophotometry and atomic force microscopy, and the SF16 hydrogel was analyzed using scanning electron microscopy. The effects of the SF16 hydrogel on the viability and growth of live cells was first assessed in vitro, on PC12 cells. The in vivo test model involved the repair of a nerve gap with tubular nerve guides, through which it was possible to identify if the SF16 hydrogel would have the potential to enhance nerve regeneration. In this model physiological saline was set as the negative control, and collagen as the positive control. Walking track analysis and electrophysiological methods were used to evaluate the functional recovery of the nerve at 4 and 8 weeks after surgery. Results: Analysis of the SF16 peptide’s characteristics indicated that it consisted of a well-defined secondary structure and exhibited self-assembly. Results of scanning electron microscopy showed that the peptide based hydrogel may represent a porous scaffold that is viable for repair of peripheral nerve injury. Analysis of cell culture also supported that the hydrogel was an effective

Lentiviral-mediated targeted NF-kappaB blockade in dorsal spinal cord glia attenuates sciatic nerve injury-induced neuropathic pain in the rat.

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Meunier, Alice; Latrémolière, Alban; Dominguez, Elisa; Mauborgne, Annie; Philippe, Stéphanie; Hamon, Michel; Mallet, Jacques; Benoliel, Jean-Jacques; Pohl, Michel

2007-04-01

Neuropathic pain developing after peripheral nerve injury is associated with altered neuronal and glial cell functions in the spinal cord. Activated glia produces algogenic mediators, exacerbating pain. Among the different intracellular pathways possibly involved in the modified glial function, the nuclear factor kappaB (NF-kappaB) system is of particular interest, as numerous genes encoding inflammation- and pain-related molecules are controlled by this transcription factor. NF-kappaB is a pleiotropic factor also involved in central nervous system homeostasy. To study its role in chronic pain, it is thus essential to inhibit the NF-kappaB pathway selectively in activated spinal glial cells. Here, we show that when restricted to spinal cord and targeted to glial cells, lentiviral vector-mediated delivery of NF-kappaB super- repressor IkappaBalpha resulted in an inhibition of the NF-kappaB pathway activated in the rat spinal cord after sciatic nerve injury (chronic constriction injury, CCI). Concomitantly, IkappaBalpha overproduction prevented the enhanced expression of interleukin-6 and of inducible nitric oxide synthase associated with chronic constriction injury and resulted in prolonged antihyperalgesic and antiallodynic effects. These data show that targeted blockade of NF-kappaB activity in spinal glia efficiently alleviates pain behavior in CCI rats, demonstrating the active participation of the glial NF-kappaB pathway in the development of neuropathic pain after peripheral nerve injury.

Fabrication and Optimization of Gelatin/ Nano Bioglass Conduits for Peripheral Nerve Regeneration

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M. Foroutan Koudehi

2014-07-01

Full Text Available Introduction & Objective: Peripheral nerve injury is common in trauma patients and 4.5% of all soft-tissue injuries are accompanied by defects of peripheral nerve. Peripheral nerve injuries can lead to lifetime loss of function and permanent disfigurement. Designed conduits com-prised of natural and synthetic materials are now widely used in the construction of damaged tissues. The aim of this project was to prepare nanocomposite conduits from gelatin and bioglass for damaged peripheral nerve reconstruction. Materials & Methods: In this experimental study,compound water solution of gelatin and nano bioglass synthesized through sol gel method, was made. After preparing the solution, special mandrels were dipped in solution several times and freeze dried in order to be emptied of wa-ter via sublimation. The conduits had the following dimensions: internal diameter: 1.6 mm, outside diameter: 2.2 mm and length about 12 mm. In order to evaluate the biocompatibility of conduits we used cytotoxicity test by Chinese ovary cells and MTT assay by Miapaca-2 (pancreatic cancer cell line. Results: The prepared nano bioglass and conduits were characterized using transmission elec-tron microscopy, scanning electron microscopy, fourier transformed infrared spectroscopy and X-ray diffraction. Results of biocompatibility test showed no sign of cytotoxicity and cells were found to be attached to the pore walls offered by the conduits. Conclusion: According to the results, nano bioglass conduits could be a good candidate for peripheral nerve regeneration. (Sci J Hamadan Univ Med Sci 2014; 21 (2:152-160

A Study of Tapping by the Unaffected Finger of Patients Presenting with Central and Peripheral Nerve Damage

OpenAIRE

Lingli eZhang; Xiuying eHan; peihong eli; yang eliu; yulian ezhu; zhusheng eyu

2015-01-01

Aim: Whether the unaffected function of the hand of patients presenting with nerve injury is affected remains inconclusive. We aimed to evaluate whether there are differences in finger tapping following central or peripheral nerve injury compared with the unaffected hand and the ipsilateral hand of a healthy subject.Methods: 30 right brain stroke patients with hemiplegia, 30 left arm peripheral nerve injury cases and 60 healthy people were selected. We tested finger tapping of the right hands...

Platelet-rich plasma, an adjuvant biological therapy to assist peripheral nerve repair

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Mikel Sánchez

2017-01-01

Full Text Available Therapies such as direct tension-free microsurgical repair or transplantation of a nerve autograft, are nowadays used to treat traumatic peripheral nerve injuries (PNI, focused on the enhancement of the intrinsic regenerative potential of injured axons. However, these therapies fail to recreate the suitable cellular and molecular microenvironment of peripheral nerve repair and in some cases, the functional recovery of nerve injuries is incomplete. Thus, new biomedical engineering strategies based on tissue engineering approaches through molecular intervention and scaffolding offer promising outcomes on the field. In this sense, evidence is accumulating in both, preclinical and clinical settings, indicating that platelet-rich plasma products, and fibrin scaffold obtained from this technology, hold an important therapeutic potential as a neuroprotective, neurogenic and neuroinflammatory therapeutic modulator system, as well as enhancing the sensory and motor functional nerve muscle unit recovery.

Reciprocal regulation of nuclear factor kappa B and its inhibitor ZAS3 after peripheral nerve injury

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Madiai Francesca

2006-01-01

Full Text Available Abstract Background NF-κB binds to the κB motif to regulate transcription of genes involved in growth, immunity and inflammation, and plays a pivotal role in the production of pro-inflammatory cytokines after nerve injuries. The zinc finger protein ZAS3 also binds to the κB or similar motif. In addition to competition for common DNA sites, in vitro experiments have shown that ZAS3 can inhibit NF-κB via the association with TRAF2 to inhibit the nuclear translocation of NF-κB. However, the physiological significance of the ZAS3-mediated inhibition of NF-κB has not been demonstrated. The purpose of this study is to characterize ZAS3 proteins in nervous tissues and to use spinal nerve ligation, a neuropathic pain model, to demonstrate a functional relationship between ZAS3 and NF-κB. Results Immunohistochemical experiments show that ZAS3 is expressed in specific regions of the central and peripheral nervous system. Abundant ZAS3 expression is found in the trigeminal ganglion, hippocampal formation, dorsal root ganglia, and motoneurons. Low levels of ZAS3 expressions are also found in the cerebral cortex and in the grey matter of the spinal cord. In those nervous tissues, ZAS3 is expressed mainly in the cell bodies of neurons and astrocytes. Together with results of Western blot analyses, the data suggest that ZAS3 protein isoforms with differential cellular distribution are produced in a cell-specific manner. Further, neuropathic pain confirmed by persistent mechanical allodynia was manifested in rats seven days after L5 and L6 lumbar spinal nerve ligation. Changes in gene expression, including a decrease in ZAS3 and an increase in the p65 subunit of NF-κB were observed in dorsal root ganglion ipsilateral to the ligation when compared to the contralateral side. Conclusion ZAS3 is expressed in nervous tissues involved in cognitive function and pain modulation. The down-regulation of ZAS3 after peripheral nerve injury may lead to activation of

[Damage to cranial and peripheral nerves following patency restoration of the internal carotid artery].

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Myrcha, P; Ciostek, P; Szopiński, P; Noszczyk, W

2001-01-01

The aim of the study was an assessment of the incidence of injury to cranial and peripheral nerves as complication of patency restoration of the internal carotid artery, and analysis of the effect of peripheral nerve injury on the results of carotid patency restoration. From Oct 1987 to Sept 1999 543 procedures were carried out for restoration of patency of the internal carotid artery. After the operation hypoglossus nerve injury was found in 7 cases (1.4%), vagus injury in 9 (1.8%). Signs of exclusively recurrent laryngeal nerve damage were found in 6 cases (1.2%). Glossopharyngeus nerve was damaged in 2 cases (0.4%), transient phrenic nerve palsy as a result of conduction anaesthesia was noted in 2 cases (0.4%). Damage to the transverse cervical nerve was found in 96 cases (60%). In 2 patients (1.2%) lower position of mouth angle was due to section of the mandibular ramus of the facial nerve. In another 2 cases skin sensation disturbances were a consequence of lesion of the auricularis magnus nerve and always they coexisted with signs of transverse cervical nerve damage. damage to the cranial nerves during operation for carotid patency restoration are frequent but mostly they are not connected with any health risks and often they regress spontaneously.

Role of metallothioneins in peripheral nerve function and regeneration

DEFF Research Database (Denmark)

Ceballos, D; Lago, N; Verdú, E

2003-01-01

The physiological role of the metallothionein (MT) family of proteins during peripheral nerve injury and regeneration was examined in Mt1+ 2 and Mt3 knockout (KO) mice. To this end, the right sciatic nerve was crushed, and the regeneration distance was evaluated by the pinch test 2-7 days....... The improved regeneration observed with the Mt3 KO mice was confirmed by compound nerve action potentials that were recorded from digital nerves at 14 dpl only in this group. We conclude that Mt3 normally inhibits peripheral nerve regeneration........ Moreover, the number of regenerating axons in the distal tibial nerve was significantly higher in Mt3KO mice than in the other two strains at 14 dpl. Immunoreactive profiles to protein gene product 9.5 were present in the epidermis and the sweat glands of the plantar skin of the hindpaw of the Mt3 KO group...

Allotransplanted neurons used to repair peripheral nerve injury do not elicit overt immunogenicity.

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Weimin Liu

Full Text Available A major problem hindering the development of autograft alternatives for repairing peripheral nerve injuries is immunogenicity. We have previously shown successful regeneration in transected rat sciatic nerves using conduits filled with allogeneic dorsal root ganglion (DRG cells without any immunosuppression. In this study, we re-examined the immunogenicity of our DRG neuron implanted conduits as a potential strategy to overcome transplant rejection. A biodegradable NeuraGen® tube was infused with pure DRG neurons or Schwann cells cultured from a rat strain differing from the host rats and used to repair 8 mm gaps in the sciatic nerve. We observed enhanced regeneration with allogeneic cells compared to empty conduits 16 weeks post-surgery, but morphological analyses suggest recovery comparable to the healthy nerves was not achieved. The degree of regeneration was indistinguishable between DRG and Schwann cell allografts although immunogenicity assessments revealed substantially increased presence of Interferon gamma (IFN-γ in Schwann cell allografts compared to the DRG allografts by two weeks post-surgery. Macrophage infiltration of the regenerated nerve graft in the DRG group 16 weeks post-surgery was below the level of the empty conduit (0.56 fold change from NG; p<0.05 while the Schwann cell group revealed significantly higher counts (1.29 fold change from NG; p<0.001. Major histocompatibility complex I (MHC I molecules were present in significantly increased levels in the DRG and Schwann cell allograft groups compared to the hollow NG conduit and the Sham healthy nerve. Our results confirmed previous studies that have reported Schwann cells as being immunogenic, likely due to MHC I expression. Nerve gap injuries are difficult to repair; our data suggest that DRG neurons are superior medium to implant inside conduit tubes due to reduced immunogenicity and represent a potential treatment strategy that could be preferable to the current gold

Evaluation of radiation-induced peripheral nerve injury in rabbits with MR neurography using diffusion tensor imaging and T2 measurements: Correlation with histological and functional changes.

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Wan, Qi; Wang, Shiyang; Zhou, Jiaxuan; Zou, Qiao; Deng, Yingshi; Wang, Shouyang; Zheng, Xiaoying; Li, Xinchun

2016-06-01

To investigate the potential of diffusion tensor imaging (DTI) and T2 measurements in the evaluation of radiation-induced peripheral nerve injury (RIPNI). RIPNI was produced in a randomly selected side of sciatic nerve in each of 21 rabbits while the contralateral side served as the control. The limb function and MR parameters were evaluated over a 4-month period. Fractional anisotropy (FA), axial diffusivity (λ∥ ), radial diffusivity (λ⊥ ) and T2 values were obtained using 3T MR for quantitative analysis. Two animals were randomly killed for histological evaluation at each timepoint. The T2 value of irradiated nerve increased at 1 day (63.95 ± 15.60, P = 0.012) and was restored at 1 month (52.34 ± 5.38, P = 0.105). It increased progressively at 2 to 4 months (60.39 ± 10.60, 66.96 ± 6.08, 75.51 ± 7.39, all P evaluate RIPNI compared with T2 measurements. FA and λ⊥ are promising quantitative indices in monitoring RIPNI. J. Magn. Reson. Imaging 2016;43:1492-1499. © 2015 Wiley Periodicals, Inc.

Curcumin promotes nerve regeneration and functional recovery after sciatic nerve crush injury in diabetic rats.

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Ma, Junxiong; Yu, Hailong; Liu, Jun; Chen, Yu; Wang, Qi; Xiang, Liangbi

2016-01-01

Curcumin is capable of promoting peripheral nerve regeneration in normal condition. However, it is unclear whether its beneficial effect on nerve regeneration still exists under diabetic mellitus. The present study was designed to investigate such a possibility. Diabetes in rats was developed by a single dose of streptozotocin at 50 mg/kg. Immediately after nerve crush injury, the diabetic rats were intraperitoneally administrated daily for 4 weeks with curcumin (50 mg/kg, 100 mg/kg and 300 mg/kg), or normal saline, respectively. The axonal regeneration was investigated by morphometric analysis and retrograde labeling. The functional recovery was evaluated by electrophysiological studies and behavioral analysis. Axonal regeneration and functional recovery was significantly enhanced by curcumin, which were significantly better than those in vehicle saline group. In addition, high doses of curcumin (100 mg/kg and 300 mg/kg) achieved better axonal regeneration and functional recovery than low dose (50 mg/kg). In conclusion, curcumin is capable of promoting nerve regeneration after sciatic nerve crush injury in diabetes mellitus, highlighting its therapeutic values as a neuroprotective agent for peripheral nerve injury repair in diabetes mellitus. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Tumors of peripheral nerves

International Nuclear Information System (INIS)

Ho, Michael; Lutz, Amelie M.

2017-01-01

Differentiation between malignant and benign tumors of peripheral nerves in the early stages is challenging; however, due to the unfavorable prognosis of malignant tumors early identification is required. To show the possibilities for detection, differential diagnosis and clinical management of peripheral nerve tumors by imaging appearance in magnetic resonance (MR) neurography. Review of current literature available in PubMed and MEDLINE, supplemented by the authors' own observations in clinical practice. Although not pathognomonic, several imaging features have been reported for a differentiation between distinct peripheral nerve tumors. The use of MR neurography enables detection and initial differential diagnosis in tumors of peripheral nerves. Furthermore, it plays an important role in clinical follow-up, targeted biopsy and surgical planning. (orig.) [de

Emerging nanotechnology approaches in tissue engineering for peripheral nerve regeneration.

Science.gov (United States)

Cunha, Carla; Panseri, Silvia; Antonini, Stefania

2011-02-01

Effective nerve regeneration and functional recovery subsequent to peripheral nerve injury is still a clinical challenge. Autologous nerve graft transplantation is a feasible treatment in several clinical cases, but it is limited by donor site morbidity and insufficient donor tissue, impairing complete functional recovery. Tissue engineering has introduced innovative approaches to promote and guide peripheral nerve regeneration by using biomimetic conduits creating favorable microenvironments for nervous ingrowth, but despite the development of a plethora of nerve prostheses, few approaches have as yet entered the clinic. Promising strategies using nanotechnology have recently been proposed, such as the use of scaffolds with functionalized cell-binding domains, the use of guidance channels with cell-scale internally oriented fibers, and the possibility of sustained release of neurotrophic factors. This review addresses the fabrication, advantages, drawbacks, and results achieved by the most recent nanotechnology approaches in view of future solutions for peripheral nerve repair. Peripheral nerve repair strategies are very limited despite numerous advances on the field of neurosciences and regenerative medicine. This review discusses nanotechnology based strategies including scaffolds with functionalized cell binding domains, the use of guidance channels, and the potential use of sustained release neurotropic factors. Copyright © 2011 Elsevier Inc. All rights reserved.

Electrical muscle stimulation elevates intramuscular BDNF and GDNF mRNA following peripheral nerve injury and repair in rats.

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Willand, Michael P; Rosa, Elyse; Michalski, Bernadeta; Zhang, Jennifer J; Gordon, Tessa; Fahnestock, Margaret; Borschel, Gregory H

2016-10-15

Despite advances in surgery, patients with nerve injuries frequently have functional deficits. We previously demonstrated in a rat model that daily electrical muscle stimulation (EMS) following peripheral nerve injury and repair enhances reinnervation, detectable as early as two weeks post-injury. In this study, we explain the enhanced early reinnervation observed with electrical stimulation. In two groups of rats, the tibial nerve was transected and immediately repaired. Gastrocnemius muscles were implanted with intramuscular electrodes for sham or muscle stimulation. Muscles were stimulated daily, eliciting 600 contractions for one hour/day, repeated five days per week. Sixteen days following nerve injury, muscles were assessed for functional reinnervation by motor unit number estimation methods using electromyographic recording. In a separate cohort of rats, surgical and electrical stimulation procedures were identical but muscles and distal nerve stumps were harvested for molecular analysis. We observed that stimulated muscles had significantly higher motor unit number counts. Intramuscular levels of brain-derived and glial cell line-derived neurotrophic factor (BDNF and GDNF) mRNA were significantly upregulated in muscles that underwent daily electrical stimulation compared to those without stimulation. The corresponding levels of trophic factor mRNA within the distal stump were not different from one another, indicating that the intramuscular electrical stimulus does not modulate Schwann cell-derived trophic factor transcription. Stimulation over a three-month period maintained elevated muscle-derived GDNF but not BDNF mRNA. In conclusion, EMS elevates intramuscular trophic factor mRNA levels which may explain how EMS enhances neural regeneration following nerve injury. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Normal and sonographic anatomy of selected peripheral nerves. Part III: Peripheral nerves of the lower limb.

Science.gov (United States)

Kowalska, Berta; Sudoł-Szopińska, Iwona

2012-06-01

The ultrasonographic examination is currently increasingly used in imaging peripheral nerves, serving to supplement the physical examination, electromyography and magnetic resonance imaging. As in the case of other USG imaging studies, the examination of peripheral nerves is non-invasive and well-tolerated by patients. The typical ultrasonographic picture of peripheral nerves as well as the examination technique have been discussed in part I of this article series, following the example of the median nerve. Part II of the series presented the normal anatomy and the technique for examining the peripheral nerves of the upper limb. This part of the article series focuses on the anatomy and technique for examining twelve normal peripheral nerves of the lower extremity: the iliohypogastric and ilioinguinal nerves, the lateral cutaneous nerve of the thigh, the pudendal, sciatic, tibial, sural, medial plantar, lateral plantar, common peroneal, deep peroneal and superficial peroneal nerves. It includes diagrams showing the proper positioning of the sonographic probe, plus USG images of the successively discussed nerves and their surrounding structures. The ultrasonographic appearance of the peripheral nerves in the lower limb is identical to the nerves in the upper limb. However, when imaging the lower extremity, convex probes are more often utilized, to capture deeply-seated nerves. The examination technique, similarly to that used in visualizing the nerves of upper extremity, consists of locating the nerve at a characteristic anatomic reference point and tracking it using the "elevator technique". All 3 parts of the article series should serve as an introduction to a discussion of peripheral nerve pathologies, which will be presented in subsequent issues of the "Journal of Ultrasonography".

NR2B Expression in Rat DRG Is Differentially Regulated Following Peripheral Nerve Injuries That Lead to Transient or Sustained Stimuli-Evoked Hypersensitivity.

Science.gov (United States)

Norcini, Monica; Sideris, Alexandra; Adler, Samantha M; Hernandez, Lourdes A M; Zhang, Jin; Blanck, Thomas J J; Recio-Pinto, Esperanza

2016-01-01

Following injury, primary sensory neurons undergo changes that drive central sensitization and contribute to the maintenance of persistent hypersensitivity. NR2B expression in the dorsal root ganglia (DRG) has not been previously examined in neuropathic pain models. Here, we investigated if changes in NR2B expression within the DRG are associated with hypersensitivities that result from peripheral nerve injuries. This was done by comparing the NR2B expression in the DRG derived from two modalities of the spared nerve injury (SNI) model, since each variant produces different neuropathic pain phenotypes. Using the electronic von Frey to stimulate the spared and non-spared regions of the hindpaws, we demonstrated that sural-SNI animals develop sustained neuropathic pain in both regions while the tibial-SNI animals recover. NR2B expression was measured at Day 23 and Day 86 post-injury. At Day 23 and 86 post-injury, sural-SNI animals display strong hypersensitivity, whereas tibial-SNI animals display 50 and 100% recovery from post-injury-induced hypersensitivity, respectively. In tibial-SNI at Day 86, but not at Day 23 the perinuclear region of the neuronal somata displayed an increase in NR2B protein. This retention of NR2B protein within the perinuclear region, which will render them non-functional, correlates with the recovery observed in tibial-SNI. In sural-SNI at Day 86, DRG displayed an increase in NR2B mRNA which correlates with the development of sustained hypersensitivity in this model. The increase in NR2B mRNA was not associated with an increase in NR2B protein within the neuronal somata. The latter may result from a decrease in kinesin Kif17, since Kif17 mediates NR2B transport to the soma's plasma membrane. In both SNIs, microglia/macrophages showed a transient increase in NR2B protein detected at Day 23 but not at Day 86, which correlates with the initial post-injury induced hypersensitivity in both SNIs. In tibial-SNI at Day 86, but not at Day 23

Lentiviral-mediated Targeted NF-κB Blockade in Dorsal Spinal Cord Glia Attenuates Sciatic Nerve Injury-induced Neuropathic Pain in the Rat.

Science.gov (United States)

Meunier, Alice; Latrémolière, Alban; Dominguez, Elisa; Mauborgne, Annie; Philippe, Stéphanie; Hamon, Michel; Mallet, Jacques; Benoliel, Jean-Jacques; Pohl, Michel

2007-04-01

Neuropathic pain developing after peripheral nerve injury is associated with altered neuronal and glial cell functions in the spinal cord. Activated glia produces algogenic mediators, exacerbating pain. Among the different intracellular pathways possibly involved in the modified glial function, the nuclear factor κB (NF-κB) system is of particular interest, as numerous genes encoding inflammation- and pain-related molecules are controlled by this transcription factor. NF-κB is a pleiotropic factor also involved in central nervous system homeostasy. To study its role in chronic pain, it is thus essential to inhibit the NF-κB pathway selectively in activated spinal glial cells. Here, we show that when restricted to spinal cord and targeted to glial cells, lentiviral vector-mediated delivery of NF-κB super- repressor IκBα resulted in an inhibition of the NF-κB pathway activated in the rat spinal cord after sciatic nerve injury (chronic constriction injury, CCI). Concomitantly, IκBα overproduction prevented the enhanced expression of interleukin-6 and of inducible nitric oxide synthase associated with chronic constriction injury and resulted in prolonged antihyperalgesic and antiallodynic effects. These data show that targeted blockade of NF-κB activity in spinal glia efficiently alleviates pain behavior in CCI rats, demonstrating the active participation of the glial NF-κB pathway in the development of neuropathic pain after peripheral nerve injury. Copyright © 2007 The American Society of Gene Therapy. Published by Elsevier Inc. All rights reserved.

Peripheral nerve regeneration with conduits: use of vein tubes.

Science.gov (United States)

Sabongi, Rodrigo Guerra; Fernandes, Marcela; Dos Santos, João Baptista Gomes

2015-04-01

Treatment of peripheral nerve injuries remains a challenge to modern medicine due to the complexity of the neurobiological nerve regenerating process. There is a greater challenge when the transected nerve ends are not amenable to primary end-to-end tensionless neurorraphy. When facing a segmental nerve defect, great effort has been made to develop an alternative to the autologous nerve graft in order to circumvent morbidity at donor site, such as neuroma formation, scarring and permanent loss of function. Tubolization techniques have been developed to bridge nerve gaps and have been extensively studied in numerous experimental and clinical trials. The use of a conduit intends to act as a vehicle for moderation and modulation of the cellular and molecular ambience for nerve regeneration. Among several conduits, vein tubes were validated for clinical application with improving outcomes over the years. This article aims to address the investigation and treatment of segmental nerve injury and draw the current panorama on the use of vein tubes as an autogenous nerve conduit.

Peripheral nerve regeneration with conduits: use of vein tubes

Directory of Open Access Journals (Sweden)

Rodrigo Guerra Sabongi

2015-01-01

Full Text Available Treatment of peripheral nerve injuries remains a challenge to modern medicine due to the complexity of the neurobiological nerve regenerating process. There is a greater challenge when the transected nerve ends are not amenable to primary end-to-end tensionless neurorraphy. When facing a segmental nerve defect, great effort has been made to develop an alternative to the autologous nerve graft in order to circumvent morbidity at donor site, such as neuroma formation, scarring and permanent loss of function. Tubolization techniques have been developed to bridge nerve gaps and have been extensively studied in numerous experimental and clinical trials. The use of a conduit intends to act as a vehicle for moderation and modulation of the cellular and molecular ambience for nerve regeneration. Among several conduits, vein tubes were validated for clinical application with improving outcomes over the years. This article aims to address the investigation and treatment of segmental nerve injury and draw the current panorama on the use of vein tubes as an autogenous nerve conduit.

Carvedilol prevents functional deficits in peripheral nerve mitochondria of rats with oxaliplatin-evoked painful peripheral neuropathy

International Nuclear Information System (INIS)

Areti, Aparna; Komirishetty, Prashanth; Kumar, Ashutosh

2017-01-01

Oxaliplatin use as chemotherapeutic agent is frequently limited by cumulative neurotoxicity which may compromise quality of life. Reports relate this neurotoxic effect to oxidative stress and mitochondrial dysfunction in peripheral nerves and dorsal root ganglion (DRG). Carvedilol is an antihypertensive drug, has also been appreciated for its antioxidant and mitoprotective properties. Carvedilol co-treatment did not reduce the anti-tumor effects of oxaliplatin in human colon cancer cells (HT-29), but exhibited free radical scavenging activity against oxaliplatin-induced oxidative stress in neuronal cells (Neuro-2a). Hence, the present study was designed to investigate the effect of carvedilol in the experimental model of oxaliplatin-induced peripheral neuropathy (OIPN) in Sprague-Dawley rats. Oxaliplatin reduced the sensory nerve conduction velocity and produced the thermal and mechanical nociception. Carvedilol significantly (P < 0.001) attenuated these functional and sensorimotor deficits. It also counteracted oxidative/nitrosative stress by reducing the levels of nitrotyrosine and improving the mitochondrial superoxide dismutase expression in both sciatic nerve and DRG tissues. It improved the mitochondrial function and prevented the oxaliplatin-induced alteration in mitochondrial membrane potential in sciatic nerve thus prevented loss of intra epidermal nerve fiber density in the foot pads. Together the results prompt the use of carvedilol along with chemotherapy with oxaliplatin to prevent the peripheral neuropathy. - Graphical abstract: Schematic representation neuroprotective mechanisms of carvedilol in oxaliplatin-induced peripheral neuropathy. - Highlights: • Oxaliplatin-induced mitochondrial dysfunction causes neurotoxicity. • Mitochondrial dysfunction leads to bioenergetic and functional deficits. • Carvedilol alleviated oxaliplatin-induced behavioural and functional changes. • Targeting mitochondria with carvedilol attenuated neuropathic pain.

Carvedilol prevents functional deficits in peripheral nerve mitochondria of rats with oxaliplatin-evoked painful peripheral neuropathy

Energy Technology Data Exchange (ETDEWEB)

Areti, Aparna; Komirishetty, Prashanth; Kumar, Ashutosh, E-mail: ashutosh.niperhyd@gov.in

2017-05-01

Oxaliplatin use as chemotherapeutic agent is frequently limited by cumulative neurotoxicity which may compromise quality of life. Reports relate this neurotoxic effect to oxidative stress and mitochondrial dysfunction in peripheral nerves and dorsal root ganglion (DRG). Carvedilol is an antihypertensive drug, has also been appreciated for its antioxidant and mitoprotective properties. Carvedilol co-treatment did not reduce the anti-tumor effects of oxaliplatin in human colon cancer cells (HT-29), but exhibited free radical scavenging activity against oxaliplatin-induced oxidative stress in neuronal cells (Neuro-2a). Hence, the present study was designed to investigate the effect of carvedilol in the experimental model of oxaliplatin-induced peripheral neuropathy (OIPN) in Sprague-Dawley rats. Oxaliplatin reduced the sensory nerve conduction velocity and produced the thermal and mechanical nociception. Carvedilol significantly (P < 0.001) attenuated these functional and sensorimotor deficits. It also counteracted oxidative/nitrosative stress by reducing the levels of nitrotyrosine and improving the mitochondrial superoxide dismutase expression in both sciatic nerve and DRG tissues. It improved the mitochondrial function and prevented the oxaliplatin-induced alteration in mitochondrial membrane potential in sciatic nerve thus prevented loss of intra epidermal nerve fiber density in the foot pads. Together the results prompt the use of carvedilol along with chemotherapy with oxaliplatin to prevent the peripheral neuropathy. - Graphical abstract: Schematic representation neuroprotective mechanisms of carvedilol in oxaliplatin-induced peripheral neuropathy. - Highlights: • Oxaliplatin-induced mitochondrial dysfunction causes neurotoxicity. • Mitochondrial dysfunction leads to bioenergetic and functional deficits. • Carvedilol alleviated oxaliplatin-induced behavioural and functional changes. • Targeting mitochondria with carvedilol attenuated neuropathic pain.

Adipose-Derived Stem Cells Promote Peripheral Nerve Regeneration In Vivo without Differentiation into Schwann-Like Lineage.

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Sowa, Yoshihiro; Kishida, Tsunao; Imura, Tetsuya; Numajiri, Toshiaki; Nishino, Kenichi; Tabata, Yasuhiko; Mazda, Osam

2016-02-01

During recent decades, multipotent stem cells were found to reside in the adipose tissue, and these adipose-derived stem cells were shown to play beneficial roles, like those of Schwann cells, in peripheral nerve regeneration. However, it has not been well established whether adipose-derived stem cells offer beneficial effects to peripheral nerve injuries in vivo as Schwann cells do. Furthermore, the in situ survival and differentiation of adipose-derived stem cells after transplantation at the injured peripheral nerve tissue remain to be fully elucidated. Adipose-derived stem cells and Schwann cells were transplanted with gelatin hydrogel tubes at the artificially blunted sciatic nerve lesion in mice. Neuroregenerative abilities of them were comparably estimated. Cre-loxP-mediated fate tracking was performed to visualize survival in vivo of transplanted adipose-derived stem cells and to investigate whether they differentiated into Schwann linage cells at the peripheral nerve injury site. The transplantation of adipose-derived stem cells promoted regeneration of axons, formation of myelin, and restoration of denervation muscle atrophy to levels comparable to those achieved by Schwann cell transplantation. The adipose-derived stem cells survived for at least 4 weeks after transplantation without differentiating into Schwann cells. Transplanted adipose-derived stem cells did not differentiate into Schwann cells but promoted peripheral nerve regeneration at the injured site. The neuroregenerative ability was comparable to that of Schwann cells. Adipose-derived stem cells at an undifferentiated stage may be used as an alternative cell source for autologous cell therapy for patients with peripheral nerve injury.

