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Sample records for peripheral nerve equilibrium

  1. Peripheral Nerve Disorders

    MedlinePlus

    ... spinal cord. Like static on a telephone line, peripheral nerve disorders distort or interrupt the messages between the brain ... body. There are more than 100 kinds of peripheral nerve disorders. They can affect one nerve or many nerves. ...

  2. [Ganglia of peripheral nerves].

    PubMed

    Tatagiba, M; Penkert, G; Samii, M

    1993-01-01

    The authors present two different types of ganglion affecting the peripheral nerves: extraneural and intraneural ganglion. Compression of peripheral nerves by articular ganglions is well known. The surgical management involves the complete removal of the lesion with preservation of most nerve fascicles. Intraneural ganglion is an uncommon lesion which affects the nerve diffusely. The nerve fascicles are usually intimately involved between the cysts, making complete removal of all cysts impossible. There is no agreement about the best surgical management to be applied in these cases. Two possibilities are available: opening of the epineural sheath lengthwise and pressing out the lesion; or resection of the affected part of the nerve and performing a nerve reconstruction. While in case of extraneural ganglion the postoperative clinical evolution is very favourable, only long follow up studies will reveal in case of intraneural ganglion the best surgical approach. PMID:8128785

  3. Barriers of the peripheral nerve

    PubMed Central

    Peltonen, Sirkku; Alanne, Maria; Peltonen, Juha

    2013-01-01

    This review introduces the traditionally defined anatomic compartments of the peripheral nerves based on light and electron microscopic topography and then explores the cellular and the most recent molecular basis of the different barrier functions operative in peripheral nerves. We also elucidate where, and how, the homeostasis of the normal human peripheral nerve is controlled in situ and how claudin-containing tight junctions contribute to the barriers of peripheral nerve. Also, the human timeline of the development of the barriers of the peripheral nerve is depicted. Finally, potential future therapeutic modalities interfering with the barriers of the peripheral nerve are discussed. PMID:24665400

  4. Ultrasound of Peripheral Nerves

    PubMed Central

    Suk, Jung Im; Walker, Francis O.; Cartwright, Michael S.

    2013-01-01

    Over the last decade, neuromuscular ultrasound has emerged as a useful tool for the diagnosis of peripheral nerve disorders. This article reviews sonographic findings of normal nerves including key quantitative ultrasound measurements that are helpful in the evaluation of focal and possibly generalized peripheral neuropathies. It also discusses several recent papers outlining the evidence base for the use of this technology, as well as new findings in compressive, traumatic, and generalized neuropathies. Ultrasound is well suited for use in electrodiagnostic laboratories where physicians, experienced in both the clinical evaluation of patients and the application of hands-on technology, can integrate findings from the patient’s history, physical examination, electrophysiological studies, and imaging for diagnosis and management. PMID:23314937

  5. Malignant Peripheral Nerve Sheath Tumor.

    PubMed

    James, Aaron W; Shurell, Elizabeth; Singh, Arun; Dry, Sarah M; Eilber, Fritz C

    2016-10-01

    Malignant peripheral nerve sheath tumor (MPNST) is the sixth most common type of soft tissue sarcoma. Most MPNSTs arise in association with a peripheral nerve or preexisting neurofibroma. Neurofibromatosis type is the most important risk factor for MPNST. Tumor size and fludeoxyglucose F 18 avidity are among the most helpful parameters to distinguish MPNST from a benign peripheral nerve sheath tumor. The histopathologic diagnosis is predominantly a diagnosis of light microscopy. Immunohistochemical stains are most helpful to distinguish high-grade MPNST from its histologic mimics. Current surgical management of high-grade MPNST is similar to that of other high-grade soft tissue sarcomas. PMID:27591499

  6. Peripheral nerve conduits: technology update

    PubMed Central

    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

  7. [Peripheral Nerve Injuries in Sports].

    PubMed

    Tettenborn, B; Mehnert, S; Reuter, I

    2016-09-01

    Peripheral nerve injuries due to sports are relatively rare but the exact incidence is not known due to a lack of epidemiological studies. Particular sports activities tend to cause certain peripheral nerve injuries including direct acute compression or stretching, repetitive compression and stretching over time, or another mechanism such as ischemia or laceration. These nerve lesions may be severe and delay or preclude the athlete's return to sports, especially in cases with delayed diagnosis. Repetitive and vigorous use or overuse makes the athlete vulnerable to disorders of the peripheral nerves, and sports equipment may cause compression of the nerves. Depending on etiology, the treatment is primarily conservative and includes physiotherapy, modification of movements and sports equipment, shoe inserts, splinting, antiphlogistic drugs, sometimes local administration of glucocorticoids or, lately, the use of extracorporeal shock waves. Most often, cessation of the offending physical activity is necessary. Surgery is only indicated in the rare cases of direct traumatic nerve injury or when symptoms are refractory to conservative therapy. Prognosis mainly depends on the etiology and the available options of modifying measures.This article is based on the publications "Reuter I, Mehnert S. Engpasssyndrome peripherer Nerven bei Sportlern". Akt Neurol 2012;39:292-308 and Sportverl Sportschad 2013;27:130-146. PMID:27607069

  8. Peripheral nerve disease in pregnancy.

    PubMed

    Klein, Autumn

    2013-06-01

    Neuropathies during pregnancy and the postpartum period are common and are usually due to compression around pregnancy and childbirth. The most common peripheral neuropathies are Bell's palsy, carpal tunnel syndrome (CTS), and lower extremity neuropathies. Although most neuropathies are usually reversible, associated disabilities or morbidities can limit functioning and require therapy. Nerve conduction study tests and imaging should only be considered if symptoms are unusual or prolonged. Some neuropathies may be associated with preeclampsia or an inherent underlying neuropathy that increases the risk of nerve injury. All neuropathies in pregnancy should be followed as some may be persistent and require follow-up. PMID:23563878

  9. Detection of peripheral nerve pathology

    PubMed Central

    Seelig, Michael J.; Baker, Jonathan C.; Mackinnon, Susan E.; Pestronk, Alan

    2013-01-01

    Objective: To compare accuracy of ultrasound and MRI for detecting focal peripheral nerve pathology, excluding idiopathic carpal or cubital tunnel syndromes. Methods: We performed a retrospective review of patients referred for neuromuscular ultrasound to identify patients who had ultrasound and MRI of the same limb for suspected brachial plexopathy or mononeuropathies, excluding carpal/cubital tunnel syndromes. Ultrasound and MRI results were compared to diagnoses determined by surgical or, if not performed, clinical/electrodiagnostic evaluation. Results: We identified 53 patients who had both ultrasound and MRI of whom 46 (87%) had nerve pathology diagnosed by surgical (n = 39) or clinical/electrodiagnostic (n = 14) evaluation. Ultrasound detected the diagnosed nerve pathology (true positive) more often than MRI (43/46 vs 31/46, p < 0.001). Nerve pathology was correctly excluded (true negative) with equal frequency by MRI and ultrasound (both 6/7). In 25% (13/53), ultrasound was accurate (true positive or true negative) when MRI was not. These pathologies were typically (10/13) long (>2 cm) and only occasionally (2/13) outside the MRI field of view. MRI missed multifocal pathology identified with ultrasound in 6 of 7 patients, often (5/7) because pathology was outside the MRI field of view. Conclusions: Imaging frequently detects peripheral nerve pathology and contributes to the differential diagnosis in patients with mononeuropathies and brachial plexopathies. Ultrasound is more sensitive than MRI (93% vs 67%), has equivalent specificity (86%), and better identifies multifocal lesions than MRI. In sonographically accessible regions ultrasound is the preferred initial imaging modality for anatomic evaluation of suspected peripheral nervous system lesions. PMID:23553474

  10. Ultrasound-Guided Peripheral Nerve Procedures.

    PubMed

    Strakowski, Jeffrey A

    2016-08-01

    Ultrasound guidance allows real-time visualization of the needle in peripheral nerve procedures, improving accuracy and safety. Sonographic visualization of the peripheral nerve and surrounding anatomy can provide valuable information for diagnostic purposes and procedure enhancement. Common procedures discussed are the suprascapular nerve at the suprascapular notch, deep branch of the radial nerve at the supinator, median nerve at the pronator teres and carpal tunnel, lateral cutaneous nerve of the thigh, superficial fibular nerve at the leg, tibial nerve at the ankle, and interdigital neuroma. For each procedure, the indications, relevant anatomy, preprocedural scanning technique, and injection procedure itself are detailed. PMID:27468673

  11. Continuous peripheral nerve blocks in children.

    PubMed

    Dadure, C; Capdevila, X

    2005-06-01

    In recent years, regional anaesthesia in children has generated increasing interest. Continuous peripheral nerve blocks have an important role in the anaesthetic arsenal, allowing effective, safe and prolonged postoperative pain management. Indications for continuous peripheral nerve blocks depend on benefits/risks analysis of each technique for each patient. The indications include surgery associated with intense postoperative pain, surgery requiring painful physical therapy, and complex regional pain syndrome. Continuous peripheral nerve blocks are usually performed under general anaesthesia or sedation, and require appropriate equipment in order to decrease the risk of nerve injury. New techniques, such as transcutaneous stimulation or ultrasound guidance, appear to facilitate nerve and plexus identification in paediatric patients. Nevertheless, continuous peripheral nerve block may mask compartment syndrome in certain surgical procedure or trauma. Finally, ropivacaine appears to be the best local anaesthetic for continuous peripheral nerve blocks in children, requiring low flow rate with low concentration of the local anaesthetic. PMID:15966500

  12. Raman microspectroscopy for visualization of peripheral nerves

    NASA Astrophysics Data System (ADS)

    Minamikawa, Takeo; Harada, Yoshinori; Koizumi, Noriaki; Takamatsu, Tetsuro

    2013-02-01

    The peripheral nervous system plays an important role in motility, sensory, and autonomic functions of the human body. Preservation of peripheral nerves in surgery is essential for improving quality of life of patients. To preserve peripheral nerves, detection of ne peripheral nerves that cannot be identi ed by human eye or under white light imaging is necessary. In this study, we sought to provide a proof-of-principle demonstration of a label-free detection technique of peripheral nerve tissues against adjacent tissues that employs spontaneous Raman microspectroscopy. A line-illumination confocal Raman microscope was used for the experiment. A laser operating at the wavelength of 532 nm was used as an excitation laser light. We obtained Raman spectra of peripheral nerve, brous connective tissue, skeletal muscle, blood vessel, and adipose tissue of Wistar rats, and extracted speci c spectral features of peripheral nerves and adjacent tissues. By applying multivariate image analysis, peripheral nerves were clearly detected against adjacent tissues without any preprocessing neither xation nor staining. These results suggest the potential of the Raman spectroscopic observation for noninvasive and label-free nerve detection, and we expect this method could be a key technique for nerve-sparing surgery.

  13. Tissue engineered constructs for peripheral nerve surgery

    PubMed Central

    Johnson, P. J.; Wood, M. D.; Moore, A. M.; Mackinnon, S. E.

    2013-01-01

    Summary Background Tissue engineering has been defined as “an interdisciplinary field that applies the principles of engineering and life sciences toward the development of biological substitutes that restore, maintain, or improve tissue function or a whole organ”. Traumatic peripheral nerve injury resulting in significant tissue loss at the zone of injury necessitates the need for a bridge or scaffold for regenerating axons from the proximal stump to reach the distal stump. Methods A review of the literature was used to provide information on the components necessary for the development of a tissue engineered peripheral nerve substitute. Then, a comprehensive review of the literature is presented composed of the studies devoted to this goal. Results Extensive research has been directed toward the development of a tissue engineered peripheral nerve substitute to act as a bridge for regenerating axons from the proximal nerve stump seeking the distal nerve. Ideally this nerve substitute would consist of a scaffold component that mimics the extracellular matrix of the peripheral nerve and a cellular component that serves to stimulate and support regenerating peripheral nerve axons. Conclusions The field of tissue engineering should consider its challenge to not only meet the autograft “gold standard” but also to understand what drives and inhibits nerve regeneration in order to surpass the results of an autograft. PMID:24385980

  14. Malignant Peripheral Nerve Sheath Tumors.

    PubMed

    Durbin, Adam D; Ki, Dong Hyuk; He, Shuning; Look, A Thomas

    2016-01-01

    Malignant peripheral nerve sheath tumors (MPNST) are tumors derived from Schwann cells or Schwann cell precursors. Although rare overall, the incidence of MPNST has increased with improved clinical management of patients with the neurofibromatosis type 1 (NF1) tumor predisposition syndrome. Unfortunately, current treatment modalities for MPNST are limited, with no targeted therapies available and poor efficacy of conventional radiation and chemotherapeutic regimens. Many murine and zebrafish models of MPNST have been developed, which have helped to elucidate the genes and pathways that are dysregulated in MPNST tumorigenesis, including the p53, and the RB1, PI3K-Akt-mTOR, RAS-ERK and Wnt signaling pathways. Preclinical results have suggested that new therapies, including mTOR and ERK inhibitors, may synergize with conventional chemotherapy in human tumors. The discovery of new genome editing technologies, like CRISPR-cas9, and their successful application to the zebrafish model will enable rapid progress in the faithful modeling of MPNST molecular pathogenesis. The zebrafish model is especially suited for high throughput screening of new targeted therapeutics as well as drugs approved for other purposes, which may help to bring enhanced treatment modalities into human clinical trials for this devastating disease. PMID:27165368

  15. Perioperative lower extremity peripheral nerve traction injuries.

    PubMed

    Plastaras, Christopher T; Chhatre, Akhil; Kotcharian, Ashot S

    2014-01-01

    Peripheral nerve traction injuries may occur after surgical care and can involve any of the lower extremity large peripheral nerves. In this review, the authors discuss injuries after knee or hip surgical intervention. The diagnosis, including electrodiagnostic studies, is time sensitive and also relies on a detailed history and physical examination. Successful prevention and treatment involve familiarity with risk and predisposing factors as well as prophylactic measures. PMID:24267207

  16. Peripheral nerve injuries in the athlete.

    PubMed

    Feinberg, J H; Nadler, S F; Krivickas, L S

    1997-12-01

    Peripheral nerves are susceptible to injury in the athlete because of the excessive physiological demands that are made on both the neurological structures and the soft tissues that protect them. The common mechanisms of injury are compression, traction, ischaemia and laceration. Seddon's original classification system for nerve injuries based on neurophysiological changes is the most widely used. Grade 1 nerve injury is a neuropraxic condition, grade 2 is axonal degeneration and grade 3 is nerve transection. Peripheral nerve injuries are more common in the upper extremities than the lower extremities, tend to be sport specific, and often have a biomechanical component. While the more acute and catastrophic neurological injuries are usually obvious, many remain subclinical and are not recognised before neurological damage is permanent. Early detection allows initiation of a proper rehabilitation programme and modification of biomechanics before the nerve injury becomes irreversible. Recognition of nerve injuries requires an understanding of peripheral neuroanatomy, knowledge of common sites of nerve injury and an awareness of the types of peripheral nerve injuries that are common and unique to each sport. The electrodiagnostic exam, usually referred to as the 'EMG', consists of nerve conduction studies and the needle electrode examination. It is used to determine the site and degree of neurological injury and to predict outcome. It should be performed by a neurologist or physiatrist (physician specialising in physical medicine and rehabilitation), trained and skilled in this procedure. Timing is essential if the study is to provide maximal information. Findings such as decreased recruitment after injury and conduction block at the site of injury may be apparent immediately after injury but other findings such as abnormal spontaneous activity may take several weeks to develop. The electrodiagnostic test assists with both diagnosis of the injury and in predicting

  17. Chapter 11: Tissue engineering of peripheral nerves.

    PubMed

    Battiston, Bruno; Raimondo, Stefania; Tos, Pierluigi; Gaidano, Valentina; Audisio, Chiara; Scevola, Anna; Perroteau, Isabelle; Geuna, Stefano

    2009-01-01

    Tissue engineering of peripheral nerves has seen an increasing interest over the last years and, similarly to many other fields of regenerative medicine, great expectations have risen within the general public to its potential clinical application in the treatment of damaged nerves. However, in spite of the scientific advancements, applications to the patients is still very limited and it appears that to optimize the strategy for the tissue engineering of the peripheral nerves in the clinical view, researchers have to strive for a new level of innovation which will bring together (in a multitranslational approach) the main pillars of tissue engineering: namely (1) microsurgery, (2) cell and tissue transplantation, (3) material science, and (4) gene transfer. This review paper provides an overview of these four key approaches to peripheral nerve tissue engineering. While some of these issues will also be specifically addressed in other papers in this special issue on peripheral nerve regeneration of the International Review of Neurobiology, in this paper we will focus on an example of successful translational research in tissue engineering, namely nerve reconstruction by muscle-vein-combined nerve scaffolds. PMID:19682640

  18. Neurophysiological approach to disorders of peripheral nerve.

    PubMed

    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 methods including nerve conduction studies and electromyography used in the study of patients suspected of having a neuropathy and the significance of the findings are discussed in detail and more novel and experimental methods are mentioned. Diagnostic considerations are based on a flow chart classifying neuropathies into eight categories based on mode of onset, distribution, and electrophysiological findings, and the electrophysiological characteristics in each type of neuropathy are discussed. PMID:23931776

  19. Effects of Laser Irradiation on Peripheral Nerve

    NASA Astrophysics Data System (ADS)

    Baxter, G. D.; Chow, R.; Armati, P.; Bjordal, J. M.; Laakso, L.

    2009-06-01

    A literature review was undertaken to determine the electrophysiological effects of Laser Irradiation (LI) on peripheral mammalian nerves, as a means of elucidating the potential mechanisms underlying pain relief associated with laser therapy. Relevant computerized databases and reference lists were searched, and experts consulted for further articles. A total of 38 studies, comprising 82 separate experiments were identified. In human studies, all types of LI (red and infrared, pulsed and cw) slowed nerve conduction velocity, and reduced compound action potential of irradiated nerves. In animal studies, infrared LI suppressed conduction velocity, as well as noxious stimulation evoked potential. This review thus indicates the potential of laser irradiation to inhibit activity in peripheral nerves, and highlights one potential mechanism of action for laser-mediated pain relief.

  20. Peripheral nerve regeneration and neurotrophic factors

    PubMed Central

    TERENGHI, GIORGIO

    1999-01-01

    The role of neurotrophic factors in the maintenance and survival of peripheral neuronal cells has been the subject of numerous studies. Administration of exogenous neurotrophic factors after nerve injury has been shown to mimic the effect of target organ-derived trophic factors on neuronal cells. After axotomy and during peripheral nerve regeneration, the neurotrophins NGF, NT-3 and BDNF show a well defined and selective beneficial effect on the survival and phenotypic expression of primary sensory neurons in dorsal root ganglia and of motoneurons in spinal cord. Other neurotrophic factors such as CNTF, GDNF and LIF also exert a variety of actions on neuronal cells, which appear to overlap and complement those of the neurotrophins. In addition, there is an indirect contribution of GGF to nerve regeneration. GGF is produced by neurons and stimulates proliferation of Schwann cells, underlining the close interaction between neuronal and glial cells during peripheral nerve regeneration. Different possibilities have been investigated for the delivery of growth factors to the injured neurons, in search of a suitable system for clinical applications. The studies reviewed in this article show the therapeutic potential of neurotrophic factors for the treatment of peripheral nerve injury and for neuropathies. PMID:10227662

  1. Radiation-induced malignant and atypical peripheral nerve sheath tumors

    SciTech Connect

    Foley, K.M.; Woodruff, J.M.; Ellis, F.T.; Posner, J.B.

    1980-04-01

    The reported peripheral nerve complications of therapeutic irradiation in humans include brachial and lumbar plexus fibrosis and cranial and peripheral nerve atrophy. We have encountered 9 patients with malignant (7) and atypical (2) peripheral nerve tumors occurring in an irradiated site suggesting that such tumors represent another delayed effect of radiation treatment on peripheral nerve. In all instances the radio-theray was within an acceptable radiation dosage, yet 3 patients developed local radiation-induced skin and bony abnormalities. The malignant peripheral nerve sheath tumors developed only in the radiation port. Animal studies support the clinical observation that malignant peripheral nerve sheath tumors can occur as a delayed effect of irradiation.

  2. Peripheral nerve morphogenesis induced by scaffold micropatterning

    PubMed Central

    Memon, Danish; Boneschi, Filippo Martinelli; Madaghiele, Marta; Brambilla, Paola; Del Carro, Ubaldo; Taveggia, Carla; Riva, Nilo; Trimarco, Amelia; Lopez, Ignazio D.; Comi, Giancarlo; Pluchino, Stefano; Martino, Gianvito; Sannino, Alessandro; Quattrini, Angelo

    2014-01-01

    Several bioengineering approaches have been proposed for peripheral nervous system repair, with limited results and still open questions about the underlying molecular mechanisms. We assessed the biological processes that occur after the implantation of collagen scaffold with a peculiar porous microstructure of the wall in a rat sciatic nerve transection model compared to commercial collagen conduits and nerve crush injury using functional, histological and genome wide analyses. We demonstrated that within 60 days, our conduit had been completely substituted by a normal nerve. Gene expression analysis documented a precise sequential regulation of known genes involved in angiogenesis, Schwann cells/axons interactions and myelination, together with a selective modulation of key biological pathways for nerve morphogenesis induced by porous matrices. These data suggest that the scaffold’s microstructure profoundly influences cell behaviors and creates an instructive micro-environment to enhance nerve morphogenesis that can be exploited to improve recovery and understand the molecular differences between repair and regeneration. PMID:24559639

  3. Massive exophytic malignant peripheral nerve sheath tumor.

    PubMed

    Khorsand, Derek; Porrino, Jack; Flaherty, Erin; Bandhlish, Anshu; Davidson, Darin

    2016-06-01

    We present a case of a solitary neurofibroma involving the right posterior shoulder of a 69-year-old man with degeneration into a massive, malignant peripheral nerve sheath tumor measuring more than 3 times the average reported size. The radiographic, magnetic resonance imaging, and computed tomographic features are compared with the gross appearance and pathology. PMID:27257459

  4. Stem cell salvage of injured peripheral nerve.

    PubMed

    Grimoldi, Nadia; Colleoni, Federica; Tiberio, Francesca; Vetrano, Ignazio G; Cappellari, Alberto; Costa, Antonella; Belicchi, Marzia; Razini, Paola; Giordano, Rosaria; Spagnoli, Diego; Pluderi, Mauro; Gatti, Stefano; Morbin, Michela; Gaini, Sergio M; Rebulla, Paolo; Bresolin, Nereo; Torrente, Yvan

    2015-01-01

    We previously developed a collagen tube filled with autologous skin-derived stem cells (SDSCs) for bridging long rat sciatic nerve gaps. Here we present a case report describing a compassionate use of this graft for repairing the polyinjured motor and sensory nerves of the upper arms of a patient. Preclinical assessment was performed with collagen/SDSC implantation in rats after sectioning the sciatic nerve. For the patient, during the 3-year follow-up period, functional recovery of injured median and ulnar nerves was assessed by pinch gauge test and static two-point discrimination and touch test with monofilaments, along with electrophysiological and MRI examinations. Preclinical experiments in rats revealed rescue of sciatic nerve and no side effects of patient-derived SDSC transplantation (30 and 180 days of treatment). In the patient treatment, motor and sensory functions of the median nerve demonstrated ongoing recovery postimplantation during the follow-up period. The results indicate that the collagen/SDSC artificial nerve graft could be used for surgical repair of larger defects in major lesions of peripheral nerves, increasing patient quality of life by saving the upper arms from amputation. PMID:24268028

  5. 21 CFR 868.2775 - Electrical peripheral nerve stimulator.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Electrical peripheral nerve stimulator. 868.2775... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Monitoring Devices § 868.2775 Electrical peripheral nerve stimulator. (a) Identification. An electrical peripheral nerve stimulator (neuromuscular blockade monitor)...

  6. 21 CFR 868.2775 - Electrical peripheral nerve stimulator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Electrical peripheral nerve stimulator. 868.2775... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Monitoring Devices § 868.2775 Electrical peripheral nerve stimulator. (a) Identification. An electrical peripheral nerve stimulator (neuromuscular blockade monitor)...

  7. In vitro models for peripheral nerve regeneration.

    PubMed

    Geuna, S; Raimondo, S; Fregnan, F; Haastert-Talini, K; Grothe, C

    2016-02-01

    The study of peripheral nerve repair and regeneration is particularly relevant in the light of the high clinical incidence of nerve lesions. However, the clinical outcome after nerve lesions is often far from satisfactory and the functional recovery is almost never complete. Therefore, a number of therapeutic approaches are being investigated, ranging from local delivery of trophic factors and other molecules to bioactive biomaterials and complex nerve prostheses. Translation of the new therapeutic approaches to the patient always requires a final pre-clinical step using in vivo animal models. The need to limit as much as possible animal use in biomedical research, however, makes the preliminary use of in vitro models mandatory from an ethical point of view. In this article, the different types of in vitro models available today for the study of peripheral nerve regeneration have been ranked by adopting a three-step stair model based on their increasing ethical impact: (i) cell line-based models, which raise no ethical concern; (ii) primary cell-based models, which have low ethical impact as animal use, although necessary, is limited; and (iii) organotypic ex vivo-based models, which raise moderate ethical concerns as the use of laboratory animals is required although with much lower impact on animal wellbeing in comparison to in vivo models of peripheral nerve regeneration. This article aims to help researchers in selecting the best experimental approach for their scientific goals driven by the 'Three Rs' (3Rs) rules (Replacement, Reduction or Refinement of animal use in research) for scientific research. PMID:26309051

  8. Tendon Transfers for Combined Peripheral Nerve Injuries.

    PubMed

    Makarewich, Christopher A; Hutchinson, Douglas T

    2016-08-01

    Combined peripheral nerve injuries present a unique set of challenges to the hand surgeon when considering tendon transfers. They are often associated with severe soft tissue trauma, including lacerations to remaining innervated muscles and tendons, significant scar formation, and substantial sensory loss. In the case of combined nerve injuries, there are typically fewer options for tendon transfers due to fewer tendons of shared function that are expendable as well as associated injuries to tendon or muscle bellies. As such, careful preoperative planning must be performed to make the most of remaining muscle tendon units. PMID:27387081

  9. Repair of peripheral nerve with vein wrapping*

    PubMed Central

    LEUZZI, S.; ARMENIO, A.; LEONE, L.; DE SANTIS, V.; DI TURI, A.; ANNOSCIA, P.; BUFANO, L.; PASCONE, M.

    2014-01-01

    Objective The post–traumatic neuro-anastomosis must be protected from the surrounding environment. This barrier must be biologically inert, biodegradable, not compressing but protecting the nerve. Formation of painful neuroma is one of the major issues with neuro-anastomosis; currently there is no consensus on post-repair neuroma prevention. Aim of this study is to evaluate the efficacy of neuroanastomosis performed with venous sheath to reduce painful neuromas formation, improve the electrical conductivity of the repaired nerve, and reduce the discrepancies of the sectioned nerve stumps. Patients and methods From a trauma population of 320 patients treated in a single centre between January 2008 and December 2011, twenty-six patients were identified as having an injury to at least one of the peripheral nerves of the arm and enrolled in the study. Patients were divided into two groups. In the group A (16 patients) the end-to-end nerve suture was wrapped in a vein sheath and compared with the group B (10 patients) in which a simple end-to-end neurorrhaphy was performed. The venous segment used to cover the nerve micro-suture was harvested from the superficial veins of the forearm. The parameters analyzed were: functional recovery of motor nerves, sensitivity and pain. Results Average follow-up was 14 months (range: 12–24 months). The group A showed a more rapid motor and sensory recovery and a reduction of the painful symptoms compared to the control group (B). Conclusions The Authors demonstrated that, in their experience, the venous sheath provides a valid solution to avoid the dispersion of the nerve fibres, to prevent adherent scars and painful neuromas formation. Moreover it can compensate the different size of two nerve stumps, allowing, thereby, a more rapid functional and sensitive recovery without expensive devices. PMID:24841688

  10. Sonography of Common Peripheral Nerve Disorders With Clinical Correlation.

    PubMed

    Jacobson, Jon A; Wilson, Thomas J; Yang, Lynda J-S

    2016-04-01

    Sonography is now considered an effective method to evaluate peripheral nerves. Low cost, high resolution, the ability to image an entire limb in a short time, and dynamic assessment are several of the positive attributes of sonography. This article will review the normal appearance of peripheral nerves as shown with sonography. In addition, the most common applications for sonography of the peripheral nerves will be reviewed, which include entrapment neuropathies, intraneural ganglion cyst, nerve trauma, and peripheral nerve sheath tumors. Clinical information related to nerve disorders is also included, as it provides valuable information that can be obtained during sonographic examinations, increasing diagnostic accuracy. PMID:26931790

  11. Perspectives in regeneration and tissue engineering of peripheral nerves.

    PubMed

    Raimondo, Stefania; Fornaro, Michele; Tos, Pierluigi; Battiston, Bruno; Giacobini-Robecchi, Maria G; Geuna, Stefano

    2011-07-01

    Peripheral nerve injury is a common casualty and although peripheral nerve fibers retain a considerable regeneration potential also in the adult, recovery is usually rather poor, especially in case of large nerve defects. The aim of this paper is to address the perspectives in regeneration and tissue engineering after peripheral nerve injury by reviewing the relevant experimental studies in animal models. After a brief overview of the morphological changes related to peripheral nerve injury and regeneration, the paper will address the evolution of peripheral nerve tissue engineering with special focus on transplantation strategies, from organs and tissues to cells and genes, that can be carried out, particularly in case of severe nerve lesions with substance loss. Finally, the need for integrated research which goes beyond therapeutic strategies based on single approaches is emphasized, and the importance of bringing together the various complimentary disciplines which can contribute to the definition of effective new strategies for regenerating the injured peripheral nerve is outlined. PMID:21474294

  12. Role of ultrasound in evaluation of peripheral nerves

    PubMed Central

    Lawande, Ashwin D; Warrier, Sudhir S; Joshi, Mukund S

    2014-01-01

    Ultrasonography (USG) is an excellent cost-effective modality in imaging of peripheral nerves. With the newer high-frequency probes with different footprints which allow high-resolution imaging at relatively superficial location, USG can detect and evaluate traumatic, inflammatory, infective, neoplastic, and compressive pathologies of the peripheral nerves. This article describes the technique for evaluation of nerves by USG as well as the USG appearances of normal and diseased peripheral nerves. PMID:25114388

  13. Peripheral nerve morphogenesis induced by scaffold micropatterning.

    PubMed

    Cerri, Federica; Salvatore, Luca; Memon, Danish; Martinelli Boneschi, Filippo; Madaghiele, Marta; Brambilla, Paola; Del Carro, Ubaldo; Taveggia, Carla; Riva, Nilo; Trimarco, Amelia; Lopez, Ignazio D; Comi, Giancarlo; Pluchino, Stefano; Martino, Gianvito; Sannino, Alessandro; Quattrini, Angelo

    2014-04-01

    Several bioengineering approaches have been proposed for peripheral nervous system repair, with limited results and still open questions about the underlying molecular mechanisms. We assessed the biological processes that occur after the implantation of collagen scaffold with a peculiar porous micro-structure of the wall in a rat sciatic nerve transection model compared to commercial collagen conduits and nerve crush injury using functional, histological and genome wide analyses. We demonstrated that within 60 days, our conduit had been completely substituted by a normal nerve. Gene expression analysis documented a precise sequential regulation of known genes involved in angiogenesis, Schwann cells/axons interactions and myelination, together with a selective modulation of key biological pathways for nerve morphogenesis induced by porous matrices. These data suggest that the scaffold's micro-structure profoundly influences cell behaviors and creates an instructive micro-environment to enhance nerve morphogenesis that can be exploited to improve recovery and understand the molecular differences between repair and regeneration. PMID:24559639

  14. Optical stimulation of peripheral nerves in vivo

    NASA Astrophysics Data System (ADS)

    Wells, Jonathon D.