Injectable systems and implantable conduits for peripheral nerve repair

International Nuclear Information System (INIS)

Lin, Yen-Chih; Marra, Kacey G

2012-01-01

Acute sensory problems following peripheral nerve injury include pain and loss of sensation. Approximately 360 000 people in the United States suffer from upper extremity paralytic syndromes every year. Restoration of sufficient functional recovery after long-gap peripheral nerve damage remains a clinical challenge. Potential nerve repair therapies have increased in the past decade as the field of tissue engineering expands. The following review describes the use of biomaterials in nerve tissue engineering. Namely, the use of both synthetic and natural biomaterials, including non-degradable and degradable nerve grafts, is addressed. The enhancement of axonal regeneration can be achieved by further modification of the nerve guides. These approaches include injectable hydrogel fillers, controlled drug delivery systems, and cell incorporation. Hydrogels are a class of liquid–gel biomaterials with high water content. Injectable and gelling hydrogels can serve as growth factor delivery vehicles and cell carriers for tissue engineering applications. While natural hydrogels and polymers are suitable for short gap nerve repair, the use of polymers for relatively long gaps remains a clinical challenge. (paper)

Intraoperative Ultrasound for Peripheral Nerve Applications.

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Willsey, Matthew; Wilson, Thomas J; Henning, Phillip Troy; Yang, Lynda J-S

2017-10-01

Offering real-time, high-resolution images via intraoperative ultrasound is advantageous for a variety of peripheral nerve applications. To highlight the advantages of ultrasound, its extraoperative uses are reviewed. The current intraoperative uses, including nerve localization, real-time evaluation of peripheral nerve tumors, and implantation of leads for peripheral nerve stimulation, are reviewed. Although intraoperative peripheral nerve localization has been performed previously using guide wires and surgical dyes, the authors' approach using ultrasound-guided instrument clamps helps guide surgical dissection to the target nerve, which could lead to more timely operations and shorter incisions. Copyright © 2017 Elsevier Inc. All rights reserved.

Biomedical engineering strategies for peripheral nerve repair: surgical applications, state of the art, and future challenges.

Science.gov (United States)

Pfister, Bryan J; Gordon, Tessa; Loverde, Joseph R; Kochar, Arshneel S; Mackinnon, Susan E; Cullen, D Kacy

2011-01-01

Damage to the peripheral nervous system is surprisingly common and occurs primarily from trauma or a complication of surgery. Although recovery of nerve function occurs in many mild injuries, outcomes are often unsatisfactory following severe trauma. Nerve repair and regeneration presents unique clinical challenges and opportunities, and substantial contributions can be made through the informed application of biomedical engineering strategies. This article reviews the clinical presentations and classification of nerve injuries, in addition to the state of the art for surgical decision-making and repair strategies. This discussion presents specific challenges that must be addressed to realistically improve the treatment of nerve injuries and promote widespread recovery. In particular, nerve defects a few centimeters in length use a sensory nerve autograft as the standard technique; however, this approach is limited by the availability of donor nerve and comorbidity associated with additional surgery. Moreover, we currently have an inadequate ability to noninvasively assess the degree of nerve injury and to track axonal regeneration. As a result, wait-and-see surgical decisions can lead to undesirable and less successful "delayed" repair procedures. In this fight for time, degeneration of the distal nerve support structure and target progresses, ultimately blunting complete functional recovery. Thus, the most pressing challenges in peripheral nerve repair include the development of tissue-engineered nerve grafts that match or exceed the performance of autografts, the ability to noninvasively assess nerve damage and track axonal regeneration, and approaches to maintain the efficacy of the distal pathway and targets during the regenerative process. Biomedical engineering strategies can address these issues to substantially contribute at both the basic and applied levels, improving surgical management and functional recovery following severe peripheral nerve injury.

Oxidative stress and nerve damage: Role in chemotherapy induced peripheral neuropathy

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Aparna Areti

2014-01-01

Full Text Available Peripheral neuropathy is a severe dose limiting toxicity associated with cancer chemotherapy. Ever since it was identified, the clear pathological mechanisms underlying chemotherapy induced peripheral neuropathy (CIPN remain sparse and considerable involvement of oxidative stress and neuroinflammation has been realized recently. Despite the empirical use of antioxidants in the therapy of CIPN, the oxidative stress mediated neuronal damage in peripheral neuropathy is still debatable. The current review focuses on nerve damage due to oxidative stress and mitochondrial dysfunction as key pathogenic mechanisms involved in CIPN. Oxidative stress as a central mediator of apoptosis, neuroinflammation, metabolic disturbances and bioenergetic failure in neurons has been highlighted in this review along with a summary of research on dietary antioxidants and other nutraceuticals which have undergone prospective controlled clinical trials in patients undergoing chemotherapy.

Cortical Reorganization in Dual Innervation by Single Peripheral Nerve.

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Zheng, Mou-Xiong; Shen, Yun-Dong; Hua, Xu-Yun; Hou, Ao-Lin; Zhu, Yi; Xu, Wen-Dong

2017-09-21

Functional recovery after peripheral nerve injury and repair is related with cortical reorganization. However, the mechanism of innervating dual targets by 1 donor nerve is largely unknown. To investigate the cortical reorganization when the phrenic nerve simultaneously innervates the diaphragm and biceps. Total brachial plexus (C5-T1) injury rats were repaired by phrenic nerve-musculocutaneous nerve transfer with end-to-side (n = 15) or end-to-end (n = 15) neurorrhaphy. Brachial plexus avulsion (n = 5) and sham surgery (n = 5) rats were included for control. Behavioral observation, electromyography, and histologic studies were used for confirming peripheral nerve reinnervation. Cortical representations of the diaphragm and reinnervated biceps were studied by intracortical microstimulation techniques before and at months 0.5, 3, 5, 7, and 10 after surgery. At month 0.5 after complete brachial plexus injury, the motor representation of the injured forelimb disappeared. The diaphragm representation was preserved in the "end-to-side" group but absent in the "end-to-end" group. Rhythmic contraction of biceps appeared in "end-to-end" and "end-to-side" groups, and the biceps representation reappeared in the original biceps and diaphragm areas at months 3 and 5. At month 10, it was completely located in the original biceps area in the "end-to-end" group. Part of the biceps representation remained in the original diaphragm area in the "end-to-side" group. Destroying the contralateral motor cortex did not eliminate respiration-related contraction of biceps. The brain tends to resume biceps representation from the original diaphragm area to the original biceps area following phrenic nerve transfer. The original diaphragm area partly preserves reinnervated biceps representation after end-to-side transfer. Copyright © 2017 by the Congress of Neurological Surgeons

Normal and sonographic anatomy of selected peripheral nerves. Part III: Peripheral nerves of the lower limb

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Berta Kowalska

2012-06-01

Full Text Available The ultrasonographic examination is currently increasingly used in imaging peripheral nerves, serving to supplement the physical examination, electromyography and magnetic resonance imaging. As in the case of other USG imaging studies, the examination of peripheral nerves is non-invasive and well-tolerated by patients. The typical ultrasonographic picture of peripheral nerves as well as the examination technique have been discussed in part I of this article series, following the example of the median nerve. Part II of the series presented the normal anatomy and the technique for examining the peripheral nerves of the upper limb. This part of the article series focuses on the anatomy and technique for examining twelve normal peripheral nerves of the lower extremity: the iliohypogastric and ilioinguinal nerves, the lateral cutaneous nerve of the thigh, the pudendal, sciatic, tibial, sural, medial plantar, lateral plantar, common peroneal, deep peroneal and superficial peroneal nerves. It includes diagrams showing the proper positioning of the sonographic probe, plus USG images of the successively discussed nerves and their surrounding structures. The ultrasonographic appearance of the peripheral nerves in the lower limb is identical to the nerves in the upper limb. However, when imaging the lower extremity, convex probes are more often utilized, to capture deeply-seated nerves. The examination technique, similarly to that used in visualizing the nerves of upper extremity, consists of locating the nerve at a characteristic anatomic reference point and tracking it using the “elevator technique”. All 3 parts of the article series should serve as an introduction to a discussion of peripheral nerve pathologies, which will be presented in subsequent issues of the “Journal of Ultrasonography”.

Correspondence in relation to the case report "Capnography as an aid in localizing the phrenic nerve in brachial plexus surgery. Technical note." published in May issue of Journal of Brachial Plexus and Peripheral Nerve Injury

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Bhakta Pradipta

2008-10-01

Full Text Available Abstract Comment on 'Capnography as an aid in localizing the phrenic nerve in brachial plexus surgery. Technical note' Bhagat H, Agarwal A, Sharma MS Journal of Brachial Plexus and Peripheral Nerve Injury 2008, 3:14 (22 May 2008

Nerve ultrasound shows subclinical peripheral nerve involvement in neurofibromatosis type 2.

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Telleman, Johan A; Stellingwerff, Menno D; Brekelmans, Geert J; Visser, Leo H

2018-02-01

Neurofibromatosis type 2 (NF2) is mainly associated with central nervous system (CNS) tumors. Peripheral nerve involvement is described in symptomatic patients, but evidence of subclinical peripheral nerve involvement is scarce. We conducted a cross-sectional pilot study in 2 asymptomatic and 3 minimally symptomatic patients with NF2 to detect subclinical peripheral nerve involvement. Patients underwent clinical examination, nerve conduction studies (NCS), and high-resolution ultrasonography (HRUS). A total of 30 schwannomas were found, divided over 20 nerve segments (33.9% of all investigated nerve segments). All patients had at least 1 schwannoma. Schwannomas were identified with HRUS in 37% of clinically unaffected nerve segments and 50% of nerve segments with normal NCS findings. HRUS shows frequent subclinical peripheral nerve involvement in NF2. Clinicians should consider peripheral nerve involvement as a cause of weakness and sensory loss in the extremities in patients with this disease. Muscle Nerve 57: 312-316, 2018. © 2017 Wiley Periodicals, Inc.

Interest of Electrostimulation of Peripheral Motor Nerves during Percutaneous Thermal Ablation

International Nuclear Information System (INIS)

Tsoumakidou, Georgia; Garnon, Julien; Ramamurthy, Nitin; Buy, Xavier; Gangi, Afshin

2013-01-01

Purpose: We present our experience of utilizing peripheral nerve electrostimulation as a complementary monitoring technique during percutaneous thermal ablation procedures; and we highlight its utility and feasibility in the prevention of iatrogenic neurologic thermal injury. Methods: Peripheral motor nerve electrostimulation was performed in 12 patients undergoing percutaneous image-guided thermal ablations of spinal/pelvic lesions in close proximity to the spinal cord and nerve roots. Electrostimulation was used in addition to existing insulation (active warming/cooling with hydrodissection, passive insulation with CO 2 insufflation) and temperature monitoring (thermocouples) techniques. Impending neurologic deficit was defined as a visual reduction of muscle response or need for a stronger electric current to evoke muscle contraction, compared with baseline. Results: Significant reduction of the muscle response to electrostimulation was observed in three patients during the ablation, necessitating temporary interruption, followed by injection of warm/cool saline. This resulted in complete recovery of the muscle response in two cases, while for the third patient the response did not improve and the procedure was terminated. No patient experienced postoperative motor deficit. Conclusion: Peripheral motor nerve electrostimulation is a simple, easily accessible technique allowing early detection of impending neurologic injury during percutaneous image-guided thermal ablation. It complements existing monitoring techniques and provides a functional assessment along the whole length of the nerve

Interest of Electrostimulation of Peripheral Motor Nerves during Percutaneous Thermal Ablation

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Tsoumakidou, Georgia, E-mail: gtsoumakidou@yahoo.com; Garnon, Julien, E-mail: juliengarnon@gmail.com; Ramamurthy, Nitin, E-mail: nitin_ramamurthy@hotmail.com; Buy, Xavier, E-mail: xbuy@ymail.com; Gangi, Afshin, E-mail: gangi@unistra.fr [University Hospital of Strasbourg (France)

2013-12-15

Purpose: We present our experience of utilizing peripheral nerve electrostimulation as a complementary monitoring technique during percutaneous thermal ablation procedures; and we highlight its utility and feasibility in the prevention of iatrogenic neurologic thermal injury. Methods: Peripheral motor nerve electrostimulation was performed in 12 patients undergoing percutaneous image-guided thermal ablations of spinal/pelvic lesions in close proximity to the spinal cord and nerve roots. Electrostimulation was used in addition to existing insulation (active warming/cooling with hydrodissection, passive insulation with CO{sub 2} insufflation) and temperature monitoring (thermocouples) techniques. Impending neurologic deficit was defined as a visual reduction of muscle response or need for a stronger electric current to evoke muscle contraction, compared with baseline. Results: Significant reduction of the muscle response to electrostimulation was observed in three patients during the ablation, necessitating temporary interruption, followed by injection of warm/cool saline. This resulted in complete recovery of the muscle response in two cases, while for the third patient the response did not improve and the procedure was terminated. No patient experienced postoperative motor deficit. Conclusion: Peripheral motor nerve electrostimulation is a simple, easily accessible technique allowing early detection of impending neurologic injury during percutaneous image-guided thermal ablation. It complements existing monitoring techniques and provides a functional assessment along the whole length of the nerve.

Long term clinical outcome of peripheral nerve stimulation in patients with chronic peripheral neuropathic pain

DEFF Research Database (Denmark)

Calenbergh, F. Van; Gybels, J.; Laere, K. Van

2009-01-01

BACKGROUND: Chronic neuropathic pain after injury to a peripheral nerve is known to be resistant to treatment. Peripheral nerve stimulation is one of the possible treatment options, which is, however, not performed frequently. In recent years we have witnessed a renewed interest for PNS. The aim...... of the present study was to evaluate the long-term clinical efficacy of PNS in a group of patients with peripheral neuropathic pain treated with PNS since the 1980s. METHODS: Of an original series of 11 patients, 5 patients could be invited for clinical examination, detailed assessment of clinical pain and QST...... functioning) also showed positive effects. Quantitative Sensory Testing results did not show significant differences in cold pain and heat pain thresholds between the "ON" and "OFF" conditions. CONCLUSION: In selected patients with peripheral neuropathic pain PNS remains effective even after more than 20...

A Long-Gap Peripheral Nerve Injury Therapy Using Human Skeletal Muscle-Derived Stem Cells (Sk-SCs: An Achievement of Significant Morphological, Numerical and Functional Recovery.

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Tetsuro Tamaki

Full Text Available Losses in vital functions of the somatic motor and sensory nervous system are induced by severe long-gap peripheral nerve transection injury. In such cases, autologous nerve grafts are the gold standard treatment, despite the unavoidable sacrifice of other healthy functions, whereas the prognosis is not always favorable. Here, we use human skeletal muscle-derived stem cells (Sk-SCs to reconstitute the function after long nerve-gap injury. Muscles samples were obtained from the amputated legs from 9 patients following unforeseen accidents. The Sk-SCs were isolated using conditioned collagenase solution, and sorted as CD34+/45- (Sk-34 and CD34-/45-/29+ (Sk-DN/29+ cells. Cells were separately cultured/expanded under optimal conditions for 2 weeks, then injected into the athymic nude mice sciatic nerve long-gap model (7-mm bridging an acellular conduit. After 8-12 weeks, active cell engraftment was observed only in the Sk-34 cell transplanted group, showing preferential differentiation into Schwann cells and perineurial/endoneurial cells, as well as formation of the myelin sheath and perineurium/endoneurium surrounding regenerated axons, resulted in 87% of numerical recovery. Differentiation into vascular cell lineage (pericyte and endothelial cells were also observed. A significant tetanic tension recovery (over 90% of downstream muscles following electrical stimulation of the sciatic nerve (at upper portion of the gap was also achieved. In contrast, Sk-DN/29+ cells were completely eliminated during the first 4 weeks, but relatively higher numerical (83% vs. 41% in axon and functional (80% vs. 60% in tetanus recovery than control were observed. Noteworthy, significant increase in the formation of vascular networks in the conduit during the early stage (first 2 weeks of recovery was observed in both groups with the expression of key factors (mRNA and protein levels, suggesting the paracrine effects to angiogenesis. These results suggested that the

A Long-Gap Peripheral Nerve Injury Therapy Using Human Skeletal Muscle-Derived Stem Cells (Sk-SCs): An Achievement of Significant Morphological, Numerical and Functional Recovery.

Science.gov (United States)

Tamaki, Tetsuro; Hirata, Maki; Nakajima, Nobuyuki; Saito, Kosuke; Hashimoto, Hiroyuki; Soeda, Shuichi; Uchiyama, Yoshiyasu; Watanabe, Masahiko

2016-01-01

Losses in vital functions of the somatic motor and sensory nervous system are induced by severe long-gap peripheral nerve transection injury. In such cases, autologous nerve grafts are the gold standard treatment, despite the unavoidable sacrifice of other healthy functions, whereas the prognosis is not always favorable. Here, we use human skeletal muscle-derived stem cells (Sk-SCs) to reconstitute the function after long nerve-gap injury. Muscles samples were obtained from the amputated legs from 9 patients following unforeseen accidents. The Sk-SCs were isolated using conditioned collagenase solution, and sorted as CD34+/45- (Sk-34) and CD34-/45-/29+ (Sk-DN/29+) cells. Cells were separately cultured/expanded under optimal conditions for 2 weeks, then injected into the athymic nude mice sciatic nerve long-gap model (7-mm) bridging an acellular conduit. After 8-12 weeks, active cell engraftment was observed only in the Sk-34 cell transplanted group, showing preferential differentiation into Schwann cells and perineurial/endoneurial cells, as well as formation of the myelin sheath and perineurium/endoneurium surrounding regenerated axons, resulted in 87% of numerical recovery. Differentiation into vascular cell lineage (pericyte and endothelial cells) were also observed. A significant tetanic tension recovery (over 90%) of downstream muscles following electrical stimulation of the sciatic nerve (at upper portion of the gap) was also achieved. In contrast, Sk-DN/29+ cells were completely eliminated during the first 4 weeks, but relatively higher numerical (83% vs. 41% in axon) and functional (80% vs. 60% in tetanus) recovery than control were observed. Noteworthy, significant increase in the formation of vascular networks in the conduit during the early stage (first 2 weeks) of recovery was observed in both groups with the expression of key factors (mRNA and protein levels), suggesting the paracrine effects to angiogenesis. These results suggested that the human Sk

Nanofiber Nerve Guide for Peripheral Nerve Repair and Regeneration

Science.gov (United States)

2016-04-01

1 Award Number: W81XWH-11-2-0047 TITLE: Nanofiber Nerve Guide for Peripheral Nerve Repair and Regeneration PRINCIPAL INVESTIGATOR: Ahmet Höke...TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-11-2-0047 Nanofiber nerve guide for peripheral nerve repair and regeneration 5b. GRANT NUMBER...goal of this collaborative research project was to develop next generation engineered nerve guide conduits (NGCs) with aligned nanofibers and

Cathepsin B-dependent motor neuron death after nerve injury in the adult mouse

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Sun, Li; Wu, Zhou; Baba, Masashi [Department of Aging Science and Pharmacology, Faculty of Dental Sciences, Kyushu University, Maidashi 3-1-1, Fukuoka 812-8582 (Japan); Peters, Christoph [Institute fuer Molekulare Medizin und Zellforshung, Albert-Ludwings-Universitaet Freiburg, D-79104 Freiburg (Germany); Uchiyama, Yasuo [Department of Cell Biology and Neuroscience, Juntendo University Graduate School of Medicine, Tokyo (Japan); Nakanishi, Hiroshi, E-mail: nakan@dent.kyushu-u.ac.jp [Department of Aging Science and Pharmacology, Faculty of Dental Sciences, Kyushu University, Maidashi 3-1-1, Fukuoka 812-8582 (Japan)

2010-08-27

Research highlights: {yields} Cathepsin B (CB), a lysosomal cysteine protease, is expressed in neuron and glia. {yields} CB increased in hypogrossal nucleus neurons after nerve injury in adult mice. {yields} CB-deficiency significantly increased the mean survival ratio of injured neurons. {yields} Thus, CB plays a critical role in axotomy-induced neuronal death in adult mice. -- Abstract: There are significant differences in the rate of neuronal death after peripheral nerve injury between species. The rate of neuronal death of motor neurons after nerve injury in the adult rats is very low, whereas that in adult mice is relatively high. However, the understanding of the mechanism underlying axotomy-induced motor neuron death in adult mice is limited. Cathepsin B (CB), a typical cysteine lysosomal protease, has been implicated in three major morphologically distinct pathways of cell death; apoptosis, necrosis and autophagic cell death. The possible involvement of CB in the neuronal death of hypogrossal nucleus (HGN) neurons after nerve injury in adult mice was thus examined. Quantitative analyses showed the mean survival ratio of HGN neurons in CB-deficient (CB-/-) adult mice after nerve injury was significantly greater than that in the wild-type mice. At the same time, proliferation of microglia in the injured side of the HGN of CB-/- adult mice was markedly reduced compared with that in the wild-type mice. On the injured side of the HGN in the wild-type adult mice, both pro- and mature forms of CB markedly increased in accordance with the increase in the membrane-bound form of LC3 (LC3-II), a marker protein of autophagy. Furthermore, the increase in CB preceded an increase in the expression of Noxa, a major executor for axotomy-induced motor neuron death in the adult mouse. Conversely, expression of neither Noxa or LC3-II was observed in the HGN of adult CB-/- mice after nerve injury. These observations strongly suggest that CB plays a critical role in axotomy-induced

Cathepsin B-dependent motor neuron death after nerve injury in the adult mouse

International Nuclear Information System (INIS)

Sun, Li; Wu, Zhou; Baba, Masashi; Peters, Christoph; Uchiyama, Yasuo; Nakanishi, Hiroshi

2010-01-01

Research highlights: → Cathepsin B (CB), a lysosomal cysteine protease, is expressed in neuron and glia. → CB increased in hypogrossal nucleus neurons after nerve injury in adult mice. → CB-deficiency significantly increased the mean survival ratio of injured neurons. → Thus, CB plays a critical role in axotomy-induced neuronal death in adult mice. -- Abstract: There are significant differences in the rate of neuronal death after peripheral nerve injury between species. The rate of neuronal death of motor neurons after nerve injury in the adult rats is very low, whereas that in adult mice is relatively high. However, the understanding of the mechanism underlying axotomy-induced motor neuron death in adult mice is limited. Cathepsin B (CB), a typical cysteine lysosomal protease, has been implicated in three major morphologically distinct pathways of cell death; apoptosis, necrosis and autophagic cell death. The possible involvement of CB in the neuronal death of hypogrossal nucleus (HGN) neurons after nerve injury in adult mice was thus examined. Quantitative analyses showed the mean survival ratio of HGN neurons in CB-deficient (CB-/-) adult mice after nerve injury was significantly greater than that in the wild-type mice. At the same time, proliferation of microglia in the injured side of the HGN of CB-/- adult mice was markedly reduced compared with that in the wild-type mice. On the injured side of the HGN in the wild-type adult mice, both pro- and mature forms of CB markedly increased in accordance with the increase in the membrane-bound form of LC3 (LC3-II), a marker protein of autophagy. Furthermore, the increase in CB preceded an increase in the expression of Noxa, a major executor for axotomy-induced motor neuron death in the adult mouse. Conversely, expression of neither Noxa or LC3-II was observed in the HGN of adult CB-/- mice after nerve injury. These observations strongly suggest that CB plays a critical role in axotomy-induced mortor neuron

Analgesic effect of piracetam on peripheral neuropathic pain induced by chronic constriction injury of sciatic nerve in rats.

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Mehta, Ashish K; Bhati, Yogendra; Tripathi, Chakra D; Sharma, Krishna K

2014-08-01

Despite immense advances in the treatment strategies, management of neuropathic pain remains unsatisfactory. Piracetam is a prototype of nootropic drugs, used to improve cognitive impairment. The present study was designed to investigate the effect of piracetam on peripheral neuropathic pain in rats. Neuropathic pain was induced by the chronic constriction injury of the sciatic nerve. Following this, piracetam was intraperitoneally administered for 2 weeks in doses of 50, 100 and 200 mg/kg, and pain was assessed by employing the behavioural tests for thermal hyperalgesia (hot plate and tail flick tests) and cold allodynia (acetone test). After the induction of neuropathic pain, significant development of thermal hyperalgesia and cold allodynia was observed. The administration of piracetam (50 mg/kg) did not have any significant effect on all the behavioural tests. Further, piracetam (100 mg/kg) also had no effect on the hot plate and tail flick tests; however it significantly decreased the paw withdrawal duration in the acetone test. Piracetam in a dose of 200 mg/kg significantly modulated neuropathic pain as observed from the increased hot plate and tail flick latencies, and decreased paw withdrawal duration (in acetone test). Therefore, the present study suggests the potential use of piracetam in the treatment of neuropathic pain, which merits further clinical investigation.

Femoral Nerve Injury Following a Lumbar Plexus Blockade

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İrfan Güngör

2014-06-01

Full Text Available Background: Lumbar plexus blockade (LPB combined with sciatic nerve block (SNB is frequently used for lower extremity surgery. Perioperative nerve injury is a rarely encountered complication of peripheral nerve blocks (PNB. Case Report: Here we report a 44-year-old male patient who developed a partial femoral nerve injury (FNI following a LPB which was performed before the surgery of a patellar fracture. The clinical and electroneuromyographic findings of the patient were recovered almost completely within the following six months. Conclusion: The presented case demonstrated a FNI despite the absence of any pain or paresthesia sensation, with the disappearance of motor response under 0.3 mA of neurostimulation in the experienced hands.

Additive antinociceptive effects of a combination of vitamin C and vitamin E after peripheral nerve injury.

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Ruirui Lu

Full Text Available Accumulating evidence indicates that increased generation of reactive oxygen species (ROS contributes to the development of exaggerated pain hypersensitivity during persistent pain. In the present study, we investigated the antinociceptive efficacy of the antioxidants vitamin C and vitamin E in mouse models of inflammatory and neuropathic pain. We show that systemic administration of a combination of vitamins C and E inhibited the early behavioral responses to formalin injection and the neuropathic pain behavior after peripheral nerve injury, but not the inflammatory pain behavior induced by Complete Freund's Adjuvant. In contrast, vitamin C or vitamin E given alone failed to affect the nociceptive behavior in all tested models. The attenuated neuropathic pain behavior induced by the vitamin C and E combination was paralleled by a reduced p38 phosphorylation in the spinal cord and in dorsal root ganglia, and was also observed after intrathecal injection of the vitamins. Moreover, the vitamin C and E combination ameliorated the allodynia induced by an intrathecally delivered ROS donor. Our results suggest that administration of vitamins C and E in combination may exert synergistic antinociceptive effects, and further indicate that ROS essentially contribute to nociceptive processing in special pain states.

Peripheral facial nerve lesions induce changes in the firing properties of primary motor cortex layer 5 pyramidal cells.

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Múnera, A; Cuestas, D M; Troncoso, J

2012-10-25

Facial nerve lesions elicit long-lasting changes in vibrissal primary motor cortex (M1) muscular representation in rodents. Reorganization of cortical representation has been attributed to potentiation of preexisting horizontal connections coming from neighboring muscle representation. However, changes in layer 5 pyramidal neuron activity induced by facial nerve lesion have not yet been explored. To do so, the effect of irreversible facial nerve injury on electrophysiological properties of layer 5 pyramidal neurons was characterized. Twenty-four adult male Wistar rats were randomly subjected to two experimental treatments: either surgical transection of mandibular and buccal branches of the facial nerve (n=18) or sham surgery (n=6). Unitary and population activity of vibrissal M1 layer 5 pyramidal neurons recorded in vivo under general anesthesia was compared between sham-operated and facial nerve-injured animals. Injured animals were allowed either one (n=6), three (n=6), or five (n=6) weeks recovery before recording in order to characterize the evolution of changes in electrophysiological activity. As compared to control, facial nerve-injured animals displayed the following sustained and significant changes in spontaneous activity: increased basal firing frequency, decreased spike-associated local field oscillation amplitude, and decreased spontaneous theta burst firing frequency. Significant changes in evoked-activity with whisker pad stimulation included: increased short latency population spike amplitude, decreased long latency population oscillations amplitude and frequency, and decreased peak frequency during evoked single-unit burst firing. Taken together, such changes demonstrate that peripheral facial nerve lesions induce robust and sustained changes of layer 5 pyramidal neurons in vibrissal motor cortex. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

An autologously generated platelet-rich plasma suturable membrane may enhance peripheral nerve regeneration after neurorraphy in an acute injury model of sciatic nerve neurotmesis.

Science.gov (United States)

Giannessi, Elisabetta; Coli, Alessandra; Stornelli, Maria Rita; Miragliotta, Vincenzo; Pirone, Andrea; Lenzi, Carla; Burchielli, Silvia; Vozzi, Giovanni; De Maria, Carmelo; Giorgetti, Margherita

2014-11-01

The aim of this study was to investigate the ability of suturable platelet-rich plasma (PRP) membrane to promote peripheral nerve regeneration after neurotmesis and neurorraphy. A total of 36 rats were used: 32 animals underwent surgery and were split in two groups. An interim sacrifice was performed at 6 weeks postsurgery and final sacrifice at 12 weeks; four animals did not sustain nerve injury and served as control. Clinical, electromyographic (EMG), gross, and histological changes were assessed. The EMG signal was evaluated for its amplitude and frequency spectrum. Number of regenerating fibers, their diameter, and myelin thickness were histologically analyzed. Both EMG parameters showed a significant (p neurorraphy improves the nerve regeneration process in a rat sciatic nerve model. The use of PRP as a suturable membrane could perform an action not only as a source of bioactive proteins but also as a nerve guide to hold the scar reaction and thus improve axonal regeneration. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Changes in the blood-nerve barrier after sciatic nerve cold injury: indications supporting early treatment

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Hao Li

2015-01-01

Full Text Available Severe edema in the endoneurium can occur after non-freezing cold injury to the peripheral nerve, which suggests damage to the blood-nerve barrier. To determine the effects of cold injury on the blood-nerve barrier, the sciatic nerve on one side of Wistar rats was treated with low temperatures (3-5°C for 2 hours. The contralateral sciatic nerve was used as a control. We assessed changes in the nerves using Evans blue as a fluid tracer and morphological methods. Excess fluid was found in the endoneurium 1 day after cold injury, though the tight junctions between cells remained closed. From 3 to 5 days after the cold injury, the fluid was still present, but the tight junctions were open. Less tracer leakage was found from 3 to 5 days after the cold injury compared with 1 day after injury. The cold injury resulted in a breakdown of the blood-nerve barrier function, which caused endoneurial edema. However, during the early period, the breakdown of the blood-nerve barrier did not include the opening of tight junctions, but was due to other factors. Excessive fluid volume produced a large increase in the endoneurial fluid pressure, prevented liquid penetration into the endoneurium from the microvasculature. These results suggest that drug treatment to patients with cold injuries should be administered during the early period after injury because it may be more difficult for the drug to reach the injury site through the microcirculation after the tissue fluid pressure becomes elevated.

Effect of Platelet-Rich Fibrin on Peripheral Nerve Regeneration.

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Şenses, Fatma; Önder, Mustafa E; Koçyiğit, Ismail D; Kul, Oğuz; Aydin, Gülümser; Inal, Elem; Atil, Fethi; Tekin, Umut

2016-10-01

This study aimed to evaluate the effect of platelet-rich fibrin (PRF) on peripheral nerve regeneration on the sciatic nerve of rats by using functional, histopathologic, and electrophysiologic analyses. Thirty female Wistar rats were divided randomly into 3 experimental groups. In group 1 (G1), which was the control group, the sciatic nerve was transected and sutured (n = 10). In group 2 (G2), the sciatic nerve was transected, sutured, and then covered with PRF as a membrane (n = 10). In group 3 (G3), the sciatic nerve was transected, sutured by leaving a 5-mm gap, and then covered by PRF as a nerve guide (n = 10). Functional, histopathologic, and electrophysiologic analyses were performed. The total histopathologic semiquantitative score was significantly higher in G1 compared to G2 and G3 (P < 0.05). Myelin thickness and capillaries were significantly lower in G3 compared to G1 (P < 0.05). There was no statistically significant difference between the groups with regard to the functional and electrophysiologic results. The study results suggest that PRF decreases functional recovery in sciatic nerve injury. Further studies are required to determine the efficacy of PRF on peripheral nerve regeneration.

Comparison of Nerve Excitability Testing, Nerve Conduction Velocity, and Behavioral Observations for Acrylamide Induced Peripheral Neuropathy

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Nerve excitability (NE) testing is a sensitive method to test for peripheral neurotoxicity in humans,and may be more sensitive than compound nerve action potential (CNAP) or nerve conduction velocity (NCV).We used acrylamide to compare the NE and CNAP/NCV methods. Behavioral test...

Resuscitation therapy for traumatic brain injury-induced coma in rats: mechanisms of median nerve electrical stimulation

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Zhen Feng

2015-01-01

Full Text Available In this study, rats were put into traumatic brain injury-induced coma and treated with median nerve electrical stimulation. We explored the wake-promoting effect, and possible mechanisms, of median nerve electrical stimulation. Electrical stimulation upregulated the expression levels of orexin-A and its receptor OX1R in the rat prefrontal cortex. Orexin-A expression gradually increased with increasing stimulation, while OX1R expression reached a peak at 12 hours and then decreased. In addition, after the OX1R antagonist, SB334867, was injected into the brain of rats after traumatic brain injury, fewer rats were restored to consciousness, and orexin-A and OXIR expression in the prefrontal cortex was downregulated. Our findings indicate that median nerve electrical stimulation induced an up-regulation of orexin-A and OX1R expression in the prefrontal cortex of traumatic brain injury-induced coma rats, which may be a potential mechanism involved in the wake-promoting effects of median nerve electrical stimulation.

Thermo-sensitive TRP channels in peripheral nerve injury: a review of their role in cold intolerance.

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Kambiz, S; Duraku, L S; Holstege, J C; Hovius, S E R; Ruigrok, T J H; Walbeehm, E T

2014-05-01

One of the sensory complications of traumatic peripheral nerve injury is thermal intolerance, which manifests in humans mainly as cold intolerance. It has a major effect on the quality of life, and adequate therapy is not yet available. In order to better understand the pathophysiological background of thermal intolerance, we focus first on the various transient receptor potential (TRP) channels that are involved in temperature sensation, including their presence in peripheral nerves and in keratinocytes. Second, the role of thermo-sensitive TRP channels in cold and heat intolerance is described showing three different mechanisms that contribute to thermal intolerance in the skin: (a) an increased expression of TRP channels on nerve fibres and on keratinocytes, (b) a lower activation threshold of TRP channels and (c) the sprouting of non-injured nerve fibres. Finally, the data that are available on the effects of TRP channel agonists and antagonists and their clinical use are discussed. In conclusion, TRP channels play a major role in temperature sensation and in cold and heat intolerance. Unfortunately, the available pharmaceutical agents that successfully target TRP channels and counteract thermal intolerance are still very limited. Yet, our focus should remain on TRP channels since it is difficult to imagine a reliable treatment for thermal intolerance that will not involve TRP channels. Copyright © 2013 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Novel drug delivering conduit for peripheral nerve regeneration

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Labroo, Pratima; Shea, Jill; Edwards, Kyle; Ho, Scott; Davis, Brett; Sant, Himanshu; Goodwin, Isak; Gale, Bruce; Agarwal, Jay

2017-12-01

Objective. This paper describes the design of a novel drug delivery apparatus integrated with a poly lactic-co-glycolic acid (PLGA) based nerve guide conduit for controlled local delivery of nerve growth factor (NGF) and application in peripheral nerve gap injury. Approach. An NGF dosage curve was acquired to determine the minimum in vitro concentration for optimal neurite outgrowth of dorsal root ganglion (DRG) cells; PLGA based drug delivery devices were then designed and tested in vitro and in vivo across 15 mm rat sciatic nerve gap injury model. Main results. The drug delivery nerve guide was able to release NGF for 28 d at concentrations (0.1-10 ng ml-1) that were shown to enhance DRG neurite growth. Furthermore, the released NGF was bioactive and able to enhance DRG neurite growth. Following these tests, optimized NGF-releasing nerve conduits were implanted across 15 mm sciatic nerve gaps in a rat model, where they demonstrated significant myelination and muscle innervation in vivo as compared to empty nerve conduits (p  design process and provides increased versatility for releasing a variety of different growth factors. This innovative device has the potential for broad applicability and allows for easier customization to change the type of drugs and dosage of individual drugs without devising a completely new biomaterial-drug conjugate each time.

The percentage of macrophage numbers in rat model of sciatic nerve crush injury

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Satrio Wicaksono

2016-02-01

Full Text Available ABSTRACT Excessive accumulation of macrophages in sciatic nerve fascicles inhibits regeneration of peripheral nerves. The aim of this study is to determine the percentage of the macrophages inside and outside of the fascicles at the proximal, at the site of injury and at the distal segment of rat model of sciatic nerve crush injury. Thirty male 3 months age Wistar rats of 200-230 g were divided into sham-operation group and crush injury group. Termination was performed on day 3, 7, and 14 after crush injury. Immunohistochemical examination was done using anti CD68 antibody. Counting of immunopositive and immunonegative cells was done on three representative fields for extrafascicular and intrafascicular area of proximal, injury and distal segments. The data was presented as percentage of immunopositive cells. The percentage of the macrophages was significantly increased in crush injury group compared to the sham-operated group in all segments of the peripheral nerves. While the percentage of macrophages outside fascicle in all segments of sciatic nerve and within the fascicle in the proximal segment reached its peak on day 3, the percentage of macrophages within the fascicles at the site of injury and distal segments reached the peak later at day 7. In conclusions, accumulation of macrophages outside the nerve fascicles occurs at the beginning of the injury, and then followed later by the accumulation of macrophages within nerve fascicles

Delayed repair of the peripheral nerve: a novel model in the rat sciatic nerve.

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Wu, Peng; Spinner, Robert J; Gu, Yudong; Yaszemski, Michael J; Windebank, Anthony J; Wang, Huan

2013-03-30

Peripheral nerve reconstruction is seldom done in the acute phase of nerve injury due to concomitant injuries and the uncertainty of the extent of nerve damage. A proper model that mimics true clinical scenarios is critical but lacking. The aim of this study is to develop a standardized, delayed sciatic nerve repair model in rats and validate the feasibility of direct secondary neurrorraphy after various delay intervals. Immediately or 1, 4, 6, 8 and 12 weeks after sciatic nerve transection, nerve repair was carried out. A successful tension-free direct neurorraphy (TFDN) was defined when the gap was shorter than 4.0 mm and the stumps could be reapproximated with 10-0 stitches without detachment. Compound muscle action potential (CMAP) was recorded postoperatively. Gaps between the two nerve stumps ranged from 0 to 9 mm, the average being 1.36, 2.85, 3.43, 3.83 and 6.4 mm in rats with 1, 4, 6, 8 and 12 week delay, respectively. The rate of successful TFDN was 78% overall. CMAP values of 1 and 4 week delay groups were not different from the immediate repair group, whereas CMAP amplitudes of 6, 8 and 12 week delay groups were significantly lower. A novel, standardized delayed nerve repair model is established. For this model to be sensitive, the interval between nerve injury and secondary repair should be at least over 4 weeks. Thereafter the longer the delay, the more challenging the model is for nerve regeneration. The choice of delay intervals can be tailored to meet specific requirements in future studies. Copyright © 2013 Elsevier B.V. All rights reserved.

Rehabilitation of extremity war injuries with lesion of peripheral nerves in "PRAXIS" Centre for Physical Medicine and Rehabilitation, Sarajevo

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Džemal Pecar

2003-08-01

Full Text Available Polytrauma with significant lesion of peripheral nerves is a specific war injury. It is also one of the most delicate problems in rehabilitation treatment because it requires a close cooperation with surgeon and timely surgical interventions. Based on our experience, the best results in the treatment of injured persons with lesion of peripheralnerves have been accomplished after the surgical treatment. Results in the neurolysis were better than those accomplished in neurorrhaphy. Total of 436 patients with lesion of peripheral nerves were recorded and 56 patients with plexus lesion. Out of this number, 78 patients (about 15% had surgical treatment (41 neurorrhaphy and 37 neurolysis. Due to lack of adequate ENMG diagnostics, the objective valorisation of treatment outcome was not possible.

Curcumin accelerates the repair of sciatic nerve injury in rats through reducing Schwann cells apoptosis and promoting myelinization.

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Zhao, Zhiwei; Li, Xiaoling; Li, Qing

2017-08-01

Schwann cells (SCs) play an indispensable role in the repair and regeneration of injured peripheral nerve. Curcumin can reduce SCs apoptosis, and promote the regeneration and functional recovery of injured peripheral nerves. However, the corresponding mechanisms are not clear. The article was aimed to explore the effect and corresponding mechanisms of curcumin on the repair of sciatic nerve injury in rats. After surgery induced sciatic nerve injury, the model rats were divided into three groups and treated with curcumin, curcumin+PD98059 and curcumin+IGF-1 respectively for 4days. The phosphorylation of Erk1/2 and Akt, and the expression of LC3-II, Beclin 1 and p62 were measured using western blotting. After treatment for 60days, myelination of the injured sciatic nerve was evaluated by MBP immunohistochemical staining and the expression of PMP22, Fibrin and S100 were determined using qRT-PCR and western blotting. In vitro, RSC96 cells were starved for 12h to induce autophagy, and received DMSO, curcumin, PD98059+curcumin, IGF-1+curcumin and BFA1 respectively. The phosphorylation of Erk1/2、Akt and the expression of LC3-II, Beclin 1, p62, PMP22, Fibrin and S100 were measured using western blotting, and the cell apoptosis was detected by flow cytometry. Curcumin could promote injury-induced cell autophagy, remyelination and axon regeneration in sciatic nerve of rats. In vitro, curcumin could accelerate cell autophagy through regulating autophagy related Erk1/2 and Akt pathway, prevent cell apoptosis and promote expression of PMP22 and S100, and reduced deposition of Fibrin in cultured RSC96 SCs. Curcumin could accelerate injured sciatic nerve repair in rats through reducing SCs apoptosis and promoting myelinization. Copyright © 2017. Published by Elsevier Masson SAS.

Identification of regeneration-associated genes after central and peripheral nerve injury in the adult rat

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Brook Gary A

2003-05-01

Full Text Available Abstract Background It is well known that neurons of the peripheral nervous system have the capacity to regenerate a severed axon leading to functional recovery, whereas neurons of the central nervous system do not regenerate successfully after injury. The underlying molecular programs initiated by axotomized peripheral and central nervous system neurons are not yet fully understood. Results To gain insight into the molecular mechanisms underlying the process of regeneration in the nervous system, differential display polymerase chain reaction has been used to identify differentially expressed genes following axotomy of peripheral and central nerve fibers. For this purpose, axotomy induced changes of regenerating facial nucleus neurons, and non-regenerating red nucleus and Clarke's nucleus neurons have been analyzed in an intra-animal side-to-side comparison. One hundred and thirty five gene fragments have been isolated, of which 69 correspond to known genes encoding for a number of different functional classes of proteins such as transcription factors, signaling molecules, homeobox-genes, receptors and proteins involved in metabolism. Sixty gene fragments correspond to genomic mouse sequences without known function. In situ-hybridization has been used to confirm differential expression and to analyze the cellular localization of these gene fragments. Twenty one genes (~15% have been demonstrated to be differentially expressed. Conclusions The detailed analysis of differentially expressed genes in different lesion paradigms provides new insights into the molecular mechanisms underlying the process of regeneration and may lead to the identification of genes which play key roles in functional repair of central nervous tissues.

Apoptosis-inducing effect of selective sensory or motor nerve injury on skeletal muscle atrophy

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Lei ZHAO

2011-09-01

Full Text Available Objective To explore the apoptosis-inducing effect of selective sensory or motor nerve injury on skeletal muscle atrophy.Methods Thirty healthy adult SD rats were randomly divided into three groups,namely,ventral root transection group(VRT group,received left L4-L6 ventral rhizotomy,dorsal root transection group(DRT group,received left L4-L6 dorsal rhizotomy,and sciatic nerve transection group(SNT group,received left sciatic nerve transection.Each group comprised 10 SD rats.The bilateral gastrocnemius was harvested 10 weeks after operation to observe the apoptosis and Fas/FasL expression of the skeletal muscle cells through fluorescent labeling,transmission electron microscopy,and immunohistochemistry.Result Ten weeks after the denervation,apoptosis-related changes,especially obvious changes of the nuclear apoptotic morphology,were observed in the skeletal muscle cells.The aggregation degree of the nucleus and the expression of Fas/FasL increased in the following order: DRT group,VRT group,and SNT group.No apoptotic body,but early apoptotic morphology,was found in the denervated gastrocnemius through transmission electron microscopy.Conclusions The effect of motor nerve injury on skeletal muscle atrophy is more serious than that of sensory nerve injury.The rebuilding of motor nerves should be preferentially considered in the clinical treatment of muscle atrophy induced by denervation.

Biomaterials Approaches for Utilizing the Regenerative Potential of the Peripheral Nerve Injury Microenvironment

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Wrobel, Melissa Renee

following classical activation (M1/pro-inflammatory) with lipopolysaccharide (LPS; 1microg/mL) and would accelerate the transformation of Schwann cells from an immature state fol-lowing injury to a mature/pro-myelinating one. Cell phenotypes were functionally assessed using quantified reverse transcription polymerase chain reaction (qRT-PCR), immunofluorescence, and sandwich-ELISA based antibody arrays to measure changes in mRNA expression, mor-phology, and cytokine release, respectively. Macrophages cultured with the SCM and HA fibers had significantly reduced M1 gene expression, released lower levels of M1 cytokines (IL-1a, RANTES and TFN-a) and assumed an elongated morphology indicative of M2. These cues also induced changes in the Schwann cells including significantly reduced area, increased elongation, decreased expression of immature genes (GFAP) and increased expression of mature genes (Krox20 and Oct6). These results suggest that the SCM and HA nanofibers could trigger non-neuronal cells towards regenerative programs more quickly than traditional PNI interventions. Changes induced by biomaterials have distinct benefits over the use of immunomodulatory cy-tokines and would be a novel approach to direct repair. Our collective studies offer improved in-sight into the endogenous potential of the injured peripheral nerve and offer ways to incorporate intrinsic repair cues into a biomaterial system for treating large gaps.

Normal and sonographic anatomy of selected peripheral nerves. Part II: Peripheral nerves of the upper limb

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Berta Kowalska

2012-06-01

Full Text Available The ultrasonographic examination is frequently used for imaging peripheral nerves. It serves to supplement the physical examination, electromyography, and magnetic resonance imaging. As in the case of other USG imaging studies, the examination of peripheral nerves is non-invasive, well-tolerated by patients, and relatively inexpensive. Part I of this article series described in detail the characteristic USG picture of peripheral nerves and the proper examination technique, following the example of the median nerve. This nerve is among the most often examined peripheral nerves of the upper limb. This part presents describes the normal anatomy and ultrasound picture of the remaining large nerve branches in the upper extremity and neck – the spinal accessory nerve, the brachial plexus, the suprascapular, axillary, musculocutaneous, radial and ulnar nerves. Their normal anatomy and ultrasonographic appearance have been described, including the division into individual branches. For each of them, specific reference points have been presented, to facilitate the location of the set trunk and its further monitoring. Sites for the application of the ultrasonographic probe at each reference point have been indicated. In the case of the ulnar nerve, the dynamic component of the examination was emphasized. The text is illustrated with images of probe positioning, diagrams of the normal course of the nerves as well as a series of ultrasonographic pictures of normal nerves of the upper limb. This article aims to serve as a guide in the ultrasound examination of the peripheral nerves of the upper extremity. It should be remembered that a thorough knowledge of the area’s topographic anatomy is required for this type of examination.

Investigation of cell adhesion in chitosan membranes for peripheral nerve regeneration

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Carvalho, Cristiana R.; López-Cebral, Rita; Silva-Correia, Joana; Silva, Joana M.; Mano, João F.; Silva, Tiago H. [3B' s Research Group - Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark – Parque de Ciência e Tecnologia, 4805-017, Barco, Guimarães (Portugal); ICVS/3B' s - PT Government Associate Laboratory, Braga, Guimarães (Portugal); Freier, Thomas [MEDOVENT GmbH, Friedrich-Koenig-Str. 3, D-55129 Mainz (Germany); Reis, Rui L. [3B' s Research Group - Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark – Parque de Ciência e Tecnologia, 4805-017, Barco, Guimarães (Portugal); ICVS/3B' s - PT Government Associate Laboratory, Braga, Guimarães (Portugal); Oliveira, Joaquim M., E-mail: miguel.oliveira@dep.uminho.pt [3B' s Research Group - Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark – Parque de Ciência e Tecnologia, 4805-017, Barco, Guimarães (Portugal); ICVS/3B' s - PT Government Associate Laboratory, Braga, Guimarães (Portugal)

2017-02-01

Peripheral nerve injuries have produced major concerns in regenerative medicine for several years, as the recovery of normal nerve function continues to be a significant clinical challenge. Chitosan (CHT), because of its good biocompatibility, biodegradability and physicochemical properties, has been widely used as a biomaterial in tissue engineering scaffolding. In this study, CHT membranes were produced with three different Degrees of Acetylation (DA), envisioning its application in peripheral nerve regeneration. The three CHT membranes (DA I: 1%, DA II: 2%, DA III: 5%) were extensively characterized and were found to have a smooth and flat surface, with DA III membrane having slightly higher roughness and surface energy. All the membranes presented suitable mechanical properties and did not show any signs of calcification after SBF test. Biodegradability was similar for all samples, and adequate to physically support neurite outgrowth. The in vitro cell culture results indicate selective cell adhesion. The CHT membranes favoured Schwann cells invasion and proliferation, with a display of appropriate cytoskeletal morphology. At the same time they presented low fibroblast infiltration. This fact may be greatly beneficial for the prevention of fibrotic tissue formation, a common phenomenon impairing peripheral nerve regeneration. The great deal of results obtained during this work permitted to select the formulation with the greatest potential for further biological tests. - Highlights: • Three chitosan membranes were produced with very specific degrees of acetylation (DA I: 1%, DA II: 2%, DA III: 5%). • Physicochemical characterization of the membranes showed their suitability for peripheral nerve regeneration purposes. • In vitro cellular tests confirmed the potential of the membranes as peripheral nerve regeneration systems. • The results indicated that DA III membrane should be the one considered for further peripheral nerve regeneration studies.

Investigation of cell adhesion in chitosan membranes for peripheral nerve regeneration

International Nuclear Information System (INIS)

Carvalho, Cristiana R.; López-Cebral, Rita; Silva-Correia, Joana; Silva, Joana M.; Mano, João F.; Silva, Tiago H.; Freier, Thomas; Reis, Rui L.; Oliveira, Joaquim M.

2017-01-01

Peripheral nerve injuries have produced major concerns in regenerative medicine for several years, as the recovery of normal nerve function continues to be a significant clinical challenge. Chitosan (CHT), because of its good biocompatibility, biodegradability and physicochemical properties, has been widely used as a biomaterial in tissue engineering scaffolding. In this study, CHT membranes were produced with three different Degrees of Acetylation (DA), envisioning its application in peripheral nerve regeneration. The three CHT membranes (DA I: 1%, DA II: 2%, DA III: 5%) were extensively characterized and were found to have a smooth and flat surface, with DA III membrane having slightly higher roughness and surface energy. All the membranes presented suitable mechanical properties and did not show any signs of calcification after SBF test. Biodegradability was similar for all samples, and adequate to physically support neurite outgrowth. The in vitro cell culture results indicate selective cell adhesion. The CHT membranes favoured Schwann cells invasion and proliferation, with a display of appropriate cytoskeletal morphology. At the same time they presented low fibroblast infiltration. This fact may be greatly beneficial for the prevention of fibrotic tissue formation, a common phenomenon impairing peripheral nerve regeneration. The great deal of results obtained during this work permitted to select the formulation with the greatest potential for further biological tests. - Highlights: • Three chitosan membranes were produced with very specific degrees of acetylation (DA I: 1%, DA II: 2%, DA III: 5%). • Physicochemical characterization of the membranes showed their suitability for peripheral nerve regeneration purposes. • In vitro cellular tests confirmed the potential of the membranes as peripheral nerve regeneration systems. • The results indicated that DA III membrane should be the one considered for further peripheral nerve regeneration studies.

Large A-fiber activity is required for microglial proliferation and p38 MAPK activation in the spinal cord: different effects of resiniferatoxin and bupivacaine on spinal microglial changes after spared nerve injury

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Decosterd Isabelle

2009-09-01

Full Text Available Abstract Background After peripheral nerve injury, spontaneous ectopic activity arising from the peripheral axons plays an important role in inducing central sensitization and neuropathic pain. Recent evidence indicates that activation of spinal cord microglia also contributes to the development of neuropathic pain. In particular, activation of p38 mitogen-activated protein kinase (MAPK in spinal microglia is required for the development of mechanical allodynia. However, activity-dependent activation of microglia after nerve injury has not been fully addressed. To determine whether spontaneous activity from C- or A-fibers is required for microglial activation, we used resiniferatoxin (RTX to block the conduction of transient receptor potential vanilloid subtype 1 (TRPV1 positive fibers (mostly C- and Aδ-fibers and bupivacaine microspheres to block all fibers of the sciatic nerve in rats before spared nerve injury (SNI, and observed spinal microglial changes 2 days later. Results SNI induced robust mechanical allodynia and p38 activation in spinal microglia. SNI also induced marked cell proliferation in the spinal cord, and all the proliferating cells (BrdU+ were microglia (Iba1+. Bupivacaine induced a complete sensory and motor blockade and also significantly inhibited p38 activation and microglial proliferation in the spinal cord. In contrast, and although it produced an efficient nociceptive block, RTX failed to inhibit p38 activation and microglial proliferation in the spinal cord. Conclusion (1 Blocking peripheral input in TRPV1-positive fibers (presumably C-fibers is not enough to prevent nerve injury-induced spinal microglial activation. (2 Peripheral input from large myelinated fibers is important for microglial activation. (3 Microglial activation is associated with mechanical allodynia.

Synovial sarcoma mimicking benign peripheral nerve sheath tumor

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Larque, Ana B.; Nielsen, G.P.; Chebib, Ivan [Massachusetts General Hospital and Harvard Medical School, Department of Pathology, Boston, MA (United States); Bredella, Miriam A. [Massachusetts General Hospital and Harvard Medical School, Department of Radiology, Boston, MA (United States)

2017-11-15

To assess the radiographic and clinicopathologic features of synovial sarcoma of the nerve that were clinically or radiologically interpreted as benign peripheral nerve sheath tumor. Five patients with synovial sarcoma arising from the peripheral nerve and interpreted clinically and radiologically as peripheral nerve sheath tumors were identified. Clinicopathologic and imaging features were evaluated. There were three females and two males, ranging in age from 28 to 50 (mean 35.8) years. Most patients (4/5) complained of a mass, discomfort or pain. MR images demonstrated a heterogeneous, enhancing, soft tissue mass contiguous with the neurovascular bundle. On histologic examination, most tumors were monophasic synovial sarcoma (4/5). At the time of surgery, all tumors were noted to arise along or within a peripheral nerve. All patients were alive with no evidence of disease with median follow-up of 44 (range 32-237) months. For comparison, approximately 775 benign peripheral nerve sheath tumors of the extremities were identified during the same time period. Primary synovial sarcoma of the nerve can mimic peripheral nerve sheath tumors clinically and on imaging and should be included in the differential diagnosis for tumors arising from peripheral nerves. (orig.)

Etiology and mechanisms of ulnar and median forearm nerve injuries

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Puzović Vladimir

2015-01-01

Full Text Available Bacgraund/Aim. Most often injuries of brachial plexus and its branches disable the injured from using their arms and/or hands. The aim of this study was to investigate the etiology and mechanisms of median and ulnar forearm nerves injuries. Methods. This retrospective cohort study included 99 patients surgically treated in the Clinic of Neurosurgery, Clinical Center of Serbia, from January 1st, 2000 to December 31st, 2010. All data are obtained from the patients' histories. Results. The majority of the injured patients were male, 81 (81.8%, while only 18 (18.2% were females, both mainly with nerve injuries of the distal forearm - 75 (75.6%. Two injury mechanisms were present, transection in 85 patients and traction and contusion in 14 of the patients. The most frequent etiological factor of nerve injuries was cutting, in 61 of the patients. Nerve injuries are often associated with other injuries. In the studied patients there were 22 vascular injuries, 33 muscle and tendon injuries and 20 bone fractures. Conclusion. The majority of those patients with peripheral nerve injuries are represented in the working age population, which is a major socioeconomic problem. In our study 66 out of 99 patients were between 17 and 40 years old, in the most productive age. The fact that the majority of patients had nerve injuries of the distal forearm and that they are operated within the first 6 months after injury, promises them good functional prognosis.

Electrophysiological evaluation of phrenic nerve injury during cardiac surgery – a prospective, controlled, clinical study

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Ege Turan

2004-01-01

Full Text Available Abstract Background According to some reports, left hemidiaphragmatic paralysis due to phrenic nerve injury may occur following cardiac surgery. The purpose of this study was to document the effects on phrenic nerve injury of whole body hypothermia, use of ice-slush around the heart and mammary artery harvesting. Methods Electrophysiology of phrenic nerves was studied bilaterally in 78 subjects before and three weeks after cardiac or peripheral vascular surgery. In 49 patients, coronary artery bypass grafting (CABG and heart valve replacement with moderate hypothermic (mean 28°C cardiopulmonary bypass (CPB were performed. In the other 29, CABG with beating heart was performed, or, in several cases, peripheral vascular surgery with normothermia. Results In all patients, measurements of bilateral phrenic nerve function were within normal limits before surgery. Three weeks after surgery, left phrenic nerve function was absent in five patients in the CPB and hypothermia group (3 in CABG and 2 in valve replacement. No phrenic nerve dysfunction was observed after surgery in the CABG with beating heart (no CPB or the peripheral vascular groups. Except in the five patients with left phrenic nerve paralysis, mean phrenic nerve conduction latency time (ms and amplitude (mV did not differ statistically before and after surgery in either group (p > 0.05. Conclusions Our results indicate that CPB with hypothermia and local ice-slush application around the heart play a role in phrenic nerve injury following cardiac surgery. Furthermore, phrenic nerve injury during cardiac surgery occurred in 10.2 % of our patients (CABG with CPB plus valve surgery.

In vivo assessment of peripheral nerve regeneration by diffusion tensor imaging.

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Morisaki, Shinsuke; Kawai, Yuko; Umeda, Masahiro; Nishi, Mayumi; Oda, Ryo; Fujiwara, Hiroyoshi; Yamada, Kei; Higuchi, Toshihiro; Tanaka, Chuzo; Kawata, Mitsuhiro; Kubo, Toshikazu

2011-03-01

To evaluate the sensitivity of diffusion tensor imaging (DTI) in assessing peripheral nerve regeneration in vivo. We assessed the changes in the DTI parameters and histological analyses after nerve injury to examine degeneration and regeneration in the rat sciatic nerves. For magnetic resonance imaging (MRI), 16 rats were randomly divided into two groups: group P (permanently crushed; n = 7) and group T (temporally crushed; n = 9). Serial MRI of the right leg was performed before the operation, and then performed at the timepoints of 1, 2, 3, and 4 weeks after the crush injury. The changes in fractional anisotropy (FA), axial diffusivity (λ(∥)), and radial diffusivity (λ(⟂)) were quantified. For histological analyses, the number of axons and the myelinated axon areas were quantified. Decreased FA and increased λ(⟂) were observed in the degenerative phase, and increased FA and decreased λ(⟂) were observed in the regenerative phase. The changes in FA and λ(⟂) were strongly correlated with histological changes, including axonal and myelin regeneration. DTI parameters, especially λ(⟂) , can be good indicators for peripheral nerve regeneration and can be applied as noninvasive diagnostic tools for a variety of neurological diseases. Copyright © 2011 Wiley-Liss, Inc.

Transplantation of olfactory ensheathing cells as adjunct cell therapy for peripheral nerve injury.

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Radtke, Christine; Wewetzer, Konstantin; Reimers, Kerstin; Vogt, Peter M

2011-01-01

Traumatic events, such as work place trauma or motor vehicle accident violence, result in a significant number of severe peripheral nerve lesions, including nerve crush and nerve disruption defects. Transplantation of myelin-forming cells, such as Schwann cells (SCs) or olfactory ensheathing cells (OECs), may be beneficial to the regenerative process because the applied cells could mediate neurotrophic and neuroprotective effects by secretion of chemokines. Moreover, myelin-forming cells are capable of bridging the repair site by establishing an environment permissive to axonal regeneration. The cell types that are subject to intense investigation include SCs and OECs either derived from the olfactory bulb or the olfactory mucosa, stromal cells from bone marrow (mesenchymal stem cells, MSCs), and adipose tissue-derived cells. OECs reside in the peripheral and central nervous system and have been suggested to display unique regenerative properties. However, so far OECs were mainly used in experimental studies to foster central regeneration and it was not until recently that their regeneration-promoting activity for the peripheral nervous system was recognized. In the present review, we summarize recent experimental evidence regarding the regenerative effects of OECs applied to the peripheral nervous system that may be relevant to design novel autologous cell transplantation therapies. © 2011 Cognizant Comm. Corp.

Label-free photoacoustic microscopy of peripheral nerves

Science.gov (United States)

Matthews, Thomas Paul; Zhang, Chi; Yao, Da-Kang; Maslov, Konstantin; Wang, Lihong V.

2014-01-01

Peripheral neuropathy is a common neurological problem that affects millions of people worldwide. Diagnosis and treatment of this condition are often hindered by the difficulties in making objective, noninvasive measurements of nerve fibers. Photoacoustic microscopy (PAM) has the ability to obtain high resolution, specific images of peripheral nerves without exogenous contrast. We demonstrated the first proof-of-concept imaging of peripheral nerves using PAM. As validated by both standard histology and photoacoustic spectroscopy, the origin of photoacoustic signals is myelin, the primary source of lipids in the nerves. An extracted sciatic nerve sandwiched between two layers of chicken tissue was imaged by PAM to mimic the in vivo case. Ordered fibrous structures inside the nerve, caused by the bundles of myelin-coated axons, could be observed clearly. With further technical improvements, PAM can potentially be applied to monitor and diagnose peripheral neuropathies.