    This dissertation documents the emergence and validation of a new clinical tool that bridges the fields of biomedical optics and neuroscience. The research herein describes an innovative method for direct neurostimulation with pulsed infrared laser light. Safety and effectiveness of this technique are first demonstrated through functional stimulation of the rat sciatic nerve in vivo. The Holmium:YAG laser (lambda = 2.12 mum) is shown to operate at an optimal wavelength for peripheral nerve stimulation with advantages over standard electrical neural stimulation; including contact-free stimulation, high spatial selectivity, and lack of a stimulation artifact. The underlying biophysical mechanism responsible for transient optical nerve stimulation appears to be a small, absorption driven thermal gradient sustained at the axonal layer of nerve. Results explicitly prove that low frequency optical stimulation can reliably stimulate without resulting in tissue thermal damage. Based on the positive results from animal studies, these optimal laser parameters were utilized to move this research into the clinic with a combined safety and efficacy study in human subjects undergoing selective dorsal rhizotomy. The clinical Holmium:YAG laser was used to effectively stimulate human dorsal spinal roots and elicit functional muscle responses recorded during surgery without evidence of nerve damage. Overall these results predict that this technology can be a valuable clinical tool in various neurosurgical applications.

  15. Clinical outcomes for Conduits and Scaffolds in peripheral nerve repair

    PubMed Central

    Gerth, David J; Tashiro, Jun; Thaller, Seth R

    2015-01-01

    The gold standard of peripheral nerve repair is nerve autograft when tensionless repair is not possible. Use of nerve autograft has several shortcomings, however. These include limited availability of donor tissue, sacrifice of a functional nerve, and possible neuroma formation. In order to address these deficiencies, researchers have developed a variety of biomaterials available for repair of peripheral nerve gaps. We review the clinical studies published in the English literature detailing outcomes and reconstructive options. Regardless of the material used or the type of nerve repaired, outcomes are generally similar to nerve autograft in gaps less than 3 cm. New biomaterials currently under preclinical evaluation may provide improvements in outcomes. PMID:25685760

  16. Axonal transport disruption in peripheral nerve disease

    PubMed Central

    Lloyd, Thomas E.

    2015-01-01

    Many neurodegenerative diseases and neuropathies have been proposed to be caused by a disruption of axonal transport. However, the mechanisms whereby impaired transport causes disease remain unclear. Proposed mechanisms include impairment in delivery of organelles such as mitochondria, defective retrograde neurotrophic signaling, and disruption of the synaptic vesicle cycle within the synaptic terminal. Simple model organisms such as the fruitfly, Drosophila melanogaster, allow live imaging of axonal transport to be combined with high-throughput genetic screens and are providing insights into the pathophysiology of peripheral nerve diseases. PMID:23279432

  17. Malignant Peripheral Nerve Sheath Tumor of the Infraorbital Nerve.

    PubMed

    D'Addino, José Luis; Piccoletti, Laura; Pigni, María Mercedes; de Gordon, Maria José Rodriguez Arenas

    2016-06-01

    The objective of this study is to report a large, rare, and ulcerative infiltrated skin lesion. Its diagnosis, therapeutic management, and progress are described. The patient is a 78-year-old white man, who presented with a 12-month ulcerative perforated lesion that had affected and infiltrated the skin, with easy bleeding. He had a history of hypertension, although controlled, was a 40-year smoker, had chronic atrial fibrillation, diabetes, and microangiopathy. During the consultation, the patient also presented with ocular obstruction due to an inability to open the eye. He mentioned having reduced vision. The computed tomography scan showed upper maxilla osteolysis without eye involvement. We underwent a radical resection in which upper maxilla and the anterior orbital margin were included. We used a Becker-type flap that allowed us to rebuild the cheek and to complete a modified neck dissection. Progress was favorable; the patient recovered ocular motility and his vision improved to 20/200. The final biopsy result was "malignant peripheral nerve sheath tumor, malignant schwannoma." Malignant schwannoma of the peripheral nerve is extremely rare. The total resection and reconstruction being completed in one surgery represented a challenge due to the difficulty in obtaining tissues in addition to the necessity of an oncological resection. PMID:27162577

  18. Magnetic resonance neurography of peripheral nerve tumors and tumorlike conditions.

    PubMed

    Ahlawat, Shivani; Chhabra, Avneesh; Blakely, Jaishri

    2014-02-01

    Peripheral nerve enlargement may be seen in multiple conditions including hereditary or inflammatory neuropathies, sporadic or syndromic peripheral nerve sheath tumors, perineurioma, posttraumatic neuroma, and intraneural ganglion. Malignancies such as neurolymphoma, intraneural metastases, or sarcomas may also affect the peripheral nervous system and result in nerve enlargement. The imaging appearance and differentiating factors become especially relevant in the setting of tumor syndromes such as neurofibromatosis type 1, neurofibromatosis type 2, and schwannomatosis. This article reviews the typical magnetic resonance neurography imaging appearances of neurogenic as well as nonneurogenic neoplasms and tumorlike lesions of peripheral nerves, with emphasis on distinguishing factors. PMID:24210319

  19. Regulation of Peripheral Nerve Stimulation Technology.

    PubMed

    Birk, Daniel M; Yin, Dali; Slavin, Konstantin V

    2015-01-01

    The number of peripheral nerve stimulation (PNS) indications, targets, and devices is expanding, yet the development of the technology has been slow because many devices used for PNS do not have formal regulatory approval. Manufacturers have not sought Food and Drug Administration (FDA) approval for PNS devices because of a perceived lack of interest amongst practitioners and patients. Without FDA approval, companies cannot invest in marketing to educate the implanters and the patients about the benefits of PNS in the treatment of chronic pain. Violation of this has resulted in governmental investigation and prosecution. Most of the PNS devices currently used to treat chronic pain are FDA approved for epidural spinal cord stimulation. Many of the complications seen in PNS surgery can be attributed to the lack of purpose-built hardware with FDA approval. Despite the lack of regulatory approval, there are insurance companies that approve PNS procedures when deemed medically necessary. As the targets and indications for PNS continue to expand, there will be an even greater need for customized technological solutions. It is up to the medical device industry to invest in the design and marketing of PNS technology and seek out FDA approval. Market forces will continue to push PNS into the mainstream and physicians will increasingly have the choice to implant devices specifically designed and approved to treat chronic peripheral nerve pain. PMID:26394389

  20. Sural nerve defects after nerve biopsy or nerve transfer as a sensory regeneration model for peripheral nerve conduit implantation.

    PubMed

    Radtke, C; Kocsis, J D; Reimers, K; Allmeling, C; Vogt, P M

    2013-09-01

    Nerve repair after injury can be effectively accomplished by direct suture approximation of the proximal and distal segments. This is more successful if coadaptation can be achieved without tension. Currently, the gold standard repair of larger deficits is the transplantation of an autologous sensory sural nerve graft. However, a significant disadvantage of this technique is the inevitable donor morbidity (sensory loss, neuroma and scar formation) after harvesting of the sural nerve. Moreover, limitation of autologous donor nerve length and fixed diameter of the available sural nerve are major drawbacks of current autograft treatment. Another approach that was introduced for nerve repair is the implantation of alloplastic nerve tubes made of, for example, poly-L-lactide. In these, nerve stumps of the transected nerves are surgically bridged using the biosynthetic conduit. A number of experimental studies, primarily in rodents, indicate axonal regeneration and remyelination after implantation of various conduits. However, only limited clinical studies with conduit implantation have been performed in acute peripheral nerve injuries particularly on digital nerves. Clinical transfer of animal studies, which can be carefully calibrated for site and extent of injury, to humans is difficult to interpret due to the intrinsic variability in human nerve injuries. This prevents effective quantification of improvement and induces bias in the study. Therefore, standardization of lesion/repair in human studies is warranted. Here we propose to use sural nerve defects, induced due to nerve graft harvesting or from diagnostic nerve biopsies as a model site to enable standardization of nerve conduit implantation. This would help better with the characterization of the implants and its effectiveness in axonal regeneration and remyelination. Nerve regeneration can be assessed, for example, by recovery of sensation, measured non-invasively by threshold to von Frey filaments and cold

  1. Continuous peripheral nerve block for battlefield anesthesia and evacuation.

    PubMed

    Buckenmaier, Chester C; McKnight, Geselle M; Winkley, James V; Bleckner, Lisa L; Shannon, Clarence; Klein, Stephen M; Lyons, Robert C; Chiles, John H

    2005-01-01

    Peripheral nerve and continuous peripheral nerve block (CPNB) have the potential to be valuable techniques in combat anesthesia. We describe the first successful application of CPNB in the pain management and surgical management of a combat casualty as he was evacuated from the Iraqi battlefield to the United States. PMID:15765463

  2. 21 CFR 868.2775 - Electrical peripheral nerve stimulator.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Electrical peripheral nerve stimulator. 868.2775 Section 868.2775 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Monitoring Devices § 868.2775 Electrical peripheral nerve stimulator. (a) Identification....

  3. 21 CFR 868.2775 - Electrical peripheral nerve stimulator.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Electrical peripheral nerve stimulator. 868.2775 Section 868.2775 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Monitoring Devices § 868.2775 Electrical peripheral nerve stimulator. (a) Identification....

  4. Physiological and pharmacologic aspects of peripheral nerve blocks

    PubMed Central

    Vadhanan, Prasanna; Tripaty, Debendra Kumar; Adinarayanan, S.

    2015-01-01

    A successful peripheral nerve block not only involves a proper technique, but also a thorough knowledge and understanding of the physiology of nerve conduction and pharmacology of local anesthetics (LAs). This article focuses on what happens after the block. Pharmacodynamics of LAs, underlying mechanisms of clinically observable phenomena such as differential blockade, tachyphylaxis, C fiber resistance, tonic and phasic blockade and effect of volume and concentration of LAs. Judicious use of additives along with LAs in peripheral nerve blocks can prolong analgesia. An entirely new group of drugs-neurotoxins has shown potential as local anesthetics. Various methods are available now to prolong the duration of peripheral nerve blocks. PMID:26330722

  5. Edaravone promotes functional recovery after mechanical peripheral nerve injury

    PubMed Central

    Zhang, Teng; Li, Zhengwei; Dong, Jianli; Nan, Feng; Li, Tao; Yu, Qing

    2014-01-01

    Edaravone has been shown to reduce ischemia/reperfusion-induced peripheral nerve injury. However, the therapeutic effect of edaravone on peripheral nerve injury caused by mechanical factors is unknown. In the present study, we established a peripheral nerve injury model by crushing the sciatic nerve using hemostatic forceps, and then administered edaravone 3 mg/kg intraperitoneally. The sciatic functional index and superoxide dismutase activity of the sciatic nerve were increased, and the malondialdehyde level was decreased in animals in the edaravone group compared with those in the model group. Bcl-2 expression was increased, but Bax expression was decreased in anterior horn cells of the L4-6 spinal cord segments. These results indicated that edaravone has a neuroprotective effect following peripheral nerve injury caused by mechanical factors through alleviating free radical damage to cells and inhibiting lipid peroxidation, as well as regulating apoptosis-related protein expression. PMID:25374594

  6. Label-free photoacoustic microscopy of peripheral nerves

    NASA Astrophysics Data System (ADS)

    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.

  7. Label-free photoacoustic microscopy of peripheral nerves

    PubMed Central

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

    2014-01-01

    Abstract. 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. PMID:24395587

  8. Schwann cell spectrins modulate peripheral nerve myelination

    PubMed Central

    Susuki, Keiichiro; Raphael, Alya R.; Ogawa, Yasuhiro; Stankewich, Michael C.; Peles, Elior; Talbot, William S.; Rasband, Matthew N.

    2011-01-01

    During peripheral nerve development, Schwann cells ensheathe axons and form myelin to enable rapid and efficient action potential propagation. Although myelination requires profound changes in Schwann cell shape, how neuron–glia interactions converge on the Schwann cell cytoskeleton to induce these changes is unknown. Here, we demonstrate that the submembranous cytoskeletal proteins αII and βII spectrin are polarized in Schwann cells and colocalize with signaling molecules known to modulate myelination in vitro. Silencing expression of these spectrins inhibited myelination in vitro, and remyelination in vivo. Furthermore, myelination was disrupted in motor nerves of zebrafish lacking αII spectrin. Finally, we demonstrate that loss of spectrin significantly reduces both F-actin in the Schwann cell cytoskeleton and the Nectin-like protein, Necl4, at the contact site between Schwann cells and axons. Therefore, we propose αII and βII spectrin in Schwann cells integrate the neuron–glia interactions mediated by membrane proteins into the actin-dependent cytoskeletal rearrangements necessary for myelination. PMID:21518878

  9. Three-dimensional Reconstruction of Peripheral Nerve Internal Fascicular Groups

    PubMed Central

    Zhong, Yingchun; Wang, Liping; Dong, Jianghui; Zhang, Yi; Luo, Peng; Qi, Jian; Liu, Xiaolin; Xian, Cory J.

    2015-01-01

    Peripheral nerves are important pathways for receiving afferent sensory impulses and sending out efferent motor instructions, as carried out by sensory nerve fibers and motor nerve fibers. It has remained a great challenge to functionally reconnect nerve internal fiber bundles (or fascicles) in nerve repair. One possible solution may be to establish a 3D nerve fascicle visualization system. This study described the key technology of 3D peripheral nerve fascicle reconstruction. Firstly, fixed nerve segments were embedded with position lines, cryostat-sectioned continuously, stained and imaged histologically. Position line cross-sections were identified using a trained support vector machine method, and the coordinates of their central pixels were obtained. Then, nerve section images were registered using the bilinear method, and edges of fascicles were extracted using an improved gradient vector flow snake method. Subsequently, fascicle types were identified automatically using the multi-directional gradient and second-order gradient method. Finally, a 3D virtual model of internal fascicles was obtained after section images were processed. This technique was successfully applied for 3D reconstruction for the median nerve of the hand-wrist and cubital fossa regions and the gastrocnemius nerve. This nerve internal fascicle 3D reconstruction technology would be helpful for aiding peripheral nerve repair and virtual surgery. PMID:26596642

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

    PubMed Central

    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

  11. A bioengineered peripheral nerve construct using aligned peptide amphiphile nanofibers

    PubMed Central

    Yalom, Anisa; Berns, Eric J.; Stephanopoulos, Nicholas; McClendon, Mark T.; Segovia, Luis A.; Spigelman, Igor; Stupp, Samuel I.; Jarrahy, Reza

    2014-01-01

    Peripheral nerve injuries can result in lifelong disability. Primary coaptation is the treatment of choice when the gap between transected nerve ends is short. Long nerve gaps seen in more complex injuries often require autologous nerve grafts or nerve conduits implemented into the repair. Nerve grafts, however, cause morbidity and functional loss at donor sites, which are limited in number. Nerve conduits, in turn, lack an internal scaffold to support and guide axonal regeneration, resulting in decreased efficacy over longer nerve gap lengths. By comparison, peptide amphiphiles (PAs) are molecules that can self-assemble into nanofibers, which can be aligned to mimic the native architecture of peripheral nerve. As such, they represent a potential substrate for use in a bioengineered nerve graft substitute. To examine this, we cultured Schwann cells with bioactive PAs (RGDS-PA, IKVAV-PA) to determine their ability to attach to and proliferate within the biomaterial. Next, we devised a PA construct for use in a peripheral nerve critical sized defect model. Rat sciatic nerve defects were created and reconstructed with autologous nerve, PLGA conduits filled with various forms of aligned PAs, or left unrepaired. Motor and sensory recovery were determined and compared among groups. Our results demonstrate that Schwann cells are able to adhere to and proliferate in aligned PA gels, with greater efficacy in bioactive PAs compared to the backbone-PA alone. In vivo testing revealed recovery of motor and sensory function in animals treated with conduit/PA constructs comparable to animals treated with autologous nerve grafts. Functional recovery in conduit/PA and autologous graft groups was significantly faster than in animals treated with empty PLGA conduits. Histological examinations also demonstrated increased axonal and Schwann cell regeneration within the reconstructed nerve gap in animals treated with conduit/PA constructs. These results indicate that PA nanofibers may

  12. Repairing Peripheral Nerves: Is there a Role for Carbon Nanotubes?

    PubMed

    Oprych, Karen M; Whitby, Raymond L D; Mikhalovsky, Sergey V; Tomlins, Paul; Adu, Jimi

    2016-06-01

    Peripheral nerve injury continues to be a major global health problem that can result in debilitating neurological deficits and neuropathic pain. Current state-of-the-art treatment involves reforming the damaged nerve pathway using a nerve autograft. Engineered nerve repair conduits can provide an alternative to the nerve autograft avoiding the inevitable tissue damage caused at the graft donor site. Commercially available nerve repair conduits are currently only considered suitable for repairing small nerve lesions; the design and performance of engineered conduits requires significant improvements to enable their use for repairing larger nerve defects. Carbon nanotubes (CNTs) are an emerging novel material for biomedical applications currently being developed for a range of therapeutic technologies including scaffolds for engineering and interfacing with neurological tissues. CNTs possess a unique set of physicochemical properties that could be useful within nerve repair conduits. This progress report aims to evaluate and consolidate the current literature pertinent to CNTs as a biomaterial for supporting peripheral nerve regeneration. The report is presented in the context of the state-of-the-art in nerve repair conduit design; outlining how CNTs may enhance the performance of next generation peripheral nerve repair conduits. PMID:27027923

  13. PERIPHERAL NERVE REGENERATION: CELL THERAPY AND NEUROTROPHIC FACTORS

    PubMed Central

    Sebben, Alessandra Deise; Lichtenfels, Martina; da Silva, Jefferson Luis Braga

    2015-01-01

    Peripheral nerve trauma results in functional loss in the innervated organ, and recovery without surgical intervention is rare. Many surgical techniques can be used for nerve repair. Among these, the tubulization technique can be highlighted: this allows regenerative factors to be introduced into the chamber. Cell therapy and tissue engineering have arisen as an alternative for stimulating and aiding peripheral nerve regeneration. Therefore, the aim of this review was to provide a survey and analysis on the results from experimental and clinical studies that used cell therapy and tissue engineering as tools for optimizing the regeneration process. The articles used came from the LILACS, Medline and SciELO scientific databases. Articles on the use of stem cells, Schwann cells, growth factors, collagen, laminin and platelet-rich plasma for peripheral nerve repair were summarized over the course of the review. Based on these studies, it could be concluded that the use of stem cells derived from different sources presents promising results relating to nerve regeneration, because these cells have a capacity for neuronal differentiation, thus demonstrating effective functional results. The use of tubes containing bioactive elements with controlled release also optimizes the nerve repair, thus promoting greater myelination and axonal growth of peripheral nerves. Another promising treatment is the use of platelet-rich plasma, which not only releases growth factors that are important in nerve repair, but also serves as a carrier for exogenous factors, thereby stimulating the proliferation of specific cells for peripheral nerve repair. PMID:27027067

  14. Handcrafted multilayer PDMS microchannel scaffolds for peripheral nerve regeneration.

    PubMed

    Hossain, Ridwan; Kim, Bongkyun; Pankratz, Rachel; Ajam, Ali; Park, Sungreol; Biswal, Sibani L; Choi, Yoonsu

    2015-12-01

    Injuries that result in the loss of limb functionality may be caused by the severing of the peripheral nerves within the affected limb. Several bioengineered peripheral nerve scaffolds have been developed in order to provide the physical support and topographical guidance necessary for the naturally disorganized axon outgrowth to reattach to distal nerve stumps as an alternative to other procedures, like nerve grafting. PDMS has been chosen for the base material of the scaffolds due to its biocompatibility, flexibility, transparency, and well-developed fabrication techniques. The process of observing the axon outgrowth across the nerve gaps with PDMS scaffolds has been challenging due to the limited number and fineness of longitudinal sections that can be extracted from harvested nerve tissue samples after implantation. To address this, multilayer microchannel scaffolds were developed with the object of providing more refined longitudinal observation of axon outgrowth by longitudinally 'sectioning' the device during fabrication, removing the need for much of the sample preparation process. This device was then implanted into the sciatic nerves of Lewis rats, and then harvested after two and four weeks to analyze the difference in nerve regeneration between two different time periods. The present layer by layer structure, which is separable after nerve regeneration and is treated as an individual layer during the histology process, provides the details of biological events during axonal regeneration. Confocal microscopic imaging showed the details of peripheral nerve regeneration including nerve branches and growth cones observable from within the microchannels of the multilayer PDMS microchannel scaffolds. PMID:26494637

  15. [Perioperative analgesia with continuous peripheral nerve blocks in children].

    PubMed

    Dadure, C; Capdevila, X

    2007-02-01

    Recently, regional anaesthesia in children has generated increasing interest. But single injection techniques have a limited duration of postoperative analgesia. Then, continuous peripheral nerve blocks have taken an important position in the anaesthetic arsenal, allowing an effective, safe and prolonged postoperative pain management. As adults, indications for continuous peripheral nerve blocks depend on the analysis of individual benefits/risks ratio. Main indications are intense postoperative pain surgical procedures, with or without postoperative rehabilitation, and complex regional pain syndrome. Contraindications to these procedures are rather similar to those in adults, plus parental and/or children refusal. Continuous peripheral nerve blocks are usually performed under general anaesthesia or sedation in children, and require appropriate equipment in order to decrease the risk of nerve injury. New techniques, such as transcutaneous nerve stimulation or ultrasound guidance, appeared to facilitate nerve and plexus approach identification in paediatric patients. Nevertheless, continuous peripheral nerve block may theoretically mask a compartment syndrome after trauma surgical procedures. Finally, ropivacaine appears to be the most appropriate drug for continuous peripheral nerve blocks in children, requiring low flow rates and concentrations of local anaesthetic. These techniques may facilitate early ambulation by an improved pain management or even postoperative analgesia at home with disposable pumps. One might infer from the current review that excellent pain relief coupled with a reduction of side effects would contribute to improve the quality of life and to decrease the frequency of disabling behavioural modifications in children, sometimes psychologically injured by hospital stay and postoperative pain. PMID:17174518

  16. Effect of Artificial Nerve Conduit Vascularization on Peripheral Nerve in a Necrotic Bed

    PubMed Central

    Iijima, Yuki; Murayama, Akira; Takeshita, Katsushi

    2016-01-01

    Background: Several types of artificial nerve conduit have been used for bridging peripheral nerve gaps as an alternative to autologous nerves. However, their efficacy in repairing nerve injuries accompanied by surrounding tissue damage remains unclear. We fabricated a novel nerve conduit vascularized by superficial inferior epigastric (SIE) vessels and evaluated whether it could promote axonal regeneration in a necrotic bed. Methods: A 15-mm nerve conduit was implanted beneath the SIE vessels in the groin of a rat to supply it with blood vessels 2 weeks before nerve reconstruction. We removed a 13-mm segment of the sciatic nerve and then pressed a heated iron against the dorsal thigh muscle to produce a burn. The defects were immediately repaired with an autograft (n = 10), nerve conduit graft (n = 8), or vascularized nerve conduit graft (n = 8). Recovery of motor function was examined for 18 weeks after surgery. The regenerated nerves were electrophysiologically and histologically evaluated. Results: The vascularity of the nerve conduit implanted beneath the SIE vessels was confirmed histologically 2 weeks after implantation. Between 14 and 18 weeks after surgery, motor function of the vascularized conduit group was significantly better than that of the nonvascularized conduit group. Electrophysiological and histological evaluations revealed that although the improvement did not reach the level of reinnervation achieved by an autograft, the vascularized nerve conduit improved axonal regeneration more than did the conduit alone. Conclusion: Vascularization of artificial nerve conduits accelerated peripheral nerve regeneration, but further research is required to improve the quality of nerve regeneration. PMID:27257595

  17. Biomaterials for the Development of Peripheral Nerve Guidance Conduits

    PubMed Central

    Nectow, Alexander R.; Marra, Kacey G.

    2012-01-01

    Currently, surgical treatments for peripheral nerve injury are less than satisfactory. The gold standard of treatment for peripheral nerve gaps >5 mm is the autologous nerve graft; however, this treatment is associated with a variety of clinical complications, such as donor site morbidity, limited availability, nerve site mismatch, and the formation of neuromas. Despite many recent advances in the field, clinical studies implementing the use of artificial nerve guides have yielded results that are yet to surpass those of autografts. Thus, the development of a nerve guidance conduit, which could match the effectiveness of the autologous nerve graft, would be beneficial to the field of peripheral nerve surgery. Design strategies to improve surgical outcomes have included the development of biopolymers and synthetic polymers as primary scaffolds with tailored mechanical and physical properties, luminal “fillers” such as laminin and fibronectin as secondary internal scaffolds, surface micropatterning, stem cell inclusion, and controlled release of neurotrophic factors. The current article highlights approaches to peripheral nerve repair through a channel or conduit, implementing chemical and physical growth and guidance cues to direct that repair process. PMID:21812591

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

    EPA Science Inventory

    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...

  19. A simple model of radial nerve injury in the rhesus monkey to evaluate peripheral nerve repair.

    PubMed

    Wang, Dong; Huang, Xijun; Fu, Guo; Gu, Liqiang; Liu, Xiaolin; Wang, Honggang; Hu, Jun; Yi, Jianhua; Niu, Xiaofeng; Zhu, Qingtang

    2014-05-15

    Current research on bone marrow stem cell transplantation and autologous or xenogenic nerve transplantation for peripheral nerve regeneration has mainly focused on the repair of peripheral nerve defects in rodents. In this study, we established a standardized experimental model of radial nerve defects in primates and evaluated the effect of repair on peripheral nerve injury. We repaired 2.5-cm lesions in the radial nerve of rhesus monkeys by transplantation of autografts, acellular allografts, or acellular allografts seeded with autologous bone marrow stem cells. Five months after surgery, regenerated nerve tissue was assessed for function, electrophysiology, and histomorphometry. Postoperative functional recovery was evaluated by the wrist-extension test. Compared with the simple autografts, the acellular allografts and allografts seeded with bone marrow stem cells facilitated remarkable recovery of the wrist-extension functions in the rhesus monkeys. This functional improvement was coupled with radial nerve distal axon growth, a higher percentage of neuron survival, increased nerve fiber density and diameter, increased myelin sheath thickness, and increased nerve conduction velocities and peak amplitudes of compound motor action potentials. Furthermore, the quality of nerve regeneration in the bone marrow stem cells-laden allografts group was comparable to that achieved with autografts. The wrist-extension test is a simple behavioral method for objective quantification of peripheral nerve regeneration. PMID:25206757

  20. Advances and Future Applications of Augmented Peripheral Nerve Regeneration.

    PubMed

    Jones, Salazar; Eisenberg, Howard M; Jia, Xiaofeng

    2016-01-01

    Peripheral nerve injuries remain a significant source of long lasting morbidity, disability, and economic costs. Much research continues to be performed in areas related to improving the surgical outcomes of peripheral nerve repair. In this review, the physiology of peripheral nerve regeneration and the multitude of efforts to improve surgical outcomes are discussed. Improvements in tissue engineering that have allowed for the use of synthetic conduits seeded with neurotrophic factors are highlighted. Selected pre-clinical and available clinical data using cell based methods such as Schwann cell, undifferentiated, and differentiated stem cell transplantation to guide and enhance peripheral nerve regeneration are presented. The limitations that still exist in the utility of neurotrophic factors and cell-based therapies are outlined. Strategies that are most promising for translation into the clinical arena are suggested. PMID:27618010

  1. Use of nerve elongator to repair short-distance peripheral nerve defects: a prospective randomized study

    PubMed Central

    Bai, Lu; Wang, Tian-bing; Wang, Xin; Zhang, Wei-wen; Xu, Ji-hai; Cai, Xiao-ming; Zhou, Dan-ya; Cai, Li-bing; Pan, Jia-dong; Tian, Min-tao; Chen, Hong; Zhang, Dian-ying; Fu, Zhong-guo; Zhang, Pei-xun; Jiang, Bao-guo

    2015-01-01

    Repair techniques for short-distance peripheral nerve defects, including adjacent joint flexion to reduce the distance between the nerve stump defects, “nerve splint” suturing, and nerve sleeve connection, have some disadvantages. Therefore, we designed a repair technique involving intraoperative tension-free application of a nerve elongator and obtained good outcomes in the repair of short-distance peripheral nerve defects in a previous animal study. The present study compared the clinical outcomes between the use of this nerve elongator and performance of the conventional method in the repair of short-distance transection injuries in human elbows. The 3-, 6-, and 12-month postoperative follow-up results demonstrated that early neurological function recovery was better in the nerve elongation group than in the conventional group, but no significant difference in long-term neurological function recovery was detected between the two groups. In the nerve elongation group, the nerves were sutured without tension, and the duration of postoperative immobilization of the elbow was decreased. Elbow function rehabilitation was significantly better in the nerve elongation group than in the control group. Moreover, there were no security risks. The results of this study confirm that the use of this nerve elongator for repair of short-distance peripheral nerve defects is safe and effective. PMID:25788924

  2. Distribution of sodium channels during nerve elongation in rat peripheral nerve.

    PubMed

    Ichimura, Harumitsu; Shiga, Takashi; Abe, Ichiro; Hara, Yuki; Terui, Naoto; Tsujino, Akihito; Ochiai, Naoyuki

    2005-01-01

    A number of studies have investigated electrophysiological and morphological changes of peripheral nerves during gradual elongation. There has been, however, no report on the distribution of sodium channels at Ranvier's nodes during peripheral nerve elongation. We investigated peripheral nerve injury after the gradual elongation of rat sciatic nerves. Indirect nerve elongation was induced by leg lengthening at a rate of 3 mm/day by 15 or 30 mm. At 7 days after the leg lengthening, the electrophysiological properties of sciatic nerves, the ultrastructures of the Ranvier's nodes and axons, and the distribution of voltage-dependent sodium channels were examined. In the control nerves, most sodium channels were localized at Ranvier's nodes in myelinated axons, providing the physiological basis of saltatory conduction. In the elongated nerves, both the amplitude and conduction velocity of compound nerve action potential decreased following leg lengthening. The elongated nerves also showed paranodal demyelination in Ranvier's nodes longer than those in the control group. In addition, the distribution of sodium channels became diffuse or disappeared at Ranvier's nodes of elongated nerves. The diffuse distribution and/or disappearance of sodium channels may underlie the electrophysiological changes in compound nerve action potential induced by nerve elongation. PMID:15815871

  3. The role of exosomes in peripheral nerve regeneration

    PubMed Central

    Ching, Rosanna C.; Kingham, Paul J.

    2015-01-01

    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. PMID:26109947

  4. Visualization of nerve fibers and their relationship to peripheral nerve tumors by diffusion tensor imaging.

    PubMed

    Cage, Tene A; Yuh, Esther L; Hou, Stephanie W; Birk, Harjus; Simon, Neil G; Noss, Roger; Rao, Anuradha; Chin, Cynthia T; Kliot, Michel

    2015-09-01

    OBJECT The majority of growing and/or symptomatic peripheral nerve tumors are schwannomas and neurofibromas. They are almost always benign and can usually be resected while minimizing motor and sensory deficits if approached with the proper expertise and techniques. Intraoperative electrophysiological stimulation and recording techniques allow the surgeon to map the surface of the tumor in an effort to identify and thus avoid damaging functioning nerve fibers. Recently, MR diffusion tensor imaging (DTI) techniques have permitted the visualization of axons, because of their anisotropic properties, in peripheral nerves. The object of this study was to compare the distribution of nerve fibers as revealed by direct electrical stimulation with that seen on preoperative MR DTI. METHODS The authors conducted a retrospective chart review of patients with a peripheral nerve or nerve root tumor between March 2012 and January 2014. Diffusion tensor imaging and intraoperative data had been prospectively collected for patients with peripheral nerve tumors that were resected. Preoperative identification of the nerve fiber location in relation to the nerve tumor surface as seen on DTI studies was compared with the nerve fiber's intraoperative localization using electrophysiological stimulation and recordings. RESULTS In 23 patients eligible for study there was good correlation between nerve fiber location on DTI and its anatomical location seen intraoperatively. Diffusion tensor imaging demonstrated the relationship of nerve fibers relative to the tumor with 95.7% sensitivity, 66.7% specificity, 75% positive predictive value, and 93.8% negative predictive value. CONCLUSIONS Preoperative DTI techniques are useful in helping the peripheral nerve surgeon to both determine the risks involved in resecting a nerve tumor and plan the safest surgical approach. PMID:26323818

  5. 21 CFR 868.2775 - Electrical peripheral nerve stimulator.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Electrical peripheral nerve stimulator. 868.2775 Section 868.2775 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Monitoring Devices § 868.2775 Electrical peripheral...

  6. Intraoperative peripheral nerve injury in colorectal surgery. An update.

    PubMed

    Colsa Gutiérrez, Pablo; Viadero Cervera, Raquel; Morales-García, Dieter; Ingelmo Setién, Alfredo

    2016-03-01

    Intraoperative peripheral nerve injury during colorectal surgery procedures is a potentially serious complication that is often underestimated. The Trendelenburg position, use of inappropriately padded armboards and excessive shoulder abduction may encourage the development of brachial plexopathy during laparoscopic procedures. In open colorectal surgery, nerve injuries are less common. It usually involves the femoral plexus associated with lithotomy position and self-retaining retractor systems. Although in most cases the recovery is mostly complete, treatment consists of physical therapy to prevent muscular atrophy, protection of hypoesthesic skin areas and analgesics for neuropathic pain. The aim of the present study is to review the incidence, prevention and management of intraoperative peripheral nerve injury. PMID:26008880

  7. A Romanian therapeutic approach to peripheral nerve injury.

    PubMed

    Zegrea, I; Chivu, Laura Ioana; Albu, Mădălina Georgiana; Zamfirescu, D; Chivu, R D; Ion, Daniela Adriana; Lascăr, I

    2012-01-01

    The study of nerve regeneration and functional recovery of the injured peripheral nerves represents a worldwide subject of clinical and scientific research. Our team aimed to obtain the first guide for nerve regeneration, bioartificial and biodegradable, using exclusively Romanian resources and having the advantages of price and quality, over the imported nerve conduits already used in clinical practice. First steps of this project consisted in obtaining the prototype of nerve guide conduit and its' testing in vitro and in vivo. Tests of physicochemical characterization, FTIR (Fourier Transform Infrared) spectrometry, thermal analysis (differential calorimetry, thermo-gravimetry), electron microscopy, water absorption and enzymatic degradation of the obtained prototype were followed by in vivo testing. The first results, obtained on a group of Brown Norway rats who suffered experimental lesions of 1 cm at the level of left sciatic nerve, which have then been repaired using the Romanian conduit prototype, are favorable in terms of biocompatibility, biodegradable capacity and support of nerve regeneration. PMID:22732806

  8. [Research Progress in Seeding Cells of Peripheral Nerve].

    PubMed

    Shi, Gengqiang; Hu, Yi

    2015-04-01

    Seeding cells play an important role in the peripheral nerve damage repair. Seeding cells studied conse- quently in peripheral nerve are Schwann cells, bone marrow mesenchymal stem cells and neural stem cells. Schwann cells, the first seeding cells, are various unique glial cells in the peripheral nervous system, which can form the myelin sheath for insulation and package of the neuron projecting axons in the peripheral nervous system so that the conduction velocity of the nerve signal was accelerated. It can be proved that Schwann cells played an important role in the maintenance of peripheral nerve function and in the regeneration process after peripheral nerve injury. The second, bone marrow mesenchymal stem cells are the various mesenchymal stem cells mainly exist in the systemic connective tissues and organs. These functional stem cells are often studied at present, and it has been found that they have exuberant proliferation and differentiation potentials. Neural stem cells, mentioned the third in sequence, are the kind of pluripotent cells with multi-directional differentiation, which could conduct the self-renewal function, and generate and differentiate neurons, astrocytes and oligodendrocytes through asymmetric cell division. These three types of seed cells are discussed in this paper. PMID:26211274

  9. [Development of Researches on Acupuncture Treatment of Peripheral Nerve Injury].

    PubMed

    Tao, Xing; Ma, Tie-ming

    2016-02-01

    Peripheral nerve injury is a common clinical disease. Acupuncture therapy has been demonstrated to be effective in improving nerve injury in clinical practice, but its underlying mechanisms in prompting tissue repair basically remain unknown. In the present paper, the authors reviewed some descriptions of traditional Chinese medicine on peripheral nerve injury and treatment, and recent development of researches on acupuncture treatment of it in both clinical practice and animal studies. Clinical trials demonstrated that acupuncture treatment can relieve nerve injury induced pain, ameliorate both sensory and motor functions. Experimental studies showed that acupuncture stimulation may promote nerve repair by reducing desquamation of medullary sheath of nerve fibers, inhibiting apoptosis of nerve cells, and up-regulating expression of myelin basic protein, Slit-1 protein and gene, etc. In addition, acupuncture intervention may also improve the microenvironment of neural regeneration including increase of the proliferation and differentiation of Schwann cells and release of various types of neurotrophic factors. However, its mechanisms underlying accelerating rehabilitation of peripheral nerve injury need being researched further. PMID:27141630

  10. Resident Exposure to Peripheral Nerve Surgical Procedures During Residency Training.

    PubMed

    Gil, Joseph A; Daniels, Alan H; Akelman, Edward

    2016-05-01

    Background Variability in case exposures has been identified for orthopaedic surgery residents. It is not known if this variability exists for peripheral nerve procedures. Objective The objective of this study was to assess ACGME case log data for graduating orthopaedic surgery, plastic surgery, general surgery, and neurological surgery residents for peripheral nerve surgical procedures and to evaluate intraspecialty and interspecialty variability in case volume. Methods Surgical case logs from 2009 to 2014 for the 4 specialties were compared for peripheral nerve surgery experience. Peripheral nerve case volume between specialties was performed utilizing a paired t test, 95% confidence intervals were calculated, and linear regression was calculated to assess the trends. Results The average number of peripheral nerve procedures performed per graduating resident was 54.2 for orthopaedic surgery residents, 62.8 for independent plastic surgery residents, 84.6 for integrated plastic surgery residents, 22.4 for neurological surgery residents, and 0.4 for surgery residents. Intraspecialty comparison of the 10th and 90th percentile peripheral nerve case volume in 2012 revealed remarkable variability in training. There was a 3.9-fold difference within orthopaedic surgery, a 5.0-fold difference within independent plastic surgery residents, an 8.8-fold difference for residents from integrated plastic surgery programs, and a 7.0-fold difference within the neurological surgery group. Conclusions There is interspecialty and intraspecialty variability in peripheral nerve surgery volume for orthopaedic, plastic, neurological, and general surgery residents. Caseload is not the sole determinant of training quality as mentorship, didactics, case breadth, and complexity play an important role in training. PMID:27168883

  11. Case Study: Osseous Pathology with Peripheral Nerve Entrapment and Neuromata.

    PubMed

    Barrett, Stephen L

    2016-04-01

    This case illustrates the complexity and interrelationship of osseous pathology with peripheral nerve entrapment and neuromata. She had an iatrogenic nerve injury of a branch of the medial dorsal cutaneous nerve causing her painful scar. Secondarily, she developed an injury to her common peroneal nerve from the cast immobilization, resulting in palsy/drop foot. The tarsal tunnel entrapment was likely a sequela of the cast immobilization and chronic swelling. Her postoperative chronic pain was compounded by the failure to use grommets with the polymeric silicon (Silastic) implant at the initial surgery, leading to a breakdown of the implant with subsequent detritic synovitis. PMID:27013419

  12. Serial anthropometry predicts peripheral nerve dysfunction in a community cohort

    PubMed Central

    Ylitalo, Kelly R.; Herman, William H.; Harlow, Siobán D.

    2012-01-01

    Background Obesity is a risk factor for glucose intolerance, but the independent role of obesity in the development of peripheral neuropathy is unclear. This study assessed the impact of body size trajectories on prevalent nerve dysfunction in community-dwelling women with and without glucose intolerance. Methods Annual (1996–2008) anthropometric measures of weight, height, waist circumference, and body mass index (BMI, weight[kg]/height[m2]) were assessed in the Study of Women's Health Across the Nation – Michigan site. Glucose intolerance was defined annually based on current use of diabetes medications, self-reported diabetes diagnosis, and, when available, fasting glucose. Peripheral nerve dysfunction in 2008 was defined as abnormal monofilament testing or ≥4 symptoms or signs. Linear mixed models were used to determine trajectories of anthropometry by subsequently-identified nerve dysfunction status. Results Mean BMI was 32.4 kg/m2 at baseline and 27.8% of women had nerve dysfunction in 2008. BMI, weight, and waist circumference increased over time. Women who would have nerve dysfunction were significantly larger than women without dysfunction, independent of glucose intolerance. At mean baseline age of 46, BMI, weight, and waist circumference differed significantly (p-value<0.01) by subsequent nerve dysfunction status, independent of glucose intolerance and hypertension. These body size differences were maintained but not exacerbated over time. Conclusions Peripheral nerve dysfunction is prevalent among community-dwelling women. Twelve years before the nerve assessment, anthropometry differed between women who would and would not have nerve dysfunction, differences that were maintained over time. Obesity deserves attention as an important and potentially modifiable risk factor for peripheral nerve dysfunction. PMID:23161607

  13. Decellularisation and histological characterisation of porcine peripheral nerves.

    PubMed

    Zilic, Leyla; Wilshaw, Stacy-Paul; Haycock, John W

    2016-09-01

    Peripheral nerve injuries affect a large proportion of the global population, often causing significant morbidity and loss of function. Current treatment strategies include the use of implantable nerve guide conduits (NGC's) to direct regenerating axons between the proximal and distal ends of the nerve gap. However, NGC's are limited in their effectiveness at promoting regeneration Current NGCs are not suitable as substrates for supporting either neuronal or Schwann cell growth, as they lack an architecture similar to that of the native extracellular matrix (ECM) of the nerve. The aim of this study was to create an acellular porcine peripheral nerve using a novel decellularisation protocol, in order to eliminate the immunogenic cellular components of the tissue, while preserving the three-dimensional histoarchitecture and ECM components. Porcine peripheral nerve (sciatic branches were decellularised using a low concentration (0.1%; w/v) sodium dodecyl sulphate in conjunction with hypotonic buffers and protease inhibitors, and then sterilised using 0.1% (v/v) peracetic acid. Quantitative and qualitative analysis revealed a ≥95% (w/w) reduction in DNA content as well as preservation of the nerve fascicles and connective tissue. Acellular nerves were shown to have retained key ECM components such as collagen, laminin and fibronectin. Slow strain rate to failure testing demonstrated the biomechanical properties of acellular nerves to be comparable to fresh controls. In conclusion, we report the production of a biocompatible, biomechanically functional acellular scaffold, which may have use in peripheral nerve repair. Biotechnol. Bioeng. 2016;113: 2041-2053. © 2016 The Authors. Biotechnology and Bioengineering published by Wiley Periodicals, Inc. PMID:26926914

  14. Dynamic regulation of Schwann cell enhancers after peripheral nerve injury.

    PubMed

    Hung, Holly A; Sun, Guannan; Keles, Sunduz; Svaren, John

    2015-03-13

    Myelination of the peripheral nervous system is required for axonal function and long term stability. After peripheral nerve injury, Schwann cells transition from axon myelination to a demyelinated state that supports neuronal survival and ultimately remyelination of axons. Reprogramming of gene expression patterns during development and injury responses is shaped by the actions of distal regulatory elements that integrate the actions of multiple transcription factors. We used ChIP-seq to measure changes in histone H3K27 acetylation, a mark of active enhancers, to identify enhancers in myelinating rat peripheral nerve and their dynamics after demyelinating nerve injury. Analysis of injury-induced enhancers identified enriched motifs for c-Jun, a transcription factor required for Schwann cells to support nerve regeneration. We identify a c-Jun-bound enhancer in the gene for Runx2, a transcription factor induced after nerve injury, and we show that Runx2 is required for activation of other induced genes. In contrast, enhancers that lose H3K27ac after nerve injury are enriched for binding sites of the Sox10 and early growth response 2 (Egr2/Krox20) transcription factors, which are critical determinants of Schwann cell differentiation. Egr2 expression is lost after nerve injury, and many Egr2-binding sites lose H3K27ac after nerve injury. However, the majority of Egr2-bound enhancers retain H3K27ac, indicating that other transcription factors maintain active enhancer status after nerve injury. The global epigenomic changes in H3K27ac deposition pinpoint dynamic changes in enhancers that mediate the effects of transcription factors that control Schwann cell myelination and peripheral nervous system responses to nerve injury. PMID:25614629

  15. Let-7 microRNAs Regenerate Peripheral Nerve Regeneration by Targeting Nerve Growth Factor

    PubMed Central

    Li, Shiying; Wang, Xinghui; Gu, Yun; Chen, Chu; Wang, Yaxian; Liu, Jie; Hu, Wen; Yu, Bin; Wang, Yongjun; Ding, Fei; Liu, Yan; Gu, Xiaosong

    2015-01-01

    Peripheral nerve injury is a common clinical problem. Nerve growth factor (NGF) promotes peripheral nerve regeneration, but its clinical applications are limited by several constraints. In this study, we found that the time-dependent expression profiles of eight let-7 family members in the injured nerve after sciatic nerve injury were roughly similar to each other. Let-7 microRNAs (miRNAs) significantly reduced cell proliferation and migration of primary Schwann cells (SCs) by directly targeting NGF and suppressing its protein translation. Following sciatic nerve injury, the temporal change in let-7 miRNA expression was negatively correlated with that in NGF expression. Inhibition of let-7 miRNAs increased NGF secretion by primary cultured SCs and enhanced axonal outgrowth from a coculture of primary SCs and dorsal root gangalion neurons. In vivo tests indicated that let-7 inhibition promoted SCs migration and axon outgrowth within a regenerative microenvironment. In addition, the inhibitory effect of let-7 miRNAs on SCs apoptosis might serve as an early stress response to nerve injury, but this effect seemed to be not mediated through a NGF-dependent pathway. Collectively, our results provide a new insight into let-7 miRNA regulation of peripheral nerve regeneration and suggest a potential therapy for repair of peripheral nerve injury. PMID:25394845

  16. Neural tissue engineering options for peripheral nerve regeneration.

    PubMed

    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. PMID:24818883

  17. Peripheral nerve enhancement based on multi-scale Hessian matrix

    NASA Astrophysics Data System (ADS)

    Ma, Xiuli; Li, Hui; Zhou, Xueli; Wan, Wanggen

    2011-06-01

    To improve the precision of nerve segmentation in CT images, a new comparability function is proposed in this paper to enhance the contrast between nerve structure and other surrounding tissues. It is based on nerve's characteristic, i.e. dark tubular structure, and a thorough analysis of the multi-scale Hessian matrix. By comparability function, the gray range of interested nerve structure can be automatically determined, which combines the multi-scale Hessian matrix eigenvalues with intensity information of original nerve CT images. The experimental results show that the improved algorithm can not only enhance the continuous nerve of tubular structure, but also clearly reflect its bifurcations and crossovers. It is very important and significant to the computer-aided disease diagnosis of peripheral nervous system.

  18. Are human peripheral nerves sensitive to X-ray imaging?

    PubMed

    Scopel, Jonas Francisco; de Souza Queiroz, Luciano; O'Dowd, Francis Pierce; Júnior, Marcondes Cavalcante França; Nucci, Anamarli; Hönnicke, Marcelo Gonçalves

    2015-01-01

    Diagnostic imaging techniques play an important role in assessing the exact location, cause, and extent of a nerve lesion, thus allowing clinicians to diagnose and manage more effectively a variety of pathological conditions, such as entrapment syndromes, traumatic injuries, and space-occupying lesions. Ultrasound and nuclear magnetic resonance imaging are becoming useful methods for this purpose, but they still lack spatial resolution. In this regard, recent phase contrast x-ray imaging experiments of peripheral nerve allowed the visualization of each nerve fiber surrounded by its myelin sheath as clearly as optical microscopy. In the present study, we attempted to produce high-resolution x-ray phase contrast images of a human sciatic nerve by using synchrotron radiation propagation-based imaging. The images showed high contrast and high spatial resolution, allowing clear identification of each fascicle structure and surrounding connective tissue. The outstanding result is the detection of such structures by phase contrast x-ray tomography of a thick human sciatic nerve section. This may further enable the identification of diverse pathological patterns, such as Wallerian degeneration, hypertrophic neuropathy, inflammatory infiltration, leprosy neuropathy and amyloid deposits. To the best of our knowledge, this is the first successful phase contrast x-ray imaging experiment of a human peripheral nerve sample. Our long-term goal is to develop peripheral nerve imaging methods that could supersede biopsy procedures. PMID:25757086

  19. Are Human Peripheral Nerves Sensitive to X-Ray Imaging?

    PubMed Central

    Scopel, Jonas Francisco; de Souza Queiroz, Luciano; O’Dowd, Francis Pierce; Júnior, Marcondes Cavalcante França; Nucci, Anamarli; Hönnicke, Marcelo Gonçalves

    2015-01-01

    Diagnostic imaging techniques play an important role in assessing the exact location, cause, and extent of a nerve lesion, thus allowing clinicians to diagnose and manage more effectively a variety of pathological conditions, such as entrapment syndromes, traumatic injuries, and space-occupying lesions. Ultrasound and nuclear magnetic resonance imaging are becoming useful methods for this purpose, but they still lack spatial resolution. In this regard, recent phase contrast x-ray imaging experiments of peripheral nerve allowed the visualization of each nerve fiber surrounded by its myelin sheath as clearly as optical microscopy. In the present study, we attempted to produce high-resolution x-ray phase contrast images of a human sciatic nerve by using synchrotron radiation propagation-based imaging. The images showed high contrast and high spatial resolution, allowing clear identification of each fascicle structure and surrounding connective tissue. The outstanding result is the detection of such structures by phase contrast x-ray tomography of a thick human sciatic nerve section. This may further enable the identification of diverse pathological patterns, such as Wallerian degeneration, hypertrophic neuropathy, inflammatory infiltration, leprosy neuropathy and amyloid deposits. To the best of our knowledge, this is the first successful phase contrast x-ray imaging experiment of a human peripheral nerve sample. Our long-term goal is to develop peripheral nerve imaging methods that could supersede biopsy procedures. PMID:25757086

  20. Effect of oblique nerve grafting on peripheral nerve regeneration in rats.

    PubMed

    Kotulska, Katarzyna; Marcol, Wiesław; Larysz-Brysz, Magdalena; Tendera, Zofia; Malinowska-Kołodziej, Izabela; Slusarczyk, Wojciech; Jedrzejowska-Szypułka, Halina; Lewin-Kowalik, Joanna

    2006-01-01

    Current methods of peripheral nerve repair are to rejoin cut nerve stumps directly or to bridge large gaps with autologous nerve grafts. In both cases the surface of nerve stump endings is typically cut perpendicularly to the long axis of the nerve. The outcome of such operations, however, is still not satisfactory. In this study, we examine the effect of oblique nerve cutting and grafting on morphological as well as functional features of regeneration. In adult rats, sciatic nerve was cut and rejoined either directly or using an autologous graft, at 90 degrees or 30 degrees angle. Functional regeneration was assessed by walking track analysis during 12-week follow-up. Afterwards muscle weight was measured and histological studies were performed. The latter included nerve fibers and Schwann cells counting, as well as visualization of scar formation and epineural fibrosis. Nerves cut obliquely and rejoined showed better functional recovery than perpendicularly transected. Similar effect was observed after oblique grafting when compared to perpendicular one. Numbers of nerve fibers growing into the distal stump of the nerve as well as the number of Schwann cells were significantly higher in obliquely than in perpendicularly operated nerves. Moreover, growing axons were arranged more regularly following oblique treatment. These data indicate that joining or grafting the nerve stumps at acute angle is a more profitable method of nerve repair than the standard procedure performed at right angle. PMID:17066410

  1. Central changes in primary afferent fibers following peripheral nerve lesions.

    PubMed

    Coggeshall, R E; Lekan, H A; Doubell, T P; Allchorne, A; Woolf, C J

    1997-04-01

    Cutting or crushing rat sciatic nerve does not significantly reduce the number of central myelinated sensory axons in the dorsal roots entering the fourth and fifth lumbar segments even over very extended periods of time. Unmyelinated axons were reduced by approximately 50%, but only long after sciatic nerve lesions (four to eight months), and reinnervation of the peripheral target did not rescue these axons. This indicates that a peripheral nerve lesion sets up a slowly developing but major shift towards large afferent fiber domination of primary afferent input into the spinal cord. In addition, since myelinated axons are never lost, this is good evidence that the cells that give rise to these fibers are also not lost. If this is the case, this would indicate that adult primary sensory neurons with myelinated axons do not depend on peripheral target innervation for survival. PMID:9130791

  2. 21 CFR 882.5870 - Implanted peripheral nerve stimulator for pain relief.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Implanted peripheral nerve stimulator for pain....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...

  3. 21 CFR 882.5870 - Implanted peripheral nerve stimulator for pain relief.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Implanted peripheral nerve stimulator for pain....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...

  4. 21 CFR 882.5870 - Implanted peripheral nerve stimulator for pain relief.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Implanted peripheral nerve stimulator for pain....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...

  5. 21 CFR 882.5870 - Implanted peripheral nerve stimulator for pain relief.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Implanted peripheral nerve stimulator for pain....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...

  6. 21 CFR 882.5870 - Implanted peripheral nerve stimulator for pain relief.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Implanted peripheral nerve stimulator for pain....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...