Malignant peripheral nerve sheath tumor of the oculomotor nerve

DEFF Research Database (Denmark)

Kozic, D; Nagulic, M; Ostojic, J

2006-01-01

We present the short-term follow-up magnetic resonance (MR) studies and 1H-MR spectroscopy in a child with malignant peripheral nerve sheath tumor of the oculomotor nerve associated with other less aggressive cranial nerve schwannomas. The tumor revealed perineural extension and diffuse nerve...

Toxicity to sensory neurons and Schwann cells in experimental linezolid-induced peripheral neuropathy.

Science.gov (United States)

Bobylev, Ilja; Maru, Helina; Joshi, Abhijeet R; Lehmann, Helmar C

2016-03-01

Peripheral neuropathy is a common side effect of prolonged treatment with linezolid. This study aimed to explore injurious effects of linezolid on cells of the peripheral nervous system and to establish in vivo and in vitro models of linezolid-induced peripheral neuropathy. C57BL/6 mice were treated with linezolid or vehicle over a total period of 4 weeks. Animals were monitored by weight, nerve conduction studies and behavioural tests. Neuropathic changes were assessed by morphometry on sciatic nerves and epidermal nerve fibre density in skin sections. Rodent sensory neuron and Schwann cell cultures were exposed to linezolid in vitro and assessed for mitochondrial dysfunction. Prolonged treatment with linezolid induced a mild, predominantly small sensory fibre neuropathy in vivo. Exposure of Schwann cells and sensory neurons to linezolid in vitro caused mitochondrial dysfunction primarily in neurons (and less prominently in Schwann cells). Sensory axonopathy could be partially prevented by co-administration of the Na(+)/Ca(2+) exchanger blocker KB-R7943. Clinical and pathological features of linezolid-induced peripheral neuropathy can be replicated in in vivo and in vitro models. Mitochondrial dysfunction may contribute to the axonal damage to sensory neurons that occurs after linezolid exposure. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Delivery of adipose-derived stem cells in poloxamer hydrogel improves peripheral nerve regeneration.

Science.gov (United States)

Allbright, Kassandra O; Bliley, Jacqueline M; Havis, Emmanuelle; Kim, Deok-Yeol; Dibernardo, Gabriella A; Grybowski, Damian; Waldner, Matthias; James, Isaac B; Sivak, Wesley N; Rubin, J Peter; Marra, Kacey G

2018-02-06

Peripheral nerve damage is associated with high long-term morbidity. Because of beneficial secretome, immunomodulatory effects, and ease of clinical translation, transplantation with adipose-derived stem cells (ASC) represents a promising therapeutic modality. Effect of ASC delivery in poloxamer hydrogel was assessed in a rat sciatic nerve model of critical-sized (1.5 cm) peripheral nerve injury. Nerve/muscle unit regeneration was assessed via immunostaining explanted nerve, quantitative polymerase chain reaction (qPCR), and histological analysis of reinnervating gastrocnemius muscle. On the basis of viability data, 10% poloxamer hydrogel was selected for in vivo study. Six weeks after transection and repair, the group treated with poloxamer delivered ASCs demonstrated longest axonal regrowth. The qPCR results indicated that the inclusion of ASCs appeared to result in expression of factors that aid in reinnervating muscle tissue. Delivery of ASCs in poloxamer addresses multiple facets of the complexity of nerve/muscle unit regeneration, representing a promising avenue for further study. Muscle Nerve, 2018. © 2018 Wiley Periodicals, Inc.

Normal tissue tolerance to external beam radiation therapy: Peripheral nerves

International Nuclear Information System (INIS)

Henriques de Figueiredo, B.; Dejean, C.; Sargos, P.; Kantor, G.; Huchet, A.; Mamou, N.; Loiseau, H.

2010-01-01

Plexopathies and peripheral neuropathies appear progressively and with several years delay after radiotherapy. These lesions are observed principally after three clinical situations: supraclavicular and axillar irradiations for breast cancer, pelvic irradiations for various pathologies and limb irradiations for soft tissue sarcomas. Peripheral nerves and plexus (brachial and lumbosacral) are described as serial structures and are supposed to receive less than a given maximum dose linked to the occurrence of late injury. Literature data, mostly ancient, define the maximum tolerable dose to a threshold of 60 Gy and highlight also a great influence of fractionation and high fraction doses. For peripheral nerves, most frequent late effects are pain with significant differences of occurrence between 50 and 60 Gy. At last, associated pathologies (diabetes, vascular pathology, neuropathy) and associated treatments have probably to be taken into account as additional factors, which may increase the risk of these late radiation complications. (authors)

Short-term low-frequency electrical stimulation enhanced remyelination of injured peripheral nerves by inducing the promyelination effect of brain-derived neurotrophic factor on Schwann cell polarization.

Science.gov (United States)

Wan, Lidan; Xia, Rong; Ding, Wenlong

2010-09-01

Electrical stimulation (ES) has been found to aid repair of nerve injuries and have been shown to increase and direct neurite outgrowth during stimulation. However, the effect of ES on peripheral remyelination after nerve damage has been investigated less well, and the mechanism underlying its action remains unclear. In the present study, the crush-injured sciatic nerves in rats were subjected to 1 hr of continuous ES (20 Hz, 100 microsec, 3 V). Electron microscopy and nerve morphometry were performed to investigate the extent of regenerated nerve myelination. The expression profiles of P0, Par-3, and brain-derived neurotrophic factor (BDNF) in the injuried sciatic nerves and in the dorsal root ganglion neuron/Schwann cell cocultures were examined by Western blotting. Par-3 localization in the sciatic nerves was determined by immunohistochemistry to demonstrate Schwann cell polarization during myelination. We reported that 20-Hz ES increased the number of myelinated fibers and the thickness myelin sheath at 4 and 8 weeks postinjury. P0 level in the ES-treated groups, both in vitro and in vivo, was enhanced compared with the controls. The earlier peak of Par-3 in the ES-treated groups indicated an earlier initiation of Schwann cell myelination. Additionally, ES significantly elevated BDNF expression in nerve tissues and in cocultures. ES on the site of nerve injury potentiates axonal regrowth and myelin maturation during peripheral nerve regeneration. Furthermore, the therapeutic actions of ES on myelination are mediated via enhanced BDNF signals, which drive the promyelination effect on Schwann cells at the onset of myelination.

Early regenerative effects of NGF-transduced Schwann cells in peripheral nerve repair.

Science.gov (United States)

Shakhbazau, Antos; Kawasoe, Jean; Hoyng, Stefan A; Kumar, Ranjan; van Minnen, Jan; Verhaagen, Joost; Midha, Rajiv

2012-05-01

Peripheral nerve injury leads to a rapid and robust increase in the synthesis of neurotrophins which guide and support regenerating axons. To further optimize neurotrophin supply at the earliest stages of regeneration, we over-expressed NGF in Schwann cells (SCs) by transducing these cells with a lentiviral vector encoding NGF (NGF-SCs). Transplantation of NGF-SCs in a rat sciatic nerve transection/repair model led to significant increase of NGF levels 2weeks after injury and correspondingly to substantial improvement in axonal regeneration. Numbers of NF200, ChAT and CGRP-positive axon profiles, as well as the gastrocnemius muscle weights, were significantly higher in the NGF-Schwann cell group compared to the animals that received control SCs transduced with a lentiviral vector encoding GFP (GFP-SCs). Comparison with other models of NGF application signifies the important role of this neurotrophin during the early stages of regeneration, and supports the importance of developing combined gene and cell therapy for peripheral nerve repair. Copyright © 2012 Elsevier Inc. All rights reserved.

Peripheral nervous system involvement in chronic spinal cord injury

DEFF Research Database (Denmark)

Tankisi, Hatice; Pugdahl, Kirsten; Rasmussen, Mikkel Mylius

2015-01-01

Introduction: Upper motor neuron disorders are believed to leave the peripheral nervous system (PNS) intact. In this study we examined whether there is evidence of PNS involvement in spinal cord injury (SCI). Methods: Twelve subjects with chronic low cervical or thoracic SCI were included......), and the amount of SA correlated inversely with reflex activity and nerve length. Fibular nerve entrapment across the knee was seen in 6 subjects, and sciatic nerve entrapment was seen in 1. Apart from entrapment neuropathies, NCS changes were found predominantly in motor nerves. Conclusion: The presence...

Peripheral Nerve Regeneration by Secretomes of Stem Cells from Human Exfoliated Deciduous Teeth.

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Sugimura-Wakayama, Yukiko; Katagiri, Wataru; Osugi, Masashi; Kawai, Takamasa; Ogata, Kenichi; Sakaguchi, Kohei; Hibi, Hideharu

2015-11-15

Peripheral nerve regeneration across nerve gaps is often suboptimal, with poor functional recovery. Stem cell transplantation-based regenerative therapy is a promising approach for axon regeneration and functional recovery of peripheral nerve injury; however, the mechanisms remain controversial and unclear. Recent studies suggest that transplanted stem cells promote tissue regeneration through a paracrine mechanism. We investigated the effects of conditioned media derived from stem cells from human exfoliated deciduous teeth (SHED-CM) on peripheral nerve regeneration. In vitro, SHED-CM-treated Schwann cells exhibited significantly increased proliferation, migration, and the expression of neuron-, extracellular matrix (ECM)-, and angiogenesis-related genes. SHED-CM stimulated neuritogenesis of dorsal root ganglia and increased cell viability. Similarly, SHED-CM enhanced tube formation in an angiogenesis assay. In vivo, a 10-mm rat sciatic nerve gap model was bridged by silicon conduits containing SHED-CM or serum-free Dulbecco's modified Eagle's medium. Light and electron microscopy confirmed that the number of myelinated axons and axon-to-fiber ratio (G-ratio) were significantly higher in the SHED-CM group at 12 weeks after nerve transection surgery. The sciatic functional index (SFI) and gastrocnemius (target muscle) wet weight ratio demonstrated functional recovery. Increased compound muscle action potentials and increased SFI in the SHED-CM group suggested sciatic nerve reinnervation of the target muscle and improved functional recovery. We also observed reduced muscle atrophy in the SHED-CM group. Thus, SHEDs may secrete various trophic factors that enhance peripheral nerve regeneration through multiple mechanisms. SHED-CM may therefore provide a novel therapy that creates a more desirable extracellular microenvironment for peripheral nerve regeneration.

Peripheral nerve involvement in Bell's palsy

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J. A. Bueri

1984-12-01

Full Text Available A group of patients with Bell's palsy were studied in order to disclose the presence of subclinical peripheral nerve involvement. 20 patients, 8 male and 12 female, with recent Bell's palsy as their unique disease were examined, in all cases other causes of polyneuropathy were ruled out. Patients were investigated with CSF examination, facial nerve latencies in the affected and in the sound sides, and maximal motor nerve conduction velocities, as well as motor terminal latencies from the right median and peroneal nerves. CSF laboratory examination was normal in all cases. Facial nerve latencies were abnormal in all patients in the affected side, and they differed significantly from those of control group in the clinically sound side. Half of the patients showed abnormal values in the maximal motor nerve conduction velocities and motor terminal latencies of the right median and peroneal nerves. These results agree with previous reports which have pointed out that other cranial nerves may be affected in Bell's palsy. However, we have found a higher frequency of peripheral nerve involvement in this entity. These findings, support the hypothesis that in some patients Bell's palsy is the component of a more widespread disease, affecting other cranial and peripheral nerves.

Neurologic Evaluation and Management of Perioperative Nerve Injury.

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Watson, James C; Huntoon, Marc A

2015-01-01

Neurologic injury after regional anesthesia or pain medicine procedures is rare. Postprocedural neurologic deficits may create high levels of anxiety for the patient and practitioner, although most deficits are limited in severity and can be expected to fully resolve with time. Postoperative anesthesia-related neuraxial and peripheral nerve injuries are reviewed to define an efficient, structured approach to these complications. Emphasis is placed on acutely stratifying the urgency and scope of diagnostic testing or consultation necessity, initiating appropriate definitive treatments, and defining appropriate out-of-hospital follow-up and symptom management. Studies pertinent to the recognition, evaluation, and treatment of neurologic assessment of perioperative nerve injury and published since the last advisory on the topic are reviewed and a new structured algorithmic approach is proposed. The evolving literature on postoperative inflammatory neuropathies is reviewed to help define the clinical criteria and to identify patients who would benefit from early neurological evaluation. New sections review potential acute interventions to improve neurologic outcome and long-term management of neuropathic pain resulting from perioperative nerve injury.

Investigation on the mechanism of peripheral axonal injury in glaucoma

Directory of Open Access Journals (Sweden)

Jun- Hong Zhao

2013-05-01

Full Text Available AIM: To compare the angles of longitudinal section of sclera around optic nerve heads and the never fiber layer changes in healthy adults and patients with glaucoma, and to investigate the mechanism of peripheral retinal axonal injury, with the combined knowledge of biomechanics. METHODS: The optical nerves and their peripheral tissue specimen in the 12 eyes from health adult donators and 12 eyes from glaucoma patient donators were dyed by Glees' method to compare the angles of longitudinal section of sclera around optic nerve heads(through optic nerve center, and to observe the anatomical features of the peripheral retinal axons. RESULTS: The mean angle of longitudinal section of sclera around optic nerve in healthy adults was 73.3°, while that in patients with absolute glaucoma was 75.6°. The difference showed no significance(t=1.44, P>0.05. There was a sharp bend in the course of peripheral optical fiber in healthy adults. However, the optic nerve fiber disappeared completely in patients with glaucoma end stage. CONCLUSION: The angle between the medial edge and leading edge of sclera(around optic nerve headsis an acute angle. The optical fiber in glaucoma end stage disappeared completely. The phenomenon may be related to high intraocular pressure, the sclera shape, the shear modulus of sclera and axons, and “axonal bending-injury” mechanism.

Matching of motor-sensory modality in the rodent femoral nerve model shows no enhanced effect on peripheral nerve regeneration

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Kawamura, David H.; Johnson, Philip J.; Moore, Amy M.; Magill, Christina K.; Hunter, Daniel A.; Ray, Wilson Z.; Tung, Thomas HH.; Mackinnon, Susan E.

2010-01-01

The treatment of peripheral nerve injuries with nerve gaps largely consists of autologous nerve grafting utilizing sensory nerve donors. Underlying this clinical practice is the assumption that sensory autografts provide a suitable substrate for motoneuron regeneration, thereby facilitating motor endplate reinnervation and functional recovery. This study examined the role of nerve graft modality on axonal regeneration, comparing motor nerve regeneration through motor, sensory, and mixed nerve isografts in the Lewis rat. A total of 100 rats underwent grafting of the motor or sensory branch of the femoral nerve with histomorphometric analysis performed after 5, 6, or 7 weeks. Analysis demonstrated similar nerve regeneration in motor, sensory, and mixed nerve grafts at all three time points. These data indicate that matching of motor-sensory modality in the rat femoral nerve does not confer improved axonal regeneration through nerve isografts. PMID:20122927

Deficiency in monocarboxylate transporter 1 (MCT1) in mice delays regeneration of peripheral nerves following sciatic nerve crush

KAUST Repository

Morrison, Brett M.; Tsingalia, Akivaga; Vidensky, Svetlana; Lee, Youngjin; Jin, Lin; Farah, Mohamed H.; Lengacher, Sylvain; Magistretti, Pierre J.; Pellerin, Luc; Rothsteinb, Jeffrey D.

2015-01-01

Peripheral nerve regeneration following injury occurs spontaneously, but many of the processes require metabolic energy. The mechanism of energy supply to axons has not previously been determined. In the central nervous system, monocarboxylate transporter 1 (MCT1), expressed in oligodendroglia, is critical for supplying lactate or other energy metabolites to axons. In the current study, MCT1 is shown to localize within the peripheral nervous system to perineurial cells, dorsal root ganglion neurons, and Schwann cells by MCT1 immunofluorescence in wild-type mice and tdTomato fluorescence in MCT1 BAC reporter mice. To investigate whether MCT1 is necessary for peripheral nerve regeneration, sciatic nerves of MCT1 heterozygous mice are crushed and peripheral nerve regeneration was quantified electrophysiologically and anatomically. Compound muscle action potential (CMAP) recovery is delayed from a median of 21. days in wild-type mice to greater than 38. days in MCT1 heterozygote mice. In fact, half of the MCT1 heterozygote mice have no recovery of CMAP at 42. days, while all of the wild-type mice recovered. In addition, muscle fibers remain 40% more atrophic and neuromuscular junctions 40% more denervated at 42. days post-crush in the MCT1 heterozygote mice than wild-type mice. The delay in nerve regeneration is not only in motor axons, as the number of regenerated axons in the sural sensory nerve of MCT1 heterozygote mice at 4. weeks and tibial mixed sensory and motor nerve at 3. weeks is also significantly reduced compared to wild-type mice. This delay in regeneration may be partly due to failed Schwann cell function, as there is reduced early phagocytosis of myelin debris and remyelination of axon segments. These data for the first time demonstrate that MCT1 is critical for regeneration of both sensory and motor axons in mice following sciatic nerve crush.

Combination of Tramadol with Minocycline Exerted Synergistic Effects on a Rat Model of Nerve Injury-Induced Neuropathic Pain

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Xiao-Peng Mei

2012-09-01

Full Text Available Neuropathic pain is a refractory clinical problem. Certain drugs, such as tramadol, proved useful for the treatment of neuropathic pain by inhibiting the activity of nociceptive neurons. Moreover, studies indicated that suppression or modulation of glial activation could prevent or reverse neuropathic pain, for example with the microglia inhibitor minocycline. However, few present clinical therapeutics focused on both neuronal and glial participation when treating neuropathic pain. Therefore, the present study hypothesized that combination of tramadol with minocycline as neuronal and glial activation inhibitor may exert some synergistic effects on spinal nerve ligation (SNL-induced neuropathic pain. Intrathecal tramadol or minocycline relieved SNL-induced mechanical allodynia in a dose-dependent manner. SNL-induced spinal dorsal horn Fos or OX42 expression was downregulated by intrathecal tramadol or minocycline. Combination of tramadol with minocycline exerted powerful and synergistic effects on SNL-induced neuropathic pain also in a dose-dependent manner. Moreover, the drug combination enhanced the suppression effects on SNL-induced spinal dorsal horn Fos and OX42 expression, compared to either drug administered alone. These results indicated that combination of tramadol with minocycline could exert synergistic effects on peripheral nerve injury-induced neuropathic pain; thus, a new strategy for treating neuropathic pain by breaking the interaction between neurons and glia bilaterally was also proposed.

Complex stimulation of peripheral nerve regeneration after deferred neurorrhaphy

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Ivanov A.N.

2017-09-01

Full Text Available The aim is to study the complex stimulation effect including skin autotransplantation and electrical stimulation of the sciatic nerve on microcircular, electrophysiological and morphological changes after deferred neurorrhaphy in rats. Material and methods. The experiment was performed in 50 albino rats divided into control, comparative and experimental groups. In the experimental group, on the background of deferred neurorrhaphy, skin autotransplantation and electrical stimulation of the sciatic nerve had been carried out. In the comparative group only deferred neurorrhaphy was performed. Research methods included laser doppler flowmetry, electroneuromyography and morphological analysis of the operated nerve. Results. Complex stimulation including skin autotransplantation and direct action of electrical pulses on the sciatic nerve after its deferred neurorrhaphy causes restoration of bloodstream in the operated limb, promotes intensification of restoration of nerve fibers. Conclusion. Intensification of sciatic nerve regeneration after deferred neurorrhaphy in rats under the influence of complex stimulation including full-thickness skin graft autotransplantation and direct action of electrical pulses substantiates experimentally appropriateness of clinical testing of the given method for treatment of patients with peripheral nerve injuries.

Hydrogel derived from porcine decellularized nerve tissue as a promising biomaterial for repairing peripheral nerve defects.

Science.gov (United States)

Lin, Tao; Liu, Sheng; Chen, Shihao; Qiu, Shuai; Rao, Zilong; Liu, Jianghui; Zhu, Shuang; Yan, Liwei; Mao, Haiquan; Zhu, Qingtang; Quan, Daping; Liu, Xiaolin

2018-06-01

Decellularized matrix hydrogels derived from tissues or organs have been used for tissue repair due to their biocompatibility, tunability, and tissue-specific extracellular matrix (ECM) components. However, the preparation of decellularized peripheral nerve matrix hydrogels and their use to repair nerve defects have not been reported. Here, we developed a hydrogel from porcine decellularized nerve matrix (pDNM-G), which was confirmed to have minimal DNA content and retain collagen and glycosaminoglycans content, thereby allowing gelatinization. The pDNM-G exhibited a nanofibrous structure similar to that of natural ECM, and a ∼280-Pa storage modulus at 10 mg/mL similar to that of native neural tissues. Western blot and liquid chromatography tandem mass spectrometry analysis revealed that the pDNM-G consisted mostly of ECM proteins and contained primary ECM-related proteins, including fibronectin and collagen I and IV). In vitro experiments showed that pDNM-G supported Schwann cell proliferation and preserved cell morphology. Additionally, in a 15-mm rat sciatic nerve defect model, pDNM-G was combined with electrospun poly(lactic-acid)-co-poly(trimethylene-carbonate)conduits to bridge the defect, which did not elicit an adverse immune response and promoted the activation of M2 macrophages associated with a constructive remodeling response. Morphological analyses and electrophysiological and functional examinations revealed that the regenerative outcomes achieved by pDNM-G were superior to those by empty conduits and closed to those using rat decellularized nerve matrix allograft scaffolds. These findings indicated that pDNM-G, with its preserved ECM composition and nanofibrous structure, represents a promising biomaterial for peripheral nerve regeneration. Decellularized nerve allografts have been widely used to treat peripheral nerve injury. However, given their limited availability and lack of bioactive factors, efforts have been made to improve the efficacy

Best time window for the use of calcium-modulating agents to improve functional recovery in injured peripheral nerves-An experiment in rats.

Science.gov (United States)

Yan, Yuhui; Shen, Feng-Yi; Agresti, Michael; Zhang, Lin-Ling; Matloub, Hani S; LoGiudice, John A; Havlik, Robert; Li, Jifeng; Gu, Yu-Dong; Yan, Ji-Geng

2017-09-01

Peripheral nerve injury can have a devastating effect on daily life. Calcium concentrations in nerve fibers drastically increase after nerve injury, and this activates downstream processes leading to neuron death. Our previous studies showed that calcium-modulating agents decrease calcium accumulation, which aids in regeneration of injured peripheral nerves; however, the optimal therapeutic window for this application has not yet been identified. In this study, we show that calcium clearance after nerve injury is positively correlated with functional recovery in rats suffering from a crushed sciatic nerve injury. After the nerve injury, calcium accumulation increased. Peak volume is from 2 to 8 weeks post injury; calcium accumulation then gradually decreased over the following 24-week period. The compound muscle action potential (CMAP) measurement from the extensor digitorum longus muscle recovered to nearly normal levels in 24 weeks. Simultaneously, real-time polymerase chain reaction results showed that upregulation of calcium-ATPase (a membrane protein that transports calcium out of nerve fibers) mRNA peaked at 12 weeks. These results suggest that without intervention, the peak in calcium-ATPase mRNA expression in the injured nerve occurs after the peak in calcium accumulation, and CMAP recovery continues beyond 24 weeks. Immediately using calcium-modulating agents after crushed nerve injury improved functional recovery. These studies suggest that a crucial time frame in which to initiate effective clinical approaches to accelerate calcium clearance and nerve regeneration would be prior to 2 weeks post injury. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Increase of transcription factor EB (TFEB) and lysosomes in rat DRG neurons and their transportation to the central nerve terminal in dorsal horn after nerve injury.

Science.gov (United States)

Jung, J; Uesugi, N; Jeong, N Y; Park, B S; Konishi, H; Kiyama, H

2016-01-28

In the spinal dorsal horn (DH), nerve injury activates microglia and induces neuropathic pain. Several studies clarified an involvement of adenosine triphosphate (ATP) in the microglial activation. However, the origin of ATP together with the release mechanism is unclear. Recent in vitro study revealed that an ATP marker, quinacrine, in lysosomes was released from neurite terminal of dorsal root ganglion (DRG) neurons to extracellular space via lysosomal exocytosis. Here, we demonstrate a possibility that the lysosomal ingredient including ATP released from DRG neurons by lysosomal-exocytosis is an additional source of the glial activation in DH after nerve injury. After rat L5 spinal nerve ligation (SNL), mRNA for transcription factor EB (TFEB), a transcription factor controlling lysosomal activation and exocytosis, was induced in the DRG. Simultaneously both lysosomal protein, LAMP1- and vesicular nuclear transporter (VNUT)-positive vesicles were increased in L5 DRG neurons and ipsilateral DH. The quinacrine staining in DH was increased and co-localized with LAMP1 immunoreactivity after nerve injury. In DH, LAMP1-positive vesicles were also co-localized with a peripheral nerve marker, Isolectin B4 (IB4) lectin. Injection of the adenovirus encoding mCherry-LAMP1 into DRG showed that mCherry-positive lysosomes are transported to the central nerve terminal in DH. These findings suggest that activation of lysosome synthesis including ATP packaging in DRG, the central transportation of the lysosome, and subsequent its exocytosis from the central nerve terminal of DRG neurons in response to nerve injury could be a partial mechanism for activation of microglia in DH. This lysosome-mediated microglia activation mechanism may provide another clue to control nociception and pain. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Side Effects: Nerve Problems (Peripheral Neuropathy)

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Nerve problems, such as peripheral neuropathy, can be caused by cancer treatment. Learn about signs and symptoms of nerve changes. Find out how to prevent or manage nerve problems during cancer treatment.

The Proximal Medial Sural Nerve Biopsy Model: A Standardised and Reproducible Baseline Clinical Model for the Translational Evaluation of Bioengineered Nerve Guides

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Ahmet Bozkurt

2014-01-01

Full Text Available Autologous nerve transplantation (ANT is the clinical gold standard for the reconstruction of peripheral nerve defects. A large number of bioengineered nerve guides have been tested under laboratory conditions as an alternative to the ANT. The step from experimental studies to the implementation of the device in the clinical setting is often substantial and the outcome is unpredictable. This is mainly linked to the heterogeneity of clinical peripheral nerve injuries, which is very different from standardized animal studies. In search of a reproducible human model for the implantation of bioengineered nerve guides, we propose the reconstruction of sural nerve defects after routine nerve biopsy as a first or baseline study. Our concept uses the medial sural nerve of patients undergoing diagnostic nerve biopsy (≥2 cm. The biopsy-induced nerve gap was immediately reconstructed by implantation of the novel microstructured nerve guide, Neuromaix, as part of an ongoing first-in-human study. Here we present (i a detailed list of inclusion and exclusion criteria, (ii a detailed description of the surgical procedure, and (iii a follow-up concept with multimodal sensory evaluation techniques. The proximal medial sural nerve biopsy model can serve as a preliminarynature of the injuries or baseline nerve lesion model. In a subsequent step, newly developed nerve guides could be tested in more unpredictable and challenging clinical peripheral nerve lesions (e.g., following trauma which have reduced comparability due to the different nature of the injuries (e.g., site of injury and length of nerve gap.

Early regenerative effects of NGF-transduced Schwann cells in peripheral nerve repair

NARCIS (Netherlands)

Shakhbazau, A.; Kawasoe, J.; Hoyng, S.A.; Kumar, R.; van Minnen, J.; Verhaagen, J.; Midha, R.

2012-01-01

Peripheral nerve injury leads to a rapid and robust increase in the synthesis of neurotrophins which guide and support regenerating axons. To further optimize neurotrophin supply at the earliest stages of regeneration, we over-expressed NGF in Schwann cells (SCs) by transducing these cells with a

Case report of a patient with peripheral facial nerve palsy

OpenAIRE

Rysová, Jana

2013-01-01

Title of bachelor's thesis: Case report of a patient with peripheral facial nerve palsy Summary: Teoretical part of bachelor's thesis contains theoretical foundation of peripheral facial nerve palsy. Practical part of bachelor's thesis contains physiotherapeutic case report of patient with peripheral facial nerve palsy. Key words: peripheral facial nerve palsy, casuistry, rehabilitation

Regeneration of long-distance peripheral nerve defects after delayed reconstruction in healthy and diabetic rats is supported by immunomodulatory chitosan nerve guides.

Science.gov (United States)

Stenberg, Lena; Stößel, Maria; Ronchi, Giulia; Geuna, Stefano; Yin, Yaobin; Mommert, Susanne; Mårtensson, Lisa; Metzen, Jennifer; Grothe, Claudia; Dahlin, Lars B; Haastert-Talini, Kirsten

2017-07-18

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. 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. No considerable differences appear for the delayed nerve regeneration

Neuronal calcium-binding proteins 1/2 localize to dorsal root ganglia and excitatory spinal neurons and are regulated by nerve injury

DEFF Research Database (Denmark)

Zhang, Ming Dong; Tortoriello, Giuseppe; Hsueh, Brian

2014-01-01

, and nerve injury-induced regulation of NECAB1/NECAB2 in mouse dorsal root ganglia (DRGs) and spinal cord. In DRGs, NECAB1/2 are expressed in around 70% of mainly small- and medium-sized neurons. Many colocalize with calcitonin gene-related peptide and isolectin B4, and thus represent nociceptors. NECAB1....../2 neurons are much more abundant in DRGs than the Ca2+-binding proteins (parvalbumin, calbindin, calretinin, and secretagogin) studied to date. In the spinal cord, the NECAB1/2 distribution is mainly complementary. NECAB1 labels interneurons and a plexus of processes in superficial layers of the dorsal horn....... In the dorsal horn, most NECAB1/2 neurons are glutamatergic. Both NECAB1/2 are transported into dorsal roots and peripheral nerves. Peripheral nerve injury reduces NECAB2, but not NECAB1, expression in DRG neurons. Our study identifies NECAB1/2 as abundant Ca2+-binding proteins in pain-related DRG neurons...

Drug-induced peripheral neuropathy

DEFF Research Database (Denmark)

Vilholm, Ole Jakob; Christensen, Alex Alban; Zedan, Ahmed

2014-01-01

Peripheral neuropathy can be caused by medication, and various descriptions have been applied for this condition. In this MiniReview, the term 'drug-induced peripheral neuropathy' (DIPN) is used with the suggested definition: Damage to nerves of the peripheral nervous system caused by a chemical...... substance used in the treatment, cure, prevention or diagnosis of a disease. Optic neuropathy is included in this definition. A distinction between DIPN and other aetiologies of peripheral neuropathy is often quite difficult and thus, the aim of this MiniReview is to discuss the major agents associated...

Peripheral nerve regeneration through P(DLLA-epsilon-CL) nerve guides

NARCIS (Netherlands)

Den Dunnen, WFA; Meek, MF; Robinson, PH; Schakernraad, JM

1998-01-01

P(DLLA-epsilon-CL) nerve guides can be used perfectly for short nerve gaps in rats, and are even better than short autologous nerve grafts. The tube dimensions, such as the internal diameter and wall thickness, are very important for the final outcome of peripheral nerve regeneration, as well as the

The Effects of Electrocautery on Peripheral Nerve: An Experimental Study.