  7. Use of superficial peroneal nerve graft for treating peripheral nerve injuries☆

    PubMed Central

    Ribak, Samuel; da Silva Filho, Paulo Roberto Ferreira; Tietzmann, Alexandre; Hirata, Helton Hiroshi; de Mattos, Carlos Augusto; da Gama, Sérgio Augusto Machado

    2016-01-01

    Objective To evaluate the clinical results from treating chronic peripheral nerve injuries using the superficial peroneal nerve as a graft donor source. Methods This was a study on eleven patients with peripheral nerve injuries in the upper limbs that were treated with grafts from the sensitive branch of the superficial peroneal nerve. The mean time interval between the dates of the injury and surgery was 93 days. The ulnar nerve was injured in eight cases and the median nerve in six. There were three cases of injury to both nerves. In the surgery, a longitudinal incision was made on the anterolateral face of the ankle, thus viewing the superficial peroneal nerve, which was located anteriorly to the extensor digitorum longus muscle. Proximally, the deep fascia between the extensor digitorum longus and the peroneal longus muscles was dissected. Next, the motor branch of the short peroneal muscle (one of the branches of the superficial peroneal nerve) was identified. The proximal limit of the sensitive branch was found at this point. Results The average space between the nerve stumps was 3.8 cm. The average length of the grafts was 16.44 cm. The number of segments used was two to four cables. In evaluating the recovery of sensitivity, 27.2% evolved to S2+, 54.5% to S3 and 18.1% to S3+. Regarding motor recovery, 72.7% presented grade 4 and 27.2% grade 3. There was no motor deficit in the donor area. A sensitive deficit in the lateral dorsal region of the ankle and the dorsal region of the foot was observed. None of the patients presented complaints in relation to walking. Conclusions Use of the superficial peroneal nerve as a graft source for treating peripheral nerve injuries is safe and provides good clinical results similar to those from other nerve graft sources. PMID:26962502

  8. Chitosan crosslinked flat scaffolds for peripheral nerve regeneration.

    PubMed

    Fregnan, F; Ciglieri, E; Tos, P; Crosio, A; Ciardelli, G; Ruini, F; Tonda-Turo, C; Geuna, S; Raimondo, S

    2016-01-01

    Chitosan (CS) has been widely used in a variety of biomedical applications, including peripheral nerve repair, due to its excellent biocompatibility, biodegradability, readily availability and antibacterial activity. In this study, CS flat membranes, crosslinked with dibasic sodium phosphate (DSP) alone (CS/DSP) or in association with the γ-glycidoxypropyltrimethoxysilane (CS/GPTMS_DSP), were fabricated with a solvent casting technique. The constituent ratio of crosslinking agents and CS were previously selected to obtain a composite material having both adequate mechanical properties and high biocompatibility. In vitro cytotoxicity tests showed that both CS membranes allowed cell survival and proliferation. Moreover, CS/GPTMS_DSP membranes promoted cell adhesion, induced Schwann cell-like morphology and supported neurite outgrowth from dorsal root ganglia explants. Preliminary in vivo tests carried out on both types of nerve scaffolds (CS/DSP and CS/GPTMS_DSP membranes) demonstrated their potential for: (i) protecting, as a membrane, the site of nerve crush or repair by end-to-end surgery and avoiding post-operative nerve adhesion; (ii) bridging, as a conduit, the two nerve stumps after a severe peripheral nerve lesion with substance loss. A 1 cm gap on rat median nerve was repaired using CS/DSP and CS/GPTMS_DSP conduits to further investigate their ability to induce nerve regeneration in vivo. CS/GPTMS_DSP tubes resulted to be more fragile during suturing and, along a 12 week post-operative lapse of time, they detached from the distal nerve stump. On the contrary CS/DSP conduits promoted nerve fiber regeneration and functional recovery, leading to an outcome comparable to median nerve repaired by autograft. PMID:27508969

  9. Emerging issues in peripheral nerve repair☆

    PubMed Central

    Geuna, Stefano; Tos, Pierluigi; Battiston, Bruno

    2012-01-01

    It is today widely acknowledged that nerve repair is now more than a matter of perfect microsurgical reconstruction only and that, to further improve clinical outcome, the involvement of different scientific disciplines is required. This evolving reconstructive/regenerative approach is based on the interdisciplinary and integrated pillars of tissue engineering such as reconstructive microsurgery, transplantation and biomaterials. In this paper, some of the most promising innovations for the tissue engineering of nerves, emerging from basic science investigation, are critically overviewed with special focus on those approaches that appear today to be more suitable for clinical translation. PMID:25538748

  10. Emerging issues in peripheral nerve repair.

    PubMed

    Geuna, Stefano; Tos, Pierluigi; Battiston, Bruno

    2012-10-15

    It is today widely acknowledged that nerve repair is now more than a matter of perfect microsurgical reconstruction only and that, to further improve clinical outcome, the involvement of different scientific disciplines is required. This evolving reconstructive/regenerative approach is based on the interdisciplinary and integrated pillars of tissue engineering such as reconstructive microsurgery, transplantation and biomaterials. In this paper, some of the most promising innovations for the tissue engineering of nerves, emerging from basic science investigation, are critically overviewed with special focus on those approaches that appear today to be more suitable for clinical translation. PMID:25538748

  11. Melatonin and its therapeutic actions on peripheral nerve regeneration.

    PubMed

    Behram Kandemir, Y; Sarikcioglu, L

    2015-01-01

    Melatonin has many different roles in the human body, including its importance in circadian rhythms, sleep physiology, mental status, reproduction, tumour development, ageing, and many other physiologic processes. Although there are more than hundreds of studies on effects of melatonin in several tissues, its effects on peripheral nerve has been documented in a limited number of studies. This paper focused to review the available literature in terms of several actions and effects of melatonin (beneficial or toxic effects) on well-known peripheral nerve injury models. PMID:26339807

  12. Malignant peripheral nerve sheath tumor of the parotid gland.

    PubMed

    Chis, Octavian; Albu, Silviu

    2014-09-01

    Malignant peripheral nerve sheath tumor (MPNST) refers to spindle cell sarcomas arising from or separating in the direction of cells of the peripheral nerve sheath. The MPNST of the parotid gland is an extremely rare tumor, usually having a poor prognosis, and only a few cases been described in the literature. In this article, we report the diagnostic and therapeutic challenges related to a new case of MPNST of the parotid. Diagnosis was made based on clinical, imaging (computed tomography scan), histologic, and immunohistochemistry findings. Despite comprehensive treatment--complete surgical resection and radiotherapy--the tumor displayed a highly aggressive course. PMID:25153067

  13. Peripheral nerve/field stimulation for neuropathic pain.

    PubMed

    Deogaonkar, Milind; Slavin, Konstantin V

    2014-01-01

    Peripheral nerve stimulation and peripheral nerve field stimulation are emerging as a viable neuromodulatory therapy in the treatment of refractory pain. Although the technology of percutaneous stimulation has been available for decades, recent advancements have broadened the number of indications. Success of treatment revolves around identifying the correct patient population, and the selection and placement of the appropriate electrodes and implantable pulse generators. Most results to date have come from case reports and retrospective studies. However, given the promising outcomes in reducing otherwise medically refractory pain, future randomized controlled studies are needed to assess this emerging technology. PMID:24262894

  14. Chitosan-film enhanced chitosan nerve guides for long-distance regeneration of peripheral nerves.

    PubMed

    Meyer, Cora; Stenberg, Lena; Gonzalez-Perez, Francisco; Wrobel, Sandra; Ronchi, Giulia; Udina, Esther; Suganuma, Seigo; Geuna, Stefano; Navarro, Xavier; Dahlin, Lars B; Grothe, Claudia; Haastert-Talini, Kirsten

    2016-01-01

    Biosynthetic nerve grafts are developed in order to complement or replace autologous nerve grafts for peripheral nerve reconstruction. Artificial nerve guides currently approved for clinical use are not widely applied in reconstructive surgery as they still have limitations especially when it comes to critical distance repair. Here we report a comprehensive analysis of fine-tuned chitosan nerve guides (CNGs) enhanced by introduction of a longitudinal chitosan film to reconstruct critical length 15 mm sciatic nerve defects in adult healthy Wistar or diabetic Goto-Kakizaki rats. Short and long term investigations demonstrated that the CNGs enhanced by the guiding structure of the introduced chitosan film significantly improved functional and morphological results of nerve regeneration in comparison to simple hollow CNGs. Importantly, this was detectable both in healthy and in diabetic rats (short term) and the regeneration outcome almost reached the outcome after autologous nerve grafting (long term). Hollow CNGs provide properties likely leading to a wider clinical acceptance than other artificial nerve guides and their performance can be increased by simple introduction of a chitosan film with the same advantageous properties. Therefore, the chitosan film enhanced CNGs represent a new generation medical device for peripheral nerve reconstruction. PMID:26517563

  15. Optical Biopsy of Peripheral Nerve Using Confocal Laser Endomicroscopy: A New Tool for Nerve Surgeons?

    PubMed

    Crowe, Christopher S; Liao, Joseph C; Curtin, Catherine M

    2015-09-01

    Peripheral nerve injuries remain a challenge for reconstructive surgeons with many patients obtaining suboptimal results. Understanding the level of injury is imperative for successful repair. Current methods for distinguishing healthy from damaged nerve are time consuming and possess limited efficacy. Confocal laser endomicroscopy (CLE) is an emerging optical biopsy technology that enables dynamic, high resolution, sub-surface imaging of live tissue. Porcine sciatic nerve was either left undamaged or briefly clamped to simulate injury. Diluted fluorescein was applied topically to the nerve. CLE imaging was performed by direct contact of the probe with nerve tissue. Images representative of both damaged and undamaged nerve fibers were collected and compared to routine H&E histology. Optical biopsy of undamaged nerve revealed bands of longitudinal nerve fibers, distinct from surrounding adipose and connective tissue. When damaged, these bands appear truncated and terminate in blebs of opacity. H&E staining revealed similar features in damaged nerve fibers. These results prompt development of a protocol for imaging peripheral nerves intraoperatively. To this end, improving surgeons' ability to understand the level of injury through real-time imaging will allow for faster and more informed operative decisions than the current standard permits. PMID:26430636

  16. Optical Biopsy of Peripheral Nerve Using Confocal Laser Endomicroscopy: A New Tool for Nerve Surgeons?

    PubMed Central

    Liao, Joseph C; Curtin, Catherine M

    2015-01-01

    Peripheral nerve injuries remain a challenge for reconstructive surgeons with many patients obtaining suboptimal results. Understanding the level of injury is imperative for successful repair. Current methods for distinguishing healthy from damaged nerve are time consuming and possess limited efficacy. Confocal laser endomicroscopy (CLE) is an emerging optical biopsy technology that enables dynamic, high resolution, sub-surface imaging of live tissue. Porcine sciatic nerve was either left undamaged or briefly clamped to simulate injury. Diluted fluorescein was applied topically to the nerve. CLE imaging was performed by direct contact of the probe with nerve tissue. Images representative of both damaged and undamaged nerve fibers were collected and compared to routine H&E histology. Optical biopsy of undamaged nerve revealed bands of longitudinal nerve fibers, distinct from surrounding adipose and connective tissue. When damaged, these bands appear truncated and terminate in blebs of opacity. H&E staining revealed similar features in damaged nerve fibers. These results prompt development of a protocol for imaging peripheral nerves intraoperatively. To this end, improving surgeons' ability to understand the level of injury through real-time imaging will allow for faster and more informed operative decisions than the current standard permits. PMID:26430636

  17. Nanotechnology and bio-functionalisation for peripheral nerve regeneration

    PubMed Central

    Sedaghati, Tina; Seifalian, Alexander M.

    2015-01-01

    There is a high clinical demand for new smart biomaterials, which stimulate neuronal cell proliferation, migration and increase cell-material interaction to facilitate nerve regeneration across these critical-sized defects. This article briefly reviews several up-to-date published studies using Arginine-Glycine-Aspartic acid peptide sequence, nanocomposite based on polyhedral oligomeric silsesquioxane nanoparticle and nanofibrous scaffolds as promising strategies to enhance peripheral nerve regeneration by influencing cellular behaviour such as attachment, spreading and proliferation. The aim is to establish the potent manipulations, which are simple and easy to employ in the clinical conditions for nerve regeneration and repair. PMID:26487832

  18. From the battlefront: peripheral nerve surgery in modern day warfare.

    PubMed

    Ecklund, James M; Ling, Geoffrey S F

    2009-01-01

    Warfare historically causes a large number of peripheral nerve injuries. During the current global war on terror, an increased use of advanced regional anesthesia techniques appears to have significantly reduced pain syndromes that have been previously reported with missile-induced nerve injuries. Additionally, a new program has been established to develop advanced prosthetic devises that can interface with neural tissue to obtain direct neural control. As this technology matures, the functional restoration gained from these new generation prosthetic devices may exceed that which can be obtained by standard nerve repair techniques. PMID:19064183

  19. Spinal cord response to laser treatment of injured peripheral nerve

    SciTech Connect

    Rochkind, S.; Vogler, I.; Barr-Nea, L. )

    1990-01-01

    The authors describe the changes occurring in the spinal cord of rats subjected to crush injury of the sciatic nerve followed by low-power laser irradiation of the injured nerve. Such laser treatment of the crushed peripheral nerve has been found to mitigate the degenerative changes in the corresponding neurons of the spinal cord and induce proliferation of neuroglia both in astrocytes and oligodendrocytes. This suggests a higher metabolism in neurons and a better ability for myelin production under the influence of laser treatment.

  20. Adrenergic vasoconstriction in peripheral nerves of the rabbit

    SciTech Connect

    Selander, D.; Mansson, L.G.; Karlsson, L.; Svanvik, J.

    1985-01-01

    The blood flow in the sciatic nerve of the rabbit was estimated from the wash out of intraneurally injected /sup 133/Xe. To avoid diffusion of the tracer into the surrounding muscular tissue, the nerve was covered by a gas-tight plastic film. Using this technique, the basal blood flow in the sciatic nerve was estimated to 35 ml X min-1 X 100 g-1. It was found that intraarterial norepinephrine and electrical stimulation of the lumbar sympathetic chain strongly reduced the wash out of /sup 133/Xe, which only can be explained by a pronounced reduction of the blood flow in the nerve itself. The blood flow again increased within 4 min of stopping the infusion of norepinephrine or the sympathetic stimulation. The prolonged effect and higher neurotoxicity of local anesthetics containing adrenaline may be explained by an alpha receptor-mediated vasoconstriction of the microvessels of peripheral nerves.

  1. Ultrasound Guidance for Deep Peripheral Nerve Blocks: A Brief Review

    PubMed Central

    Wadhwa, Anupama; Kandadai, Sunitha Kanchi; Tongpresert, Sujittra; Obal, Detlef; Gebhard, Ralf Erich

    2011-01-01

    Nerve stimulation and ultrasound have been introduced to the practice of regional anesthesia mostly in the last two decades. Ultrasound did not gain as much popularity as the nerve stimulation until a decade ago because of the simplicity, accuracy and portability of the nerve stimulator. Ultrasound is now available in most academic centers practicing regional anesthesia and is a popular tool amongst trainees for performance of nerve blocks. This review article specifically discusses the role of ultrasonography for deeply situated nerves or plexuses such as the infraclavicular block for the upper extremity and lumbar plexus and sciatic nerve blocks for the lower extremity. Transitioning from nerve stimulation to ultrasound-guided blocks alone or in combination is beneficial in certain scenarios. However, not every patient undergoing regional anesthesia technique benefits from the use of ultrasound, especially when circumstances resulting in difficult visualization such as deep nerve blocks and/or block performed by inexperienced ultrasonographers. The use of ultrasound does not replace experience and knowledge of relevant anatomy, especially for visualization of deep structures. In certain scenarios, ultrasound may not offer additional value and substantial amount of time may be spent trying to find relevant structures or even provide a false sense of security, especially to an inexperienced operator. We look at available literature on the role of ultrasound for the performance of deep peripheral nerve blocks and its benefits. PMID:21808644

  2. Peripheral nerve regeneration with conduits: use of vein tubes

    PubMed Central

    Sabongi, Rodrigo Guerra; Fernandes, Marcela; dos Santos, João 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 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. PMID:26170802

  3. Past, Present, and Future of Nerve Conduits in the Treatment of Peripheral Nerve Injury

    PubMed Central

    Muheremu, Aikeremujiang; Ao, Qiang

    2015-01-01

    With significant advances in the research and application of nerve conduits, they have been used to repair peripheral nerve injury for several decades. Nerve conduits range from biological tubes to synthetic tubes, and from nondegradable tubes to biodegradable tubes. Researchers have explored hollow tubes, tubes filled with scaffolds containing neurotrophic factors, and those seeded with Schwann cells or stem cells. The therapeutic effect of nerve conduits is improving with increasing choice of conduit material, new construction of conduits, and the inclusion of neurotrophic factors and support cells in the conduits. Improvements in functional outcomes are expected when these are optimized for use in clinical practice. PMID:26491662

  4. Laminin-based Nanomaterials for Peripheral Nerve Tissue Engineering

    NASA Astrophysics Data System (ADS)

    Neal, Rebekah Anne

    Peripheral nerve transection occurs commonly in traumatic injury, causing motor and sensory deficits distal to the site of injury. One option for surgical repair is the nerve conduit. Conduits currently on the market are hollow tubes into which the nerve ends are sutured. Although these conduits fill the gap, they often fail due to the slow rate of regeneration over long gaps. To facilitate increased speed of regeneration and greater potential for functional recovery, the ideal conduit should provide biochemically relevant signals and physical guidance cues, thus playing an active role in peripheral nerve regeneration. In this dissertation, I fabricated laminin-1 and laminin-polycaprolactone (PCL) blend nanofibers that mimic the geometry and functionality of the peripheral nerve basement membrane. These fibers resist hydration in aqueous media and require no harsh chemical crosslinkers. Adhesion and differentiation of both neuron-like and neuroprogenitor cells is improved on laminin nanofibrous meshes over two-dimensional laminin substrates. Blend meshes with varying laminin content were characterized for composition, tensile properties, degradation rates, and bioactivity in terms of cell attachment and axonal elongation. I have established that 10% (wt) laminin content is sufficient to retain the significant neurite-promoting effects of laminin critical in peripheral nerve repair. In addition, I utilized modified collector plate design to manipulate electric field gradients during electrospinning for the fabrication of aligned nanofibers. These aligned substrates provide enhanced directional guidance cues to the regenerating axons. Finally, I replicated the clinical problem of peripheral nerve transection using a rat tibial nerve defect model for conduit implantation. When the lumens of conduits were filled with nanofiber meshes of varying laminin content and alignment, I observed significant recovery of sensory and motor function over six weeks. This recovery was

  5. [Management of peripheral facial nerve palsy in children].

    PubMed

    Tabarki, B

    2014-10-01

    Peripheral facial nerve palsy may (secondary) or may not have a detectable cause (idiopathic facial palsy or Bell's palsy). Idiopathic facial palsy is the common form of facial palsy. It remains diagnosis by exclusion. The prognosis is more favourable in children than in adults. We present current diagnostic procedures and recommendations regarding treatment in children. PMID:25048647

  6. A novel bioactive nerve conduit for the repair of peripheral nerve injury

    PubMed Central

    Li, Bin-bin; Yin, Yi-xia; Yan, Qiong-jiao; Wang, Xin-yu; Li, Shi-pu

    2016-01-01

    The use of a nerve conduit provides an opportunity to regulate cytokines, growth factors and neurotrophins in peripheral nerve regeneration and avoid autograft defects. We constructed a poly-D-L-lactide (PDLLA)-based nerve conduit that was modified using poly{(lactic acid)-co-[(glycolic acid)-alt-(L-lysine)]} and β-tricalcium phosphate. The effectiveness of this bioactive PDLLA-based nerve conduit was compared to that of PDLLA-only conduit in the nerve regeneration following a 10-mm sciatic nerve injury in rats. We observed the nerve morphology in the early period of regeneration, 35 days post injury, using hematoxylin-eosin and methylene blue staining. Compared with the PDLLA conduit, the nerve fibers in the PDLLA-based bioactive nerve conduit were thicker and more regular in size. Muscle fibers in the soleus muscle had greater diameters in the PDLLA bioactive group than in the PDLLA only group. The PDLLA-based bioactive nerve conduit is a promising strategy for repair after sciatic nerve injury. PMID:26981105

  7. Use new PLGL-RGD-NGF nerve conduits for promoting peripheral nerve regeneration

    PubMed Central

    2012-01-01

    Background Nerve conduits provide a promising strategy for peripheral nerve injury repair. However, the efficiency of nerve conduits to enhance nerve regeneration and functional recovery is often inferior to that of autografts. Nerve conduits require additional factors such as cell adhesion molecules and neurotrophic factors to provide a more conducive microenvironment for nerve regeneration. Methods In the present study, poly{(lactic acid)-co-[(glycolic acid)-alt-(L-lysine)]} (PLGL) was modified by grafting Gly-Arg-Gly-Asp-Gly (RGD peptide) and nerve growth factor (NGF) for fabricating new PLGL-RGD-NGF nerve conduits to promote nerve regeneration and functional recovery. PLGL-RGD-NGF nerve conduits were tested in the rat sciatic nerve transection model. Rat sciatic nerves were cut off to form a 10 mm defect and repaired with the nerve conduits. All of the 32 Wistar rats were randomly divided into 4 groups: group PLGL-RGD-NGF, group PLGL-RGD, group PLGL and group autograft. At 3 months after surgery, the regenerated rat sciatic nerve was evaluated by footprint analysis, electrophysiology, and histologic assessment. Experimental data were processed using the statistical software SPSS 10.0. Results The sciatic function index value of groups PLGL-RGD-NGF and autograft was significantly higher than those of groups PLGL-RGD and PLGL. The nerve conduction velocities of groups PLGL-RGD-NGF and autograft were significantly faster than those of groups PLGL-RGD and PLGL. The regenerated nerves of groups PLGL-RGD-NGF and autograft were more mature than those of groups PLGL-RGD and PLGL. There was no significant difference between groups PLGL-RGD-NGF and autograft. Conclusions PLGL-RGD-NGF nerve conduits are more effective in regenerating nerves than both PLGL-RGD nerve conduits and PLGL nerve conduits. The effect is as good as that of an autograft. This work established the platform for further development of the use of PLGL-RGD-NGF nerve conduits for clinical nerve repair

  8. Tissue engineering and peripheral nerve reconstruction: an overview.

    PubMed

    Geuna, Stefano; Gnavi, Sara; Perroteau, Isabelle; Tos, Pierluigi; Battiston, Bruno

    2013-01-01

    Nerve repair is no more regarded as merely a matter of microsurgical reconstruction. To define this evolving reconstructive/regenerative approach, the term tissue engineering is being increasingly used since it reflects the search for interdisciplinary and integrated treatment strategies. However, the drawback of this new approach is its intrinsic complexity, which is the result of the variety of scientific disciplines involved. This chapter presents a synthetic overview of the state of the art in peripheral nerve tissue engineering with a look forward at the most promising innovations emerging from basic science investigation. This review is intended to set the stage for the collection of papers in the thematic issue of the International Review of Neurobiology that is focused on the various interdisciplinary approaches in peripheral nerve tissue engineering. PMID:24083430

  9. Motor Neuron Activation in Peripheral Nerves Using Infrared Neural Stimulation

    PubMed Central

    Peterson, EJ; Tyler, DJ

    2014-01-01

    Objective Localized activation of peripheral axons may improve selectivity of peripheral nerve interfaces. Infrared neural stimulation (INS) employs localized delivery to activate neural tissue. This study investigated INS to determine whether localized delivery limited functionality in larger mammalian nerves. Approach The rabbit sciatic nerve was stimulated extraneurally with 1875 nm-wavelength infrared light, electrical stimulation, or a combination of both. Infrared-sensitive regions (ISR) of the nerve surface and electromyogram (EMG) recruitment of the Medial Gastrocnemius, Lateral Gastrocnemius, Soleus, and Tibialis Anterior were the primary output measures. Stimulation applied included infrared-only, electrical-only, and combined infrared and electrical. Main results 81% of nerves tested were sensitive to INS, with 1.7± 0.5 ISR detected per nerve. INS was selective to a single muscle within 81% of identified ISR. Activation energy threshold did not change significantly with stimulus power, but motor activation decreased significantly when radiant power was decreased. Maximum INS levels typically recruited up to 2–9% of any muscle. Combined infrared and electrical stimulation differed significantly from electrical recruitment in 7% of cases. Significance The observed selectivity of INS indicates it may be useful in augmenting rehabilitation, but significant challenges remain in increasing sensitivity and response magnitude to improve the functionality of INS. PMID:24310923

  10. Motor neuron activation in peripheral nerves using infrared neural stimulation

    NASA Astrophysics Data System (ADS)

    Peterson, E. J.; Tyler, D. J.

    2014-02-01

    Objective. Localized activation of peripheral axons may improve selectivity of peripheral nerve interfaces. Infrared neural stimulation (INS) employs localized delivery to activate neural tissue. This study investigated INS to determine whether localized delivery limited functionality in larger mammalian nerves. Approach. The rabbit sciatic nerve was stimulated extraneurally with 1875 nm wavelength infrared light, electrical stimulation, or a combination of both. Infrared-sensitive regions (ISR) of the nerve surface and electromyogram (EMG) recruitment of the Medial Gastrocnemius, Lateral Gastrocnemius, Soleus, and Tibialis Anterior were the primary output measures. Stimulation applied included infrared-only, electrical-only, and combined infrared and electrical. Main results. 81% of nerves tested were sensitive to INS, with 1.7 ± 0.5 ISR detected per nerve. INS was selective to a single muscle within 81% of identified ISR. Activation energy threshold did not change significantly with stimulus power, but motor activation decreased significantly when radiant power was decreased. Maximum INS levels typically recruited up to 2-9% of any muscle. Combined infrared and electrical stimulation differed significantly from electrical recruitment in 7% of cases. Significance. The observed selectivity of INS indicates that it may be useful in augmenting rehabilitation, but significant challenges remain in increasing sensitivity and response magnitude to improve the functionality of INS.

  11. Controversies related to electromagnetic field exposure on peripheral nerves.

    PubMed

    Say, Ferhat; Altunkaynak, Berrin Zuhal; Coşkun, Sina; Deniz, Ömür Gülsüm; Yıldız, Çağrı; Altun, Gamze; Kaplan, Arife Ahsen; Kaya, Sefa Ersan; Pişkin, Ahmet

    2016-09-01

    Electromagnetic field (EMF) is a pervasive environmental presence in modern society. In recent years, mobile phone usage has increased rapidly throughout the world. As mobile phones are generally held close to the head while talking, studies have mostly focused on the central and peripheral nervous system. There is a need for further research to ascertain the real effect of EMF exposure on the nervous system. Several studies have clearly demonstrated that EMF emitted by cell phones could affect the systems of the body as well as functions. However, the adverse effects of EMF emitted by mobile phones on the peripheral nerves are still controversial. Therefore, this review summarizes current knowledge on the possible positive or negative effects of electromagnetic field on peripheral nerves. PMID:26718608

  12. [Surgical treatment of lower extremity peripheral nerve injuries].

    PubMed

    Kaiser, Radek

    2016-01-01

    Peripheral nerve injuries of the lower extremities are not frequent. The most common are traction injury of the peroneal nerve at the knee level or iatrogenic trauma of the pelvic nerves during abdominal surgery. Civil sharp injuries are rare.Indications for surgical revision follow the general rules of nerve surgery. Sharp injury should be treated as soon as possible, ideally within 72 hours. Closed lesions are indicated for surgery if a complete denervation remains unchanged three months after the injury. Best results can be achieved within six months from the injury. Irritations caused by bone fragments or scarring or by iatrogenic injury (clamps, cement, screws, etc.) may be revised later. However, the most important is early clinical examination in a specialized neurosurgical department. PMID:27256143

  13. Lectin histochemistry of normal and neoplastic peripheral nerve sheath. 1. Lectin binding pattern of normal peripheral nerve in man.

    PubMed

    Matsumura, K; Nakasu, S; Nioka, H; Handa, J

    1993-01-01

    The binding patterns of lectins to normal peripheral nerves were examined. Twelve biotinylated lectins were used in this study; Canavalia ensiformis (Con A), Pisum sativum (PSA), Lens culinaris (LCA), Ricinus communis 1 (RCA-1), Arachis hypogaea (PNA), Glycine max (SBA), Sophora japonica (SJA), Bandeiraea simplicifolia 1 (BSL-1), Triticum vulgaris (WGA), succinylated WGA (s-WGA), Ulex europaeus 1 (UEA-1) and Helix pomatia (HPA). Cytoplasm of Schwann cells and perineurial cells was stained by Con A, PSA, LCA, s-WGA and WGA. PNA showed specific binding to perineurial cells, while after neuraminidase treatment stain with this lectin was demonstrated also in Schwann cells. Myelin sheaths were stained with fewer lectins. SBA and HPA with sialic acid removal rarely showed reactivity to the peripheral nerve structure in surgical specimens, in contrast to clear staining of Schwann cells, perineurial cells and myelin sheaths in autopsy specimens. The present study shows distinct lectin stainings of specific structures of the normal human peripheral nerves, and provides important basic information on the alterations of lectin binding patterns during pathological processes in the peripheral nerves. PMID:8310810

  14. The Role of Current Techniques and Concepts in Peripheral Nerve Repair

    PubMed Central

    Houschyar, K. S.; Momeni, A.; Pyles, M. N.; Cha, J. Y.; Maan, Z. N.; Duscher, D.; Jew, O. S.; Siemers, F.; van Schoonhoven, J.