Science.gov (United States)

Karalezli, Nazim; Koktekir, Ender; Yildirim, Serhat; Toy, Hatice; Oz, Mehmet; Yuceturk, Aydin

2016-05-01

BACKGROUND The aim of this study was to assess the usability of an electrocautery device as nerve stimulator and to investigate histopathologically the adverse effects of electrocautery at low power on rat sciatic nerves. METHODS A total of 36 female Sprague-Dawley albino rats were divided into six groups according to the power applied to their sciatic nerves (1, 2, 3, 4, 5 and 6 W, respectively). Pathologic changes were studied by microscopic examination and scored (no change = 0, mild = 1, moderate = 2, severe = 3). Multiple comparisons were provided for all groups by the Bonferroni test (one-way analysis of variance). A p value  0.05) Variable motor responses and foot deformities were observed at the different power levels. CONCLUSION Although electrocautery devices provoke motor responses if getting in contact with peripheral nerves as do nerve stimulators, their use induces histopathologically adverse effects even at the lowest power. Their use around peripheral nerves should be avoided. Georg Thieme Verlag KG Stuttgart · New York.

Karolinska institutet 200-year anniversary. Symposium on traumatic injuries in the nervous system: injuries to the spinal cord and peripheral nervous system - injuries and repair, pain problems, lesions to brachial plexus.

Science.gov (United States)

Sköld, Mattias K; Svensson, Mikael; Tsao, Jack; Hultgren, Thomas; Landegren, Thomas; Carlstedt, Thomas; Cullheim, Staffan

2011-01-01

The Karolinska Institutet 200-year anniversary symposium on injuries to the spinal cord and peripheral nervous system gathered expertise in the spinal cord, spinal nerve, and peripheral nerve injury field spanning from molecular prerequisites for nerve regeneration to clinical methods in nerve repair and rehabilitation. The topics presented at the meeting covered findings on adult neural stem cells that when transplanted to the hypoglossal nucleus in the rat could integrate with its host and promote neuron survival. Studies on vascularization after intraspinal replantation of ventral nerve roots and microarray studies in ventral root replantation as a tool for mapping of biological patterns typical for neuronal regeneration were discussed. Different immune molecules in neurons and glia and their very specific roles in synapse plasticity after injury were presented. Novel strategies in repair of injured peripheral nerves with ethyl-cyanoacrylate adhesive showed functional recovery comparable to that of conventional epineural sutures. Various aspects on surgical techniques which are available to improve function of the limb, once the nerve regeneration after brachial plexus lesions and repair has reached its limit were presented. Moreover, neurogenic pain after amputation and its treatment with mirror therapy were shown to be followed by dramatic decrease in phantom limb pain. Finally clinical experiences on surgical techniques to repair avulsed spinal nerve root and the motoric as well as sensoric regain of function were presented.

Heparin-Poloxamer Thermosensitive Hydrogel Loaded with bFGF and NGF Enhances Peripheral Nerve Regeneration in Diabetic Rats.

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Li, Rui; Li, Yiyang; Wu, Yanqing; Zhao, Yingzheng; Chen, Huanwen; Yuan, Yuan; Xu, Ke; Zhang, Hongyu; Lu, Yingfeng; Wang, Jian; Li, Xiaokun; Jia, Xiaofeng; Xiao, Jian

2018-06-01

Peripheral nerve injury (PNI) is a major burden to society with limited therapeutic options, and novel biomaterials have great potential for shifting the current paradigm of treatment. With a rising prevalence of chronic illnesses such as diabetes mellitus (DM), treatment of PNI is further complicated, and only few studies have proposed therapies suitable for peripheral nerve regeneration in DM. To provide a supportive environment to restore structure and/or function of nerves in DM, we developed a novel thermo-sensitive heparin-poloxamer (HP) hydrogel co-delivered with basic fibroblast growth factor (bFGF) and nerve growth factor (NGF) in diabetic rats with sciatic nerve crush injury. The delivery vehicle not only had a good affinity for large amounts of growth factors (GFs), but also controlled their release in a steady fashion, preventing degradation in vitro. In vivo, compared with HP hydrogel alone or direct GFs administration, GFs-HP hydrogel treatment is more effective at facilitating Schwann cell (SC) proliferation, leading to an increased expression of nerve associated structural proteins, enhanced axonal regeneration and remyelination, and improved recovery of motor function (all p nerve regeneration in patients with DM. Copyright © 2018 Elsevier Ltd. All rights reserved.

Experimental strategies to promote functional recovery after peripheral nerve injuries.

Science.gov (United States)

Gordon, Tessa; Sulaiman, Olawale; Boyd, J Gordon

2003-12-01

The capacity of Schwann cells (SCs) in the peripheral nervous system to support axonal regeneration, in contrast to the oligodendrocytes in the central nervous system, has led to the misconception that peripheral nerve regeneration always restores function. Here, we consider how prolonged periods of time that injured neurons remain without targets during axonal regeneration (chronic axotomy) and that SCs in the distal nerve stumps remain chronically denervated (chronic denervation) progressively reduce the number of motoneurons that regenerate their axons. We demonstrate the effectiveness of low-dose, brain-derived neurotrophic and glial-derived neurotrophic factors to counteract the effects of chronic axotomy in promoting axonal regeneration. High-dose brain-derived neurotrophic factor (BDNF) on the other hand, acting through the p75 receptor, inhibits axonal regeneration and may be a factor in stopping regenerating axons from forming neuromuscular connections in skeletal muscle. The immunophilin, FK506, is also effective in promoting axonal regeneration after chronic axotomy. Chronic denervation of SCs (>1 month) severely deters axonal regeneration, although the few motor axons that do regenerate to reinnervate muscles become myelinated and form enlarged motor units in the reinnervated muscles. We found that in vitro incubation of chronically denervated SCs with transforming growth factor-beta re-established their growth-supportive phenotype in vivo, consistent with the idea that the interaction between invading macrophages and denervated SCs during Wallerian degeneration is essential to sustain axonal regeneration by promoting the growth-supportive SC phenotype. Finally, we consider the effectiveness of a brief period of 20 Hz electrical stimulation in promoting the regeneration of axons across the surgical gap after nerve repair.

Karolinska Institutet 200-Year Anniversary. Symposium on Traumatic Injuries in the Nervous System: Injuries to the Spinal Cord and Peripheral Nervous System – Injuries and Repair, Pain Problems, Lesions to Brachial Plexus

Science.gov (United States)

Sköld, Mattias K.; Svensson, Mikael; Tsao, Jack; Hultgren, Thomas; Landegren, Thomas; Carlstedt, Thomas; Cullheim, Staffan

2011-01-01

The Karolinska Institutet 200-year anniversary symposium on injuries to the spinal cord and peripheral nervous system gathered expertise in the spinal cord, spinal nerve, and peripheral nerve injury field spanning from molecular prerequisites for nerve regeneration to clinical methods in nerve repair and rehabilitation. The topics presented at the meeting covered findings on adult neural stem cells that when transplanted to the hypoglossal nucleus in the rat could integrate with its host and promote neuron survival. Studies on vascularization after intraspinal replantation of ventral nerve roots and microarray studies in ventral root replantation as a tool for mapping of biological patterns typical for neuronal regeneration were discussed. Different immune molecules in neurons and glia and their very specific roles in synapse plasticity after injury were presented. Novel strategies in repair of injured peripheral nerves with ethyl-cyanoacrylate adhesive showed functional recovery comparable to that of conventional epineural sutures. Various aspects on surgical techniques which are available to improve function of the limb, once the nerve regeneration after brachial plexus lesions and repair has reached its limit were presented. Moreover, neurogenic pain after amputation and its treatment with mirror therapy were shown to be followed by dramatic decrease in phantom limb pain. Finally clinical experiences on surgical techniques to repair avulsed spinal nerve root and the motoric as well as sensoric regain of function were presented. PMID:21629875

Changes in the structural properties of peripheral nerves after transection.

Science.gov (United States)

Toby, E B; Meyer, B M; Schwappach, J; Alvine, G

1996-11-01

Changes in peripheral nerve structural properties after transection were measured weekly for 5 weeks in the distal stump of the sciatic nerve in 50 Sprague-Dawley rats. Each week after transection, the distal stump of the transected nerve showed increased stiffness when compared to intact nerves. Linear elastic stiffness reached a maximum at weeks 1 and 2 after transection, when the transected nerves were 15% stiffer than the contralateral control sides. Toughness was also increased and reached a maximum at week 4 with a 50% difference between values for experimental and control sides. Overall failure load was between 21% and 27% greater, peaking at week 3. An increase in stiffness of the distal stump would result in increased tension at the suture line, as the nerve gap is overcome when performing a delayed neurorraphy. These data suggest, with respect to structural properties, that an end-to-end repair should be carried out at the time of injury; after only 1 week, significant stiffness in the distal segment of the nerve developed, which should result in an increase in tension at the repair site.

Development of regenerative peripheral nerve interfaces for motor control of neuroprosthetic devices

Science.gov (United States)

Kemp, Stephen W. P.; Urbanchek, Melanie G.; Irwin, Zachary T.; Chestek, Cynthia A.; Cederna, Paul S.

2017-05-01

Traumatic peripheral nerve injuries suffered during amputation commonly results in debilitating neuropathic pain in the affected limb. Modern prosthetic technologies allow for intuitive, simultaneous control of multiple degrees of freedom. However, these state-of-the-art devices require separate, independent control signals for each degree of freedom, which is currently not possible. As a result, amputees reject up to 75% of myoelectric devices preferring instead to use body-powered artificial limbs which offer subtle sensory feedback. Without meaningful and intuitive sensory feedback, even the most advanced myoelectric prostheses remain insensate, burdensome, and are associated with enormous cognitive demand and mental fatigue. The ideal prosthetic device is one which is capable of providing intuitive somatosensory feedback essential for interaction with the environment. Critical to the design of such a bioprosthetic device is the development of a reliable biologic interface between human and machine. This ideal patient-prosthetic interface allows for transmission of both afferent somatosensory information and efferent motor signals for a closed-loop feedback system of neural control. Our lab has developed the Regenerative Peripheral Nerve Interface (RPNI) as a biologic nerve interface designed for stable integration of a prosthetic device with transected peripheral nerves in a residual limb. The RPNI is constructed by surgically implanting the distal end of a transected peripheral nerve into an autogenous muscle graft. Animal experiments in our lab have shown recording of motor signals from RPNI's implanted into both rodents and monkeys. Here, we achieve high amplitude EMG signals with a high signal to noise (SNR) ratio.

Cranial nerve threshold for thermal injury induced by MRI-guided high-intensity focused ultrasound (MRgHIFU): preliminary results on an optic nerve model.

Science.gov (United States)

Harnof, Sagi; Zibly, Zion; Cohen, Zvi; Shaw, Andrew; Schlaff, Cody; Kassel, Neal F

2013-04-01

Future clinical applications of magnetic resonance imaging-guided high-intensity focused ultrasound (MRgHIFU) are moving toward the management of different intracranial pathologies. We sought to validate the production, safety, and efficacy of thermal injury to cranial nerves generated by MRgHIFU. In this study, five female domestic pigs underwent a standard bifrontal craniectomy under general anesthesia. Treatment was then given using an MRgHIFU system to induce hyperthermic ablative sonication (6 to 10 s; 50 to 2000 J.) Histological analyses were done to confirm nerve damage; temperature measured on the optic nerve was approximately 53.4°C (range: 39°C to 70°C.) Histology demonstrated a clear definition between a necrotic, transitional zone, and normal tissue. MRgHIFU induces targeted thermal injury to nervous tissue within a specific threshold of 50°C to 60°C with the tissue near the sonication center yielding the greatest effect; adjacent tissue showed minimal changes. Additional studies utilizing this technology are required to further establish accurate threshold parameters for optic nerve thermo-ablation.

21 CFR 882.5870 - Implanted peripheral nerve stimulator for pain relief.

Science.gov (United States)

2010-04-01

....5870 Implanted peripheral nerve stimulator for pain relief. (a) Identification. An implanted peripheral nerve stimulator for pain relief is a device that is used to stimulate electrically a peripheral nerve... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Implanted peripheral nerve stimulator for pain...

Trends in the design of nerve guidance channels in peripheral nerve tissue engineering.

Science.gov (United States)

Chiono, Valeria; Tonda-Turo, Chiara

2015-08-01

The current trend of peripheral nerve tissue engineering is the design of advanced nerve guidance channels (NGCs) acting as physical guidance for regeneration of nerves across lesions. NGCs should present multifunctional properties aiming to direct the sprouting of axons from the proximal nerve end, to concentrate growth factors secreted by the injured nerve ends, and to reduce the ingrowth of scar tissue into the injury site. A critical aspect in the design of NGCs is conferring them the ability to provide topographic, chemotactic and haptotactic cues that lead to functional nerve regeneration thus increasing the axon growth rate and avoiding or minimizing end-organ (e.g. muscle) atrophy. The present work reviews the recent state of the art in NGCs engineering and defines the external guide and internal fillers structural and compositional requirements that should be satisfied to improve nerve regeneration, especially in the case of large gaps (>2 cm). Techniques for NGCs fabrication were described highlighting the innovative approaches direct to enhance the regeneration of axon stumps compared to current clinical treatments. Furthermore, the possibility to apply stem cells as internal cues to the NGCs was discussed focusing on scaffold properties necessary to ensure cell survival. Finally, the optimized features for NGCs design were summarized showing as multifunctional cues are needed to produce NGCs having improved results in clinics. Copyright © 2015 Elsevier Ltd. All rights reserved.

Ulnar nerve injury associated with trampoline injuries.

Science.gov (United States)

Maclin, Melvin M; Novak, Christine B; Mackinnon, Susan E

2004-08-01

This study reports three cases of ulnar neuropathy after trampoline injuries in children. A chart review was performed on children who sustained an ulnar nerve injury from a trampoline accident. In all cases, surgical intervention was required. Injuries included upper-extremity fractures in two cases and an upper-extremity laceration in one case. All cases required surgical exploration with internal neurolysis and ulnar nerve transposition. Nerve grafts were used in two cases and an additional nerve transfer was used in one case. All patients had return of intrinsic hand function and sensation after surgery. Children should be followed for evolution of ulnar nerve neuropathy after upper-extremity injury with consideration for electrical studies and surgical exploration if there is no improvement after 3 months.

Arachidonic acid containing phosphatidylcholine increases due to microglial activation in ipsilateral spinal dorsal horn following spared sciatic nerve injury.

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Tomohiro Banno

Full Text Available Peripheral nerve injury induces substantial molecular changes in the somatosensory system that leads to maladaptive plasticity and cause neuropathic pain. Understanding the molecular pathways responsible for the development of neuropathic pain is essential to the development of novel rationally designed therapeutics. Although lipids make up to half of the dry weight of the spinal cord, their relation with the development of neuropathic pain is poorly understood. We aimed to elucidate the regulation of spinal lipids in response to neuropathic peripheral nerve injury in mice by utilizing matrix-assisted laser desorption/ionization imaging mass spectrometry, which allows visualization of lipid distribution within the cord. We found that arachidonic acid (AA containing [PC(diacyl-16:0/20:4+K]+ was increased temporarily at superficial ipsilateral dorsal horn seven days after spared nerve injury (SNI. The spatiotemporal changes in lipid concentration resembled microglia activation as defined by ionized calcium binding adaptor molecule 1 (Iba1 immunohistochemistry. Suppression of microglial function through minocycline administration resulted in attenuation of hypersensitivity and reduces [PC(diacyl-16:0/20:4+K]+ elevation in the spinal dorsal horn. These data suggested that AA containing [PC(diacyl-16:0/20:4+K]+ is related to hypersensitivity evoked by SNI and implicate microglial cell activation in this lipid production.

Peripheral facial nerve dysfunction: CT evaluation

Energy Technology Data Exchange (ETDEWEB)

Disbro, M.A.; Harnsberger, H.R.; Osborn, A.G.

1985-06-01

Peripheral facial nerve dysfunction may have a clinically apparent or occult cause. The authors reviewed the clinical and radiographic records of 36 patients with peripheral facial nerve dysfunction to obtain information on the location of the suspected lesion and the number, sequence, and type of radiographic evaluations performed. Inadequate clinical evaluations before computed tomography (CT) was done and unnecessary CT examinations were also noted. They have suggested a practical clinical and radiographic scheme to evaluate progressive peripheral facial dysfunction with no apparent cause. If this scheme is applied, unnecessary radiologic tests and delays in diagnosis and treatment may be avoided.

The emergence of adolescent onset pain hypersensitivity following neonatal nerve injury

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Vega-Avelaira David

2012-04-01

Full Text Available Abstract Background Peripheral nerve injuries can trigger neuropathic pain in adults but cause little or no pain when they are sustained in infancy or early childhood. This is confirmed in rodent models where neonatal nerve injury causes no pain behaviour. However, delayed pain can arise in man some considerable time after nerve damage and to examine this following early life nerve injury we have carried out a longer term follow up of rat pain behaviour into adolescence and adulthood. Results Spared nerve injury (SNI or sham surgery was performed on 10 day old (P10 rat pups and mechanical nociceptive reflex thresholds were analysed 3, 7, 14, 21, 28, 38 and 44 days post surgery. While mechanical thresholds on the ipsilateral side are not significantly different from controls for the first 2–3 weeks post P10 surgery, after that time period, beginning at 21 days post surgery (P31, the SNI group developed following early life nerve injury significant hypersensitivity compared to the other groups. Ipsilateral mechanical nociceptive threshold was 2-fold below that of the contralateral and sham thresholds at 21 days post surgery (SNI-ipsilateral 28 (±5 g control groups 69 (±9 g, p Conclusions We report a novel consequence of early life nerve injury whereby mechanical hypersensitivity only emerges later in life. This delayed adolescent onset in mechanical pain thresholds is accompanied by neuroimmune activation and NMDA dependent central sensitization of spinal nociceptive circuits. This delayed onset in mechanical pain sensitivity may provide clues to understand the long term effects of early injury such as late onset phantom pain and the emergence of complex adolescent chronic pain syndromes.

Effect of Exosomes from Rat Adipose-Derived Mesenchymal Stem Cells on Neurite Outgrowth and Sciatic Nerve Regeneration After Crush Injury.

Science.gov (United States)

Bucan, Vesna; Vaslaitis, Desiree; Peck, Claas-Tido; Strauß, Sarah; Vogt, Peter M; Radtke, Christine

2018-06-21

Peripheral nerve injury requires optimal conditions in both macro-environment and microenvironment for promotion of axonal regeneration. However, most repair strategies of traumatic peripheral nerve injury often lead to dissatisfying results in clinical outcome. Though various strategies have been carried out to improve the macro-environment, the underlying molecular mechanism of axon regeneration in the microenvironment provided by nerve conduit remains unclear. In this study, we evaluate the effects of from adipose-derived mesenchymal stem cells (adMSCs) originating exosomes with respect to sciatic nerve regeneration and neurite growth. Molecular and immunohistochemical techniques were used to investigate the presence of characteristic exosome markers. A co-culture system was established to determine the effect of exosomes on neurite elongation in vitro. The in vivo walking behaviour of rats was evaluated by footprint analysis, and the nerve regeneration was assessed by immunocytochemistry. adMSCs secrete nano-vesicles known as exosomes, which increase neurite outgrowth in vitro and enhance regeneration after sciatic nerve injury in vivo. Furthermore, we showed the presence of neural growth factors transcripts in adMSC exosomes for the first time. Our results demonstrate that exosomes, constitutively produced by adMSCs, are involved in peripheral nerve regeneration and have the potential to be utilised as a therapeutic tool for effective tissue-engineered nerves.

A novel experimental rat model of peripheral nerve scarring that reliably mimics post-surgical complications and recurring adhesions

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Angela Lemke

2017-08-01

Full Text Available Inflammation, fibrosis and perineural adhesions with the surrounding tissue are common pathological processes following nerve injury and surgical interventions on peripheral nerves in human patients. These features can reoccur following external neurolysis, currently the most common surgical treatment for peripheral nerve scarring, thus leading to renewed nerve function impairment and chronic pain. To enable a successful evaluation of new therapeutic approaches, it is crucial to use a reproducible animal model that mimics the main clinical symptoms occurring in human patients. However, a clinically relevant model combining both histological and functional alterations has not been published to date. We therefore developed a reliable rat model that exhibits the essential pathological processes of peripheral nerve scarring. In our study, we present a novel method for the induction of nerve scarring by applying glutaraldehyde-containing glue that is known to cause nerve injury in humans. After a 3-week contact period with the sciatic nerve in female Sprague Dawley rats, we could demonstrate severe intra- and perineural scarring that resulted in grade 3 adhesions and major impairments in the electrophysiological peak amplitude compared with sham control (P=0.0478. Immunohistochemical analysis of the nerve structure revealed vigorous nerve inflammation and recruitment of T cells and macrophages. Also, distinct nerve degeneration was determined by immunostaining. These pathological alterations were further reflected in significant functional deficiencies, as determined by the analysis of relevant gait parameters as well as the quantification of the sciatic functional index starting at week 1 post-operation (P<0.01. Moreover, with this model we could, for the first time, demonstrate not only the primary formation, but also the recurrence, of severe adhesions 1 week after glue removal, imitating a major clinical challenge. As a comparison, we tested a

Enhanced synthesis and secretion of apolipoprotein E from sciatic nerves of streptozotocin-induced diabetic rats after injury

International Nuclear Information System (INIS)

Ishibashi, S.; Yamada, N.; Oka, Y.

1988-01-01

To elucidate the pathogenesis of diabetic neuropathy, synthesis and secretion of apolipoprotein E (apo E) from sciatic nerves after injury was studied in normal and streptozotocin-induced diabetic rats. Seven, 14, 28, 45 and 59 days after making crush injury on sciatic nerves with concomitant administration of streptozotocin (50 mg/kg body weight), the nerves were taken out and incubated with [ 35 S]methionine. The [ 35 S]labeled apo E was precipitated with specific antiserum. The amounts of apo E secreted into medium by nerves of diabetic rats were 7 times greater than those of non-diabetic rats 7 days after injury. This enhanced secretion of apo E was relatively selective for this protein, since the ratio of the immunoprecipitable apo E to the TCA preciptitable protein in the medium increased in diabetic rats. Intriguing possibility deduced from these results is that the secretion of apo E is involved in the development of diabetic neuropathy

Upregulation of EMMPRIN (OX47 in Rat Dorsal Root Ganglion Contributes to the Development of Mechanical Allodynia after Nerve Injury

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Qun Wang

2015-01-01

Full Text Available Matrix metalloproteinases (MMPs are widely implicated in inflammation and tissue remodeling associated with various neurodegenerative diseases and play an important role in nociception and allodynia. Extracellular Matrix Metalloproteinase Inducer (EMMPRIN plays a key regulatory role for MMP activities. However, the role of EMMPRIN in the development of neuropathic pain is not clear. Western blotting, real-time quantitative RT-PCR (qRT-PCR, and immunofluorescence were performed to determine the changes of messenger RNA and protein of EMMPRIN/OX47 and their cellular localization in the rat dorsal root ganglion (DRG after nerve injury. Paw withdrawal threshold test was examined to evaluate the pain behavior in spinal nerve ligation (SNL model. The lentivirus containing OX47 shRNA was injected into the DRG one day before SNL. The expression level of both mRNA and protein of OX47 was markedly upregulated in ipsilateral DRG after SNL. OX47 was mainly expressed in the extracellular matrix of DRG. Administration of shRNA targeted against OX47 in vivo remarkably attenuated mechanical allodynia induced by SNL. In conclusion, peripheral nerve injury induced upregulation of OX47 in the extracellular matrix of DRG. RNA interference against OX47 significantly suppressed the expression of OX47 mRNA and the development of mechanical allodynia. The altered expression of OX47 may contribute to the development of neuropathic pain after nerve injury.

Effects of age and insulin-like growth factor-1 on rat neurotrophin receptor expression after nerve injury.

Science.gov (United States)

Luo, T David; Alton, Timothy B; Apel, Peter J; Cai, Jiaozhong; Barnwell, Jonathan C; Sonntag, William E; Smith, Thomas L; Li, Zhongyu

2016-10-01

Neurotrophin receptors, such as p75(NTR) , direct neuronal response to injury. Insulin-like growth factor-1 receptor (IGF-1R) mediates the increase in p75(NTR) during aging. The aim of this study was to examine the effect of aging and insulin-like growth factor-1 (IGF-1) treatment on recovery after peripheral nerve injury. Young and aged rats underwent tibial nerve transection with either local saline or IGF-1 treatment. Neurotrophin receptor mRNA and protein expression were quantified. Aged rats expressed elevated baseline IGF-1R (34% higher, P = 0.01) and p75(NTR) (68% higher, P < 0.01) compared with young rats. Post-injury, aged animals expressed significantly higher p75(NTR) levels (68.5% above baseline at 4 weeks). IGF-1 treatment suppressed p75(NTR) gene expression at 4 weeks (17.2% above baseline, P = 0.002) post-injury. Local IGF-1 treatment reverses age-related declines in recovery after peripheral nerve injuries by suppressing p75(NTR) upregulation and pro-apoptotic complexes. IGF-1 may be considered a viable adjuvant therapy to current treatment modalities. Muscle Nerve 54: 769-775, 2016. © 2016 Wiley Periodicals, Inc.

Vascularization of the dorsal root ganglia and peripheral nerve of the mouse: Implications for chemical-induced peripheral sensory neuropathies

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Melemedjian Ohannes K

2008-03-01

Full Text Available Abstract Although a variety of industrial chemicals, as well as several chemotherapeutic agents used to treat cancer or HIV, preferentially induce a peripheral sensory neuropathy what remains unclear is why these agents induce a sensory vs. a motor or mixed neuropathy. Previous studies have shown that the endothelial cells that vascularize the dorsal root ganglion (DRG, which houses the primary afferent sensory neurons, are unique in that they have large fenestrations and are permeable to a variety of low and high molecular weight agents. In the present report we used whole-mount preparations, immunohistochemistry, and confocal laser scanning microscopy to show that the cell body-rich area of the L4 mouse DRG has a 7 fold higher density of CD31+ capillaries than cell fiber rich area of the DRG or the distal or proximal aspect of the sciatic nerve. This dense vascularization, coupled with the high permeability of these capillaries, may synergistically contribute, and in part explain, why many potentially neurotoxic agents preferentially accumulate and injure cells within the DRG. Currently, cancer survivors and HIV patients constitute the largest and most rapidly expanding groups that have chemically induced peripheral sensory neuropathy. Understanding the unique aspects of the vascularization of the DRG and closing the endothelial fenestrations of the rich vascular bed of capillaries that vascularize the DRG before intravenous administration of anti-neoplastic or anti-HIV therapies, may offer a mechanism based approach to attenuate these chemically induced peripheral neuropathies in these patients.

Bone marrow-derived mesenchymal stem cells versus adipose-derived mesenchymal stem cells for peripheral nerve regeneration

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Marcela Fernandes

2018-01-01

Full Text Available Studies have confirmed that bone marrow-derived mesenchymal stem cells (MSCs can be used for treatment of several nervous system diseases. However, isolation of bone marrow-derived MSCs (BMSCs is an invasive and painful process and the yield is very low. Therefore, there is a need to search for other alterative stem cell sources. Adipose-derived MSCs (ADSCs have phenotypic and gene expression profiles similar to those of BMSCs. The production of ADSCs is greater than that of BMSCs, and ADSCs proliferate faster than BMSCs. To compare the effects of venous grafts containing BMSCs or ADSCs on sciatic nerve injury, in this study, rats were randomly divided into four groups: sham (only sciatic nerve exposed, Matrigel (MG; sciatic nerve injury + intravenous transplantation of MG vehicle, ADSCs (sciatic nerve injury + intravenous MG containing ADSCs, and BMSCs (sciatic nerve injury + intravenous MG containing BMSCs groups. Sciatic functional index was calculated to evaluate the function of injured sciatic nerve. Morphologic characteristics of nerves distal to the lesion were observed by toluidine blue staining. Spinal motor neurons labeled with Fluoro-Gold were quantitatively assessed. Compared with sham-operated rats, sciatic functional index was lower, the density of small-diameter fibers was significantly increased, and the number of motor neurons significantly decreased in rats with sciatic nerve injury. Neither ADSCs nor BMSCs significantly improved the sciatic nerve function of rats with sciatic nerve injury, increased fiber density, fiber diameters, axonal diameters, myelin sheath thickness, and G ratios (axonal diameter/fiber diameter ratios in the sciatic nerve distal to the lesion site. There was no significant difference in the number of spinal motor neurons among ADSCs, BMSCs and MG groups. These results suggest that neither BMSCs nor ADSCs provide satisfactory results for peripheral nerve repair when using MG as the conductor for

Malignant Peripheral Nerve Sheath Tumour of the Maxilla

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Puja Sahai

2014-01-01

Full Text Available A 38-year-old man was diagnosed with malignant peripheral nerve sheath tumour of the maxilla. He was treated with total maxillectomy. Histopathological examination of the resected specimen revealed a close resection margin. The tumour was of high grade with an MIB-1 labelling index of almost 60%. At six weeks following the surgery, he developed local tumour relapse. The patient succumbed to the disease at five months from the time of diagnosis. The present report underlines the locally aggressive nature of malignant peripheral nerve sheath tumour of the maxilla which necessitates an early therapeutic intervention. A complete resection with clear margins is the most important prognostic factor for malignant peripheral nerve sheath tumour in the head and neck region. Adjuvant radiotherapy may be considered to improve the local control. Future research may demarcate the role of targeted therapy for patients with malignant peripheral nerve sheath tumour.

GGF2 is neuroprotective in a rat model of cavernous nerve injury-induced erectile dysfunction.

Science.gov (United States)

Burnett, Arthur L; Sezen, Sena F; Hoke, Ahmet; Caggiano, Anthony O; Iaci, Jennifer; Lagoda, Gwen; Musicki, Biljana; Bella, Anthony J

2015-04-01

Erectile dysfunction is a major complication of radical prostatectomy, commonly associated with penile neuropathy. In animal models of peripheral nerve injury, glial growth factor-2 (GGF2), a member of the neuregulin family of growth factors, has neuroprotective and neurorestorative properties, but this potential has not been established after cavernous nerve (CN) injury. The effectiveness of GGF2 in preserving axonal integrity and recovering erectile function in a rat model of radical prostatectomy-associated CN injury. Adult male Sprague-Dawley rats underwent bilateral CN crush injury (BCNI) or sham surgery. Rats were administered GGF2 (0.5, 5, or 15 mg/kg) or vehicle subcutaneously 24 hour pre and 24-hour post-BCNI, and once weekly for 5 weeks. Erectile function was assessed in response to electrical stimulation of the CN. CN survival was assessed by fluorogold retrograde axonal tracing in major pelvic ganglia (MPG). Unmyelinated axons in the CNs were quantitated by electron microscopy. Erectile function recovery, CN survival, and unmyelinated CN axon preservation in response to GGF2 treatment following BCNI. Erectile function was decreased (P cells in the MPG was reduced (P Schwann cells in the BCNI group was higher (P Schwann cell compared with the BCNI group. GGF2 promotes erectile function recovery following CN injury in conjunction with preserving unmyelinated CN fibers. Our findings suggest the clinical opportunity to develop GGF2 as a neuroprotective therapy for radical prostatectomy. © 2015 International Society for Sexual Medicine.

The Wound Microenvironment Reprograms Schwann Cells to Invasive Mesenchymal-like Cells to Drive Peripheral Nerve Regeneration.

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Clements, Melanie P; Byrne, Elizabeth; Camarillo Guerrero, Luis F; Cattin, Anne-Laure; Zakka, Leila; Ashraf, Azhaar; Burden, Jemima J; Khadayate, Sanjay; Lloyd, Alison C; Marguerat, Samuel; Parrinello, Simona

2017-09-27

Schwann cell dedifferentiation from a myelinating to a progenitor-like cell underlies the remarkable ability of peripheral nerves to regenerate following injury. However, the molecular identity of the differentiated and dedifferentiated states in vivo has been elusive. Here, we profiled Schwann cells acutely purified from intact nerves and from the wound and distal regions of severed nerves. Our analysis reveals novel facets of the dedifferentiation response, including acquisition of mesenchymal traits and a Myc module. Furthermore, wound and distal dedifferentiated Schwann cells constitute different populations, with wound cells displaying increased mesenchymal character induced by localized TGFβ signaling. TGFβ promotes invasion and crosstalks with Eph signaling via N-cadherin to drive collective migration of the Schwann cells across the wound. Consistently, Tgfbr2 deletion in Schwann cells resulted in misdirected and delayed reinnervation. Thus, the wound microenvironment is a key determinant of Schwann cell identity, and it promotes nerve repair through integration of multiple concerted signals. VIDEO ABSTRACT. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Transdermal optogenetic peripheral nerve stimulation

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Maimon, Benjamin E.; Zorzos, Anthony N.; Bendell, Rhys; Harding, Alexander; Fahmi, Mina; Srinivasan, Shriya; Calvaresi, Peter; Herr, Hugh M.

2017-06-01

Objective: A fundamental limitation in both the scientific utility and clinical translation of peripheral nerve optogenetic technologies is the optical inaccessibility of the target nerve due to the significant scattering and absorption of light in biological tissues. To date, illuminating deep nerve targets has required implantable optical sources, including fiber-optic and LED-based systems, both of which have significant drawbacks. Approach: Here we report an alternative approach involving transdermal illumination. Utilizing an intramuscular injection of ultra-high concentration AAV6-hSyn-ChR2-EYFP in rats. Main results: We demonstrate transdermal stimulation of motor nerves at 4.4 mm and 1.9 mm depth with an incident laser power of 160 mW and 10 mW, respectively. Furthermore, we employ this technique to accurately control ankle position by modulating laser power or position on the skin surface. Significance: These results have the potential to enable future scientific optogenetic studies of pathologies implicated in the peripheral nervous system for awake, freely-moving animals, as well as a basis for future clinical studies.

Clinical Evaluation of Decellularized Nerve Allograft with Autologous Bone Marrow Stem Cells to Improve Peripheral Nerve Repair and Functional Outcomes

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2017-07-01

with autologous mesenchymal stem cells . Exp Neurol. 2007 Apr; 204(2):658-66. 19. Dezawa M., et al., Sciatic nerve regeneration in rats induced by...36 23. Mimura T., et al., Peripheral nerve regeneration by transplantation of bone marrow stromal cell -derived Schwann cells in adult rats. J...AWARD NUMBER: W81XWH-15-2-0026 TITLE: Clinical Evaluation of Decellularized Nerve Allograft with Autologous Bone Marrow Stem Cells to Improve

Peripheral nerve hyperexcitability with preterminal nerve and neuromuscular junction remodeling is a hallmark of Schwartz-Jampel syndrome.

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Bauché, Stéphanie; Boerio, Delphine; Davoine, Claire-Sophie; Bernard, Véronique; Stum, Morgane; Bureau, Cécile; Fardeau, Michel; Romero, Norma Beatriz; Fontaine, Bertrand; Koenig, Jeanine; Hantaï, Daniel; Gueguen, Antoine; Fournier, Emmanuel; Eymard, Bruno; Nicole, Sophie

2013-12-01

Schwartz-Jampel syndrome (SJS) is a recessive disorder with muscle hyperactivity that results from hypomorphic mutations in the perlecan gene, a basement membrane proteoglycan. Analyses done on a mouse model have suggested that SJS is a congenital form of distal peripheral nerve hyperexcitability resulting from synaptic acetylcholinesterase deficiency, nerve terminal instability with preterminal amyelination, and subtle peripheral nerve changes. We investigated one adult patient with SJS to study this statement in humans. Perlecan deficiency due to hypomorphic mutations was observed in the patient biological samples. Electroneuromyography showed normal nerve conduction, neuromuscular transmission, and compound nerve action potentials while multiple measures of peripheral nerve excitability along the nerve trunk did not detect changes. Needle electromyography detected complex repetitive discharges without any evidence for neuromuscular transmission failure. The study of muscle biopsies containing neuromuscular junctions showed well-formed post-synaptic element, synaptic acetylcholinesterase deficiency, denervation of synaptic gutters with reinnervation by terminal sprouting, and long nonmyelinated preterminal nerve segments. These data support the notion of peripheral nerve hyperexcitability in SJS, which would originate distally from synergistic actions of peripheral nerve and neuromuscular junction changes as a result of perlecan deficiency. Copyright © 2013 Elsevier B.V. All rights reserved.

Identification of adequate vehicles to carry nerve regeneration inducers using tubulisation

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do Nascimento-Elias Adriana Helena

2012-08-01

Full Text Available Abstract Background Axonal regeneration depends on many factors, such as the type of injury and repair, age, distance from the cell body and distance of the denervated muscle, loss of surrounding tissue and the type of injured nerve. Experimental models use tubulisation with a silicone tube to research regenerative factors and substances to induce regeneration. Agarose, collagen and DMEM (Dulbecco’s modified Eagle’s medium can be used as vehicles. In this study, we compared the ability of these vehicles to induce rat sciatic nerve regeneration with the intent of finding the least active or inert substance. The experiment used 47 female Wistar rats, which were divided into four experimental groups (agarose 4%, agarose 0.4%, collagen, DMEM and one normal control group. The right sciatic nerve was exposed, and an incision was made that created a 10 mm gap between the distal and proximal stumps. A silicone tube was grafted onto each stump, and the tubes were filled with the respective media. After 70 days, the sciatic nerve was removed. We evaluated the formation of a regeneration cable, nerve fibre growth, and the functional viability of the regenerated fibres. Results Comparison among the three vehicles showed that 0.4% agarose gels had almost no effect on provoking the regeneration of peripheral nerves and that 4% agarose gels completely prevented fibre growth. The others substances were associated with profuse nerve fibre growth. Conclusions In the appropriate concentration, agarose gel may be an important vehicle for testing factors that induce regeneration without interfering with nerve growth.

Identification of adequate vehicles to carry nerve regeneration inducers using tubulisation.

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do Nascimento-Elias, Adriana Helena; Fresnesdas, Bruno César; Schiavoni, Maria Cristina Lopes; de Almeida, Natália Fernanda Gaspar; Santos, Ana Paula; de Oliveira Ramos, Jean; Junior, Wilson Marques; Barreira, Amilton Antunes

2012-08-14

Axonal regeneration depends on many factors, such as the type of injury and repair, age, distance from the cell body and distance of the denervated muscle, loss of surrounding tissue and the type of injured nerve. Experimental models use tubulisation with a silicone tube to research regenerative factors and substances to induce regeneration. Agarose, collagen and DMEM (Dulbecco's modified Eagle's medium) can be used as vehicles. In this study, we compared the ability of these vehicles to induce rat sciatic nerve regeneration with the intent of finding the least active or inert substance. The experiment used 47 female Wistar rats, which were divided into four experimental groups (agarose 4%, agarose 0.4%, collagen, DMEM) and one normal control group. The right sciatic nerve was exposed, and an incision was made that created a 10 mm gap between the distal and proximal stumps. A silicone tube was grafted onto each stump, and the tubes were filled with the respective media. After 70 days, the sciatic nerve was removed. We evaluated the formation of a regeneration cable, nerve fibre growth, and the functional viability of the regenerated fibres. Comparison among the three vehicles showed that 0.4% agarose gels had almost no effect on provoking the regeneration of peripheral nerves and that 4% agarose gels completely prevented fibre growth. The others substances were associated with profuse nerve fibre growth. In the appropriate concentration, agarose gel may be an important vehicle for testing factors that induce regeneration without interfering with nerve growth.

Sonographic identification of peripheral nerves in the forearm

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Saundra A Jackson

2016-01-01

Full Text Available Background: With the growing utilization of ultrasonography in emergency medicine combined with the concern over adequate pain management in the emergency department (ED, ultrasound guidance for peripheral nerve blockade in ED is an area of increasing interest. The medical literature has multiple reports supporting the use of ultrasound guidance in peripheral nerve blocks. However, to perform a peripheral nerve block, one must first be able to reliably identify the specific nerve before the procedure. Objective: The primary purpose of this study is to describe the number of supervised peripheral nerve examinations that are necessary for an emergency medicine physician to gain proficiency in accurately locating and identifying the median, radial, and ulnar nerves of the forearm via ultrasound. Methods: The proficiency outcome was defined as the number of attempts before a resident is able to correctly locate and identify the nerves on ten consecutive examinations. Didactic education was provided via a 1 h lecture on forearm anatomy, sonographic technique, and identification of the nerves. Participants also received two supervised hands-on examinations for each nerve. Count data are summarized using percentages or medians and range. Random effects negative binomial regression was used for modeling panel count data. Results: Complete data for the number of attempts, gender, and postgraduate year (PGY training year were available for 38 residents. Nineteen males and 19 females performed examinations. The median PGY year in practice was 3 (range 1-3, with 10 (27% in year 1, 8 (22% in year 2, and 19 (51% in year 3 or beyond. The median number (range of required supervised attempts for radial, median, and ulnar nerves was 1 (0-12, 0 (0-10, and 0 (0-17, respectively. Conclusion: We can conclude that the maximum number of supervised attempts to achieve accurate nerve identification was 17 (ulnar, 12 (radial, and 10 (median in our study. The only

Neural tissue engineering options for peripheral nerve regeneration.

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Gu, Xiaosong; Ding, Fei; Williams, David F

2014-08-01

Tissue engineered nerve grafts (TENGs) have emerged as a potential alternative to autologous nerve grafts, the gold standard for peripheral nerve repair. Typically, TENGs are composed of a biomaterial-based template that incorporates biochemical cues. A number of TENGs have been used experimentally to bridge long peripheral nerve gaps in various animal models, where the desired outcome is nerve tissue regeneration and functional recovery. So far, the translation of TENGs to the clinic for use in humans has met with a certain degree of success. In order to optimize the TENG design and further approach the matching of TENGs with autologous nerve grafts, many new cues, beyond the traditional ones, will have to be integrated into TENGs. Furthermore, there is a strong requirement for monitoring the real-time dynamic information related to the construction of TENGs. The aim of this opinion paper is to specifically and critically describe the latest advances in the field of neural tissue engineering for peripheral nerve regeneration. Here we delineate new attempts in the design of template (or scaffold) materials, especially in the context of biocompatibility, the choice and handling of support cells, and growth factor release systems. We further discuss the significance of RNAi for peripheral nerve regeneration, anticipate the potential application of RNAi reagents for TENGs, and speculate on the possible contributions of additional elements, including angiogenesis, electrical stimulation, molecular inflammatory mediators, bioactive peptides, antioxidant reagents, and cultured biological constructs, to TENGs. Finally, we consider that a diverse array of physicochemical and biological cues must be orchestrated within a TENG to create a self-consistent coordinated system with a close proximity to the regenerative microenvironment of the peripheral nervous system. Copyright © 2014 Elsevier Ltd. All rights reserved.

Stabilization, Rolling, and Addition of Other Extracellular Matrix Proteins to Collagen Hydrogels Improve Regeneration in Chitosan Guides for Long Peripheral Nerve Gaps in Rats.

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Gonzalez-Perez, Francisco; Cobianchi, Stefano; Heimann, Claudia; Phillips, James B; Udina, Esther; Navarro, Xavier

2017-03-01

Autograft is still the gold standard technique for the repair of long peripheral nerve injuries. The addition of biologically active scaffolds into the lumen of conduits to mimic the endoneurium of peripheral nerves may increase the final outcome of artificial nerve devices. Furthermore, the control of the orientation of the collagen fibers may provide some longitudinal guidance architecture providing a higher level of mesoscale tissue structure. To evaluate the regenerative capabilities of chitosan conduits enriched with extracellular matrix-based scaffolds to bridge a critical gap of 15 mm in the rat sciatic nerve. The right sciatic nerve of female Wistar Hannover rats was repaired with chitosan tubes functionalized with extracellular matrix-based scaffolds fully hydrated or stabilized and rolled to bridge a 15 mm nerve gap. Recovery was evaluated by means of electrophysiology and algesimetry tests and histological analysis 4 months after injury. Stabilized constructs enhanced the success of regeneration compared with fully hydrated scaffolds. Moreover, fibronectin-enriched scaffolds increased muscle reinnervation and number of myelinated fibers compared with laminin-enriched constructs. A mixed combination of collagen and fibronectin may be a promising internal filler for neural conduits for the repair of peripheral nerve injuries, and their stabilization may increase the quality of regeneration over long gaps. Copyright © 2017 by the Congress of Neurological Surgeons

Acute sciatic nerve crush injuries in rabbits: MRI and pathological comparative study

International Nuclear Information System (INIS)

Li Xinchun; Chen Jianyu; Wang Xinlu; Shen Jun; Liu Qingyu; Liang Biling

2004-01-01

Objective: Simulating injury mechanism in human peripheral nerve, acute sciatic nerve crush injuries model was produced in rabbits to investigate the relationship between the manifestations of MRI and pathology in order to provide the information for clinical therapy and operative plan. Methods: Thirty-two adult rabbits were randomly divided into two groups: group A (n=16) and B (n=16). In group A, the left sciatic nerves were crushed with a stress of 3.61 kg; In group B, with a stress of 10.50 kg. 4 time intervals in each group were observed in 1, 2, 4, and 8 weeks, respectively, and each time interval contained 4 rabbits. Left sciatic nerves were served as injured sides, right sciatic nerves were regarded as control sides. MRI was performed at different time interval after crush injury. Then the nerves were examined pathologically. Results: There were no obvious changes on T 1 WI in injured sides, but the injured distal segment of sciatic nerve thickened and twisted, showing high signal intensity on 3D T 2 WI, T 2 WI/SPIR, B-FFE, and T 2 WI/STIR. MRI could show abnormality of 30 sciatic nerves, the correct diagnostic rate was 93.75% and false negative rate was 6.25%. The distal sciatic nerve/muscle signal intensity ratio (SIR) of the injured sides was significantly higher than that of the control sides (P 0.05). SIR in injured side increased at 1 week, reached the peak at 2 weeks, at this time, nerve axons disappeared and lots of myelin degenerated, abduction function disappeared. SIR decreased during 4-8 weeks, the myelin sheath breakdown and Schwann cell proliferated obviously, and abduction functions were observed. The control sciatic nerves showed no abnormality in MRI and pathology. Conclusion: MRI can make the diagnosis of crush injury of sciatic nerve, and dynamic SIR measurement of nerve injury correlates well with the pathological and functional recovery process. MRI is an effective method to monitor degeneration, regeneration, and prognosis after

Molecular mechanisms of peripheral nerve regeneration: Emerging roles of microRNAs

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Di eWu

2013-04-01

Full Text Available microRNAs are small non-coding RNAs that suppress gene expression through target mRNA degradation or translation repression. Recent studies suggest that miRNA plays an important role in multiple physiological and pathological processes in the nervous system. In this review article, we described what is currently known about the mechanisms in peripheral nerve regeneration on the cellular and molecular levels. Recently, changes in microRNA expression profiles have been detected in different injury models, and emerging evidence strongly indicates that these changes promote neurons to survive and shift their physiology from maintaining a structure and supporting synaptic transmission toward a regenerative phenotype. We reviewed the putative mechanisms involved in miRNA mediated post-transcriptional regulation and pointed out several areas where future research is necessary to advance our understanding of how targeting miRNA machinery can be used as a therapeutic approach for treating nerve injuries.

Anastomotic stoma coated with chitosan film as a betamethasone dipropionate carrier for peripheral nerve regeneration

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Ping Yao

2018-01-01

Full Text Available Scar hyperplasia at the suture site is an important reason for hindering the repair effect of peripheral nerve injury anastomosis. To address this issue, two repair methods are often used. Biological agents are used to block nerve sutures and the surrounding tissue to achieve physical anti-adhesion effects. Another agent is glucocorticosteroid, which can prevent scar growth by inhibiting inflammation. However, the overall effect of promoting regeneration of the injured nerve is not satisfactory. In this regard, we envision that these two methods can be combined and lead to shared understanding for achieving improved nerve repair. In this study, the right tibial nerve was transected 1 cm above the knee to establish a rat tibial nerve injury model. The incision was directly sutured after nerve transection. The anastomotic stoma was coated with 0.5 × 0.5 cm2 chitosan sheets with betamethasone dipropionate. At 12 weeks after injury, compared with the control and poly (D, L-lactic acid groups, chitosan-betamethasone dipropionate film slowly degraded with the shape of the membrane still intact. Further, scar hyperplasia and the degree of adhesion at anastomotic stoma were obviously reduced, while the regenerated nerve fiber structure was complete and arranged in a good order in model rats. Electrophysiological study showed enhanced compound muscle action potential. Our results confirm that chitosan-betamethasone dipropionate film can effectively prevent local scar hyperplasia after tibial nerve repair and promote nerve regeneration.

Neural stem cells enhance nerve regeneration after sciatic nerve injury in rats.

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Xu, Lin; Zhou, Shuai; Feng, Guo-Ying; Zhang, Lu-Ping; Zhao, Dong-Mei; Sun, Yi; Liu, Qian; Huang, Fei

2012-10-01

With the development of tissue engineering and the shortage of autologous nerve grafts in nerve reconstruction, cell transplantation in a conduit is an alternative strategy to improve nerve regeneration. The present study evaluated the effects and mechanism of brain-derived neural stem cells (NSCs) on sciatic nerve injury in rats. At the transection of the sciatic nerve, a 10-mm gap between the nerve stumps was bridged with a silicon conduit filled with 5 × 10(5) NSCs. In control experiments, the conduit was filled with nerve growth factor (NGF) or normal saline (NS). The functional and morphological properties of regenerated nerves were investigated, and expression of hepatocyte growth factor (HGF) and NGF was measured. One week later, there was no connection through the conduit. Four or eight weeks later, fibrous connections were evident between the proximal and distal segments. Motor function was revealed by measurement of the sciatic functional index (SFI) and sciatic nerve conduction velocity (NCV). Functional recovery in the NSC and NGF groups was significantly more advanced than that in the NS group. NSCs showed significant improvement in axon myelination of the regenerated nerves. Expression of NGF and HGF in the injured sciatic nerve was significantly lower in the NS group than in the NSCs and NGF groups. These results and other advantages of NSCs, such as ease of harvest and relative abundance, suggest that NSCs could be used clinically to enhance peripheral nerve repair.

Adenoviral vector-mediated expression of a foreign gene in peripheral nerve tissue bridges implanted in the injured peripheral and central nervous system

NARCIS (Netherlands)

Blits, B; Dijkhuizen, Paul A; Carlstedt, Thomas P; Poldervaart, H A; Schiemanck, S; Boer, G J; Verhaagen, J

1999-01-01

Axons of the CNS do normally not regenerate after injury, in contrast to axons of the PNS. This is due to a different microenvironment at the site of the lesion as well as a particular intrinsic program of axonal regrowth. Although transplantation of peripheral nerve tissue bridges is perhaps the

A Physicochemically Optimized and Neuroconductive Biphasic Nerve Guidance Conduit for Peripheral Nerve Repair.

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Ryan, Alan J; Lackington, William A; Hibbitts, Alan J; Matheson, Austyn; Alekseeva, Tijna; Stejskalova, Anna; Roche, Phoebe; O'Brien, Fergal J

2017-12-01

Clinically available hollow nerve guidance conduits (NGCs) have had limited success in treating large peripheral nerve injuries. This study aims to develop a biphasic NGC combining a physicochemically optimized collagen outer conduit to bridge the transected nerve, and a neuroconductive hyaluronic acid-based luminal filler to support regeneration. The outer conduit is mechanically optimized by manipulating crosslinking and collagen density, allowing the engineering of a high wall permeability to mitigate the risk of neuroma formation, while also maintaining physiologically relevant stiffness and enzymatic degradation tuned to coincide with regeneration rates. Freeze-drying is used to seamlessly integrate the luminal filler into the conduit, creating a longitudinally aligned pore microarchitecture. The luminal stiffness is modulated to support Schwann cells, with laminin incorporation further enhancing bioactivity by improving cell attachment and metabolic activity. Additionally, this biphasic NGC is shown to support neurogenesis and gliogenesis of neural progenitor cells and axonal outgrowth from dorsal root ganglia. These findings highlight the paradigm that a successful NGC requires the concerted optimization of both a mechanical support phase capable of bridging a nerve defect and a neuroconductive phase with an architecture capable of supporting both Schwann cells and neurons in order to achieve functional regenerative outcome. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

New sonographic measures of peripheral nerves: a tool for the diagnosis of peripheral nerve involvement in leprosy

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Marco Andrey Cipriani Frade

2013-05-01

Full Text Available To evaluate ultrasonographic (US cross-sectional areas (CSAs of peripheral nerves, indexes of the differences between CSAs at the same point (∆CSAs and between tunnel (T and pre-tunnel (PT ulnar CSAs (∆TPTs in leprosy patients (LPs and healthy volunteers (HVs. Seventy-seven LPs and 49 HVs underwent bilateral US at PT and T ulnar points, as well as along the median (M and common fibular (CF nerves, to calculate the CSAs, ∆CSAs and ∆TPTs. The CSA values in HVs were lower than those in LPs (p 80% and ∆TPT had the highest specificity (> 90%. New sonographic peripheral nerve measurements (∆CSAs and ∆TPT provide an important methodological improvement in the detection of leprosy neuropathy.

Immune cell distribution and immunoglobulin levels change following sciatic nerve injury in a rat model

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Wei Yuan

2016-07-01

Full Text Available Objective(s: To investigate the systemic and local immune status of two surgical rat models of sciatic nerve injury, a crushed sciatic nerve, and a sciatic nerve transection Materials and Methods:Twenty-four adult male Sprague-Dawley rats were randomly divided into three groups: sham-operation (control group, sciatic nerve crush, and sciatic nerve transaction. Sciatic nerve surgery was performed. The percentage of CD4+ cells and the CD4+/CD8+ratio were determined by flow cytometry. Serum IgM and IgG levels were analyzed by ELISA. T-cells (CD3 and macrophages (CD68 in sciatic nerve tissue sections were identified through immunohistochemistry. Results: Compared to sham-operated controls, in rats that underwent nerve injury, the percentage of CD4+ cells and the CD4+/CD8+ ratio in the peripheral blood were significantly  decreased 7 days after surgery, serum IgM levels were increased 14 days after surgery, and serum IgG levels were increased 21 days after surgery. There were a large number of CD3+ cells and a small number of CD68+ cells in sciatic nerve tissue sections 21 days after surgery, indicating T-cell and macrophage activation and infiltration. Local IgG deposition was also detected at the nerve injury site 21 days after surgery. Conclusion: Rat humoral and cellular immune status changed following sciatic nerve injury, particularly with regard to the cellular immune response at the nerve injury site.

An anatomical study of porcine peripheral nerve and its potential use in nerve tissue engineering

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Zilic, Leyla; Garner, Philippa E; Yu, Tong; Roman, Sabiniano; Haycock, John W; Wilshaw, Stacy-Paul

2015-01-01

Current nerve tissue engineering applications are adopting xenogeneic nerve tissue as potential nerve grafts to help aid nerve regeneration. However, there is little literature that describes the exact location, anatomy and physiology of these nerves to highlight their potential as a donor graft. The aim of this study was to identify and characterise the structural and extracellular matrix (ECM) components of porcine peripheral nerves in the hind leg. Methods included the dissection of porcine nerves, localisation, characterisation and quantification of the ECM components and identification of nerve cells. Results showed a noticeable variance between porcine and rat nerve (a commonly studied species) in terms of fascicle number. The study also revealed that when porcine peripheral nerves branch, a decrease in fascicle number and size was evident. Porcine ECM and nerve fascicles were found to be predominately comprised of collagen together with glycosaminoglycans, laminin and fibronectin. Immunolabelling for nerve growth factor receptor p75 also revealed the localisation of Schwann cells around and inside the fascicles. In conclusion, it is shown that porcine peripheral nerves possess a microstructure similar to that found in rat, and is not dissimilar to human. This finding could extend to the suggestion that due to the similarities in anatomy to human nerve, porcine nerves may have utility as a nerve graft providing guidance and support to regenerating axons. PMID:26200940

Comparative study of phrenic nerve transfers with and without nerve graft for elbow flexion after global brachial plexus injury.

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Liu, Yuzhou; Lao, Jie; Gao, Kaiming; Gu, Yudong; Zhao, Xin

2014-01-01

Nerve transfer is a valuable surgical technique in peripheral nerve reconstruction, especially in brachial plexus injuries. Phrenic nerve transfer for elbow flexion was proved to be one of the optimal procedures in the treatment of brachial plexus injuries in the study of Gu et al. The aim of this study was to compare phrenic nerve transfers with and without nerve graft for elbow flexion after brachial plexus injury. A retrospective review of 33 patients treated with phrenic nerve transfer for elbow flexion in posttraumatic global root avulsion brachial plexus injury was carried out. All the 33 patients were confirmed to have global root avulsion brachial plexus injury by preoperative and intraoperative electromyography (EMG), physical examination and especially by intraoperative exploration. There were two types of phrenic nerve transfers: type1 - the phrenic nerve to anterolateral bundle of anterior division of upper trunk (14 patients); type 2 - the phrenic nerve via nerve graft to anterolateral bundle of musculocutaneous nerve (19 patients). Motor function and EMG evaluation were performed at least 3 years after surgery. The efficiency of motor function in type 1 was 86%, while it was 84% in type 2. The two groups were not statistically different in terms of Medical Research Council (MRC) grade (p=1.000) and EMG results (p=1.000). There were seven patients with more than 4 month's delay of surgery, among whom only three patients regained biceps power to M3 strength or above (43%). A total of 26 patients had reconstruction done within 4 months, among whom 25 patients recovered to M3 strength or above (96%). There was a statistically significant difference of motor function between the delay of surgery within 4 months and more than 4 months (p=0.008). Phrenic nerve transfers with and without nerve graft for elbow flexion after brachial plexus injury had no significant difference for biceps reinnervation according to MRC grading and EMG. A delay of the surgery

Magnetoneurographic evaluation of peripheral nerve regeneration

NARCIS (Netherlands)

P.D.L. Kuypers (Paul)

1998-01-01

textabstractWhen a peripheral nerve is reconstructed after it has been damaged. it is important to assess, in an early stage, whether the nerve is regenerating across the lesion. However, at present for this purpose an adequate method is not available. In this study short term changes in the

High resolution ultrasonography of the tibial nerve in diabetic peripheral neuropathy.

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Singh, Kunwarpal; Gupta, Kamlesh; Kaur, Sukhdeep

2017-12-01

High-resolution ultrasonography of the tibial nerve is a fast and non invasive tool for diagnosis of diabetic peripheral neuropathy. Our study was aimed at finding out the correlation of the cross sectional area and maximum thickness of nerve fascicles of the tibial nerve with the presence and severity of diabetic peripheral neuropathy. 75 patients with type 2 diabetes mellitus clinically diagnosed with diabetic peripheral neuropathy were analysed, and the severity of neuropathy was determined using the Toronto Clinical Neuropathy Score. 58 diabetic patients with no clinical suspicion of diabetic peripheral neuropathy and 75 healthy non-diabetic subjects were taken as controls. The cross sectional area and maximum thickness of nerve fascicles of the tibial nerves were calculated 3 cm cranial to the medial malleolus in both lower limbs. The mean cross sectional area (22.63 +/- 2.66 mm 2 ) and maximum thickness of nerve fascicles (0.70 mm) of the tibial nerves in patients with diabetic peripheral neuropathy compared with both control groups was significantly larger, and statistically significant correlation was found with the Toronto Clinical Neuropathy Score ( p peripheral neuropathy had a larger mean cross sectional area (14.40 +/- 1.72 mm 2 ) and maximum thickness of nerve fascicles of the tibial nerve (0.40 mm) than healthy non-diabetic subjects (12.42 +/- 1.01 mm 2 and 0.30 mm respectively). The cross sectional area and maximum thickness of nerve fascicles of the tibial nerve is larger in diabetic patients with or without peripheral neuropathy than in healthy control subjects, and ultrasonography can be used as a good screening tool in these patients.

Substance P immunoreactivity in the lumbar spinal cord of the turtle Trachemys dorbigni following peripheral nerve injury.

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Partata, W A; Krepsky, A M R; Xavier, L L; Marques, M; Achaval, M

2003-04-01

Immunoreactive substance P was investigated in turtle lumbar spinal cord after sciatic nerve transection. In control animals immunoreactive fibers were densest in synaptic field Ia, where the longest axons invaded synaptic field III. Positive neuronal bodies were identified in the lateral column of the dorsal horn and substance P immunoreactive varicosities were observed in the ventral horn, in close relationship with presumed motoneurons. Other varicosities appeared in the lateral and anterior funiculi. After axotomy, substance P immunoreactive fibers were reduced slightly on the side of the lesion, which was located in long fibers that invaded synaptic field III and in the varicosities of the lateral and anterior funiculus. The changes were observed at 7 days after axonal injury and persisted at 15, 30, 60 and 90 days after the lesion. These findings show that turtles should be considered as a model to study the role of substance P in peripheral axonal injury, since the distribution and temporal changes of substance P were similar to those found in mammals.

Substance P immunoreactivity in the lumbar spinal cord of the turtle Trachemys dorbigni following peripheral nerve injury

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W.A. Partata

2003-04-01

Full Text Available Immunoreactive substance P was investigated in turtle lumbar spinal cord after sciatic nerve transection. In control animals immunoreactive fibers were densest in synaptic field Ia, where the longest axons invaded synaptic field III. Positive neuronal bodies were identified in the lateral column of the dorsal horn and substance P immunoreactive varicosities were observed in the ventral horn, in close relationship with presumed motoneurons. Other varicosities appeared in the lateral and anterior funiculi. After axotomy, substance P immunoreactive fibers were reduced slightly on the side of the lesion, which was located in long fibers that invaded synaptic field III and in the varicosities of the lateral and anterior funiculus. The changes were observed at 7 days after axonal injury and persisted at 15, 30, 60 and 90 days after the lesion. These findings show that turtles should be considered as a model to study the role of substance P in peripheral axonal injury, since the distribution and temporal changes of substance P were similar to those found in mammals.

Use of paper for treatment of a peripheral nerve trauma in the rat.

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Kauppila, T; Jyväsjärvi, E; Murtomäki, S; Mansikka, H; Pertovaara, A; Virtanen, I; Liesi, P

1997-09-29

Reinnervation of the muscles and skin in the rat hindpaw was studied after transection and attempted repair of the sciatic nerve. Reconnecting the transected nerve with lens cleaning paper was at least as effective in rejoining the transected nerves as traditional microsurgical neurorraphy. Paper induced a slightly bigger fibrous scar around the site of transection than neurorraphy, but this scar did not cause impairment of functional recovery or excessive signs of neuropathic pain. We conclude that a paper graft can be used in restorative surgery of severed peripheral nerves.