    2016-01-01

    Patients with peripheral nerve injuries, especially severe injury, often face poor nerve regeneration and incomplete functional recovery, even after surgical nerve repair. This review summarizes treatment options of peripheral nerve injuries with current techniques and concepts and reviews developments in research and clinical application of these therapies. PMID:26904282

  15. The Role of Current Techniques and Concepts in Peripheral Nerve Repair.

    PubMed

    Houschyar, K S; Momeni, A; Pyles, M N; Cha, J Y; Maan, Z N; Duscher, D; Jew, O S; Siemers, F; van Schoonhoven, J

    2016-01-01

    Patients with peripheral nerve injuries, especially severe injury, often face poor nerve regeneration and incomplete functional recovery, even after surgical nerve repair. This review summarizes treatment options of peripheral nerve injuries with current techniques and concepts and reviews developments in research and clinical application of these therapies. PMID:26904282

  16. Initial observations on using magnesium metal in peripheral nerve repair.

    PubMed

    Vennemeyer, J J; Hopkins, T; Hershcovitch, M; Little, K D; Hagen, M C; Minteer, D; Hom, D B; Marra, K; Pixley, S K

    2015-03-01

    Biodegradable magnesium metal filaments placed inside biodegradable nerve conduits might provide the physical guidance support needed to improve the rate and extent of regeneration of peripheral nerves across injury gaps. In this study, we examined basic issues of magnesium metal resorption and biocompatibility by repairing sub-critical size gap injuries (6 mm) in one sciatic nerve of 24 adult male Lewis rats. Separated nerve stumps were connected with poly(caprolactone) nerve conduits, with and without magnesium filaments (0.25 mm diameter, 10 mm length), with two different conduit filler substances (saline and keratin hydrogel). At 6 weeks after implantation, magnesium degradation was examined by micro-computed tomography and histological analyses. Magnesium degradation was significantly greater when the conduits were filled with an acidic keratin hydrogel than with saline (p < 0.05). But magnesium filaments in some animals remained intact for 6 weeks. Using histological and immunocytochemical analyses, good biocompatibility of the magnesium implants was observed at 6 weeks, as shown by good development of regenerating nerve mini-fascicles and only mild inflammation in tissues even after complete degradation of the magnesium. Nerve regeneration was not interrupted by complete magnesium degradation. An initial functional evaluation, determination of size recovery of the gastrocnemius muscle, showed a slight improvement due to magnesium with the saline but not the keratin filler, compared with respective control conduits without magnesium. These results suggest that magnesium filament implants have the potential to improve repair of injured peripheral nerve defects in this rodent model. PMID:25281648

  17. Variable spatial magnetic field influences peripheral nerves regeneration in rats.

    PubMed

    Suszyński, Krzysztof; Marcol, Wiesław; Szajkowski, Sebastian; Pietrucha-Dutczak, Marita; Cieślar, Grzegorz; Sieroń, Aleksander; Lewin-Kowalik, Joanna

    2014-09-01

    Generator of spatial magnetic field is one of most recent achievements among the magnetostimulators. This apparatus allows to obtain the rotating magnetic field. This new method may be more effective than other widely used techniques of magnetostimulation and magnetotherapy. We investigated the influence of alternating, spatial magnetic field on the regeneration of the crushed rat sciatic nerves. Functional and morphological evaluations were used. After crush injury of the right sciatic nerve, Wistar C rats (n = 80) were randomly divided into four groups (control and three experimental). The experimental groups (A, B, C) were exposed (20 min/day, 5 d/week, 4 weeks) to alternating spatial magnetic field of three different intensities. Sciatic Functional Index (SFI) and tensometric assessments were performed every week after nerve crush. Forty-eight hours before the sacrificing of animals, DiI (1,1'-di-octadecyl-3,3,3',3'-tetramethyloindocarbocyanine perchlorate) was applied 5 mm distally to the crush site. Collected nerves and dorsal root ganglia (DRG) were subjected to histological and immunohistochemical staining. The survival rate of DRG neurons was estimated. Regrowth and myelination of the nerves was examined. The results of SFI and tensometric assessment showed improvement in all experimental groups as compared to control, with best outcome observed in group C, exposed to the strongest magnetic field. In addition, DRG survival rate and nerve regeneration intensity were significantly higher in the C group. Above results indicate that strong spatial alternating magnetic field exerts positive effect on peripheral nerve regeneration and its application could be taken under consideration in the therapy of injured peripheral nerves. PMID:23781984

  18. Follow-up evaluation with ultrasonography of peripheral nerve injuries after an earthquake

    PubMed Central

    Lu, Man; Wang, Yue; Yue, Linxian; Chiu, Jack; He, Fanding; Wu, Xiaojing; Zang, Bin; Lu, Bin; Yao, Xiaoke; Jiang, Zirui

    2014-01-01

    Published data on earthquake-associated peripheral nerve injury is very limited. Ultrasonography has been proven to be efficient in the clinic to diagnose peripheral nerve injury. The aim of this study was to assess the role of ultrasound in the evaluation of persistent peripheral nerve injuries 1 year after the Wenchuan earthquake. Thirty-four patients with persistent clinical symptoms and neurologic signs of impaired nerve function were evaluated with sonography prior to surgical repair. Among 34 patients, ultrasonography showed that 48 peripheral nerves were entrapped, and 11 peripheral nerves were disrupted. There was one case of misdiagnosis on ultrasonography. The concordance rate of ultrasonographic findings with those of surgical findings was 98%. A total of 48 involved nerves underwent neurolysis and the symptoms resolved. Only five nerves had scar tissue entrapment. Preoperative and postoperative clinical and ultrasonographic results were concordant, which verified that ultrasonography is useful for preoperative diagnosis and postoperative evaluation of injured peripheral nerves. PMID:25206859

  19. Malignant Peripheral Nerve Sheath Tumor -A Rare Malignancy in Mandible

    PubMed Central

    Majumdar, Sumit; Kotina, Sreekanth; Uppala, Divya; Kumar, Singam Praveen

    2016-01-01

    Malignant Peripheral Nerve Sheath Tumor (MPNST) is biologically an aggressive tumor that is usually found in the extremities, trunk and infrequently found in the head and neck area particularly in the jaws, arising from the cells allied with nerve sheath. Mandibular MPNST may either arise from a preexisting neurofibroma or develop de novo. Because of the greater variability from case to case in overall appearance both clinically and histologically, a case of MPNST of the mandible in a 25-year-old female patient is reported. The lesion was excised and immunohistological studies (S-100 & Neuron specific enolase) were conducted to confirm the neural origin. PMID:27504425

  20. Malignant Peripheral Nerve Sheath Tumor -A Rare Malignancy in Mandible.

    PubMed

    Majumdar, Sumit; Kotina, Sreekanth; Mahesh, Nirujogi; Uppala, Divya; Kumar, Singam Praveen

    2016-06-01

    Malignant Peripheral Nerve Sheath Tumor (MPNST) is biologically an aggressive tumor that is usually found in the extremities, trunk and infrequently found in the head and neck area particularly in the jaws, arising from the cells allied with nerve sheath. Mandibular MPNST may either arise from a preexisting neurofibroma or develop de novo. Because of the greater variability from case to case in overall appearance both clinically and histologically, a case of MPNST of the mandible in a 25-year-old female patient is reported. The lesion was excised and immunohistological studies (S-100 & Neuron specific enolase) were conducted to confirm the neural origin. PMID:27504425

  1. Long-term in vivo regeneration of peripheral nerves through bioengineered nerve grafts.

    PubMed

    di Summa, P G; Kalbermatten, D F; Pralong, E; Raffoul, W; Kingham, P J; Terenghi, G

    2011-05-01

    Although autologous nerve graft is still the first choice strategy in nerve reconstruction, it has the severe disadvantage of the sacrifice of a functional nerve. Cell transplantation in a bioartificial conduit is an alternative strategy to improve nerve regeneration. Nerve fibrin conduits were seeded with various cell types: primary Schwann cells (SC), SC-like differentiated bone marrow-derived mesenchymal stem cells (dMSC), SC-like differentiated adipose-derived stem cells (dASC). Two further control groups were fibrin conduits without cells and autografts. Conduits were used to bridge a 1 cm rat sciatic nerve gap in a long term experiment (16 weeks). Functional and morphological properties of regenerated nerves were investigated. A reduction in muscle atrophy was observed in the autograft and in all cell-seeded groups, when compared with the empty fibrin conduits. SC showed significant improvement in axon myelination and average fiber diameter of the regenerated nerves. dASC were the most effective cell population in terms of improvement of axonal and fiber diameter, evoked potentials at the level of the gastrocnemius muscle and regeneration of motoneurons, similar to the autografts. Given these results and other advantages of adipose derived stem cells such as ease of harvest and relative abundance, dASC could be a clinically translatable route towards new methods to enhance peripheral nerve repair. PMID:21371534

  2. Selective recovery of fascicular activity in peripheral nerves

    NASA Astrophysics Data System (ADS)

    Wodlinger, B.; Durand, D. M.

    2011-10-01

    The peripheral nerves of an amputee's residual limb still carry the information required to provide the robust, natural control signals needed to command a dexterous prosthetic limb. However, these signals are mixed in the volume conductor of the body and extracting them is an unmet challenge. A beamforming algorithm was used to leverage the spatial separation of the fascicular sources, recovering mixed pseudo-spontaneous signals with normalized mean squared error of 0.14 ± 0.10 (n = 12) in an animal model. The method was also applied to a human femoral nerve model using computer simulations and recovered all five fascicular-group signals simultaneously with R2 = 0.7 ± 0.2 at a signal-to-noise ratio of 0 dB. This technique accurately separated peripheral neural signals, potentially providing the voluntary, natural and robust command signals needed for advanced prosthetic limbs.

  3. Continuous peripheral nerve blocks: a review of the published evidence.

    PubMed

    Ilfeld, Brian M

    2011-10-01

    A continuous peripheral nerve block, also termed "perineural local anesthetic infusion," involves the percutaneous insertion of a catheter adjacent to a peripheral nerve, followed by local anesthetic administration via the catheter, providing anesthesia/analgesia for multiple days or even months. Continuous peripheral nerve blocks may be provided in the hospital setting, but the use of lightweight, portable pumps permits ambulatory infusion as well. This technique's most common application is providing analgesia after surgical procedures. However, additional indications include treating intractable hiccups; inducing a sympathectomy and vasodilation to increase blood flow after a vascular accident, digit transfer/replantation, or limb salvage; alleviating vasospasm of Raynaud disease; and treating peripheral embolism and chronic pain such as complex regional pain syndrome, phantom limb pain, trigeminal neuralgia, and cancer-induced pain. After trauma, perineural infusion can provide analgesia during transportation to a distant treatment center, or while simply awaiting surgical repair. Catheter insertion may be accomplished using many possible modalities, including nerve stimulation, ultrasound guidance, paresthesia induction, fluoroscopic imaging, and simple tactile perceptions ("facial click"). Either a nonstimulating epidural-type catheter may be used, or a "stimulating catheter" that delivers electrical current to its tip. Administered infusate generally includes exclusively long-acting, dilute, local anesthetic delivered as a bolus only, basal only, or basal-bolus combination. Documented benefits appear to be dependent on successfully improving analgesia, and include decreasing baseline/breakthrough/dynamic pain, supplemental analgesic requirements, opioid-related side effects, and sleep disturbances. In some cases, patient satisfaction and ambulation/functioning may be improved; an accelerated resumption of passive joint range-of-motion realized; and the time

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

    PubMed

    Frade, Marco Andrey Cipriani; Nogueira-Barbosa, Marcello Henrique; Lugão, Helena Barbosa; Furini, Renata Bazan; Marques Júnior, Wilson; Foss, Norma Tiraboschi

    2013-05-01

    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 < 0.0001) at the PT (5.67/9.78 mm2) and T (6.50/10.94 mm2) points, as well as at the M (5.85/8.48 mm2) and CF (8.17/14.14 mm2) nerves. The optimum CSA- receiver operating characteristic (ROC) points and sensitivities/specificities were, respectively, 6.85 mm2 and 68-85% for the PT point, 7.35 mm2 and 71-78% for the T point, 6.75 mm2 and 62-75% for the M nerve and 9.55 mm2 and 81-72% for the CF nerve. The ∆CSAs of the LPs were greater than those of the HVs at the PT point (4.02/0.85; p = 0.007), T point (3.71/0.98; p = 0.0005) and CF nerve (2.93/1.14; p = 0.015), with no difference found for the M nerve (1.41/0.95; p = 0.17). The optimum ∆CSA-ROC points, sensitivities, specificities and p-values were, respectively, 1.35, 49%, 80% and 0.003 at the PT point, 1.55, 55-85% and 0.0006 at the T point, 0.70, 58-50% and 0.73 for the M nerve and 1.25, 54-67% and 0.022 for the CF nerve. The ∆TPT in the LPs was greater than that in the HVs (4.43/1.44; p <0.0001). The optimum ∆TPT-ROC point was 2.65 (90% sensitivity/41% specificity, p < 0.0001). The ROC analysis of CSAs showed the highest specificity and sensitivity at the PT point and CF nerve, respectively. The PT and T ∆CSAs had high specificities (> 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. PMID:23778664

  5. Collagen VI regulates peripheral nerve myelination and function.

    PubMed

    Chen, Peiwen; Cescon, Matilde; Megighian, Aram; Bonaldo, Paolo

    2014-03-01

    Collagen VI is an extracellular matrix protein with broad distribution in several tissues. Although Col6a1 is expressed by Schwann cells, the role of collagen VI in the peripheral nervous system (PNS) is yet unknown. Here we show that Schwann cells, but not axons, contribute to collagen VI deposition in peripheral nerves. By using Col6a1-null mice, in which collagen VI deposition is compromised, we demonstrate that lack of collagen VI leads to increased myelin thickness (P<0.001) along with 60-130% up-regulation in myelin-associated proteins and disorganized C fibers in the PNS. The hypermyelination of PNS in Col6a1(-/-) mice is supported by alterations of signaling pathways involved in myelination, including increase of P-FAK, P-AKT, P-ERK1, P-ERK2, and P-p38 (4.15, 1.67, 2.47, 3.34, and 2.60-fold, respectively) and reduction of vimentin (0.49-fold), P-JNK (0.74-fold), and P-c-Jun (0.50-fold). Pathologically, Col6a1(-/-) mice display an impairment of nerve conduction velocity and motor coordination (P<0.05), as well as a delayed response to acute pain stimuli (P<0.001), indicating that lack of collagen VI causes functional defects of peripheral nerves. Altogether, these results indicate that collagen VI is a critical component of PNS contributing to the structural integrity and proper function of peripheral nerves. PMID:24277578

  6. Verapamil inhibits scar formation after peripheral nerve repair in vivo

    PubMed Central

    Han, A-chao; Deng, Jing-xiu; Huang, Qi-shun; Zheng, Huai-yuan; Zhou, Pan; Liu, Zhi-wei; Chen, Zhen-bing

    2016-01-01

    The calcium channel blocker, verapamil, has been shown to reduce scar formation by inhibiting fibroblast adhesion and proliferation in vitro. It was not clear whether topical application of verapamil after surgical repair of the nerve in vivo could inhibit the formation of excessive scar tissue. In this study, the right sciatic nerve of adult Sprague-Dawley rats was transected and sutured with No. 10-0 suture. The stoma was wrapped with gelfoam soaked with verapamil solution for 4 weeks. Compared with the control group (stoma wrapped with gelfoam soaked with physiological saline), the verapamil application inhibited the secretion of extracellular matrix from fibroblasts in vivo, suppressed type I and III collagen secretion and increased the total number of axons and the number of myelinated axons. These findings suggest that verapamil could reduce the formation of scar tissue and promote axon growth after peripheral nerve repair. PMID:27127494

  7. Modeling Electric Fields of Peripheral Nerve Block Needles.

    NASA Astrophysics Data System (ADS)

    Davis, James Ch.; Anderson, Norman E.; Meisel, Mark W.; Ramirez, Jason G.; Kayser Enneking, F.

    2006-03-01

    Peripheral nerve blocks present an alternative to general anesthesia in certain surgical procedures and a means of acute pain relief through continuous blockades. They have been shown to decrease the incidence of postoperative nausea and vomiting, reduce oral narcotic side effects, and improve sleep quality. Injecting needles, which carry small stimulating currents, are often used to aid in locating the target nerve bundle. With this technique, muscle responses indicate needle proximity to the corresponding nerve bundle. Failure rates in first injection attempts prompted our study of electric field distributions. Finite difference methods were used to solve for the electric fields generated by two widely used needles. Geometric differences in the needles effect variations in their electric field and current distributions. Further investigations may suggest needle modifications that result in a reduction of initial probing failures.

  8. Modeling Electric Fields of Peripheral Nerve Block Needles.

    NASA Astrophysics Data System (ADS)

    Davis, James Ch.; Ramirez, Jason G.

    2005-11-01

    Peripheral nerve blocks present an alternative to general anesthesia in certain surgical procedures and a means of acute pain relief through continuous blockades. They have been shown to decrease the incidence of postoperative nausea and vomiting, reduce oral narcotic side effects, and improve sleep quality. Injecting needles, which carry small stimulating currents, are often used to aid in locating the target nerve bundle. With this technique, muscle responses indicate needle proximity to the corresponding nerve bundle. Failure rates in first injection attempts prompted our study of electric field distributions. Finite difference methods were used to solve for the electric fields generated by two widely used needles. Differences in geometry between needles are seen to effect changes in electric field and current distributions. Further investigations may suggest needle modifications that result in a reduction of initial probing failures.

  9. Use of Vein Conduit and Isolated Nerve Graft in Peripheral Nerve Repair: A Comparative Study

    PubMed Central

    Ahmad, Imran; Akhtar, Md. Sohaib

    2014-01-01

    Aims and Objectives. The aim of this study was to evaluate the effectiveness of vein conduit in nerve repair compared with isolated nerve graft. Materials and Methods. This retrospective study was conducted at author's centre and included a total of 40 patients. All the patients had nerve defect of more than 3 cm and underwent nerve repair using nerve graft from sural nerve. In 20 cases, vein conduit (study group) was used whereas no conduit was used in other 20 cases. Patients were followed up for 2 years at the intervals of 3 months. Results. Patients had varying degree of recovery. Sensations reached to all the digits at 1 year in study groups compared to 18 months in control group. At the end of second year, 84% patients of the study group achieved 2-point discrimination of <10 mm compared to 60% only in control group. In terms of motor recovery, 82% patients achieved satisfactory hand function in study group compared to 56% in control group (P < .05). Conclusions. It was concluded that the use of vein conduit in peripheral nerve repair is more effective method than isolated nerve graft providing good sensory and motor recovery. PMID:25405029

  10. Effect of Delayed Peripheral Nerve Repair on Nerve Regeneration, Schwann Cell Function and Target Muscle Recovery

    PubMed Central

    Jonsson, Samuel; Wiberg, Rebecca; McGrath, Aleksandra M.; Novikov, Lev N.; Wiberg, Mikael; Novikova, Liudmila N.; Kingham, Paul J.

    2013-01-01

    Despite advances in surgical techniques for peripheral nerve repair, functional restitution remains incomplete. The timing of surgery is one factor influencing the extent of recovery but it is not yet clearly defined how long a delay may be tolerated before repair becomes futile. In this study, rats underwent sciatic nerve transection before immediate (0) or 1, 3, or 6 months delayed repair with a nerve graft. Regeneration of spinal motoneurons, 13 weeks after nerve repair, was assessed using retrograde labeling. Nerve tissue was also collected from the proximal and distal stumps and from the nerve graft, together with the medial gastrocnemius (MG) muscles. A dramatic decline in the number of regenerating motoneurons and myelinated axons in the distal nerve stump was observed in the 3- and 6-months delayed groups. After 3 months delay, the axonal number in the proximal stump increased 2–3 folds, accompanied by a smaller axonal area. RT-PCR of distal nerve segments revealed a decline in Schwann cells (SC) markers, most notably in the 3 and 6 month delayed repair samples. There was also a progressive increase in fibrosis and proteoglycan scar markers in the distal nerve with increased delayed repair time. The yield of SC isolated from the distal nerve segments progressively fell with increased delay in repair time but cultured SC from all groups proliferated at similar rates. MG muscle at 3- and 6-months delay repair showed a significant decline in weight (61% and 27% compared with contra-lateral side). Muscle fiber atrophy and changes to neuromuscular junctions were observed with increased delayed repair time suggestive of progressively impaired reinnervation. This study demonstrates that one of the main limiting factors for nerve regeneration after delayed repair is the distal stump. The critical time point after which the outcome of regeneration becomes too poor appears to be 3-months. PMID:23409189

  11. Electrical stimulation accelerates nerve regeneration and functional recovery in delayed peripheral nerve injury in rats.

    PubMed

    Huang, Jinghui; Zhang, Yongguang; Lu, Lei; Hu, Xueyu; Luo, Zhuojing

    2013-12-01

    The present study aims to investigate the potential of brief electrical stimulation (ES; 3 V, 20 Hz, 20 min) in improving functional recovery in delayed nerve injury repair (DNIR). The sciatic nerve of Sprague Dawley rats was transected, and the repair of nerve injury was delayed for different time durations (2, 4, 12 and 24 weeks). Brief depolarizing ES was applied to the proximal nerve stump when the transected nerve stumps were bridged with a hollow nerve conduit (5 mm in length) after delayed periods. We found that the diameter and number of regenerated axons, the thickness of myelin sheath, as well as the number of Fluoro-Gold retrograde-labeled motoneurons and sensory neurons were significantly increased by ES, suggesting that brief ES to proximal nerve stumps is capable of promoting nerve regeneration in DNIR with different delayed durations, with the longest duration of 24 weeks. In addition, the amplitude of compound muscle action potential (gastrocnemius muscle) and nerve conduction velocity were also enhanced, and gastrocnemius muscle atrophy was partially reversed by brief ES, indicating that brief ES to proximal nerve stump was able to improve functional recovery in DNIR. Furthermore, brief ES was capable of increasing brain-derived neurotrophic factor (BDNF) expression in the spinal cord in DNIR, suggesting that BDNF-mediated neurotrophin signaling might be one of the contributing factors to the beneficial effect of brief ES on DNIR. In conclusion, the present findings indicate the potential of using brief ES as a useful method to improve functional recovery for delayed repair of peripheral nerve lesions. PMID:24118464

  12. Engineering a multimodal nerve conduit for repair of injured peripheral nerve.

    PubMed

    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

  13. Engineering a multimodal nerve conduit for repair of injured peripheral nerve

    NASA Astrophysics Data System (ADS)

    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

  14. Binary Imaging Analysis for Comprehensive Quantitative Assessment of Peripheral Nerve

    PubMed Central

    Hunter, Daniel A.; Moradzadeh, Arash; Whitlock, Elizabeth L.; Brenner, Michael J.; Myckatyn, Terence M.; Wei, Cindy H.; Tung, Thomas H.H.; Mackinnon, Susan E.

    2007-01-01

    Quantitative histomorphometry is the current gold standard for objective measurement of nerve architecture and its components. Many methods still in use rely heavily upon manual techniques that are prohibitively time consuming, predisposing to operator fatigue, sampling error, and overall limited reproducibility. More recently, investigators have attempted to combine the speed of automated morphometry with the accuracy of manual and semi-automated methods. Systematic refinements in binary imaging analysis techniques combined with an algorithmic approach allow for more exhaustive characterization of nerve parameters in the surgically relevant injury paradigms of regeneration following crush, transection, and nerve gap injuries. The binary imaging method introduced here uses multiple bitplanes to achieve reproducible, high throughput quantitative assessment of peripheral nerve. Number of myelinated axons, myelinated fiber diameter, myelin thickness, fiber distributions, myelinated fiber density, and neural debris can be quantitatively evaluated with stratification of raw data by nerve component. Results of this semi-automated method are validated by comparing values against those obtained with manual techniques. The use of this approach results in more rapid, accurate, and complete assessment of myelinated axons than manual techniques. PMID:17675163

  15. Specificity of peripheral nerve regeneration: interactions at the axon level.

    PubMed

    Allodi, Ilary; Udina, Esther; Navarro, Xavier

    2012-07-01

    Peripheral nerves injuries result in paralysis, anesthesia and lack of autonomic control of the affected body areas. After injury, axons distal to the lesion are disconnected from the neuronal body and degenerate, leading to denervation of the peripheral organs. Wallerian degeneration creates a microenvironment distal to the injury site that supports axonal regrowth, while the neuron body changes in phenotype to promote axonal regeneration. The significance of axonal regeneration is to replace the degenerated distal nerve segment, and achieve reinnervation of target organs and restitution of their functions. However, axonal regeneration does not always allows for adequate functional recovery, so that after a peripheral nerve injury, patients do not recover normal motor control and fine sensibility. The lack of specificity of nerve regeneration, in terms of motor and sensory axons regrowth, pathfinding and target reinnervation, is one the main shortcomings for recovery. Key factors for successful axonal regeneration include the intrinsic changes that neurons suffer to switch their transmitter state to a pro-regenerative state and the environment that the axons find distal to the lesion site. The molecular mechanisms implicated in axonal regeneration and pathfinding after injury are complex, and take into account the cross-talk between axons and glial cells, neurotrophic factors, extracellular matrix molecules and their receptors. The aim of this review is to look at those interactions, trying to understand if some of these molecular factors are specific for motor and sensory neuron growth, and provide the basic knowledge for potential strategies to enhance and guide axonal regeneration and reinnervation of adequate target organs. PMID:22609046

  16. A flexible microchannel electrode array for peripheral nerves to interface with neural prosthetics

    NASA Astrophysics Data System (ADS)

    Landrith, Ryan; Nothnagle, Caleb; Kim, Young-tae; Wijesundara, Muthu B. J.

    2016-05-01

    In order to control neural prosthetics by recording signals from peripheral nerves with the required specificity, high density electrode arrays that can be easily implanted on very small peripheral nerves (50μm-500μm) are needed. Interfacing with these small nerves is surgically challenging due to their size and fragile nature. To address this problem, a Flexible MicroChannel Electrode Array for interfacing with small diameter peripheral nerves and nerve fascicles was developed. The electrochemical characterization and electrophysiological recordings from the common peroneal nerve of a rat are presented along with demonstration of the surgical ease-of-use of the array.

  17. Bridging long gap peripheral nerve injury using skeletal muscle-derived multipotent stem cells.

    PubMed

    Tamaki, Tetsuro

    2014-07-15

    Long gap peripheral nerve injuries usually reulting in life-changing problems for patients. Skeletal muscle derived-multipotent stem cells (Sk-MSCs) can differentiate into Schwann and perineurial/endoneurial cells, vascular relating pericytes, and endothelial and smooth muscle cells in the damaged peripheral nerve niche. Application of the Sk-MSCs in the bridging conduit for repairing long nerve gap injury resulted favorable axonal regeneration, which showing superior effects than gold standard therapy--healthy nerve autograft. This means that it does not need to sacrifice of healthy nerves or loss of related functions for repairing peripheral nerve injury. PMID:25221587

  18. Role of transcription factors in peripheral nerve regeneration.

    PubMed

    Patodia, Smriti; Raivich, Gennadij

    2012-01-01

    Following axotomy, the activation of multiple intracellular signaling cascades causes the expression of a cocktail of regeneration-associated transcription factors which interact with each other to determine the fate of the injured neurons. The nerve injury response is channeled through manifold and parallel pathways, integrating diverse inputs, and controlling a complex transcriptional output. Transcription factors form a vital link in the chain of regeneration, converting injury-induced stress signals into downstream protein expression via gene regulation. They can regulate the intrinsic ability of axons to grow, by controlling expression of whole cassettes of gene targets. In this review, we have investigated the functional roles of a number of different transcription factors - c-Jun, activating transcription factor 3, cAMP response element binding protein, signal transducer, and activator of transcription-3, CCAAT/enhancer binding proteins β and δ, Oct-6, Sox11, p53, nuclear factor kappa-light-chain-enhancer of activated B cell, and ELK3 - in peripheral nerve regeneration. Studies involving use of conditional mutants, microarrays, promoter region mapping, and different injury paradigms, have enabled us to understand their distinct as well as overlapping roles in achieving anatomical and functional regeneration after peripheral nerve injury. PMID:22363260

  19. Poly(ester urethane) guides for peripheral nerve regeneration.

    PubMed

    Chiono, Valeria; Sartori, Susanna; Rechichi, Alfonsina; Tonda-Turo, Chiara; Vozzi, Giovanni; Vozzi, Federico; D'Acunto, Mario; Salvadori, Claudia; Dini, Francesca; Barsotti, Giovanni; Carlucci, Fabio; Burchielli, Silvia; Nicolino, Silvia; Audisio, Chiara; Perroteau, Isabelle; Giusti, Paolo; Ciardelli, Gianluca

    2011-02-11

    A biocompatible and elastomeric PU was synthesized from low-molecular-weight PCL as macrodiol, CMD as chain extender and HDI as chain linker for applications in the field of peripheral nerve repair. PU cast films supported in vitro attachment and proliferation of NOBEC. The in vitro adhesion and proliferation of S5Y5 neuroblastoma cells on the inner surface of uncoated, gelatin- and PL-coated PU guides were compared. Due to their superior in vitro performance, PL-coated PU guides were tested in vivo for the repair of 1.8 cm-long defects in rat sciatic nerves. The progressive regeneration was confirmed by EMG and histological analysis showing the presence of regenerating fibers in the distal stumps. PMID:21104881

  20. Ex vivo peripheral nerve detection of rats by spontaneous Raman spectroscopy

    PubMed Central

    Minamikawa, Takeo; Harada, Yoshinori; Takamatsu, Tetsuro

    2015-01-01

    Nerve-sparing surgery is increasingly being applied to avoid functional deficits of the limbs and organs following surgery. Peripheral nerves that should be preserved are, however, sometimes misidentified due to similarity of shape and color to non-nerve tissues. To avoid misidentification of peripheral nerves, development of an in situ nerve detection method is desired. In this study, we report the label-free detection of ex vivo peripheral nerves of Wistar rats by using Raman spectroscopy. We obtained Raman spectra of peripheral nerves (myelinated and unmyelinated nerves) and their adjacent tissues of Wistar rats without any treatment such as fixation and/or staining. For the identification of tissue species and further analysis of spectral features, we proposed a principal component regression-based discriminant analysis with representative Raman spectra of peripheral nerves and their adjacent tissues. Our prediction model selectively detected myelinated nerves and unmyelinated nerves of Wistar rats with respective sensitivities of 95.5% and 88.3% and specificities of 99.4% and 93.5%. Furthermore, important spectral features for the identification of tissue species were revealed by detailed analysis of principal components of representative Raman spectra of tissues. Our proposed approach may provide a unique and powerful tool for peripheral nerve detection for nerve-sparing surgery in the future. PMID:26602842

  1. The effects of electroacupuncture on peripheral nerve regeneration in rats.

    PubMed

    Inoue, Motohiro; Hojo, Tatsuya; Yano, Tadashi; Katsumi, Yasukazu

    2003-06-01

    This study was designed to examine the effects of electroacupuncture with direct current (DC) on peripheral nerve regeneration. The left sciatic nerve of 55 7-month-old rats was crushed at the thigh. They were ramdomly allocated to four groups: distal cathode DC group (n = 15), distal anode DC group (n = 14), sham operated group (n = 13), and control group (n = 13). In the distal cathode DC group, a cathode electrode was connected to an insulated acupuncture needle inserted at 1 cm distal to the injured site, while an anode electrode was connected to a needle inserted at 1 cm proximal to the lesion. In the distal anode DC group, the anode and the cathode electrode were connected to the needle at 1 cm distal and proximal to the lesion respectively. In the sham operated group, no electrical stimulation was given to the insulated needle inserted at the same site, and in the control group, no treatment was given. Regeneration of the sciatic nerve was evaluated by the number of evoked EMGs recorded at 12 sites in the plantar region, by their latency, and by the weight ratio of the tibialis anterior at four weeks after the crush injury. Regeneration of the peripheral nerve was faster and more accelerated in the distal cathode DC group than in the other groups, while in the distal anode DC group the regeneration was delayed. This result suggested electroacupuncture with cathode distal orientation might be a useful treatment having the advantage of enabling deeper insertion with minimal tissue damage. PMID:12924841

  2. Malignant Peripheral Nerve Sheath Tumour: CT and MRI Findings.

    PubMed

    Sperandio, Massimiliano; Di Poce, Isabelle; Ricci, Aurora; Di Trapano, Roberta; Costanzo, Elisa; Di Cello, Pierfrancesco; Pelle, Fabio; Izzo, Luciano; Simonetti, Giovanni