Releasing 'brakes' to nerve regeneration: intrinsic molecular targets.

Science.gov (United States)

Krishnan, Anand; Duraikannu, Arul; Zochodne, Douglas W

2016-02-01

Restoring critical neuronal architecture after peripheral nerve injury is challenging. Although immediate regenerative responses to peripheral axon injury involve the synthesis of regeneration-associated proteins in neurons and Schwann cells, an unfavorable balance between growth facilitatory and growth inhibitory signaling impairs the growth continuum of injured peripheral nerves. Molecules involved with the signaling network of tumor suppressors play crucial roles in shifting the balance between growth and restraint during axon regeneration. An understanding of the molecular framework of tumor suppressor molecules in injured neurons and its impact on stage-specific regeneration events may expose therapeutic intervention points. In this review we discuss how signaling networks of the specific tumor suppressors PTEN, Rb1, p53, p27 and p21 are altered in injured peripheral nerves and how this impacts peripheral nerve regeneration. Insights into the roles and importance of these pathways may open new avenues for improving the neurological deficits associated with nerve injury. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Neurophysiological approach to disorders of peripheral nerve

DEFF Research Database (Denmark)

Crone, Clarissa; Krarup, Christian

2013-01-01

Disorders of the peripheral nerve system (PNS) are heterogeneous and may involve motor fibers, sensory fibers, small myelinated and unmyelinated fibers and autonomic nerve fibers, with variable anatomical distribution (single nerves, several different nerves, symmetrical affection of all nerves......, plexus, or root lesions). Furthermore pathological processes may result in either demyelination, axonal degeneration or both. In order to reach an exact diagnosis of any neuropathy electrophysiological studies are crucial to obtain information about these variables. Conventional electrophysiological...

Neurosteroid 3α-androstanediol efficiently counteracts paclitaxel-induced peripheral neuropathy and painful symptoms.

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Laurence Meyer

Full Text Available Painful peripheral neuropathy belongs to major side-effects limiting cancer chemotherapy. Paclitaxel, widely used to treat several cancers, induces neurological symptoms including burning pain, allodynia, hyperalgesia and numbness. Therefore, identification of drugs that may effectively counteract paclitaxel-induced neuropathic symptoms is crucial. Here, we combined histopathological, neurochemical, behavioral and electrophysiological methods to investigate the natural neurosteroid 3α-androstanediol (3α-DIOL ability to counteract paclitaxel-evoked peripheral nerve tissue damages and neurological symptoms. Prophylactic or corrective 3α-DIOL treatment (4 mg/kg/2 days prevented or suppressed PAC-evoked heat-thermal hyperalgesia, cold-allodynia and mechanical allodynia/hyperalgesia, by reversing to normal, decreased thermal and mechanical pain thresholds of PAC-treated rats. Electrophysiological studies demonstrated that 3α-DIOL restored control values of nerve conduction velocity and action potential peak amplitude significantly altered by PAC-treatment. 3α-DIOL also repaired PAC-induced nerve damages by restoring normal neurofilament-200 level in peripheral axons and control amount of 2',3'-cyclic-nucleotide-3'-phosphodiesterase in myelin sheaths. Decreased density of intraepidermal nerve fibers evoked by PAC-therapy was also counteracted by 3α-DIOL treatment. More importantly, 3α-DIOL beneficial effects were not sedation-dependent but resulted from its neuroprotective ability, nerve tissue repairing capacity and long-term analgesic action. Altogether, our results showing that 3α-DIOL efficiently counteracted PAC-evoked painful symptoms, also offer interesting possibilities to develop neurosteroid-based strategies against chemotherapy-induced peripheral neuropathy. This article shows that the prophylactic or corrective treatment with 3α-androstanediol prevents or suppresses PAC-evoked painful symptoms and peripheral nerve dysfunctions in

Polymeric Nerve Conduits with Contact Guidance Cues Used in Nerve Repair

Institute of Scientific and Technical Information of China (English)

G DAI; X NIU; J YIN

2016-01-01

In the modern life, the nerve injury frequently happens due to mechanical, chemical or thermal accidents. In the trivial injuries, the peripheral nerves can regenerate on their own; however, in most of the cases the clinical treatments are required, where relatively large nerve injury gaps are formed. Currently, the nerve repair can be accomplished by direct suture when the injury gap is not too large;while the autologous nerve graft working as the gold standard of peripheral nerve injury treatment for nerve injuries with larger gaps. However, the direct suture is limited by heavy tension at the suture sites, and the autologous nerve graft also has the drawbacks of donor site morbidity and insufifcient donor tissue. Recently, artiifcial nerve conduits have been developed as an alternative for clinical nerve repair to overcome the limitations associated with the above treatments. In order to further improve the efifciency of nerve conduits, various guidance cues are incorporated, including physical cues, biochemical signals, as well as support cells. First, this paper reviewed the contact guidance cues applied in nerve conduits, such as lumen ifllers, multi-channels and micro-patterns on the inner surface. Then, the paper focused on the polymeric nerve conduits with micro inner grooves. The polymeric nerve conduits were fabricated using the phase inversion-based ifber spinning techniques. The smart spinneret with grooved die was designed in the spinning platform, while different spinning conditions, including flow rates, air-gap distances, and polymer concentrations, were adjusted to investigate the inlfuence of fabrication conditions on the geometry of nerve conduits. The inner groove size in the nerve conduits can be precisely controlled in our hollow ifber spinning process, which can work as the efifcient contact guidance cue for nerve regeneration.

Adult Stem Cell-Based Enhancement of Nerve Conduit for Peripheral Nerve Repair

Science.gov (United States)

2017-10-01

acceptable donor nerves are often not available for this purpose, particularly in patients suffering multiple extremity injuries or faced with traumatic...amputations. Alternatives include the use of a blood vessel graft or a synthetic nerve guide, although these devices are only effective over distances less...of combat-related orthopaedic trauma. Given the severity of the orthopaedic injuries sustained during battlefield trauma, an acceptable donor nerve is

Clinical treatment of traumatic brain injury complicated by cranial nerve injury.

Science.gov (United States)

Jin, Hai; Wang, Sumin; Hou, Lijun; Pan, Chengguang; Li, Bo; Wang, Hui; Yu, Mingkun; Lu, Yicheng

2010-09-01

To discuss the epidemiology, diagnosis and surgical treatment of cranial nerve injury following traumatic brain injury (TBI) for the sake of raising the clinical treatment of this special category of TBI. A retrospective analysis was made of 312 patients with cranial nerve injury among 3417 TBI patients, who were admitted for treatment in this hospital. A total of 312 patients (9.1%) involving either a single nerve or multiple nerves among the 12 pairs of cranial nerves were observed. The extent of nerve injury varied and involved the olfactory nerve (66 cases), optic nerve (78 cases), oculomotor nerve (56 cases), trochlear nerve (8 cases), trigeminal nerve (4 cases), abducent nerve (12 cases), facial nerve (48 cases), acoustic nerve (10 cases), glossopharyngeal nerve (8 cases), vagus nerve (6 cases), accessory nerve (10 cases) and hypoglossal nerve (6 cases). Imaging examination revealed skull fracture in 217 cases, complicated brain contusion in 232 cases, epidural haematoma in 194 cases, subarachnoid haemorrhage in 32 cases, nasal cerebrospinal fluid (CSF) leakage in 76 cases and ear CSF leakage in 8 cases. Of the 312 patients, 46 patients died; the mortality rate associated with low cranial nerve injury was as high as 73.3%. Among the 266 surviving patients, 199 patients received conservative therapy and 67 patients received surgical therapy; the curative rates among these two groups were 61.3% (122 patients) and 86.6% (58 patients), respectively. TBI-complicated cranial nerve injury is subject to a high incidence rate, a high mortality rate and a high disability rate. Our findings suggest that the chance of recovery may be increased in cases where injuries are amenable to surgical decompression. It is necessary to study all 12 pairs of cranial nerves systematically. Clinically, it is necessary to standardise surgical indications, operation timing, surgical approaches and methods for the treatment of TBI-complicated cranial nerve injury. 2010 Elsevier Ltd. All

Morphology of Donor and Recipient Nerves Utilised in Nerve Transfers to Restore Upper Limb Function in Cervical Spinal Cord Injury

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Aurora Messina

2016-09-01

Full Text Available Loss of hand function after cervical spinal cord injury (SCI impacts heavily on independence. Multiple nerve transfer surgery has been applied successfully after cervical SCI to restore critical arm and hand functions, and the outcome depends on nerve integrity. Nerve integrity is assessed indirectly using muscle strength testing and intramuscular electromyography, but these measures cannot show the manifestation that SCI has on the peripheral nerves. We directly assessed the morphology of nerves biopsied at the time of surgery, from three patients within 18 months post injury. Our objective was to document their morphologic features. Donor nerves included teres minor, posterior axillary, brachialis, extensor carpi radialis brevis and supinator. Recipient nerves included triceps, posterior interosseus (PIN and anterior interosseus nerves (AIN. They were fixed in glutaraldehyde, processed and embedded in Araldite Epon for light microscopy. Eighty percent of nerves showed abnormalities. Most common were myelin thickening and folding, demyelination, inflammation and a reduction of large myelinated axon density. Others were a thickened perineurium, oedematous endoneurium and Renaut bodies. Significantly, very thinly myelinated axons and groups of unmyelinated axons were observed indicating regenerative efforts. Abnormalities exist in both donor and recipient nerves and they differ in appearance and aetiology. The abnormalities observed may be preventable or reversible.

BDNF gene delivery within and beyond templated agarose multi-channel guidance scaffolds enhances peripheral nerve regeneration

Science.gov (United States)

Gao, Mingyong; Lu, Paul; Lynam, Dan; Bednark, Bridget; Campana, W. Marie; Sakamoto, Jeff; Tuszynski, Mark

2016-12-01

Objective. We combined implantation of multi-channel templated agarose scaffolds with growth factor gene delivery to examine whether this combinatorial treatment can enhance peripheral axonal regeneration through long sciatic nerve gaps. Approach. 15 mm long scaffolds were templated into highly organized, strictly linear channels, mimicking the linear organization of natural nerves into fascicles of related function. Scaffolds were filled with syngeneic bone marrow stromal cells (MSCs) secreting the growth factor brain derived neurotrophic factor (BDNF), and lentiviral vectors expressing BDNF were injected into the sciatic nerve segment distal to the scaffold implantation site. Main results. Twelve weeks after injury, scaffolds supported highly linear regeneration of host axons across the 15 mm lesion gap. The incorporation of BDNF-secreting cells into scaffolds significantly increased axonal regeneration, and additional injection of viral vectors expressing BDNF into the distal segment of the transected nerve significantly enhanced axonal regeneration beyond the lesion. Significance. Combinatorial treatment with multichannel bioengineered scaffolds and distal growth factor delivery significantly improves peripheral nerve repair, rivaling the gold standard of autografts.

Participation of neuronal nitric oxide synthase in experimental neuropathic pain induced by sciatic nerve transection

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M. Chacur

2010-04-01

Full Text Available Nerve injury leads to a neuropathic pain state that results from central sensitization. This phenomenom is mediated by NMDA receptors and may involve the production of nitric oxide (NO. In this study, we investigated the expression of the neuronal isoform of NO synthase (nNOS in the spinal cord of 3-month-old male, Wistar rats after sciatic nerve transection (SNT. Our attention was focused on the dorsal part of L3-L5 segments receiving sensory inputs from the sciatic nerve. SNT resulted in the development of neuropathic pain symptoms confirmed by evaluating mechanical hyperalgesia (Randall and Selitto test and allodynia (von Frey hair test. Control animals did not present any alteration (sham-animals. The selective inhibitor of nNOS, 7-nitroindazole (0.2 and 2 µg in 50 µL, blocked hyperalgesia and allodynia induced by SNT. Immunohistochemical analysis showed that nNOS was increased (48% by day 30 in the lumbar spinal cord after SNT. This increase was observed near the central canal (Rexed’s lamina X and also in lamina I-IV of the dorsal horn. Real-time PCR results indicated an increase of nNOS mRNA detected from 1 to 30 days after SNT, with the highest increase observed 1 day after injury (1469%. Immunoblotting confirmed the increase of nNOS in the spinal cord between 1 and 15 days post-lesion (20%, reaching the greatest increase (60% 30 days after surgery. The present findings demonstrate an increase of nNOS after peripheral nerve injury that may contribute to the increase of NO production observed after peripheral neuropathy.

Painful nerve injury decreases resting cytosolic calcium concentrations in sensory neurons of rats

NARCIS (Netherlands)

Fuchs, Andreas; Lirk, Philipp; Stucky, Cheryl; Abram, Stephen E.; Hogan, Quinn H.

2005-01-01

Neuropathic pain is difficult to treat and poorly understood at the cellular level. Although cytoplasmic calcium ([Ca]c) critically regulates neuronal function, the effects of peripheral nerve injury on resting sensory neuronal [Ca]c are unknown. Resting [Ca]c was determined by microfluorometry in

Comparison of the fastest regenerating motor and sensory myelinated axons in the same peripheral nerve

DEFF Research Database (Denmark)

Moldovan, Mihai; Sørensen, Jesper; Krarup, Christian

2006-01-01

Functional outcome after peripheral nerve regeneration is often poor, particularly involving nerve injuries far from their targets. Comparison of sensory and motor axon regeneration before target reinnervation is not possible in the clinical setting, and previous experimental studies addressing...... the question of differences in growth rates of different nerve fibre populations led to conflicting results. We developed an animal model to compare growth and maturation of the fastest growing sensory and motor fibres within the same mixed nerve after Wallerian degeneration. Regeneration of cat tibial nerve...... after crush (n = 13) and section (n = 7) was monitored for up to 140 days, using implanted cuff electrodes placed around the sciatic and tibial nerves and wire electrodes at plantar muscles. To distinguish between sensory and motor fibres, recordings were carried out from L6-S2 spinal roots using cuff...

Protective effect of mulberry flavonoids on sciatic nerve in alloxan-induced diabetic rats

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Ma Song-Tao

2014-12-01

Full Text Available Mulberry leaves (Morus alba L. are a traditional Chinese medicine for blood serum glucose reduction. This study evaluated the protective effects of mulberry flavonoids on sciatic nerve in alloxan-induced diabetic rats. In this study, 80 Sprague-Dawley rats were divided into five groups: A (control, B (diabetic treated with saline, C-D (diabetic treated with 0.3, 0.1 g/kg mulberry flavonoids once a day for 8 weeks and E (diabetic treated with 0.3 mg/kg methycobal. The diabetic condition was induced by intraperitoneal injection of 200 mg/kg alloxan dissolved in saline. At the end of the experimental period, blood, and tissue samples were obtained for biochemical and histopathological investigation. Treatment with 0.3 g/kg mulberry flavonoids significantly inhibited the elevated serum glucose (P< 0.01. The increased myelin sheath area (P< 0.01, myelinated fiber cross-sectional area and extramedullary fiber number (P< 0.05 were also reduced in alloxan-induced rats treated with 0.3 g/kg mulberry flavonoids. 0.3 g/kg mulberry flavonoids also markedly decreased onion-bulb type myelin destruction and degenerative changes of mitochondria and Schwann cells. These findings demonstrate that mulberry flavonoids may improve the recovery of a severe peripheral nerve injury in alloxan-induced diabetic rats and is likely to be useful as a potential treatment on peripheral neuropathy (PN in diabetic rats.

The Role of Nerve Exploration in Supracondylar Humerus Fracture in Children with Nerve Injury

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Anuar RIM

2015-11-01

Full Text Available The supracondylar humerus fracture (SCHF in children is common and can be complicated with nerve injury either primarily immediate post-trauma or secondarily posttreatment. The concept of neurapraxic nerve injury makes most surgeons choose to ‘watch and see’ the nerve recovery before deciding second surgery if the nerve does not recover. We report three cases of nerve injury in SCHF, all of which underwent nerve exploration for different reasons. Early reduction in the Casualty is important to release the nerve tension before transferring the patient to the operation room. If close reduction fails, we proceed to explore the nerve together with open reduction of the fracture. In iatrogenic nerve injury, we recommend nerve exploration to determine the surgical procedure that is causing the injury. Primary nerve exploration will allow early assessment of the injured nerve and minimize subsequent surgery.

Ameliorative potential of Vernonia cinerea on chronic constriction injury of sciatic nerve induced neuropathic pain in rats

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VENKATA R.K. THIAGARAJAN

2014-09-01

Full Text Available The aim of the present study is to investigate the ameliorative potential of ethanolic extract of whole plant of Vernonia cinerea in the chronic constriction injury (CCI of sciatic nerve induced neuropathic pain in rats. Behavioral parameters such as a hot plate, acetone drop, paw pressure, Von Frey hair and tail immersion tests were performed to assess the degree of thermal, chemical and mechanical hyperalgesia and allodynia. Biochemical changes in sciatic nerve tissue were ruled out by estimating thiobarbituric acid reactive substances (TBARS, reduced glutathione (GSH and total calcium levels. Ethanolic extract of Vernonia cinerea and pregabalin were administered for 14 consecutive days starting from the day of surgery. CCI of sciatic nerve has been shown to induce significant changes in behavioral, biochemical and histopathological assessments when compared to the sham control group. Vernonia cinerea attenuated in a dose dependent manner the above pathological changes induced by CCI of the sciatic nerve, which is similar to attenuation of the pregabalin pretreated group. The ameliorating effect of ethanolic extract of Vernonia cinerea against CCI of sciatic nerve induced neuropathic pain may be due to the presence of flavonoids and this effect is attributed to anti-oxidative, neuroprotective and calcium channel modulator actions of these compounds.

Rapid reorganization of adult rat motor cortex somatic representation patterns after motor nerve injury.

OpenAIRE

Sanes, J N; Suner, S; Lando, J F; Donoghue, J P

1988-01-01

The potential for peripheral nerve injury to reorganize motor cortical representations was investigated in adult rats. Maps reflecting functional connections between the motor cortex and somatic musculature were generated with intracortical electrical stimulation techniques. Comparison of cortical somatotopic maps obtained in normal rats with maps generated from rats with a facial nerve lesion indicated that the forelimb and eye/eyelid representations expanded into the normal vibrissa area. R...

Transection of peripheral nerves, bridging strategies and effect evaluation

NARCIS (Netherlands)

IJkema-Paassen, J; Jansen, K; Gramsbergen, A; Meek, MF

Disruption of peripheral nerves due to trauma is a frequently Occurring clinical problem. Gaps in the nerve are bridged by guiding the regenerating nerves along autologous grafts or artificial guides. This review gives an overview oil the different methods of nerve repair techniques. Conventional

Role of TRPM8 in dorsal root ganglion in nerve injury-induced chronic pain

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Su Lin

2011-11-01

Full Text Available Abstract Background Chronic neuropathic pain is an intractable pain with few effective treatments. Moderate cold stimulation can relieve pain, and this may be a novel train of thought for exploring new methods of analgesia. Transient receptor potential melastatin 8 (TRPM8 ion channel has been proposed to be an important molecular sensor for cold. Here we investigate the role of TRPM8 in the mechanism of chronic neuropathic pain using a rat model of chronic constriction injury (CCI to the sciatic nerve. Results Mechanical allodynia, cold and thermal hyperalgesia of CCI rats began on the 4th day following surgery and maintained at the peak during the period from the 10th to 14th day after operation. The level of TRPM8 protein in L5 dorsal root ganglion (DRG ipsilateral to nerve injury was significantly increased on the 4th day after CCI, and reached the peak on the 10th day, and remained elevated on the 14th day following CCI. This time course of the alteration of TRPM8 expression was consistent with that of CCI-induced hyperalgesic response of the operated hind paw. Besides, activation of cold receptor TRPM8 of CCI rats by intrathecal application of menthol resulted in the inhibition of mechanical allodynia and thermal hyperalgesia and the enhancement of cold hyperalgesia. In contrast, downregulation of TRPM8 protein in ipsilateral L5 DRG of CCI rats by intrathecal TRPM8 antisense oligonucleotide attenuated cold hyperalgesia, but it had no effect on CCI-induced mechanical allodynia and thermal hyperalgesia. Conclusions TRPM8 may play different roles in mechanical allodynia, cold and thermal hyperalgesia that develop after nerve injury, and it is a very promising research direction for the development of new therapies for chronic neuroapthic pain.

Axillary nerve injury associated with sports.

Science.gov (United States)

Lee, Sangkook; Saetia, Kriangsak; Saha, Suparna; Kline, David G; Kim, Daniel H

2011-11-01

The aim of this retrospective study was to present and investigate axillary nerve injuries associated with sports. This study retrospectively reviewed 26 axillary nerve injuries associated with sports between the years 1985 and 2010. Preoperative status of the axillary nerve was evaluated by using the Louisiana State University Health Science Center (LSUHSC) grading system published by the senior authors. Intraoperative nerve action potential recordings were performed to check nerve conduction and assess the possibility of resection. Neurolysis, suture, and nerve grafts were used for the surgical repair of the injured nerves. In 9 patients with partial loss of function and 3 with complete loss, neurolysis based on nerve action potential recordings was the primary treatment. Two patients with complete loss of function were treated with resection and suturing and 12 with resection and nerve grafting. The minimum follow-up period was 16 months (mean 20 months). The injuries were associated with the following sports: skiing (12 cases), football (5), rugby (2), baseball (2), ice hockey (2), soccer (1), weightlifting (1), and wrestling (1). Functional recovery was excellent. Neurolysis was performed in 9 cases, resulting in an average functional recovery of LSUHSC Grade 4.2. Recovery with graft repairs averaged LSUHSC Grade 3 or better in 11 of 12 cases Surgical repair can restore useful deltoid function in patients with sports-associated axillary nerve injuries, even in cases of severe stretch-contusion injury.

An audit of traumatic nerve injury.

LENUS (Irish Health Repository)

O'Connor, G

2009-07-01

The impact of trauma in the Irish healthcare setting is considerable. We present the results of a retrospective assessment of referrals to a Neurophysiology department for suspected traumatic nerve injury. A broad range of traumatic neuropathies was demonstrated on testing, from numerous causes. We demonstrate an increased liklihood of traumatic nerve injury after fracture \\/ dislocation (p = 0.007). Our series demonstrates the need for clinicians to be aware of the possibility of nerve injury post trauma, especially after bony injury.

MRI of pathology-proven peripheral nerve amyloidosis

International Nuclear Information System (INIS)

McKenzie, Gavin A.; Broski, Stephen M.; Howe, Benjamin M.; Spinner, Robert J.; Amrami, Kimberly K.; Dispenzieri, Angela; Ringler, Michael D.

2017-01-01

To highlight the MRI characteristics of pathologically proven amyloidosis involving the peripheral nervous system (PNS) and determine the utility of MRI in directing targeted biopsy for aiding diagnosis. A retrospective study was performed for patients with pathologically proven PNS amyloidosis who also underwent MRI of the biopsied or excised nerve. MRI signal characteristics, nerve morphology, associated muscular denervation changes, and the presence of multifocal involvement were detailed. Pathology reports were reviewed to determine subtypes of amyloid. Charts were reviewed to gather patient demographics, neurological symptoms and radiologist interpretation. Four men and three women with a mean age of 62 ± 11 years (range 46-76) were identified. All patients had abnormal findings on EMG with mixed sensorimotor neuropathy. All lesions demonstrated diffuse multifocal neural involvement with T1 hypointensity, T2 hyperintensity, and variable enhancement on MRI. One lesion exhibited superimposed T2 hypointensity. Six of seven patients demonstrated associated muscular denervation changes. Peripheral nerve amyloidosis is rare, and the diagnosis is difficult because of insidious symptom onset, mixed sensorimotor neurologic deficits, and the potential for a wide variety of nerves affected. On MRI, peripheral nerve involvement is most commonly characterized by T1 hypointensity, T2 hyperintensity, variable enhancement, maintenance of the fascicular architecture with fusiform enlargement, multifocal involvement and muscular denervation changes. While this appearance mimics other inflammatory neuropathies, MRI can readily detect neural changes and direct-targeted biopsy, thus facilitating early diagnosis and appropriate management. (orig.)

MRI of pathology-proven peripheral nerve amyloidosis

Energy Technology Data Exchange (ETDEWEB)

McKenzie, Gavin A.; Broski, Stephen M.; Howe, Benjamin M.; Spinner, Robert J.; Amrami, Kimberly K.; Dispenzieri, Angela; Ringler, Michael D. [Mayo Clinic, Department of Musculoskeletal Radiology, Rochester, MN (United States)

2017-01-15

To highlight the MRI characteristics of pathologically proven amyloidosis involving the peripheral nervous system (PNS) and determine the utility of MRI in directing targeted biopsy for aiding diagnosis. A retrospective study was performed for patients with pathologically proven PNS amyloidosis who also underwent MRI of the biopsied or excised nerve. MRI signal characteristics, nerve morphology, associated muscular denervation changes, and the presence of multifocal involvement were detailed. Pathology reports were reviewed to determine subtypes of amyloid. Charts were reviewed to gather patient demographics, neurological symptoms and radiologist interpretation. Four men and three women with a mean age of 62 ± 11 years (range 46-76) were identified. All patients had abnormal findings on EMG with mixed sensorimotor neuropathy. All lesions demonstrated diffuse multifocal neural involvement with T1 hypointensity, T2 hyperintensity, and variable enhancement on MRI. One lesion exhibited superimposed T2 hypointensity. Six of seven patients demonstrated associated muscular denervation changes. Peripheral nerve amyloidosis is rare, and the diagnosis is difficult because of insidious symptom onset, mixed sensorimotor neurologic deficits, and the potential for a wide variety of nerves affected. On MRI, peripheral nerve involvement is most commonly characterized by T1 hypointensity, T2 hyperintensity, variable enhancement, maintenance of the fascicular architecture with fusiform enlargement, multifocal involvement and muscular denervation changes. While this appearance mimics other inflammatory neuropathies, MRI can readily detect neural changes and direct-targeted biopsy, thus facilitating early diagnosis and appropriate management. (orig.)

[RESEARCH PROGRESS OF PERIPHERAL NERVE SURGERY ASSISTED BY Da Vinci ROBOTIC SYSTEM].

Science.gov (United States)

Shen, Jie; Song, Diyu; Wang, Xiaoyu; Wang, Changjiang; Zhang, Shuming

2016-02-01

To summarize the research progress of peripheral nerve surgery assisted by Da Vinci robotic system. The recent domestic and international articles about peripheral nerve surgery assisted by Da Vinci robotic system were reviewed and summarized. Compared with conventional microsurgery, peripheral nerve surgery assisted by Da Vinci robotic system has distinctive advantages, such as elimination of physiological tremors and three-dimensional high-resolution vision. It is possible to perform robot assisted limb nerve surgery using either the traditional brachial plexus approach or the mini-invasive approach. The development of Da Vinci robotic system has revealed new perspectives in peripheral nerve surgery. But it has still been at the initial stage, more basic and clinical researches are still needed.

The successful use of peripheral nerve blocks for femoral amputation

DEFF Research Database (Denmark)

Bech, Birgitte Louise; Melchiors, J; Børglum, J

2009-01-01

We present a case report of four patients with severe cardiac insufficiency where peripheral nerve blocks guided by either nerve stimulation or ultrasonography were the sole anaesthetic for above-knee amputation. The patients were breathing spontaneously and remained haemodynamically stable during...... surgery. Thus, use of peripheral nerve blocks for femoral amputation in high-risk patients seems to be the technique of choice that can lower perioperative risk....

The Use of Degradable Nerve Conduits for Human Nerve Repair: A Review of the Literature

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M. F. Meek

2005-01-01

Full Text Available The management of peripheral nerve injury continues to be a major clinical challenge. The most widely used technique for bridging defects in peripheral nerves is the use of autologous nerve grafts. This technique, however, has some disadvantages. Many alternative experimental techniques have thus been developed, such as degradable nerve conduits. Degradable nerve guides have been extensively studied in animal experimental studies. However, the repair of human nerves by degradable nerve conduits has been limited to only a few clinical studies. In this paper, an overview of the available international published literature on degradable nerve conduits for bridging human peripheral nerve defects is presented for literature available until 2004. Also, the philosophy on the use of nerve guides and nerve grafts is given.

Chondroitinase C Selectively Degrades Chondroitin Sulfate Glycosaminoglycans that Inhibit Axonal Growth within the Endoneurium of Peripheral Nerve.

Science.gov (United States)

Graham, James B; Muir, David

2016-01-01

The success of peripheral nerve regeneration is highly dependent on the regrowth of axons within the endoneurial basal lamina tubes that promote target-oriented pathfinding and appropriate reinnervation. Restoration of nerve continuity at this structural level after nerve transection injury by direct repair and nerve grafting remains a major surgical challenge. Recently, biological approaches that alter the balance of growth inhibitors and promoters in nerve have shown promise to improve appropriate axonal regeneration and recovery of peripheral nerve function. Chondroitin sulfate proteoglycans (CSPGs) are known inhibitors of axonal growth. This growth inhibition is mainly associated with a CSPG's glycosaminoglycan chains. Enzymatic degradation of these chains with chondroitinase eliminates this inhibitory activity and, when applied in vivo, can improve the outcome of nerve repair. To date, these encouraging findings were obtained with chondroitinase ABC (a pan-specific chondroitinase). The aim of this study was to examine the distribution of CSPG subtypes in rodent, rabbit, and human peripheral nerve and to test more selective biological enzymatic approaches to improve appropriate axonal growth within the endoneurium and minimize aberrant growth. Here we provide evidence that the endoneurium, but not the surrounding epineurium, is rich in CSPGs that have glycosaminoglycan chains readily degraded by chondroitinase C. Biochemical studies indicate that chondroitinase C has degradation specificity for 6-sulfated glycosaminoglycans found in peripheral nerve. We found that chondroitinase C degrades and inactivates inhibitory CSPGs within the endoneurium but not so much in the surrounding nerve compartments. Cryoculture bioassays (neurons grown on tissue sections) show that chondroitinase C selectively and significantly enhanced neuritic growth associated with the endoneurial basal laminae without changing growth-inhibiting properties of the surrounding epineurium

Treatment and Follow Up Outcomes of Patients with Peroneal Nerve Injury: A Single Center Experience

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Yasar Dagistan

2017-01-01

Full Text Available Aim: Trap neuropathy is characterized by compression of the peripheral nerve into fibro osseous channels in trespassing areas of body segments. Peroneal nerve is the most frequently injured nerve in traumatic injuries of the lower extremities. In the present study, we investigated functional results of surgical treatment of patients with peroneal nerve injury who delayed visiting our clinics after the damage; we also aimed to observe the effects of this delay on prognosis. We interpreted postoperative results of the patients with EMG and physical examination findings. Material and Method: Subjects with peroneal nerve damage who visited our clinics between 2012 and 2015 were included in the present study. EMG and muscle motor strength tests were conducted pre and postoperatively for clinical assessment. Results: Of the 16 patients in the study population, 7 were men and 9 were women. The median age of the subjects was 49.6 years (14-77 years. Admission time was 9 months after injury. Causes of the peroneal nerve damage were as follows: prosthesis surgery in 4 (25%, ankle damage in 2 (12.5%, excessive squatting by agriculture workers in 4 (25%, aggressive exercise in 2 (12.5%, bone fracture in 2 (12.5%, and unknown origin in 2 (12.5%. Discussion: Peroneal nerve injury usually occurs by compression of the nerve at the head or neck of the fibula. Results of decompression surgery are usually compromising in non-traumatic nerve palsies. Period of duration between injury and diagnosis and muscular atrophy are main factors associated with success of treatment.