    2013-01-01

    Malignant peripheral nerve sheath tumour (MPNST) is extremely rare malignancy in the general population, occurring more frequently in patients with Neurofibromatosis type 1 (NF1). In the literature five cases of MPNST arising from the parapharyngeal space (PPS) in patients without neurofibromatosis have been reported. We report imaging techniques in a patient with MPNST in the PPS, who had neither a family history nor sign of NF1. Computed tomography (CT) scan and magnetic resonance imaging (MRI) were performed for a correct therapeutic planning. CT and MRI findings were correlated with hystopathological diagnosis. PMID:23970990

  3. Improved Peripheral Nerve Regeneration Using Acellular Nerve Allografts Loaded with Platelet-Rich Plasma

    PubMed Central

    Zheng, Canbin; Huang, Xijun; He, Caifeng; Jiang, Li; Quan, Daping

    2014-01-01

    Acellular nerve allografts (ANAs) behave in a similar manner to autografts in supporting axonal regeneration in the repair of short peripheral nerve defects but fail in larger defects. The objective of this article is to evaluate the effect of ANA supplemented with platelet-rich plasma (PRP) to improve nerve regeneration after surgical repair and to discuss the mechanisms that underlie this approach. Autologous PRP was obtained from rats by double-step centrifugation and was characterized by determining platelet numbers and the release of growth factors. Forty-eight Sprague–Dawley rats were randomly divided into 4 groups (12/group), identified as autograft, ANA, ANA loaded with PRP (ANA+PRP), and ANA loaded with platelet-poor plasma (PPP, ANA+PPP). All grafts were implanted to bridge long-gap (15 mm) sciatic nerve defects. We found that PRP with a high platelet concentration exhibited a sustained release of growth factors. Twelve weeks after surgery, the autograft group displayed the highest level of reinnervation, followed by the ANA+PRP group. The ANA+PRP group showed a better electrophysiology response for amplitude and conduction velocity than the ANA and ANA+PPP groups. Based on histological evaluation, the ANA+PRP and autograft groups had higher numbers of regenerating nerve fibers. Quantitative real-time polymerase chain reaction (qRT-PCR) demonstrated that PRP boosted expression of neurotrophins in the regenerated nerves. Moreover, the ANA+PRP and autograft groups showed excellent physiological outcomes in terms of the prevention of muscle atrophy. In conclusion, ANAs loaded with PRP as tissue-engineered scaffolds can enhance nerve regeneration and functional recovery after the repair of large nerve gaps nearly as well as autografts. PMID:24901030

  4. Developing an algorithm for cost-effective, clinically judicious management of peripheral nerve tumors.

    PubMed

    Birk, Harjus; Zygourakis, Corinna C; Kliot, Michel

    2016-01-01

    Peripheral nerve tumors such as neurofibromas and schwannomas have become increasingly identified secondary to improved imaging modalities including magnetic resonance neurogram and ultrasound. Given that a majority of these peripheral nerve tumors are benign lesions, it becomes important to determine appropriate management of such asymptomatic masses. We propose a normal cost-effective management paradigm for asymptomatic peripheral nerve neurofibromas and schwannomas that has been paired with economic analyses. Specifically, our management paradigm identifies patients who would benefit from surgery for asymptomatic peripheral nerve tumors, while providing cost-effective recommendations regarding clinical exams and serial imaging for such patients. PMID:27625890

  5. Developing an algorithm for cost-effective, clinically judicious management of peripheral nerve tumors

    PubMed Central

    Birk, Harjus; Zygourakis, Corinna C.; Kliot, Michel

    2016-01-01

    Peripheral nerve tumors such as neurofibromas and schwannomas have become increasingly identified secondary to improved imaging modalities including magnetic resonance neurogram and ultrasound. Given that a majority of these peripheral nerve tumors are benign lesions, it becomes important to determine appropriate management of such asymptomatic masses. We propose a normal cost-effective management paradigm for asymptomatic peripheral nerve neurofibromas and schwannomas that has been paired with economic analyses. Specifically, our management paradigm identifies patients who would benefit from surgery for asymptomatic peripheral nerve tumors, while providing cost-effective recommendations regarding clinical exams and serial imaging for such patients. PMID:27625890

  6. Biophysical Mechanisms of Transient Optical Stimulation of Peripheral Nerve

    PubMed Central

    Wells, Jonathon; Kao, Chris; Konrad, Peter; Milner, Tom; Kim, Jihoon; Mahadevan-Jansen, Anita; Jansen, E. Duco

    2007-01-01

    A new method for in vivo neural activation using low-intensity, pulsed infrared light exhibits advantages over standard electrical means by providing contact-free, spatially selective, artifact-free stimulation. Here we investigate the biophysical mechanism underlying this phenomenon by careful examination of possible photobiological effects after absorption-driven light-tissue interaction. The rat sciatic nerve preparation was stimulated in vivo with a Holmium:yttrium aluminum garnet laser (2.12 μm), free electron laser (2.1 μm), alexandrite laser (750 nm), and prototype solid-state laser nerve stimulator (1.87 μm). We systematically determined relative contributions from a list of plausible interaction types resulting in optical stimulation, including thermal, pressure, electric field, and photochemical effects. Collectively, the results support our hypothesis that direct neural activation with pulsed laser light is induced by a thermal transient. We then present data that characterize and quantify the spatial and temporal nature of this required temperature rise, including a measured surface temperature change required for stimulation of the peripheral nerve (6°C–10°C). This interaction is a photothermal effect from moderate, transient tissue heating, a temporally and spatially mediated temperature gradient at the axon level (3.8°C–6.4°C), resulting in direct or indirect activation of transmembrane ion channels causing action potential generation. PMID:17526565

  7. Acute anoxic changes in peripheral nerve: anatomic and physiologic correlations

    PubMed Central

    Punsoni, Michael; Drexler, Steven; Palaia, Thomas; Stevenson, Matthew; Stecker, Mark M

    2015-01-01

    Introduction The response of the peripheral nerve to anoxia is modulated by many factors including glucose and temperature. The purposes of this article are to demonstrate the effects of these factors on the pathological changes induced by anoxia and to compare the electrophysiologic changes and pathological changes in the same nerves. Methods Sciatic nerves were harvested from rats and placed in a perfusion apparatus where neurophysiologic responses could be recorded continuously during a 16 h experiment. After the experiment, light microscopy and electron microscopy were performed. Results Light microscopic images showed mild changes from anoxia at normoglycemia. Hypoglycemic anoxia produced massive axonal swelling while hyperglycemic anoxia produced apparent changes in the myelin. Anoxic changes were not uniform in all axons. Electron microscopy showed only minor disruptions of the cytoskeleton with anoxia during normoglycemia. At the extremes of glucose concentration especially with hyperglycemia, there was a more severe disruption of intermediate filaments and loss of axonal structure with anoxia. Hypothermia protected axons from the effect of anoxia and produced peak axonal swelling in the 17–30°C range. Conclusions The combination of hyperglycemia or hypoglycemia and anoxia produces extremely severe axonal disruption. Changes in axonal diameter are complex and are influenced by many factors. PMID:26221572

  8. Electrodiagnostic study of peripheral nerves in high-voltage electrical injury.

    PubMed

    Kwon, Ki Han; Kim, Se Hoon; Minn, Yang Ki

    2014-01-01

    It is well known that peripheral nerves are very vulnerable to electricity. However, only a small portion of individuals who have had high-voltage electrical injury exhibit peripheral nerve damage. The aim of this study was to investigate peripheral nerve damage in high-voltage electrical injury, which often occurs in the industrial field. The authors reviewed the medical records of patients who were admitted to their hospital from January 2009 to December 2011, because of electrical injuries. The results of nerve conduction studies (NCSs) were reviewed retrospectively. NCS data of the injured site were compared with those of the opposite noninjured site and follow-up data. Thirty-seven extremities were reviewed. The authors found that 18 of 33 median nerves (48.6%) showed abnormalities in at least one parameter and 15 of 36 ulnar nerves (41.7%) exhibited abnormalities. There was no evidence of demyelination. Eight patients had undergone NCS on the opposite normal extremities. The compound muscle action potential and nerve conduction velocity were higher at the normal site. Follow-up NCS were performed in 14 patients: the compound muscle action potential and nerve conduction velocity values of all patients were improved. High-voltage electricity damaged peripheral nerves by causing axonal injury rather than demyelinating injury. Hence, even if NCSs yield normal findings, peripheral nerves may be damaged. F/U studies and opposite examinations are required for the exact evaluation of peripheral nerve damage. PMID:23877148

  9. Profiling of the dynamically alteredgene expression in peripheral nerve injury using NGS RNA sequencing technique.

    PubMed

    Han, Duanyang; Chen, Yixun; Kou, Yuhui; Weng, Jian; Chen, Bo; Yu, Youlai; Zhang, Peixun; Jiang, Baoguo

    2016-01-01

    Functional recovery of peripheral nerve injuries is of major demand in clinical practice worldwide. Although, to some extent, peripheral nervous system can spontaneously regenerate, post-injury recovery is often associated with poor functional outcome. The molecular mechanism controlling the peripheral nerve repair process is still majorly unclear. In this study, by utilizing the Next Generation Sequencing (NGS) RNA sequencing technique, we aim to profile the gene expression spectrum of the peripheral nerve repair. In total, we detected 2847 were differentially expressed at day 7 post crush nerve injury. The GO, Panther, IPA and GSEA analysis was performed to decipher the biological processes involving the differentially expressed genes. Collectively, our results highlighted the inflammatory response and related signaling pathway (NFkB and TNFa signaling) play key role in peripheral nerve repair regulation. Furthermore, Network analysis illustrated that the IL10, IL18, IFN-γ and PDCD1 were four key regulators with multiple participations in peripheral nerve repair and potentially exert influence to the repair process. The expression changes of IL10, IL18, IFN-γ, PDCD1 and TNFSF14 (LIGHT) were further validated by western blot analysis. Hopefully, the present study may provide useful platform to further reveal the molecular mechanism of peripheral nerve repair and discover promising treatment target to enhance peripheral nerve regeneration. PMID:27158375

  10. Study of the effects of semiconductor laser irradiation on peripheral nerve injury

    NASA Astrophysics Data System (ADS)

    Xiong, G. X.; Li, P.

    2012-11-01

    In order to study to what extent diode laser irradiation effects peripheral nerve injury, the experimental research was made on rabbits. Experimental results show that low-energy semiconductor laser can promote axonal regeneration and improve nervous function. It is also found that simultaneous exposure of the injured peripheral nerve and corresponding spinal segments to laser irradiation may achieve the most significant results.

  11. Profiling of the dynamically alteredgene expression in peripheral nerve injury using NGS RNA sequencing technique

    PubMed Central

    Han, Duanyang; Chen, Yixun; Kou, Yuhui; Weng, Jian; Chen, Bo; Yu, Youlai; Zhang, Peixun; Jiang, Baoguo

    2016-01-01

    Functional recovery of peripheral nerve injuries is of major demand in clinical practice worldwide. Although, to some extent, peripheral nervous system can spontaneously regenerate, post-injury recovery is often associated with poor functional outcome. The molecular mechanism controlling the peripheral nerve repair process is still majorly unclear. In this study, by utilizing the Next Generation Sequencing (NGS) RNA sequencing technique, we aim to profile the gene expression spectrum of the peripheral nerve repair. In total, we detected 2847 were differentially expressed at day 7 post crush nerve injury. The GO, Panther, IPA and GSEA analysis was performed to decipher the biological processes involving the differentially expressed genes. Collectively, our results highlighted the inflammatory response and related signaling pathway (NFkB and TNFa signaling) play key role in peripheral nerve repair regulation. Furthermore, Network analysis illustrated that the IL10, IL18, IFN-γ and PDCD1 were four key regulators with multiple participations in peripheral nerve repair and potentially exert influence to the repair process. The expression changes of IL10, IL18, IFN-γ, PDCD1 and TNFSF14 (LIGHT) were further validated by western blot analysis. Hopefully, the present study may provide useful platform to further reveal the molecular mechanism of peripheral nerve repair and discover promising treatment target to enhance peripheral nerve regeneration. PMID:27158375

  12. Intravenous Transplantation of Mesenchymal Stromal Cells to Enhance Peripheral Nerve Regeneration

    PubMed Central

    Matthes, Stella M.; Reimers, Kerstin; Janssen, Insa; Kocsis, Jeffery D.; Vogt, Peter M.; Radtke, Christine

    2013-01-01

    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. PMID:24459671

  13. Malignant peripheral nerve sheath tumour in a sow.

    PubMed

    Resende, Talita P; Pereira, Carlos E R; Vannucci, Fabio A; Araujo, Fernando S; dos Santos, José Lúcio; Cassali, Geovanni D; Damasceno, Karine A; Guedes, Roberto M C

    2015-01-01

    Nodular lung lesions in swine are frequently due to abscesses or granulomatous pneumonia. Although tumours are rarely reported in modern pig farming, they should be considered as a differential diagnosis when nodular lung lesions are found. A first-parity sow exhibiting respiratory signs was euthanized. Several whitish firm nodules, not encapsulated, ranging in diameter from 0.5 to 5 cm were present in all lung lobes. Microscopically, the nodules were composed of dense neoplastic cells, mainly in Antoni types A and B patterns, infiltrative and with development of emboli. All neoplastic cells stained positively by immunohistochemistry for vimentin and S-100 protein, with variable immunostaining for glial fibrillary acidic protein and stained negative for cytokeratin. Based on the gross, histological and immunohistochemical features, the tumor was diagnosed as malignant peripheral nerve sheath tumour. PMID:26407677

  14. Composite pheochromocytoma with a malignant peripheral nerve sheath tumor: Case report and review of the literature.

    PubMed

    Namekawa, Takeshi; Utsumi, Takanobu; Imamoto, Takashi; Kawamura, Koji; Oide, Takashi; Tanaka, Tomoaki; Nihei, Naoki; Suzuki, Hiroyoshi; Nakatani, Yukio; Ichikawa, Tomohiko

    2016-07-01

    Adrenal tumors with more than one cellular component are uncommon. Furthermore, an adrenal tumor composed of a pheochromocytoma and a malignant peripheral nerve sheath tumor is extremely rare. A composite pheochromocytoma with malignant peripheral nerve sheath tumor in a 42-year-old man is reported here. After adequate preoperative control, left adrenalectomy was performed simultaneously with resection of the ipsilateral kidney for spontaneous rupture of the left adrenal tumor. Pathological findings demonstrated pheochromocytoma and malignant peripheral nerve sheath tumor in a ruptured adrenal tumor. To date, there have been only four reported cases of composite pheochromocytoma with malignant peripheral nerve sheath tumor, so the present case is only the fifth case in the world. Despite the very poor prognosis of patients with pheochromocytoma and malignant peripheral nerve sheath tumors reported in the literature, the patient remains well without evidence of recurrence or new metastatic lesions at 36 months postoperatively. PMID:27338175

  15. In vivo characterization of regenerative peripheral nerve interface function

    NASA Astrophysics Data System (ADS)

    Ursu, Daniel C.; Urbanchek, Melanie G.; Nedic, Andrej; Cederna, Paul S.; Gillespie, R. Brent

    2016-04-01

    Objective. Regenerative peripheral nerve interfaces (RPNIs) are neurotized free autologous muscle grafts equipped with electrodes to record myoelectric signals for prosthesis control. Viability of rat RPNI constructs have been demonstrated using evoked responses. In vivo RPNI characterization is the next critical step for assessment as a control modality for prosthetic devices. Approach. Two RPNIs were created in each of two rats by grafting portions of free muscle to the ends of divided peripheral nerves (peroneal in the left and tibial in the right hind limb) and placing bipolar electrodes on the graft surface. After four months, we examined in vivo electromyographic signal activity and compared these signals to muscular electromyographic signals recorded from autologous muscles in two rats serving as controls. An additional group of two rats in which the autologous muscles were denervated served to quantify cross-talk in the electrode recordings. Recordings were made while rats walked on a treadmill and a motion capture system tracked the hind limbs. Amplitude and periodicity of signals relative to gait were quantified, correlation between electromyographic and motion recording were assessed, and a decoder was trained to predict joint motion. Main Results. Raw RPNI signals were active during walking, with amplitudes of 1 mVPP, and quiet during standing, with amplitudes less than 0.1 mVPP. RPNI signals were periodic and entrained with gait. A decoder predicted bilateral ankle motion with greater than 80% reliability. Control group signal activity agreed with literature. Denervated group signals remained quiescent throughout all evaluations. Significance. In vivo myoelectric RPNI activity encodes neural activation patterns associated with gait. Signal contamination from muscles adjacent to the RPNI is minimal, as demonstrated by the low amplitude signals obtained from the Denervated group. The periodicity and entrainment to gait of RPNI recordings suggests the

  16. Paranodal dysmyelination in peripheral nerves of Trembler mice.

    PubMed

    Rosenbluth, Jack; Bobrowski-Khoury, Natasha

    2014-04-01

    Subtle defects in paranodes of myelinated nerve fibers can cause significant physiological malfunction. We have investigated myelinated fibers in the peripheral nervous system (PNS) of the Trembler mouse, a model of CMT-1A neuropathy, for evidence of such defects. Ultrastructural analysis shows that the "transverse bands," which attach the myelin sheath to the axon at the paranodal axoglial junction, are grossly diminished in number in Trembler nerve fibers. Although paranodes often appear to be greatly elongated, it is only a short region immediately adjacent to the node of Ranvier that displays transverse bands. Where transverse bands are missing, the junctional gap widens, thus reducing resistance to short circuiting of nodal action currents during saltatory conduction and increasing the likelihood that axonal K(+) channels under the myelin sheath will be activated. In addition, we find evidence that structural domains in Trembler axons are incompletely differentiated, consistent with diminution in nodal Na channel density, which could further compromise conduction. Deficiency of transverse bands may also increase susceptibility to disruption of the paranodal junction and retraction of the myelin sheath. We conclude that Trembler PNS myelinated fibers display subtle defects in paranodal and nodal regions that could contribute significantly to conduction defects and increased risk of myelin detachment. PMID:24446165

  17. Modified bacterial cellulose tubes for regeneration of damaged peripheral nerves

    PubMed Central

    Cala, Jaroslaw; Grobelski, Bartlomiej; Sygut, Dominik; Jesionek-Kupnicka, Dorota; Kolodziejczyk, Marek; Bielecki, Stanislaw; Pasieka, Zbigniew

    2013-01-01

    Introduction The subject of the experiment was bacterial nanocellulose, a natural polymer produced by bacteria – Gluconacetobacter xylinus. Following a specific modification process a cartilage-like material for restoration of damaged tissues may be produced. The obtained implants with excellent biocompatibility, mouldability, biophysical and chemical properties perfectly fit the needs of reconstructive surgery. The goal of the experiment was to develop and analyze cellulosic guidance channels in vivo for the reconstruction of damaged peripheral nerves. Material and methods The experiments were conducted on Wistar rats, femoral nerve. Cellulose was produced according to a self-patented method. In the experimental group tubulization was applied, whereas in the control traditional end-to-end connection was used. Observation time was 30, 60, 90, and 180 days. Results evaluation included histological analysis and postoperative observation of motor recovery. Results The overgrowth of connective tissue and disorganisation of neural structures was evident in 86.67% of control specimens, while for cellulosic group it was only 35% (p = 0.0022). Tubulization prevented the excessive proliferation of connective tissue and isolated from penetration with scar tissue. Autocannibalism, being probably an evidence of neurotrophic factors amassment, was observed in cellulosic group but not in the control one. Motor recovery did not differ significantly (p > 0.05). Biocompatibility of implants was affirmed by very small level of tissue response and susceptibility to vascularisation. Conclusions Cellulosic neurotubes effectively prevent the formation of neuromas. They are of very good biocompatibility and allow the accumulation of neurotrophic factors inside, thus facilitating the process of nerve regeneration. PMID:23847677

  18. Regeneration of respiratory pathways within spinal peripheral nerve grafts.

    PubMed

    Decherchi, P; Lammari-Barreault, N; Gauthier, P

    1996-01-01

    Central respiratory neurons exhibit normal activity after axonal regeneration within blind-ended peripheral nerve grafts (PNGs) inserted near the corresponding cell bodies in the medullary respiratory centers. Part of these medullary respiratory neurons project toward the spinal cord and contribute to descending respiratory pathways that control respiratory motoneurons. The present work investigates to what extent cervical respiratory pathways could be directed out of the central nervous system within PNGs inserted distant to the medullary respiratory nuclei. In adult rats (n = 13), autologous segments of the peroneal nerve were implanted into the ventrolateral part of the C2 spinal cord at the level of the descending respiratory pathways. Two to four months after grafting, electrophysiological recording of teased graft filaments (n = 562) revealed the presence of regenerated nerve fibers with unitary impulse traffic (n = 164) in all tested PNGs (n = 6). Respiratory discharges (n = 52) corresponded to efferent and afferent activity. Efferent respiratory discharges (n = 32) originated from central respiratory neurons which remained functional and preserved afferent connections. Retrograde horseradish peroxidase labeling applied to the distal cut end of PNGs (n = 7) revealed stained (42/1997) neurons in areas where respiratory cells have been described. Afferent respiratory discharges (n = 20) were synchronized with lung inflation but their origin (stretch pulmonary receptors and/or respiratory muscle receptors) was not determined. On the basis of additional data from light and electron microscopy of PNGs, comparison was made between anatomical, retrograde labeling, and electrophysiological data. The main conclusion is that spinal PNGs appear to be able to promote axonal regeneration of functional respiratory efferent and afferent pathways. PMID:8566201

  19. Biological and Electrophysiologic Effects of Poly(3,4-ethylenedioxythiophene) on Regenerating Peripheral Nerve Fibers

    PubMed Central

    Baghmanli, Ziya; Sugg, Kristoffer B.; Wei, Benjamin; Shim, Bong S.; Martin, David C.; Cederna, Paul S.; Urbanchek, Melanie G.

    2014-01-01

    Background Uninjured peripheral nerves in upper-limb amputees represent attractive sites for connectivity with neuroprostheses because their predictable internal topography allows for precise sorting of motor and sensory signals. The inclusion of poly(3,4-ethylenedioxythiophene) reduces impedance and improves charge transfer at the biotic-abiotic interface. This study evaluates the in vivo performance of poly(3,4-ethylenedioxythiophene)–coated interpositional decellularized nerve grafts across a critical nerve conduction gap, and examines the long-term effects of two different poly(3,4-ethylenedioxythiophene) formulations on regenerating peripheral nerve fibers. Methods In 48 rats, a 15-mm gap in the common peroneal nerve was repaired using a nerve graft of equivalent length, including (1) decellularized nerve chemically polymerized with poly(3,4-ethylenedioxythiophene) (dry); (2) decellularized nerve electrochemically polymerized with poly(3,4-ethylenedioxythiophene) (wet); (3) intact nerve; (4) autogenous nerve graft; (5) decellularized nerve alone; and (6) unrepaired nerve gap controls. All groups underwent electrophysiologic characterization at 3 months, and nerves were harvested for histomorphometric analysis. Results Conduction velocity was significantly faster in the dry poly(3,4-ethylenedioxythiophene) group compared with the sham, decellularized nerve, and wet poly(3,4-ethylenedioxythiophene) groups. Maximum specific force for the dry poly(3,4-ethylenedioxythiophene) group was more similar to sham than were decellularized nerve controls. Evident neural regeneration was demonstrated in both dry and wet poly(3,4-ethylenedioxythiophene) groups by the presence of normal regenerating axons on histologic cross-section. Conclusions Both poly(3,4-ethylenedioxythiophene) formulations were compatible with peripheral nerve regeneration at 3 months. This study supports poly(3,4-ethylenedioxythiophene) as a promising adjunct for peripheral nerve interfaces for

  20. [Regeneration and repair of peripheral nerves: clinical implications in facial paralysis surgery].

    PubMed

    Hontanilla, B; Vidal, A

    2000-01-01

    Peripheral nerve lesions are one of the most frequent causes of chronic incapacity. Upper or lower limb palsies due to brachial or lumbar plexus injuries, facial paralysis and nerve lesions caused by systemic diseases are one of the major goals of plastic and reconstructive surgery. However, the poor results obtained in repaired peripheral nerves during the Second World War lead to a pessimist vision of peripheral nerve repair. Nevertheless, a well understanding of microsurgical principles in reconstruction and molecular biology of nerve regeneration have improved the clinical results. Thus, although the results obtained are quite far from perfect, these procedures give to patients a hope in the recuperation of their lesions and then on function. Technical aspects in nerve repair are well established; the next step is to manipulate the biology. In this article we will comment the biological processes which appear in peripheral nerve regeneration, we will establish the main concepts on peripheral nerve repair applied in facial paralysis cases and, finally, we will proportionate some ideas about how clinical practice could be affected by manipulation of the peripheral nerve biology. PMID:11002897

  1. Vitamin B complex and vitamin B12 levels after peripheral nerve injury

    PubMed Central

    Altun, Idiris; Kurutaş, Ergül Belge

    2016-01-01

    The aim of the present study was to evaluate whether tissue levels of vitamin B complex and vitamin B12 were altered after crush-induced peripheral nerve injury in an experimental rat model. A total of 80 male Wistar rats were randomized into one control (n = 8) and six study groups (1, 6, 12, 24 hours, 3, and 7 days after experimental nerve injury; n = 12 for each group). Crush-induced peripheral nerve injury was performed on the sciatic nerves of rats in six study groups. Tissue samples from the sites of peripheral nerve injury were obtained at 1, 6, 12, 24 hours, 3 and 7 days after experimental nerve injury. Enzyme-linked immunosorbent assay results showed that tissue levels of vitamin B complex and vitamin B12 in the injured sciatic nerve were significantly greater at 1 and 12 hours after experimental nerve injury, while they were significantly lower at 7 days than in control group. Tissue level of vitamin B12 in the injured sciatic nerve was significantly lower at 1, 6, 12 and 24 hours than in the control group. These results suggest that tissue levels of vitamin B complex and vitamin B12 vary with progression of crush-induced peripheral nerve injury, and supplementation of these vitamins in the acute period may be beneficial for acceleration of nerve regeneration. PMID:27335572

  2. The Glucuronyltransferase GlcAT-P Is Required for Stretch Growth of Peripheral Nerves in Drosophila

    PubMed Central

    Pandey, Rahul; Blanco, Jorge; Udolph, Gerald

    2011-01-01

    During development, the growth of the animal body is accompanied by a concomitant elongation of the peripheral nerves, which requires the elongation of integrated nerve fibers and the axons projecting therein. Although this process is of fundamental importance to almost all organisms of the animal kingdom, very little is known about the mechanisms regulating this process. Here, we describe the identification and characterization of novel mutant alleles of GlcAT-P, the Drosophila ortholog of the mammalian glucuronyltransferase b3gat1. GlcAT-P mutants reveal shorter larval peripheral nerves and an elongated ventral nerve cord (VNC). We show that GlcAT-P is expressed in a subset of neurons in the central brain hemispheres, in some motoneurons of the ventral nerve cord as well as in central and peripheral nerve glia. We demonstrate that in GlcAT-P mutants the VNC is under tension of shorter peripheral nerves suggesting that the VNC elongates as a consequence of tension imparted by retarded peripheral nerve growth during larval development. We also provide evidence that for growth of peripheral nerve fibers GlcAT-P is critically required in hemocytes; however, glial cells are also important in this process. The glial specific repo gene acts as a modifier of GlcAT-P and loss or reduction of repo function in a GlcAT-P mutant background enhances VNC elongation. We propose a model in which hemocytes are required for aspects of glial cell biology which in turn affects the elongation of peripheral nerves during larval development. Our data also identifies GlcAT-P as a first candidate gene involved in growth of integrated peripheral nerves and therefore establishes Drosophila as an amenable in-vivo model system to study this process at the cellular and molecular level in more detail. PMID:22132223

  3. Conventional and Functional MR Imaging of Peripheral Nerve Sheath Tumors: Initial Experience

    PubMed Central

    Demehri, S.; Belzberg, A.; Blakeley, J.; Fayad, L.M.