Functional evaluation of peripheral nerve regeneration and target reinnervation in animal models: a critical overview.

Science.gov (United States)

Navarro, Xavier

2016-02-01

Peripheral nerve injuries usually lead to severe loss of motor, sensory and autonomic functions in the patients. Due to the complex requirements for adequate axonal regeneration, functional recovery is often poorly achieved. Experimental models are useful to investigate the mechanisms related to axonal regeneration and tissue reinnervation, and to test new therapeutic strategies to improve functional recovery. Therefore, objective and reliable evaluation methods should be applied for the assessment of regeneration and function restitution after nerve injury in animal models. This review gives an overview of the most useful methods to assess nerve regeneration, target reinnervation and recovery of complex sensory and motor functions, their values and limitations. The selection of methods has to be adequate to the main objective of the research study, either enhancement of axonal regeneration, improving regeneration and reinnervation of target organs by different types of nerve fibres, or increasing recovery of complex sensory and motor functions. It is generally recommended to use more than one functional method for each purpose, and also to perform morphological studies of the injured nerve and the reinnervated targets. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

alpha-MSH and Org.2766 in peripheral nerve regeneration: different routes of delivery.

Science.gov (United States)

Van der Zee, C E; Brakkee, J H; Gispen, W H

1988-03-15

The efficacy of melanocortins (alpha-MSH and an ACTH-(4-9) analog, Org.2766) in accelerating functional recovery from sciatic nerve damage following various types of subcutaneous and oral administration was assessed in the rat. Furthermore, the effectiveness of the local delivery of melanocortins to the site of injury was examined. An accelerated recovery was evident following subcutaneous constant delivery of Org.2766 from an osmotic mini-pump and from biodegradable polymere microspheres, and was as effective as repeated subcutaneous injections of alpha-MSH or Org.2766. Oral administration of Org.2766 was ineffective. Local application of Org.2766, achieved by wrapping a peptide-impregnated biodegradable gelatine foam matrix around the site of injury, facilitated recovery as well. The biodegradable microspheres and gelatine foam matrix may be of importance in eventual clinical use as effective vehicles for administration of melanocortins in the treatment of peripheral nerve damage.

Mitochondrial alterations with mitochondrial DNA depletion in the nerves of AIDS patients with peripheral neuropathy induced by 2'3'-dideoxycytidine (ddC).

Science.gov (United States)

Dalakas, M C; Semino-Mora, C; Leon-Monzon, M

2001-11-01

The 2'3'-dideoxycytidine (ddC), a nonazylated dideoxynucleoside analog used for the treatment of AIDS, causes a dose-dependent, painful, sensorimotor axonal peripheral neuropathy in up to 30% of the patients. To investigate the cause of the neuropathy, we performed morphological and molecular studies on nerve biopsy specimens from well-selected patients with ddC-neuropathy and from control subjects with disease, including patients with AIDS-related neuropathy never treated with ddC. Because ddC, in vitro, inhibits the replication of mitochondrial DNA (mtDNA), we counted the number of normal and abnormal mitochondria in a 0.04 mm(2) cross-sectional area of the nerves and quantified the copy numbers of mtDNA by competitive PCR in all specimens. A varying degree of axonal degeneration was present in all nerves. Abnormal mitochondria with enlarged size, excessive vacuolization, electron-dense concentric inclusions and degenerative myelin structures were prominent in the ddC-neuropathy and accounted for 55% +/- 2.5% of all counted mitochondria in the axon and Schwann cells, compared with 9% +/- 0.7% of the controls (p ddC-treated patients compared with the controls. We conclude that ddC induces a mitochondrial neuropathy with depletion of the nerve's mtDNA. The findings are consistent with the ability of ddC to selectively inhibit the gamma-DNA polymerase in neuronal cell lines. Toxicity to mitochondria of the peripheral nerve is a new cause of acquired neuropathy induced by exogenous toxins and may be the cause of neuropathy associated with the other neurotoxic antiretroviral drugs or toxic-metabolic conditions.

Increased response to glutamate in small diameter dorsal root ganglion neurons after sciatic nerve injury.

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Kerui Gong

Full Text Available Glutamate in the peripheral nervous system is involved in neuropathic pain, yet we know little how nerve injury alters responses to this neurotransmitter in primary sensory neurons. We recorded neuronal responses from the ex-vivo preparations of the dorsal root ganglia (DRG one week following a chronic constriction injury (CCI of the sciatic nerve in adult rats. We found that small diameter DRG neurons (30 µm were unaffected. Puff application of either glutamate, or the selective ionotropic glutamate receptor agonists alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA and kainic acid (KA, or the group I metabotropic receptor (mGluR agonist (S-3,5-dihydroxyphenylglycine (DHPG, induced larger inward currents in CCI DRGs compared to those from uninjured rats. N-methyl-D-aspartate (NMDA-induced currents were unchanged. In addition to larger inward currents following CCI, a greater number of neurons responded to glutamate, AMPA, NMDA, and DHPG, but not to KA. Western blot analysis of the DRGs revealed that CCI resulted in a 35% increase in GluA1 and a 60% decrease in GluA2, the AMPA receptor subunits, compared to uninjured controls. mGluR1 receptor expression increased by 60% in the membrane fraction, whereas mGluR5 receptor subunit expression remained unchanged after CCI. These results show that following nerve injury, small diameter DRG neurons, many of which are nociceptive, have increased excitability and an increased response to glutamate that is associated with changes in receptor expression at the neuronal membrane. Our findings provide further evidence that glutamatergic transmission in the periphery plays a role in nociception.

a technique to repair peripheral nerve injury

African Journals Online (AJOL)

attached nerve does occi.rr, and functional recovery (sensory and motor) has been demonstrated. ..... Brachial plexus. Upper trunk to lower. 19 Nov 1998 ... Fractured. 13 Mar 1998 Mid shaft hiunerus Radial nerve to. 14 Mar 1999 humerus cut.

Peripheral Nerve Function and Lower Extremity Muscle Power in Older Men

DEFF Research Database (Denmark)

Ward, Rachel E; Caserotti, Paolo; Faulkner, Kimberly

2014-01-01

To assess whether sensorimotor peripheral nerve function is associated with muscle power in community-dwelling older men.......To assess whether sensorimotor peripheral nerve function is associated with muscle power in community-dwelling older men....

Effects of graded mechanical compression of rabbit sciatic nerve on nerve blood flow and electrophysiological properties.

Science.gov (United States)

Yayama, Takafumi; Kobayashi, Shigeru; Nakanishi, Yoshitaka; Uchida, Kenzo; Kokubo, Yasuo; Miyazaki, Tsuyoshi; Takeno, Kenichi; Awara, Kosuke; Mwaka, Erisa S; Iwamoto, Yukihide; Baba, Hisatoshi

2010-04-01

Entrapment neuropathy is a frequent clinical problem that can be caused by, among other factors, mechanical compression; however, exactly how a compressive force affects the peripheral nerves remains poorly understood. In this study, using a rabbit model of sciatic nerve injury (n=12), we evaluated the time-course of changes in intraneural blood flow, compound nerve action potentials, and functioning of the blood-nerve barrier during graded mechanical compression. Nerve injury was applied using a compressor equipped with a custom-made pressure transducer. Cessation of intraneural blood flow was noted at a mean compressive force of 0.457+/-0.022 N (+/-SEM), and the compound action potential became zero at 0.486+/-0.031 N. Marked extravasation of Evans blue albumin was noted after 20 min of intraneural ischemia. The functional changes induced by compression are likely due to intraneural edema, which could subsequently result in impairment of nerve function. These changes may be critical factors in the development of symptoms associated with nerve compression. (c) 2009 Elsevier Ltd. All rights reserved.

Effect of PAS triple therapy on nerve injury, oxidative stress and inflammatory response in patients with cerebral infarction

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Li-Jun Deng

2017-10-01

Full Text Available Objective: To study the effect of probucol + aspirin + atorvastatin (PAS triple therapy on nerve injury, oxidative stress and inflammatory response in patients with cerebral infarction. Methods: Patients with acute cerebral infarction who were treated in Affiliated Hospital of Jianghan University between February 2015 and January 2015 were selected and randomly divided into the PAS group who received probucol + aspirin + atorvastatin triple therapy and the control group who received aspirin + atorvastatin double therapy. The markers of nerve injury, oxidative stress and inflammatory response were determined before treatment and 15 d after treatment. Results: 15 d after treatment, peripheral blood Keap-1 expression and serum GPX1 contents of both groups of patients were significantly higher than those before treatment while peripheral blood Nrf-2 and ARE expression as well as serum S100B, NSE, sTRAIL, FKN, HMGB-1, sICAM-1, Chemerin and 8-iso-PGF2α contents were significantly lower than those before treatment, and peripheral blood Keap-1 expression and serum GPX1 content of PAS group were significantly higher than those of control group while peripheral blood Nrf-2 and ARE expression as well as serum S100B, NSE, sTRAIL, FKN, HMGB-1, sICAM-1, Chemerin and 8-iso-PGF2α contents were significantly lower than those of control group. Conclusion: PAS triple therapy can reduce the nerve injury as well as oxidative stress response and inflammatory response in patients with cerebral infarction.

One-stage human acellular nerve allograft reconstruction for digital nerve defects

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Xue-yuan Li

2015-01-01

Full Text Available Human acellular nerve allografts have a wide range of donor origin and can effectively avoid nerve injury in the donor area. Very little is known about one-stage reconstruction of digital nerve defects. The present study observed the feasibility and effectiveness of human acellular nerve allograft in the reconstruction of < 5-cm digital nerve defects within 6 hours after injury. A total of 15 cases of nerve injury, combined with nerve defects in 18 digits from the Department of Emergency were enrolled in this study. After debridement, digital nerves were reconstructed using human acellular nerve allografts. The patients were followed up for 6-24 months after reconstruction. Mackinnon-Dellon static two-point discrimination results showed excellent and good rates of 89%. Semmes-Weinstein monofilament test demonstrated that light touch was normal, with an obvious improvement rate of 78%. These findings confirmed that human acellular nerve allograft for one-stage reconstruction of digital nerve defect after hand injury is feasible, which provides a novel trend for peripheral nerve reconstruction.

Peripheral nerve injury causes transient expression of MHC class I antigens in rat motor neurons and skeletal muscles

DEFF Research Database (Denmark)

Maehlen, J; Nennesmo, I; Olsson, A B

1989-01-01

After a peripheral nerve lesion (rat facial and sciatic) an induction of major histocompatibility complex (MHC) antigens class I was detected immunohistochemically in skeletal muscle fibers and motor neurons. This MHC expression was transient after a nerve crush, when regeneration occurred......, but persisted after a nerve cut, when regeneration was prevented. Since the time course of MHC class I expression correlates to that of regeneration a role for this cell surface molecule in regeneration may be considered....

Effect of peripheral morphine in a human model of acute inflammatory pain

DEFF Research Database (Denmark)

Lillesø, J; Hammer, N A; Pedersen, J L

2000-01-01

Several studies have demonstrated the presence of opioid inducible receptors on peripheral nerves and peripheral antinociceptive effects of opioids. However, the effects of peripheral opioid administration in man are controversial. Our study used a randomized, double-blind, placebo-controlled, th......Several studies have demonstrated the presence of opioid inducible receptors on peripheral nerves and peripheral antinociceptive effects of opioids. However, the effects of peripheral opioid administration in man are controversial. Our study used a randomized, double-blind, placebo......-controlled, three-way crossover design in a human model of acute inflammatory pain (heat injury). We studied 18 healthy volunteers who each received morphine locally (2 mg), morphine systemically (2 mg), or placebo on three separate study days. The subjects received morphine infiltration subcutaneously (s.c.). 1 h......, but local morphine infiltration neither reduced pain during the burn, nor primary or secondary hyperalgesia to mechanical and heat stimuli after the burn. In conclusion, peripherally applied morphine had no acute antinociceptive effects in this human model of acute inflammatory pain....

Silk fibroin enhances peripheral nerve regeneration by improving vascularization within nerve conduits.

Science.gov (United States)

Wang, Chunyang; Jia, Yachao; Yang, Weichao; Zhang, Cheng; Zhang, Kuihua; Chai, Yimin

2018-07-01

Silk fibroin (SF)-based nerve conduits have been widely used to bridge peripheral nerve defects. Our previous study showed that nerve regeneration in a SF-blended poly (l-lactide-co-ɛ-caprolactone) [P(LLA-CL)] nerve conduit is better than that in a P(LLA-CL) conduit. However, the involved mechanisms remain unclarified. Because angiogenesis within a nerve conduit plays an important role in nerve regeneration, vascularization of SF/P(LLA-CL) and P(LLA-CL) conduits was compared both in vitro and in vivo. In the present study, we observed that SF/P(LLA-CL) nanofibers significantly promoted fibroblast proliferation, and vascular endothelial growth factor secreted by fibroblasts seeded in SF/P(LLA-CL) nanofibers was more than seven-fold higher than that in P(LLA-CL) nanofibers. Conditioned medium of fibroblasts in the SF/P(LLA-CL) group stimulated more human umbilical vein endothelial cells (HUVEC) to form capillary-like networks and promoted faster HUVEC migration. The two kinds of nerve conduits were used to bridge 10-mm-length nerve defects in rats. At 3 weeks of reparation, the blood vessel area in the SF/P(LLA-CL) group was significantly larger than that in the P(LLA-CL) group. More regenerated axons and Schwann cells were also observed in the SF/P(LLA-CL) group, which was consistent with the results of blood vessels. Collectively, our data revealed that the SF/P(LLA-CL) nerve conduit enhances peripheral nerve regeneration by improving angiogenesis within the conduit. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2070-2077, 2018. © 2018 Wiley Periodicals, Inc.

Reconstruction of facial nerve injuries in children.

Science.gov (United States)

Fattah, Adel; Borschel, Gregory H; Zuker, Ron M

2011-05-01

Facial nerve trauma is uncommon in children, and many spontaneously recover some function; nonetheless, loss of facial nerve activity leads to functional impairment of ocular and oral sphincters and nasal orifice. In many cases, the impediment posed by facial asymmetry and reduced mimetic function more significantly affects the child's psychosocial interactions. As such, reconstruction of the facial nerve affords great benefits in quality of life. The therapeutic strategy is dependent on numerous factors, including the cause of facial nerve injury, the deficit, the prognosis for recovery, and the time elapsed since the injury. The options for treatment include a diverse range of surgical techniques including static lifts and slings, nerve repairs, nerve grafts and nerve transfers, regional, and microvascular free muscle transfer. We review our strategies for addressing facial nerve injuries in children.

Mobility-Related Consequences of Reduced Lower-Extremity Peripheral Nerve Function with Age

DEFF Research Database (Denmark)

Ward, Rachel E; Caserotti, P.; Cauley, Jane A

2016-01-01

-dwelling and institutionalized residents, 1 from a range of residential locations, and 1 of patients with peripheral arterial disease. Mean ages ranged from 71-82 years. Nerve function was assessed by vibration threshold (n=2); sensory measures and clinical signs and symptoms of neuropathy (n=2); motor nerve conduction (n=1......The objective of this study is to systematically review the relationship between lower-extremity peripheral nerve function and mobility in older adults. The National Library of Medicine (PubMed) was searched on March 23, 2015 with no limits on publication dates. One reviewer selected original...... research studies of older adults (>= 65 years) that assessed the relationship between lower-extremity peripheral nerve function and mobility-related outcomes. Participants, study design and methods of assessing peripheral nerve impairment were evaluated and results were reported and synthesized. Eight...

Tumors of peripheral nerves; Tumoren der peripheren Nerven

Energy Technology Data Exchange (ETDEWEB)

Ho, Michael [Universitaetsklinikum Zuerich, Institut fuer Diagnostische Radiologie, Zuerich (Switzerland); Lutz, Amelie M. [Stanford University School of Medicine, Department of Radiology, Stanford, CA (United States)

2017-03-15

Differentiation between malignant and benign tumors of peripheral nerves in the early stages is challenging; however, due to the unfavorable prognosis of malignant tumors early identification is required. To show the possibilities for detection, differential diagnosis and clinical management of peripheral nerve tumors by imaging appearance in magnetic resonance (MR) neurography. Review of current literature available in PubMed and MEDLINE, supplemented by the authors' own observations in clinical practice. Although not pathognomonic, several imaging features have been reported for a differentiation between distinct peripheral nerve tumors. The use of MR neurography enables detection and initial differential diagnosis in tumors of peripheral nerves. Furthermore, it plays an important role in clinical follow-up, targeted biopsy and surgical planning. (orig.) [German] Die Unterscheidung zwischen malignen und benignen Tumoren der peripheren Nerven ist im initialen Stadium schwierig. Die Frueherkennung der malignen Tumoren ist aufgrund ihrer unguenstigen Prognose jedoch wichtig. Moeglichkeiten der MR-Neurographie zur Detektion, Artdiagnostik und klinischem Management von Tumoren der peripheren Nerven anhand bildmorphologischer Charakteristika. Zusammenschau der Studienlage mittels PubMed- bzw. MEDLINE-Recherche. Zusaetzlich Darlegung teils unveroeffentlichter Erkenntnisse aus der eigenen klinischen Beobachtung. Wenn auch nicht pathognomonisch, existieren verschiedene Bildgebungszeichen zur moeglichen Unterscheidung verschiedener Tumoren der peripheren Nerven. Die MR-Neurographie ist ein geeignetes bildgebendes Verfahren zur Detektion und ersten Differenzialdiagnose von Tumoren der peripheren Nerven. Zudem kommt ihr besondere Bedeutung bei der Verlaufskontrolle, der gezielten Biopsie und der operativen Planung zu. (orig.)

Selectivity and Longevity of Peripheral-Nerve and Machine Interfaces: A Review

Directory of Open Access Journals (Sweden)

Usman Ghafoor

2017-10-01

Full Text Available For those individuals with upper-extremity amputation, a daily normal living activity is no longer possible or it requires additional effort and time. With the aim of restoring their sensory and motor functions, theoretical and technological investigations have been carried out in the field of neuroprosthetic systems. For transmission of sensory feedback, several interfacing modalities including indirect (non-invasive, direct-to-peripheral-nerve (invasive, and cortical stimulation have been applied. Peripheral nerve interfaces demonstrate an edge over the cortical interfaces due to the sensitivity in attaining cortical brain signals. The peripheral nerve interfaces are highly dependent on interface designs and are required to be biocompatible with the nerves to achieve prolonged stability and longevity. Another criterion is the selection of nerves that allows minimal invasiveness and damages as well as high selectivity for a large number of nerve fascicles. In this paper, we review the nerve-machine interface modalities noted above with more focus on peripheral nerve interfaces, which are responsible for provision of sensory feedback. The invasive interfaces for recording and stimulation of electro-neurographic signals include intra-fascicular, regenerative-type interfaces that provide multiple contact channels to a group of axons inside the nerve and the extra-neural-cuff-type interfaces that enable interaction with many axons around the periphery of the nerve. Section Current Prosthetic Technology summarizes the advancements made to date in the field of neuroprosthetics toward the achievement of a bidirectional nerve-machine interface with more focus on sensory feedback. In the Discussion section, the authors propose a hybrid interface technique for achieving better selectivity and long-term stability using the available nerve interfacing techniques.

Selectivity and Longevity of Peripheral-Nerve and Machine Interfaces: A Review

Science.gov (United States)

Ghafoor, Usman; Kim, Sohee; Hong, Keum-Shik

2017-01-01

For those individuals with upper-extremity amputation, a daily normal living activity is no longer possible or it requires additional effort and time. With the aim of restoring their sensory and motor functions, theoretical and technological investigations have been carried out in the field of neuroprosthetic systems. For transmission of sensory feedback, several interfacing modalities including indirect (non-invasive), direct-to-peripheral-nerve (invasive), and cortical stimulation have been applied. Peripheral nerve interfaces demonstrate an edge over the cortical interfaces due to the sensitivity in attaining cortical brain signals. The peripheral nerve interfaces are highly dependent on interface designs and are required to be biocompatible with the nerves to achieve prolonged stability and longevity. Another criterion is the selection of nerves that allows minimal invasiveness and damages as well as high selectivity for a large number of nerve fascicles. In this paper, we review the nerve-machine interface modalities noted above with more focus on peripheral nerve interfaces, which are responsible for provision of sensory feedback. The invasive interfaces for recording and stimulation of electro-neurographic signals include intra-fascicular, regenerative-type interfaces that provide multiple contact channels to a group of axons inside the nerve and the extra-neural-cuff-type interfaces that enable interaction with many axons around the periphery of the nerve. Section Current Prosthetic Technology summarizes the advancements made to date in the field of neuroprosthetics toward the achievement of a bidirectional nerve-machine interface with more focus on sensory feedback. In the Discussion section, the authors propose a hybrid interface technique for achieving better selectivity and long-term stability using the available nerve interfacing techniques. PMID:29163122

Peripheral nerve magnetic stimulation: influence of tissue non-homogeneity

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Papazov Sava P

2003-12-01

Full Text Available Abstract Background Peripheral nerves are situated in a highly non-homogeneous environment, including muscles, bones, blood vessels, etc. Time-varying magnetic field stimulation of the median and ulnar nerves in the carpal region is studied, with special consideration of the influence of non-homogeneities. Methods A detailed three-dimensional finite element model (FEM of the anatomy of the wrist region was built to assess the induced currents distribution by external magnetic stimulation. The electromagnetic field distribution in the non-homogeneous domain was defined as an internal Dirichlet problem using the finite element method. The boundary conditions were obtained by analysis of the vector potential field excited by external current-driven coils. Results The results include evaluation and graphical representation of the induced current field distribution at various stimulation coil positions. Comparative study for the real non-homogeneous structure with anisotropic conductivities of the tissues and a mock homogeneous media is also presented. The possibility of achieving selective stimulation of either of the two nerves is assessed. Conclusion The model developed could be useful in theoretical prediction of the current distribution in the nerves during diagnostic stimulation and therapeutic procedures involving electromagnetic excitation. The errors in applying homogeneous domain modeling rather than real non-homogeneous biological structures are demonstrated. The practical implications of the applied approach are valid for any arbitrary weakly conductive medium.

Treadmill exercise induced functional recovery after peripheral nerve repair is associated with increased levels of neurotrophic factors.

Directory of Open Access Journals (Sweden)

Jae-Sung Park

Full Text Available Benefits of exercise on nerve regeneration and functional recovery have been reported in both central and peripheral nervous system disease models. However, underlying molecular mechanisms of enhanced regeneration and improved functional outcomes are less understood. We used a peripheral nerve regeneration model that has a good correlation between functional outcomes and number of motor axons that regenerate to evaluate the impact of treadmill exercise. In this model, the median nerve was transected and repaired while the ulnar nerve was transected and prevented from regeneration. Daily treadmill exercise resulted in faster recovery of the forelimb grip function as evaluated by grip power and inverted holding test. Daily exercise also resulted in better regeneration as evaluated by recovery of compound motor action potentials, higher number of axons in the median nerve and larger myofiber size in target muscles. Furthermore, these observations correlated with higher levels of neurotrophic factors, glial derived neurotrophic factor (GDNF, brain derived neurotrophic factor (BDNF and insulin-like growth factor-1 (IGF-1, in serum, nerve and muscle suggesting that increase in muscle derived neurotrophic factors may be responsible for improved regeneration.

Effects of patterned peripheral nerve stimulation on soleus spinal motor neuron excitability

DEFF Research Database (Denmark)

Jimenez, Samuel; Mordillo-Mateos, Laura; Dileone, Michele

2018-01-01

obtained was discarded, since non-patterned 15 Hz stimulation at 110% HT led to pain scores similar to those induced by EcTBS at 110% HT, but was not able to induce any modulation of the H reflex amplitude. Together, the results provide first time evidence that peripheral continuous TBS induces a short......Spinal plasticity is thought to contribute to sensorimotor recovery of limb function in several neurological disorders and can be experimentally induced in animals and humans using different stimulation protocols. In healthy individuals, electrical continuous Theta Burst Stimulation (TBS....... In 26 healthy subjects, we examined the effects of electrical TBS given to the tibial nerve in the popliteal fossa on the excitability of lumbar spinal motoneurons as measured by H-reflex amplitude of the soleus muscle evoked by tibial nerve stimulation. Continuous TBS was given at 110% of H...

Overview of pediatric peripheral facial nerve paralysis: analysis of 40 patients.

Science.gov (United States)

Özkale, Yasemin; Erol, İlknur; Saygı, Semra; Yılmaz, İsmail

2015-02-01

Peripheral facial nerve paralysis in children might be an alarming sign of serious disease such as malignancy, systemic disease, congenital anomalies, trauma, infection, middle ear surgery, and hypertension. The cases of 40 consecutive children and adolescents who were diagnosed with peripheral facial nerve paralysis at Baskent University Adana Hospital Pediatrics and Pediatric Neurology Unit between January 2010 and January 2013 were retrospectively evaluated. We determined that the most common cause was Bell palsy, followed by infection, tumor lesion, and suspected chemotherapy toxicity. We noted that younger patients had generally poorer outcome than older patients regardless of disease etiology. Peripheral facial nerve paralysis has been reported in many countries in America and Europe; however, knowledge about its clinical features, microbiology, neuroimaging, and treatment in Turkey is incomplete. The present study demonstrated that Bell palsy and infection were the most common etiologies of peripheral facial nerve paralysis. © The Author(s) 2014.

Malignant peripheral nerve sheath tumour of the bladder associated with neurofibromatosis I.

LENUS (Irish Health Repository)

O'Brien, Julie

2008-12-01

Neurofibromatosis is a hamartomatous disorder of autonomic peripheral nerve sheaths associated with peripheral nerve sheath tumours. Most tumours are neurofibromas; however, the genitourinary system is rarely involved. We present a rare case of a nerve sheath tumour of the bladder in a young patient, which was discovered to be malignant.

Efficacy of benfotiamine versus thiamine on function and glycation products of peripheral nerves in diabetic rats.

Science.gov (United States)

Stracke, H; Hammes, H P; Werkmann, D; Mavrakis, K; Bitsch, I; Netzel, M; Geyer, J; Köpcke, W; Sauerland, C; Bretzel, R G; Federlin, K F

2001-01-01

In rats with streptozotocin (STZ) induced diabetes the effect of (watersoluble) thiamine nitrate and of (lipidsoluble) benfotiamine on peripheral nerve function (motor nerve conduction velocity) as well as on the formation of advanced glycation end-products in peripheral nerve tissue was studied. In one group of animals drug administration was started immediately after diabetes induction (prevention study) and in another group two months after diabetes induction (treatment study). Motor nerve conduction velocity (NCV) dropped by 10.5% in diabetic animals, carboxymethyl-lysine (CML) rose to a 3.5fold concentration, deoxyglucosone (3DG)-type AGE formation was increased 5.1fold compared with controls. After three months preventive administration of both vitamin B(1) preparations NCV had increased substantially compared with results in diabetic controls. It was nearly normal after six months with benfotiamine, while the administration of thiamine nitrate resulted in no further amelioration. NCV was nearly normalized after six months of benfotiamine application but not with thiamine. Furthermore, benfotiamine induced a major inhibition of neural imidazole-type AGE formation and completely prevented diabetes induced glycoxidation products (CML). Treatment with thiamine did not significantly affect AGE or cmL levels. Unlike treatment with water-soluble thiamine nitrate timely administration of liposoluble prodrug benfotiamine was effective in the prevention of functional damage and of AGE and cmL formation in nerves of diabetic rats.

Nerve injuries do occur in elbow arthroscopy.

Science.gov (United States)

Hilgersom, Nick F J; van Deurzen, Derek F P; Gerritsma, Carina L E; van der Heide, Huub J L; Malessy, Martijn J A; Eygendaal, Denise; van den Bekerom, Michel P J

2018-01-01

The purpose is to create more awareness as well as emphasize the risk of permanent nerve injury as a complication of elbow arthroscopy. Patients who underwent elbow arthroscopy complicated by permanent nerve injury were retrospectively collected. Patients were collected using two strategies: (1) by word-of-mouth throughout the Dutch Society of Shoulder and Elbow Surgery, and the Leiden University Nerve Centre, and (2) approaching two medical liability insurance companies. Medical records were reviewed to determine patient characteristics, disease history and postoperative course. Surgical records were reviewed to determine surgical details. A total of eight patients were collected, four men and four women, ageing 21-54 years. In five out of eight patients (62.5%), the ulnar nerve was affected; in the remaining three patients (37.5%), the radial nerve was involved. Possible causes for nerve injury varied among patients, such as portal placement and the use of motorized instruments. A case series on permanent nerve injury as a complication of elbow arthroscopy is presented. Reporting on this sequel in the literature is little, however, its risk is not to be underestimated. This study emphasizes that permanent nerve injury is a complication of elbow arthroscopy, concurrently increasing awareness and thereby possibly aiding to prevention. IV, case series.

Management of peripheral facial nerve palsy

OpenAIRE

Finsterer, Josef

2008-01-01

Peripheral facial nerve palsy (FNP) may (secondary FNP) or may not have a detectable cause (Bell?s palsy). Three quarters of peripheral FNP are primary and one quarter secondary. The most prevalent causes of secondary FNP are systemic viral infections, trauma, surgery, diabetes, local infections, tumor, immunological disorders, or drugs. The diagnosis of FNP relies upon the presence of typical symptoms and signs, blood chemical investigations, cerebro-spinal-fluid-investigations, X-ray of the...

Chondroitinase C Selectively Degrades Chondroitin Sulfate Glycosaminoglycans that Inhibit Axonal Growth within the Endoneurium of Peripheral Nerve.

Directory of Open Access Journals (Sweden)

James B Graham

Full Text Available The success of peripheral nerve regeneration is highly dependent on the regrowth of axons within the endoneurial basal lamina tubes that promote target-oriented pathfinding and appropriate reinnervation. Restoration of nerve continuity at this structural level after nerve transection injury by direct repair and nerve grafting remains a major surgical challenge. Recently, biological approaches that alter the balance of growth inhibitors and promoters in nerve have shown promise to improve appropriate axonal regeneration and recovery of peripheral nerve function. Chondroitin sulfate proteoglycans (CSPGs are known inhibitors of axonal growth. This growth inhibition is mainly associated with a CSPG's glycosaminoglycan chains. Enzymatic degradation of these chains with chondroitinase eliminates this inhibitory activity and, when applied in vivo, can improve the outcome of nerve repair. To date, these encouraging findings were obtained with chondroitinase ABC (a pan-specific chondroitinase. The aim of this study was to examine the distribution of CSPG subtypes in rodent, rabbit, and human peripheral nerve and to test more selective biological enzymatic approaches to improve appropriate axonal growth within the endoneurium and minimize aberrant growth. Here we provide evidence that the endoneurium, but not the surrounding epineurium, is rich in CSPGs that have glycosaminoglycan chains readily degraded by chondroitinase C. Biochemical studies indicate that chondroitinase C has degradation specificity for 6-sulfated glycosaminoglycans found in peripheral nerve. We found that chondroitinase C degrades and inactivates inhibitory CSPGs within the endoneurium but not so much in the surrounding nerve compartments. Cryoculture bioassays (neurons grown on tissue sections show that chondroitinase C selectively and significantly enhanced neuritic growth associated with the endoneurial basal laminae without changing growth-inhibiting properties of the surrounding