    2015-01-01

    BACKGROUND AND PURPOSE Differentiating benign from malignant peripheral nerve sheath tumors can be very challenging using conventional MR imaging. Our aim was to test the hypothesis that conventional and functional MR imaging can accurately diagnose malignancy in patients with indeterminate peripheral nerve sheath tumors. MATERIALS AND METHODS This institutional review board–approved, Health Insurance Portability and Accountability Act–compliant study retrospectively reviewed 61 consecutive patients with 80 indeterminate peripheral nerve sheath tumors. Of these, 31 histologically proved peripheral nerve sheath tumors imaged with conventional (unenhanced T1, fluid-sensitive, contrast-enhanced T1-weighted sequences) and functional MR imaging (DWI/apparent diffusion coefficient mapping, dynamic contrast-enhanced MR imaging) were included. Two observers independently assessed anatomic (size, morphology, signal) and functional (ADC values, early arterial enhancement by dynamic contrast-enhanced MR) features to determine interobserver agreement. The accuracy of MR imaging for differentiating malignant from benign was also determined by receiver operating characteristic analysis. RESULTS Of 31 peripheral nerve sheath tumors, there were 9 malignant (9%) and 22 benign ones (81%). With anatomic sequences, average tumor diameter (6.3 ± 1.8 versus 3.9 ± 2.3 mm, P = .009), ill-defined/infiltrative margins (77% versus 32%; P = .04), and the presence of peritumoral edema (66% versus 23%, P = .01) were different for malignant peripheral nerve sheath tumors and benign peripheral nerve sheath tumors. With functional sequences, minimum ADC (0.47 ± 0.32 × 10−3 mm2/s versus 1.08 ± 0.26 × 10−3 mm2/s; P [H11021] .0001) and the presence of early arterial enhancement (50% versus 11%; P = .03) were different for malignant peripheral nerve sheath tumors and benign peripheral nerve sheath tumors. The minimum ADC (area under receiver operating characteristic curve was 0.89; 95

  4. Sex differences in morphometric aspects of the peripheral nerves and related diseases

    PubMed Central

    Moriyama, Hiroshi; Hayashi, Shogo; Inoue, Yuriko; Itoh, Masahiro; Otsuka, Naruhito

    2016-01-01

    BACKGROUND: The elucidation of the relationship between the morphology of the peripheral nerves and the diseases would be valuable in developing new medical treatments on the assumption that characteristics of the peripheral nerves in females are different from those in males. METHODS: We used 13 kinds of the peripheral nerve. The materials were obtained from 10 Japanese female and male cadavers. We performed a morphometric analysis of nerve fibers. We estimated the total number of myelinated axons, and calculated the average transverse area and average circularity ratio of myelinated axons in the peripheral nerves. RESULTS: There was no statistically significant difference in the total number, average transverse area, or average circularity ratio of myelinated axons between the female and male specimens except for the total number of myelinated axons in the vestibular nerve and the average circularity ratio of myelinated axons in the vagus nerve. CONCLUSIONS: The lower number of myelinated axons in the female vestibular nerve may be one of the reasons why vestibular disorders have a female preponderance. Moreover, the higher average circularity ratio of myelinated axons in the male vagus nerve may be one reason why vagus nerve activity to modulate pain has a male preponderance. PMID:27589511

  5. Augmented reality guidance system for peripheral nerve blocks

    NASA Astrophysics Data System (ADS)

    Wedlake, Chris; Moore, John; Rachinsky, Maxim; Bainbridge, Daniel; Wiles, Andrew D.; Peters, Terry M.

    2010-02-01

    Peripheral nerve block treatments are ubiquitous in hospitals and pain clinics worldwide. State of the art techniques use ultrasound (US) guidance and/or electrical stimulation to verify needle tip location. However, problems such as needle-US beam alignment, poor echogenicity of block needles and US beam thickness can make it difficult for the anesthetist to know the exact needle tip location. Inaccurate therapy delivery raises obvious safety and efficacy issues. We have developed and evaluated a needle guidance system that makes use of a magnetic tracking system (MTS) to provide an augmented reality (AR) guidance platform to accurately localize the needle tip as well as its projected trajectory. Five anesthetists and five novices performed simulated nerve block deliveries in a polyvinyl alcohol phantom to compare needle guidance under US alone to US placed in our AR environment. Our phantom study demonstrated a decrease in targeting attempts, decrease in contacting of critical structures, and an increase in accuracy of 0.68 mm compared to 1.34mm RMS in US guidance alone. Currently, the MTS uses 18 and 21 gauge hypodermic needles with a 5 degree of freedom sensor located at the needle tip. These needles can only be sterilized using an ethylene oxide process. In the interest of providing clinicians with a simple and efficient guidance system, we also evaluated attaching the sensor at the needle hub as a simple clip-on device. To do this, we simultaneously performed a needle bending study to assess the reliability of a hub-based sensor.

  6. Excellent response of malignant peripheral nerve sheath tumour of retroperitoneum to radiation therapy

    PubMed Central

    Akhavan, Ali; Binesh, Fariba; Ghannadi, Fazlollah; Navabii, Hossein

    2012-01-01

    Malignant peripheral nerve sheath tumours are high-grade sarcomas originating from Schwann cells or nerve sheath cells. Most of these tumours are associated with major nerves of the body wall and extremities. The lower extremity and the retroperitoneum are the most common sites. Surgery is the cornerstone of treatment, however, radiation therapy is usually used as an adjuvant treatment. In this paper we present a 57-year-old Iranian woman with malignant peripheral nerve sheath tumour of retroperitoneum who was operated subtotally and then underwent radiation therapy which led to disappearance of all gross residual disease. PMID:23257269

  7. Irradiation effect of polarization direction and intensity of semiconductor laser on injured peripheral nerve

    NASA Astrophysics Data System (ADS)

    Guo-Xin, Xiong; Lei-lei, Xiong

    2016-08-01

    To investigate the irradiation effect of polarization direction and the intensity of a semiconductor laser on the injured peripheral nerve in rabbits, the model of the injured common peroneal nerve was established, the L5,6 spinal segments of the rabbits were irradiated, a uniform rotating polarizer was placed at the laser output which made the polarization direction and intensity of the output laser change according to the 80 Hz cosine law. The experimental results show that irradiating the spinal segment of injured nerves in rabbits with this changeable semiconductor laser can significantly promote the regeneration of injured peripheral nerves and the function recovery.

  8. Biocompatibility and Characterization of a Peptide Amphiphile Hydrogel for Applications in Peripheral Nerve Regeneration

    PubMed Central

    Black, Katie A.; Lin, Brian F.; Wonder, Emily A.; Desai, Seema S.; Chung, Eun Ji; Ulery, Bret D.; Katari, Ravi S.

    2015-01-01

    Peripheral nerve injury is a debilitating condition for which new bioengineering solutions are needed. Autografting, the gold standard in treatment, involves sacrifice of a healthy nerve and results in loss of sensation or function at the donor site. One alternative solution to autografting is to use a nerve guide conduit designed to physically guide the nerve as it regenerates across the injury gap. Such conduits are effective for short gap injuries, but fail to surpass autografting in long gap injuries. One strategy to enhance regeneration inside conduits in long gap injuries is to fill the guide conduits with a hydrogel to mimic the native extracellular matrix found in peripheral nerves. In this work, a peptide amphiphile (PA)-based hydrogel was optimized for peripheral nerve repair. Hydrogels consisting of the PA C16GSH were compared with a commercially available collagen gel. Schwann cells, a cell type important in the peripheral nerve regenerative cascade, were able to spread, proliferate, and migrate better on C16GSH gels in vitro when compared with cells seeded on collagen gels. Moreover, C16GSH gels were implanted subcutaneously in a murine model and were found to be biocompatible, degrade over time, and support angiogenesis without causing inflammation or a foreign body immune response. Taken together, these results help optimize and instruct the development of a new synthetic hydrogel as a luminal filler for conduit-mediated peripheral nerve repair. PMID:25626921

  9. A Case of Malignant Peripheral Nerve Sheath Tumor of the Hypoglossal Nerve after Stereotactic Radiosurgery Treatment

    PubMed Central

    Yang, Tong; Juric-Sekhar, Gordana; Born, Donald; Sekhar, Laligam N.

    2014-01-01

    Objectives Hypoglossal schwannomas are rare. Surgical resection has been the standard treatment modality. Radiosurgery has been increasingly used for treatment. Radiation-associated secondary malignancy/malignant transformation has not been documented in the literature for the treatment of nonvestibular schwannomas. Setting The patient was a 52-year-old man with an enlarging high cervical/skull base lesion 8.5 years after CyberKnife treatment of a presumed vagal schwannoma. A decision was made for surgical resection, and the tumor was found to originate from the hypoglossal nerve intraoperatively. Final pathology diagnosis was malignant peripheral nerve sheath tumor. Results Patient had a gross total resection. Three months after resection, he received fractionated radiation of 50 Gy in 25 fractions and a boost gamma knife radiosurgery of 10 Gy to the 50% isodose surface. He remained tumor free on repeat magnetic resonance imaging 9 months after the resection. Conclusion Although extremely rare, radiation treatment of nonvestibular schwannomas can potentially cause malignant transformation. PMID:25083387

  10. Evolution of peripheral nerve function in humans: novel insights from motor nerve excitability

    PubMed Central

    Farrar, Michelle A; Park, Susanna B; Lin, Cindy S-Y; Kiernan, Matthew C

    2013-01-01

    While substantial alterations in myelination and axonal growth have been described during maturation, their interactions with the configuration and activity of axonal membrane ion channels to achieve impulse conduction have not been fully elucidated. The present study utilized axonal excitability techniques to compare the changes in nerve function across healthy infants, children, adolescents and adults. Multiple excitability indices (stimulus–response curve, strength–duration time constant, threshold electrotonus, current–threshold relationship and recovery cycle) combined with conventional neurophysiological measures were investigated in 57 subjects (22 males, 35 females; age range 0.46–24 years), stimulating the median motor nerve at the wrist. Maturational changes in conduction velocity were paralleled by significant alterations in multiple excitability parameters, similarly reaching steady values in adolescence. Maturation was accompanied by reductions in threshold (P < 0.005) and rheobase (P= 0.001); depolarizing and hyperpolarizing electrotonus progressively reduced (P < 0.001), or ‘fanned-in’; resting current–threshold slope increased (P < 0.0001); accommodation to depolarizing currents prolonged (P < 0.0001); while greater threshold changes in refractoriness (P= 0.001) and subexcitability (P < 0.01) emerged. Taken together, the present findings suggest that passive membrane conductances and the activity of K+ conductances decrease with formation of the axo-glial junction and myelination. In turn, these functional alterations serve to enhance the efficiency and speed of impulse conduction concurrent with the acquisition of motor skills during childhood, and provide unique insight into the evolution of postnatal human peripheral nerve function. Significantly, these findings bring the dynamics of axonal development to the clinical domain and serve to further illuminate pathophysiological mechanisms that occur during development. PMID:23006483

  11. Advances of Peripheral Nerve Repair Techniques to Improve Hand Function: A Systematic Review of Literature

    PubMed Central

    P, Mafi; S, Hindocha; M, Dhital; M, Saleh

    2012-01-01

    Concepts of neuronal damage and repair date back to ancient times. The research in this topic has been growing ever since and numerous nerve repair techniques have evolved throughout the years. Due to our greater understanding of nerve injuries and repair we now distinguish between central and peripheral nervous system. In this review, we have chosen to concentrate on peripheral nerve injuries and in particular those involving the hand. There are no reviews bringing together and summarizing the latest research evidence concerning the most up-to-date techniques used to improve hand function. Therefore, by identifying and evaluating all the published literature in this field, we have summarized all the available information about the advances in peripheral nerve techniques used to improve hand function. The most important ones are the use of resorbable poly[(R)-3-hydroxybutyrate] (PHB), epineural end-to-end suturing, graft repair, nerve transfer, side to side neurorrhaphy and end to side neurorrhaphy between median, radial and ulnar nerves, nerve transplant, nerve repair, external neurolysis and epineural sutures, adjacent neurotization without nerve suturing, Agee endoscopic operation, tourniquet induced anesthesia, toe transfer and meticulous intrinsic repair, free auto nerve grafting, use of distal based neurocutaneous flaps and tubulization. At the same time we found that the patient’s age, tension of repair, time of repair, level of injury and scar formation following surgery affect the prognosis. Despite the thorough findings of this systematic review we suggest that further research in this field is needed. PMID:22431951

  12. Selective vulnerability of peripheral nerves in avian riboflavin deficiency demyelinating polyneuropathy.

    PubMed

    Cai, Z; Blumbergs, P C; Finnie, J W; Manavis, J; Thompson, P D

    2009-01-01

    Riboflavin (vitamin B2) deficiency in young chickens produces a demyelinating peripheral neuropathy. In this study, day-old broiler meat chickens were fed a riboflavin-deficient diet (1.8 mg/kg) and killed on posthatch days 6, 11, 16, 21, and 31, while control chickens were given a conventional diet containing 5.0 mg/kg riboflavin. Pathologic changes were found in sciatic, cervical, and lumbar spinal nerves of riboflavin-deficient chickens from day 11 onwards, characterized by endoneurial oedema, hypertrophic Schwann cells, tomacula (redundant myelin swellings), demyelination/remyelination, lipid deposition, and fibroblastic onion bulb formation. Similar changes were also found in large and medium intramuscular nerves, although they were less severe in the latter. However, by contrast, ventral and dorsal spinal nerve roots, distal intramuscular nerves, and subcutaneous nerves were normal at all time points examined. These findings demonstrate, for the first time, that riboflavin deficiency in young, rapidly growing chickens produces selective injury to peripheral nerve trunks, with relative sparing of spinal nerve roots and distal nerve branches to muscle and skin. These novel findings suggest that the response of Schwann cells in peripheral nerves with riboflavin deficiency differs because either there are subsets of these cells in, or there is variability in access of nutrients to, different sites within the nerves. PMID:19112122

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

    PubMed

    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. PMID:24810082

  14. A simple method for reducing autotomy in rats after peripheral nerve lesions.

    PubMed

    Sporel-Ozakat, R E; Edwards, P M; Hepgul, K T; Savas, A; Gispen, W H

    1991-02-01

    Experiments using peripheral nerve lesions (crush or transection) in rats to study repair processes are hampered by the tendency for the animals to attack the limb in which the peripheral nerves are damaged (autotomy). In this paper we describe a simple method which significantly reduces the incidence of autotomy after peripheral nerve lesions. The method consists of painting the hind paws of operated rats with a commercially available non-toxic lotion, which is used to discourage nail-biting and thumb-sucking in humans. Although the method is not absolute, it was extremely beneficial in our experiments, since the number of animals that had to be taken out of the experiment due to severe autotomy was greatly reduced. We believe that this method may prove to be as beneficial to other investigators who are using experimental peripheral nerve lesions to study the regenerative aspects of the nervous system. PMID:2062121

  15. Raman spectroscopy of non-penetrating peripheral nerve damage in swine: a tool for spectral pathology of nerves

    NASA Astrophysics Data System (ADS)

    Cilwa, Katherine E.; Slaughter, Tiffani; Elster, Eric A.; Forsberg, Jonathan A.; Crane, Nicole J.

    2015-03-01

    Over 30% of combat injuries involve peripheral nerve injury compared to only 3% in civilian trauma. In fact, nerve dysfunction is the second leading cause of long-term disability in injured service members and is present in 37% of upper limb injuries with disability. Identification and assessment of non-penetrating nerve injury in trauma patients could improve outcome and aid in therapeutic monitoring. We report the use of Raman spectroscopy as a noninvasive, non-destructive method for detection of nerve degeneration in intact nerves due to non-penetrating trauma. Nerve trauma was induced via compression and ischemia/reperfusion injury using a combat relevant swine tourniquet model (>3 hours ischemia). Control animals did not undergo compression/ischemia. Seven days post-operatively, sciatic and femoral nerves were harvested and fixed in formalin. Raman spectra of intact, peripheral nerves were collected using a fiber-optic probe with 3 mm diameter spot size and 785 nm excitation. Data was preprocessed, including fluorescence background subtraction, and Raman spectroscopic metrics were determined using custom peak fitting MATLAB scripts. The abilities of bivariate and multivariate analysis methods to predict tissue state based on Raman spectroscopic metrics are compared. Injured nerves exhibited changes in Raman metrics indicative of 45% decreased myelin content and structural damage (p<<0.01). Axonal and myelin degeneration, cell death and digestion, and inflammation of nerve tissue samples were confirmed via histology. This study demonstrates the non-invasive ability of Raman spectroscopy to detect nerve degeneration associated with non-penetrating injury, relevant to neurapraxic and axonotmetic injuries; future experiments will further explore the clinical utility of Raman spectroscopy to recognize neural injury.

  16. Peripheral nerve: from the microscopic functional unit of the axon to the biomechanically loaded macroscopic structure.

    PubMed

    Topp, Kimberly S; Boyd, Benjamin S

    2012-01-01

    Peripheral nerves are composed of motor and sensory axons, associated ensheathing Schwann cells, and organized layers of connective tissues that are in continuity with the tissues of the central nervous system. Nerve fiber anatomy facilitates conduction of electrical impulses to convey information over a distance, and the length of these polarized cells necessitates regulated axonal transport of organelles and structural proteins for normal cell function. Nerve connective tissues serve a protective function as the limb is subjected to the stresses of myriad limb positions and postures. Thus, the tissues are uniquely arranged to control the local nerve fiber environment and modulate physical stresses. In this brief review, we describe the microscopic anatomy and physiology of peripheral nerve and the biomechanical properties that enable nerve to withstand the physical stresses of everyday life. PMID:22133662

  17. N,N-diethyldithiocarbamate produces copper accumulation, lipid peroxidation, and myelin injury in rat peripheral nerve.

    PubMed

    Tonkin, Elizabeth G; Valentine, Holly L; Milatovic, Dejan M; Valentine, William M

    2004-09-01

    Previous studies have demonstrated the ability of the dithiocarbamate, disulfiram, to produce a peripheral neuropathy in humans and experimental animals and have also provided evidence that N,N-diethyldithiocarbamate (DEDC) is a proximate toxic species of disulfiram. The ability of DEDC to elevate copper levels in the brain suggests that it may also elevate levels of copper in peripheral nerve, possibly leading to oxidative stress and lipid peroxidation from redox cycling of copper. The study presented here investigates the potential of DEDC to promote copper accumulation and lipid peroxidation in peripheral nerve. Rats were administered either DEDC or deionized water by ip osmotic pumps and fed a normal diet or diet containing elevated copper, and the levels of metals, isoprostanes, and the severity of lesions in peripheral nerve and brain were assessed by ICP-AES/AAS, GC/MS, and light microscopy, respectively. Copper was the only metal that demonstrated any significant compound-related elevations relative to controls, and total copper was increased in both brain and peripheral nerve in animals administered DEDC on both diets. In contrast, lesions and elevated F2-isoprostanes were significantly increased only in peripheral nerve for the rats administered DEDC on both diets. Autometallography staining of peripheral nerve was consistent with increased metal content along the myelin sheath, but in brain, focal densities were observed, and a periportal distribution occurred in liver. These data are consistent with the peripheral nervous system being more sensitive to DEDC-mediated demyelination and demonstrate the ability of DEDC to elevate copper levels in peripheral nerve. Additionally lipid peroxidation appears to either be a contributing event in the development of demyelination, possibly through an increase of redox active copper, or a consequence of the myelin injury. PMID:15187237

  18. Pathology in practice: Peripheral nerve sheath tumor in a Shubunkin goldfish

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Peripheral nerve sheath tumors (PNSTs) have been detected in many fish species, including goldfish, several species of snapper, coho salmon, the bicolor damselfish, and rainbow smelt. They originate from neural crest cells and generally occur along the subcutaneous nerves. A viral etiology has bee...

  19. Peripheral Nerve Repair in Rats Using Composite Hydrogel-Filled Aligned Nanofiber Conduits with Incorporated Nerve Growth Factor

    PubMed Central

    Jin, Jenny; Limburg, Sonja; Joshi, Sunil K.; Landman, Rebeccah; Park, Michelle; Zhang, Qia; Kim, Hubert T.

    2013-01-01

    Repair of peripheral nerve defects with current synthetic, tubular nerve conduits generally shows inferior recovery when compared with using nerve autografts, the current gold standard. We tested the ability of composite collagen and hyaluronan hydrogels, with and without the nerve growth factor (NGF), to stimulate neurite extension on a promising aligned, nanofiber poly-L-lactide-co-caprolactone (PLCL) scaffold. In vitro, the hydrogels significantly increased neurite extension from dorsal root ganglia explants. Consistent with these results, the addition of hydrogels as luminal fillers within aligned, nanofiber tubular PLCL conduits led to improved sensory function compared to autograft repair in a critical-size defect in the sciatic nerve in a rat model. Sensory recovery was assessed 3 and 12 weeks after repair using a withdrawal assay from thermal stimulation. The addition of hydrogel did not enhance recovery of motor function in the rat model. The NGF led to dose-dependent improvements in neurite out-growth in vitro, but did not have a significant effect in vivo. In summary, composite collagen/hyaluronan hydrogels enhanced sensory neurite outgrowth in vitro and sensory recovery in vivo. The use of such hydrogels as luminal fillers for tubular nerve conduits may therefore be useful in assisting restoration of protective sensation following peripheral nerve injury. PMID:23659607

  20. Approaches to Peripheral Nerve Repair: Generations of Biomaterial Conduits Yielding to Replacing Autologous Nerve Grafts in Craniomaxillofacial Surgery.

    PubMed

    Gaudin, Robert; Knipfer, Christian; Henningsen, Anders; Smeets, Ralf; Heiland, Max; Hadlock, Tessa

    2016-01-01

    Peripheral nerve injury is a common clinical entity, which may arise due to traumatic, tumorous, or even iatrogenic injury in craniomaxillofacial surgery. Despite advances in biomaterials and techniques over the past several decades, reconstruction of nerve gaps remains a challenge. Autografts are the gold standard for nerve reconstruction. Using autografts, there is donor site morbidity, subsequent sensory deficit, and potential for neuroma development and infection. Moreover, the need for a second surgical site and limited availability of donor nerves remain a challenge. Thus, increasing efforts have been directed to develop artificial nerve guidance conduits (ANCs) as new methods to replace autografts in the future. Various synthetic conduit materials have been tested in vitro and in vivo, and several first- and second-generation conduits are FDA approved and available for purchase, while third-generation conduits still remain in experimental stages. This paper reviews the current treatment options, summarizes the published literature, and assesses future prospects for the repair of peripheral nerve injury in craniomaxillofacial surgery with a particular focus on facial nerve regeneration. PMID:27556032

  1. Approaches to Peripheral Nerve Repair: Generations of Biomaterial Conduits Yielding to Replacing Autologous Nerve Grafts in Craniomaxillofacial Surgery

    PubMed Central

    Knipfer, Christian; Hadlock, Tessa

    2016-01-01

    Peripheral nerve injury is a common clinical entity, which may arise due to traumatic, tumorous, or even iatrogenic injury in craniomaxillofacial surgery. Despite advances in biomaterials and techniques over the past several decades, reconstruction of nerve gaps remains a challenge. Autografts are the gold standard for nerve reconstruction. Using autografts, there is donor site morbidity, subsequent sensory deficit, and potential for neuroma development and infection. Moreover, the need for a second surgical site and limited availability of donor nerves remain a challenge. Thus, increasing efforts have been directed to develop artificial nerve guidance conduits (ANCs) as new methods to replace autografts in the future. Various synthetic conduit materials have been tested in vitro and in vivo, and several first- and second-generation conduits are FDA approved and available for purchase, while third-generation conduits still remain in experimental stages. This paper reviews the current treatment options, summarizes the published literature, and assesses future prospects for the repair of peripheral nerve injury in craniomaxillofacial surgery with a particular focus on facial nerve regeneration. PMID:27556032

  2. Intractable sacroiliac joint pain treated with peripheral nerve field stimulation

    PubMed Central

    Chakrabortty, Shushovan; Kumar, Sanjeev; Gupta, Deepak; Rudraraju, Sruthi

    2016-01-01

    As many as 62% low back pain patients can have sacroiliac joint (SIJ) pain. There is limited (to poor) evidence in regards to long-term pain relief with therapeutic intra-articular injections and/or conventional (heat or pulsed) radiofrequency ablations (RFAs) for SIJ pain. We report our pain-clinic experience with peripheral nerve field stimulation (PNFS) for two patients of intractable SIJ pain. They had reported absence of long-term pain relief (pain relief >50% for at least 2 weeks postinjection and at least 3 months post-RFA) with SIJ injections and SIJ RFAs. Two parallel permanent 8-contact subcutaneous stimulating leads were implanted under the skin overlying their painful SIJ. Adequate stimulation in the entire painful area was confirmed. For implantable pulse generator placement, a separate subcutaneous pocket was made in the upper buttock below the iliac crest level ipsilaterally. During the pain-clinic follow-up period, the patients had reduced their pain medications requirements by half with an additional report of more than 50% improvement in their functional status. The first patient passed away 2 years after the PNFS procedure due to medical causes unrelated to his chronic pain. The second patient has been comfortable with PNFS-induced analgesic regimen during her pain-clinic follow-up during last 5 years. In summary, PNFS can be an effective last resort option for SIJ pain wherein conventional interventional pain techniques have failed, and analgesic medication requirements are escalating or causing unwarranted side-effects. PMID:27625495

  3. Intractable sacroiliac joint pain treated with peripheral nerve field stimulation.

    PubMed

    Chakrabortty, Shushovan; Kumar, Sanjeev; Gupta, Deepak; Rudraraju, Sruthi

    2016-01-01

    As many as 62% low back pain patients can have sacroiliac joint (SIJ) pain. There is limited (to poor) evidence in regards to long-term pain relief with therapeutic intra-articular injections and/or conventional (heat or pulsed) radiofrequency ablations (RFAs) for SIJ pain. We report our pain-clinic experience with peripheral nerve field stimulation (PNFS) for two patients of intractable SIJ pain. They had reported absence of long-term pain relief (pain relief >50% for at least 2 weeks postinjection and at least 3 months post-RFA) with SIJ injections and SIJ RFAs. Two parallel permanent 8-contact subcutaneous stimulating leads were implanted under the skin overlying their painful SIJ. Adequate stimulation in the entire painful area was confirmed. For implantable pulse generator placement, a separate subcutaneous pocket was made in the upper buttock below the iliac crest level ipsilaterally. During the pain-clinic follow-up period, the patients had reduced their pain medications requirements by half with an additional report of more than 50% improvement in their functional status. The first patient passed away 2 years after the PNFS procedure due to medical causes unrelated to his chronic pain. The second patient has been comfortable with PNFS-induced analgesic regimen during her pain-clinic follow-up during last 5 years. In summary, PNFS can be an effective last resort option for SIJ pain wherein conventional interventional pain techniques have failed, and analgesic medication requirements are escalating or causing unwarranted side-effects. PMID:27625495

  4. Schwann cell mitochondrial metabolism supports long-term axonal survival and peripheral nerve function

    PubMed Central

    Viader, Andreu; Golden, Judith P.; Baloh, Robert H.; Schmidt, Robert E.; Hunter, Daniel A.; Milbrandt, Jeffrey

    2011-01-01

    Mitochondrial dysfunction is a common cause of peripheral neuropathies. While the role of neuron and axonal mitochondria in peripheral nerve disease is well appreciated, whether Schwann cell (SC) mitochondrial deficits contribute to peripheral neuropathies is unclear. Here we examine how SC mitochondrial dysfunction affects axonal survival and contributes to the decline of peripheral nerve function by generating mice with SC-specific mitochondrial deficits. These mice (Tfam-SCKOs) were produced through the tissue-specific deletion of the mitochondrial transcription factor A gene (Tfam), which is essential for mitochondrial DNA (mtDNA) transcription and maintenance. Tfam-SCKOs were viable but, as they aged, they developed a progressive peripheral neuropathy characterized by nerve conduction abnormalities as well as extensive muscle denervation. Morphological examination of Tfam-SCKO nerves revealed early preferential loss of small unmyelinated fibers followed by prominent demyelination and degeneration of larger-caliber axons. Tfam-SCKOs displayed sensory and motor deficits consistent with this pathology. Remarkably, the severe mtDNA depletion and respiratory chain abnormalities in Tfam-SCKO mice did not affect SC proliferation or survival. Mitochondrial function in SCs is therefore essential for maintenance of axonal survival and normal peripheral nerve function, suggesting that SC mitochondrial dysfunction contributes to human peripheral neuropathies. PMID:21752989

  5. Pre-differentiation of mesenchymal stromal cells in combination with a microstructured nerve guide supports peripheral nerve regeneration in the rat sciatic nerve model.

    PubMed

    Boecker, Arne Hendrik; van Neerven, Sabien Geraldine Antonia; Scheffel, Juliane; Tank, Julian; Altinova, Haktan; Seidensticker, Katrin; Deumens, Ronald; Tolba, Rene; Weis, Joachim; Brook, Gary Anthony; Pallua, Norbert; Bozkurt, Ahmet

    2016-02-01

    Many bioartificial nerve guides have been investigated pre-clinically for their nerve regeneration-supporting function, often in comparison to autologous nerve transplantation, which is still regarded as the current clinical gold standard. Enrichment of these scaffolds with cells intended to support axonal regeneration has been explored as a strategy to boost axonal regeneration across these nerve guides Ansselin et al. (1998). In the present study, 20 mm rat sciatic nerve defects were implanted with a cell-seeded microstructured collagen nerve guide (Perimaix) or an autologous nerve graft. Under the influence of seeded, pre-differentiated mesenchymal stromal cells, axons regenerated well into the Perimaix nerve guide. Myelination-related parameters, like myelin sheath thickness, benefitted from an additional seeding with pre-differentiated mesenchymal stromal cells. Furthermore, both the number of retrogradely labelled sensory neurons and the axon density within the implant were elevated in the cell-seeded scaffold group with pre-differentiated mesenchymal stromal cells. However, a pre-differentiation had no influence on functional recovery. An additional cell seeding of the Perimaix nerve guide with mesenchymal stromal cells led to an extent of functional recovery, independent of the differentiation status, similar to autologous nerve transplantation. These findings encourage further investigations on pre-differentiated mesenchymal stromal cells as a cellular support for peripheral nerve regeneration. PMID:26296589

  6. Hydrogen-rich saline promotes motor functional recovery following peripheral nerve autografting in rats

    PubMed Central

    ZHANG, YONG-GUANG; SHENG, QING-SONG; WANG, ZHI-JUN; LV, LI; ZHAO, WEI; CHEN, JIAN-MEI; XU, HAO

    2015-01-01

    Despite the application of nerve grafts and considerable microsurgical innovations, the functional recovery across a long peripheral nerve gap is generally partial and unsatisfactory. Thus, additional strategies are required to improve nerve regeneration across long nerve gaps. Hydrogen possesses antioxidant and anti-apoptotic properties, which could be neuroprotective in the treatment of peripheral nerve injury; however, such a possibility has not been experimentally tested in vivo. The aim of the present study was to investigate the effectiveness of hydrogen-rich saline in promoting nerve regeneration after 10-mm sciatic nerve autografting in rats. The rats were randomly divided into two groups and intraperitoneally administered a daily regimen of 5 ml/kg hydrogen-rich or normal saline. Axonal regeneration and functional recovery were assessed through a combination of behavioral analyses, electrophysiological evaluations, Fluoro-Gold™ retrograde tracings and histomorphological observations. The data showed that rats receiving hydrogen-rich saline achieved better axonal regeneration and functional recovery than those receiving normal saline. These findings indicated that hydrogen-rich saline promotes nerve regeneration across long gaps, suggesting that hydrogen-rich saline could be used as a neuroprotective agent for peripheral nerve injury therapy. PMID:26622383

  7. Tissue specificity in rat peripheral nerve regeneration through combined skeletal muscle and vein conduit grafts.

    PubMed

    Tos, P; Battiston, B; Geuna, S; Giacobini-Robecchi, M G; Hill, M A; Lanzetta, M; Owen, E R

    2000-01-01

    Diffusible factors from the distal stumps of transected peripheral nerves exert a neurotropic effect on regenerating nerves in vivo (specificity). This morphological study was designed to investigate the existence of tissue specificity in peripheral nerve fiber regeneration through a graft of vein filled with fresh skeletal muscle. This tubulization technique demonstrated experimental and clinical results similar to those obtained with traditional autologous nerve grafts. Specifically, we used Y-shaped grafts to assess the orientation pattern of regenerating axons in the distal stump tissue. Animal models were divided into four experimental groups. The proximal part of the Y-shaped conduit was sutured to a severed tibial nerve in all experiments. The two distal stumps were sutured to different targets: group A to two intact nerves (tibial and peroneal), group B to an intact nerve and an unvascularized tendon, group C to an intact nerve and a vascularized tendon, and group D to a nerve graft and an unvascularized tendon. Morphological evaluation by light and electron microscopy was conducted in the distal forks of the Y-shaped tube. Data showed that almost all regenerating nerve fibers spontaneously oriented towards the nerve tissue (attached or not to the peripheral innervation field), showing a good morphological pattern of regeneration in both the early and late phases of regeneration. When the distal choice was represented by a tendon (vascularized or not), very few nerve fibers were detected in the corresponding distal fork of the Y-shaped graft. These results show that, using the muscle-vein-combined grafting technique, regenerating axons are able to correctly grow and orientate within the basement membranes of the graft guided by the neurotropic lure of the distal nerve stump. PMID:10702739

  8. Intramuscular injection of bone marrow mesenchymal stem cells with small gap neurorrhaphy for peripheral nerve repair.

    PubMed

    Wang, Peiji; Zhang, Yong; Zhao, Jiaju; Jiang, Bo

    2015-01-12

    We had previously reported that small gap neurorrhaphy by scissoring and sleeve-jointing epineurium could enhance the rate and quality of peripheral nerve regeneration. To date, local implantation and systemic delivery of bone marrow mesenchymal stem cells (BMSCs) have been routinely used in nerve tissue engineering, but they each have some intrinsic limitations. We hypothesised that targeted muscular administration of BMSCs capable of reaching the damaged nerve would be advisable. Here, we investigated the therapeutic efficacy of transplantation of BMSCs through targeted muscular injection with small gap neurorrhaphy by scissoring and sleeve-jointing epineurium on repairing peripheral nerve injury in a rat model. One week after a rat model of peripheral nerve injury was established by small gap neurorrhaphy, thirty-six Sprague-Dawley rats were randomly divided into three groups (n=12): the intramuscular injection of BMSCs group (IM), the intravenous injection of BMSCs group (IV) and the intramuscular injection of phosphate-buffered solution group (PBS). The process of the nerve regeneration was assayed functionally and morphologically. The results indicated that compared to the IV-treated and PBS-treated groups, the targeted muscular injection therapy resulted in much more beneficial effects, as evidenced by increases in the sciatic function index, nerve conduction velocity, myelin sheath thickness and restoration rate of gastrocnemius muscle wet weight. In conclusion, the combination therapy of small gap neurorrhaphy and BMSC transplantation through targeted muscular injection can significantly promote the regeneration of peripheral nerve and improve the nerve's functional recovery, which may help establish a reliable approach for repairing peripheral nerve injury. PMID:25434870

  9. Magnetic stimulation of peripheral nerves in dogs: a pilot study.

    PubMed

    Soens, Iris Van; Polis, Ingeborgh E; Nijs, Jozef X; Struys, Michel M; Bhatti, Sofie F; Ham, Luc M Van

    2008-11-01

    A model for magnetic stimulation of the radial and sciatic nerves in dogs was evaluated. Onset-latencies and peak-to-peak amplitudes of magnetic and electrical stimulation of the sciatic nerve were compared, and the effect of the direction of the current in the magnetic coil on onset-latencies and peak-to-peak amplitude of the magnetic motor evoked potential was studied in both nerves. The results demonstrate that magnetic stimulation is a feasible method for stimulating the radial and sciatic nerves in dogs. No significant differences were observed in onset-latencies and peak-to-peak amplitudes during magnetic and electrical stimulation, indicating conformity between the techniques. Orthodromic or antidromic magnetic nerve stimulation resulted in no significant differences. This pilot study demonstrates the potential of magnetic stimulation of nerves in dogs. PMID:17869140

  10. Nerve guides manufactured from photocurable polymers to aid peripheral nerve repair.

    PubMed

    Pateman, Christopher J; Harding, Adam J; Glen, Adam; Taylor, Caroline S; Christmas, Claire R; Robinson, Peter P; Rimmer, Steve; Boissonade, Fiona M; Claeyssens, Frederik; Haycock, John W

    2015-05-01

    The peripheral nervous system has a limited innate capacity for self-repair following injury, and surgical intervention is often required. For injuries greater than a few millimeters autografting is standard practice although it is associated with donor site morbidity and is limited in its availability. Because of this, nerve guidance conduits (NGCs) can be viewed as an advantageous alternative, but currently have limited efficacy for short and large injury gaps in comparison to autograft. Current commercially available NGC designs rely on existing regulatory approved materials and traditional production methods, limiting improvement of their design. The aim of this study was to establish a novel method for NGC manufacture using a custom built laser-based microstereolithography (μSL) setup that incorporated a 405 nm laser source to produce 3D constructs with ∼ 50 μm resolution from a photocurable poly(ethylene glycol) resin. These were evaluated by SEM, in vitro neuronal, Schwann and dorsal root ganglion culture and in vivo using a thy-1-YFP-H mouse common fibular nerve injury model. NGCs with dimensions of 1 mm internal diameter × 5 mm length with a wall thickness of 250 μm were fabricated and capable of supporting re-innervation across a 3 mm injury gap after 21 days, with results close to that of an autograft control. The study provides a technology platform for the rapid microfabrication of biocompatible materials, a novel method for in vivo evaluation, and a benchmark for future development in more advanced NGC designs, biodegradable and larger device sizes, and longer-term implantation studies. PMID:25725557

  11. A device for emulating cuff recordings of action potentials propagating along peripheral nerves.

    PubMed

    Rieger, Robert; Schuettler, Martin; Chuang, Sheng-Chih

    2014-09-01

    This paper describes a device that emulates propagation of action potentials along a peripheral nerve, suitable for reproducible testing of bio-potential recording systems using nerve cuff electrodes. The system is a microcontroller-based stand-alone instrument which uses established nerve and electrode models to represent neural activity of real nerves recorded with a nerve cuff interface, taking into consideration electrode impedance, voltages picked up by the electrodes, and action potential propagation characteristics. The system emulates different scenarios including compound action potentials with selectable propagation velocities and naturally occurring nerve traffic from different velocity fiber populations. Measured results from a prototype implementation are reported and compared with in vitro recordings from Xenopus Laevis frog sciatic nerve, demonstrating that the electrophysiological setting is represented to a satisfactory degree, useful for the development, optimization and characterization of future recording systems. PMID:24760928

  12. Low-intensity pulsed ultrasound treatment improved the rate of autograft peripheral nerve regeneration in rat.

    PubMed

    Jiang, Wenli; Wang, Yuexiang; Tang, Jie; Peng, Jiang; Wang, Yu; Guo, Quanyi; Guo, Zhiyuan; Li, Pan; Xiao, Bo; Zhang, Jinxing

    2016-01-01

    Low intensity pulsed ultrasound (LIPUS) has been widely used in clinic for the treatment of repairing pseudarthrosis, bone fractures and of healing in various soft tissues. Some reports indicated that LIPUS accelerated peripheral nerve regeneration including Schwann cells (SCs) and injured nerves. But little is known about its appropriate intensities on autograft nerves. This study was to investigate which intensity of LIPUS improved the regeneration of gold standard postsurgical nerves in experimental rat model. Sprague-Dawley rats were made into 10 mm right side sciatic nerve reversed autologous nerve transplantation and randomly treated with 250 mW/cm(2), 500 mW/cm(2) or 750 mW/cm(2) LIPUS for 2-12 weeks after operation. Functional and pathological results showed that LIPUS of 250 mW/cm(2) significantly induced faster rate of axonal regeneration. This suggested that autograft nerve regeneration was improved. PMID:27102358

  13. Peripheral Nerve Reconstruction after Injury: A Review of Clinical and Experimental Therapies

    PubMed Central

    Grinsell, D.; Keating, C. P.

    2014-01-01

    Unlike other tissues in the body, peripheral nerve regeneration is slow and usually incomplete. Less than half of patients who undergo nerve repair after injury regain good to excellent motor or sensory function and current surgical techniques are similar to those described by Sunderland more than 60 years ago. Our increasing knowledge about nerve physiology and regeneration far outweighs our surgical abilities to reconstruct damaged nerves and successfully regenerate motor and sensory function. It is technically possible to reconstruct nerves at the fascicular level but not at the level of individual axons. Recent surgical options including nerve transfers demonstrate promise in improving outcomes for proximal nerve injuries and experimental molecular and bioengineering strategies are being developed to overcome biological roadblocks limiting patient recovery. PMID:25276813

  14. Low-intensity pulsed ultrasound treatment improved the rate of autograft peripheral nerve regeneration in rat

    PubMed Central

    Jiang, Wenli; Wang, Yuexiang; Tang, Jie; Peng, Jiang; Wang, Yu; Guo, Quanyi; Guo, Zhiyuan; Li, Pan; Xiao, Bo; Zhang, Jinxing

    2016-01-01

    Low intensity pulsed ultrasound (LIPUS) has been widely used in clinic for the treatment of repairing pseudarthrosis, bone fractures and of healing in various soft tissues. Some reports indicated that LIPUS accelerated peripheral nerve regeneration including Schwann cells (SCs) and injured nerves. But little is known about its appropriate intensities on autograft nerves. This study was to investigate which intensity of LIPUS improved the regeneration of gold standard postsurgical nerves in experimental rat model. Sprague-Dawley rats were made into 10 mm right side sciatic nerve reversed autologous nerve transplantation and randomly treated with 250 mW/cm2, 500 mW/cm2 or 750 mW/cm2 LIPUS for 2–12 weeks after operation. Functional and pathological results showed that LIPUS of 250 mW/cm2 significantly induced faster rate of axonal regeneration. This suggested that autograft nerve regeneration was improved. PMID:27102358

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

    PubMed

    Wang, Lin; Sanford, Melissa T; Xin, Zhongcheng; Lin, Guiting; Lue, Tom F

    2015-01-01

    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. PMID:25999359

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

    PubMed Central

    Wang, Lin; Sanford, Melissa T; Xin, Zhongcheng; Lin, Guiting; Lue, Tom F

    2015-01-01

    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. PMID:25999359

  17. MicroRNA machinery responds to peripheral nerve lesion in an injury-regulated pattern

    PubMed Central

    Wu, Di; Raafat, Mohamed; Pak, Elena; Hammond, Scott; Murashov, Alexander K.

    2011-01-01

    Recently, functional and potent RNA interference (RNAi) has been reported in peripheral nerve axons transfected with short-interfering RNA (siRNA). In addition, components of RNA-induced silencing complex (RISC) have been identified in axotomized sciatic nerve fibers as well as in regenerating dorsal root ganglia (DRG) neurons in vitro. Based on these observations, and on the fact that siRNA and microRNAs (miRNA) share the same effector enzymes, we hypothesized that the endogenous miRNA biosynthetic pathway would respond to peripheral nerve injury. To answer this question, we investigated changes in the expression of miRNA biosynthetic enzymes following peripheral nerve crush injury in mice. Here we show that several pivotal miRNA biosynthetic enzymes are expressed in an injury-regulated pattern in sciatic nerve in vivo, and in DRG axons in vitro. Moreover, the sciatic nerve lesion induced expression of mRNA-processing bodies (P-bodies), which are the local foci of mRNA degradation in DRG axons. In addition, a group of injury-regulated miRNAs was identified by miRNA microarray and validated by qPCR and in situ hybridization analyses. Taken together, our data support the hypothesis that the peripheral nerve regeneration processes may be regulated by miRNA pathway. PMID:21689732

  18. Low-Level Laser-Accelerated Peripheral Nerve Regeneration within a Reinforced Nerve Conduit across a Large Gap of the Transected Sciatic Nerve in Rats

    PubMed Central

    Shen, Chiung-Chyi; Yang, Yi-Chin; Huang, Tsung-Bin; Chan, Shiuh-Chuan; Liu, Bai-Shuan

    2013-01-01

    This study proposed a novel combination of neural regeneration techniques for the repair of damaged peripheral nerves. A biodegradable nerve conduit containing genipin-cross-linked gelatin was annexed using beta-tricalcium phosphate (TCP) ceramic particles (genipin-gelatin-TCP, GGT) to bridge the transection of a 15 mm sciatic nerve in rats. Two trigger points were irradiated transcutaneously using 660 nm of gallium-aluminum arsenide phosphide (GaAlAsP) via laser diodes for 2 min daily over 10 consecutive days. Walking track analysis showed a significant improvement in sciatic functional index (SFI) (P < 0.01) and pronounced improvement in the toe spreading ability of rats undergoing laser stimulation. Electrophysiological measurements (peak amplitude and area) illustrated by compound muscle action potential (CMAP) curves demonstrated that laser stimulation significantly improved nerve function and reduced muscular atrophy. Histomorphometric assessments revealed that laser stimulation accelerated nerve regeneration over a larger area of neural tissue, resulting in axons of greater diameter and myelin sheaths of greater thickness than that observed in rats treated with nerve conduits alone. Motor function, electrophysiological reactions, muscular reinnervation, and histomorphometric assessments all demonstrate that the proposed therapy accelerated the repair of transected peripheral nerves bridged using a GGT nerve conduit. PMID:23737818

  19. Spontaneous temporal changes and variability of peripheral nerve conduction analyzed using a random effects model.

    PubMed

    Krøigård, Thomas; Gaist, David; Otto, Marit; Højlund, Dorthe; Selmar, Peter E; Sindrup, Søren H

    2014-08-01

    The reproducibility of variables commonly included in studies of peripheral nerve conduction in healthy individuals has not previously been analyzed using a random effects regression model. We examined the temporal changes and variability of standard nerve conduction measures in the leg. Peroneal nerve distal motor latency, motor conduction velocity, and compound motor action potential amplitude; sural nerve sensory action potential amplitude and sensory conduction velocity; and tibial nerve minimal F-wave latency were examined in 51 healthy subjects, aged 40 to 67 years. They were reexamined after 2 and 26 weeks. There was no change in the variables except for a minor decrease in sural nerve sensory action potential amplitude and a minor increase in tibial nerve minimal F-wave latency. Reproducibility was best for peroneal nerve distal motor latency and motor conduction velocity, sural nerve sensory conduction velocity, and tibial nerve minimal F-wave latency. Between-subject variability was greater than within-subject variability. Sample sizes ranging from 21 to 128 would be required to show changes twice the magnitude of the spontaneous changes observed in this study. Nerve conduction studies have a high reproducibility, and variables are mainly unaltered during 6 months. This study provides a solid basis for the planning of future clinical trials assessing changes in nerve conduction. PMID:25083853

  20. Accelerating axonal growth promotes motor recovery after peripheral nerve injury in mice

    PubMed Central

    Ma, Chi Him Eddie; Omura, Takao; Cobos, Enrique J.; Latrémolière, Alban; Ghasemlou, Nader; Brenner, Gary J.; van Veen, Ed; Barrett, Lee; Sawada, Tomokazu; Gao, Fuying; Coppola, Giovanni; Gertler, Frank; Costigan, Michael; Geschwind, Dan; Woolf, Clifford J.

    2011-01-01

    Although peripheral nerves can regenerate after injury, proximal nerve injury in humans results in minimal restoration of motor function. One possible explanation for this is that injury-induced axonal growth is too slow. Heat shock protein 27 (Hsp27) is a regeneration-associated protein that accelerates axonal growth in vitro. Here, we have shown that it can also do this in mice after peripheral nerve injury. While rapid motor and sensory recovery occurred in mice after a sciatic nerve crush injury, there was little return of motor function after sciatic nerve transection, because of the delay in motor axons reaching their target. This was not due to a failure of axonal growth, because injured motor axons eventually fully re-extended into muscles and sensory function returned; rather, it resulted from a lack of motor end plate reinnervation. Tg mice expressing high levels of Hsp27 demonstrated enhanced restoration of motor function after nerve transection/resuture by enabling motor synapse reinnervation, but only within 5 weeks of injury. In humans with peripheral nerve injuries, shorter wait times to decompression surgery led to improved functional recovery, and, while a return of sensation occurred in all patients, motor recovery was limited. Thus, absence of motor recovery after nerve damage may result from a failure of synapse reformation after prolonged denervation rather than a failure of axonal growth. PMID:21965333

  1. Interactive modeling and simulation of peripheral nerve cords in virtual environments

    NASA Astrophysics Data System (ADS)

    Ullrich, Sebastian; Frommen, Thorsten; Eckert, Jan; Schütz, Astrid; Liao, Wei; Deserno, Thomas M.; Ntouba, Alexandre; Rossaint, Rolf; Prescher, Andreas; Kuhlen, Torsten

    2008-03-01

    This paper contributes to modeling, simulation and visualization of peripheral nerve cords. Until now, only sparse datasets of nerve cords can be found. In addition, this data has not yet been used in simulators, because it is only static. To build up a more flexible anatomical structure of peripheral nerve cords, we propose a hierarchical tree data structure where each node represents a nerve branch. The shape of the nerve segments itself is approximated by spline curves. Interactive modeling allows for the creation and editing of control points which are used for branching nerve sections, calculating spline curves and editing spline representations via cross sections. Furthermore, the control points can be attached to different anatomic structures. Through this approach, nerve cords deform in accordance to the movement of the connected structures, e.g., muscles or bones. As a result, we have developed an intuitive modeling system that runs on desktop computers and in immersive environments. It allows anatomical experts to create movable peripheral nerve cords for articulated virtual humanoids. Direct feedback of changes induced by movement or deformation is achieved by visualization in real-time. The techniques and the resulting data are already used for medical simulators.

  2. The subparaneurial compartment: A new concept in the clinicoanatomic classification of peripheral nerve lesions.

    PubMed

    Prasad, Nikhil K; Capek, Stepan; de Ruiter, Godard C W; Amrami, Kimberly K; Spinner, Robert J

    2015-10-01

    Based on our experience in treating peripheral non-neural sheath derived pathology, we have identified a novel pattern of lesion progression along the anatomic course of nerves. This report highlights the existence of a subparaneurial compartment around peripheral nerves. We first applied an anatomic framework to review MR images and intraoperative photographs of patients treated by the senior author in the last 10 years. After identifying a pattern that was consistent with subparaneurial lesion progression, we searched for other examples of cases that might exhibit this pattern. Four examples of subparaneurial pathology were identified, a hemangioma of the ulnar nerve, a ganglion cyst of the common fibular nerve, a lymphoma of the sciatic nerve and a lipoma of the ulnar nerve. All four patients were operated on and had intraoperative photographs; three had high resolution MR imaging. This report highlights the existence of pathology contained within a subparaneurial compartment, outside of the epineurium, that follows the course of the nerve and surrounds it circumferentially. The subparaneurial localization of peripheral nerve lesions has hitherto received little attention. Identification of this new pattern on preoperative MRI may have implications for surgical management. PMID:26133748

  3. International symposium on peripheral nerve repair and regeneration and 2nd club Brunelli meeting

    PubMed Central

    2010-01-01

    The International Symposium "Peripheral Nerve Repair and Regeneration and 2nd Club Brunelli Meeting" was held on December 4-5, 2009 in Turin, Italy (Organizers: Bruno Battiston, Stefano Geuna, Isabelle Perroteau, Pierluigi Tos). Interest in the study of peripheral nerve regeneration is very much alive because complete recovery of nerve function almost never occurs after nerve reconstruction and, often, the clinical outcome is rather poor. Therefore, there is a need for defining innovative strategies for improving the success of recovery after nerve lesion and repair and this meeting was intended to discuss, from a multidisciplinary point of view, some of today's most important issues in this scientific field, arising from both basic and clinical neurosciences. PMID:20214775

  4. International symposium on peripheral nerve repair and regeneration and 2nd club Brunelli meeting.

    PubMed

    Turgut, Mehmet; Geuna, Stefano

    2010-01-01

    The International Symposium "Peripheral Nerve Repair and Regeneration and 2nd Club Brunelli Meeting" was held on December 4-5, 2009 in Turin, Italy (Organizers: Bruno Battiston, Stefano Geuna, Isabelle Perroteau, Pierluigi Tos). Interest in the study of peripheral nerve regeneration is very much alive because complete recovery of nerve function almost never occurs after nerve reconstruction and, often, the clinical outcome is rather poor. Therefore, there is a need for defining innovative strategies for improving the success of recovery after nerve lesion and repair and this meeting was intended to discuss, from a multidisciplinary point of view, some of today's most important issues in this scientific field, arising from both basic and clinical neurosciences. PMID:20214775

  5. Bridging peripheral nerves using a deacetyl chitin conduit combined with short-term electrical stimulation.

    PubMed

    Zhang, Zhongli; Li, Xin; Zuo, Songjie; Xin, Jie; Zhang, Peixun

    2014-05-15

    Previous studies have demonstrated that deacetyl chitin conduit nerve bridging or electrical stimulation can effectively promote the regeneration of the injured peripheral nerve. We hypothesized that the combination of these two approaches could result in enhanced regeneration. Rats with right sciatic nerve injury were subjected to deacetyl chitin conduit bridging combined with electrical stimulation (0.1 ms, 3 V, 20 Hz, for 1 hour). At 6 and 12 weeks after treatment, nerve conduction velocity, myelinated axon number, fiber diameter, axon diameter and the thickness of the myelin sheath in the stimulation group were better than in the non-stimulation group. The results indicate that deacetyl chitin conduit bridging combined with temporary electrical stimulation can promote peripheral nerve repair. PMID:25206762

  6. Inhibition of calpains fails to improve regeneration through a peripheral nerve conduit.

    PubMed

    Hausner, Thomas; Marvaldi, Letizia; Márton, Gábor; Pajer, Krisztián; Hopf, Rudolf; Schmidhammer, Robert; Hausott, Barbara; Redl, Heinz; Nógrádi, Antal; Klimaschewski, Lars

    2014-04-30

    Intramuscular injection of the calpain inhibitor leupeptin promotes peripheral nerve regeneration in primates (Badalamente et al., 1989 [13]), and direct positive effects of leupeptin on axon outgrowth were observed in vitro (Hausott et al., 2012 [12]). In this study, we applied leupeptin (2mg/ml) directly to collagen-filled nerve conduits in the rat sciatic nerve transection model. Analysis of myelinated axons and retrogradely labeled motoneurons as well as functional 'CatWalk' video analysis did not reveal significant differences between vehicle controls and leupeptin treated animals. Therefore, leupeptin does not improve nerve regeneration via protease inhibition in regrowing axons or in surrounding Schwann cells following a single application to a peripheral nerve conduit suggesting indirect effects on motor endplate integrity if applied systemically. PMID:24631569

  7. Laser-activated protein solder for peripheral nerve repair

    NASA Astrophysics Data System (ADS)

    Trickett, Rodney I.; Lauto, Antonio; Dawes, Judith M.; Owen, Earl R.

    1995-05-01

    A 100 micrometers core optical fiber-coupled 75 mW diode laser operating at a wavelength of 800 nm has been used in conjunction with a protein solder to stripe weld severed rat tibial nerves, reducing the long operating time required for microsurgical nerve repair. Welding is produced by selective laser denaturation of the albumin based solder which contains the dye indocyanine green. Operating time for laser soldering was 10 +/- 5 min. (n equals 20) compared to 23 +/- 9 min. (n equals 10) for microsuturing. The laser solder technique resulted in patent welds with a tensile strength of 15 +/- 5 g, while microsutured nerves had a tensile strength of 40 +/- 10 g. Histopathology of the laser soldered nerves, conducted immediately after surgery, displayed solder adhesion to the outer membrane with minimal damage to the inner axons of the nerves. An in vivo study is under way comparing laser solder repaired tibial nerves to conventional microsuture repair. At the time of submission 15 laser soldered nerves and 7 sutured nerves were characterized at 3 months and showed successful regeneration with compound muscle action potentials of 27 +/- 8 mV and 29 +/- 8 mW respectively. A faster, less damaging and long lasting laser based anastomotic technique is presented.

  8. Glycomimetic functionalized collagen hydrogels for peripheral nerve repair

    NASA Astrophysics Data System (ADS)

    Masand, Shirley Narain

    Despite the innate regenerative potential of the peripheral nervous system, functional recovery is often limited. The goal of this dissertation was to develop a clinically relevant biomaterial strategy to (1) encourage the regrowth of axons and (2) direct them down their appropriate motor tracts. To this end, we use peptide mimics of two glycans, polysialic acid (PSA) and an epitope first discovered on human natural killer cells (HNK-1), to functionalize type I collagen hydrogels. Previous studies have shown that these molecules, in their glycan and glycomimetic form, are associated with acceleration of neurite outgrowth, glial cell proliferation, and motoneuron targeting. In vitro, we demonstrated the retained functionality of the peptide glycomimetics after conjugation to a type I collagen backbone. While HNK-functionalized collagen increased motor neurite outgrowth, PSA-functionalized collagen encouraged motor and sensory neurite outgrowth and Schwann cell extension and proliferation. When we introduce these glycomimetic-functionalized collagen hydrogels into a critical gap femoral nerve model, we show that both PSA and HNK-functionalized hydrogels yielded a significant increase in functional recovery when compared to saline, native and scramble-coupled hydrogels. However, there was an interesting divergence in the morphological results: PSA-functionalized hydrogels increased axon count and HNK-functionalized hydrogels increased motoneuron targeting and myelination. We believed that these differences may be attributed to distinct mechanisms by which the glycomimetics impart their benefit. Interestingly, however, we found no synergistic gain in recovery with the use of our composite hydrogels which we speculated may be due to an inadequate dose of the individual glycomimetic. To address this possibility, we show that increasing the amount of functionalized peptide functionalized in our composite hydrogels led to increases in axon count and area of regeneration

  9. In vivo integration of poly(ε-caprolactone)/gelatin nanofibrous nerve guide seeded with teeth derived stem cells for peripheral nerve regeneration.

    PubMed

    Beigi, Mohammad-Hossein; Ghasemi-Mobarakeh, Laleh; Prabhakaran, Molamma P; Karbalaie, Khadijeh; Azadeh, Hamid; Ramakrishna, Seeram; Baharvand, Hossein; Nasr-Esfahani, Mohammad-Hossein

    2014-12-01

    Artificial nanofiber nerve guides have gained huge interest in bridging nerve gaps and associated peripheral nerve regeneration due to its high surface area, flexibility and porous structure. In this study, electrospun poly (ε-caprolactone)/gelatin (PCL/Gel) nanofibrous mats were fabricated, rolled around a copper wire and fixed by medical grade adhesive to obtain a tubular shaped bio-graft, to bridge 10 mm sciatic nerve gap in in vivo rat models. Stem cells from human exfoliated deciduous tooth (SHED) were transplanted to the site of nerve injury through the nanofibrous nerve guides. In vivo experiments were performed in animal models after creating a sciatic nerve gap, such that the nerve gap was grafted using (i) nanofiber nerve guide (ii) nanofiber nerve guide seeded with SHED (iii) suturing, while an untreated nerve gap remained as the negative control. In vitro cell culture study was carried out for primary investigation of SHED-nanofiber interaction and its viability within the nerve guides after 2 and 16 weeks of implantation time. Walking track analysis, plantar test, electrophysiology and immunohistochemistry were performed to evaluate functional recovery during nerve regeneration. Vascularization was also investigated by hematoxilin/eosine (H&E) staining. Overall results showed that the SHED seeded on nanofibrous nerve guide could survive and promote axonal regeneration in rat sciatic nerves, whereby the biocompatible PCL/Gel nerve guide with cells can support axonal regeneration and could be a promising tissue engineered graft for peripheral nerve regeneration. PMID:24677613

  10. Improved peripheral nerve regeneration in streptozotocin-induced diabetic rats by oral lumbrokinase.

    PubMed

    Lee, Han-Chung; Hsu, Yuan-Man; Tsai, Chin-Chuan; Ke, Cherng-Jyh; Yao, Chun-Hsu; Chen, Yueh-Sheng

    2015-01-01

    We assessed the therapeutic effects of lumbrokinase, a group of enzymes extracted from the earthworm, on peripheral-nerve regeneration using well-defined sciatic nerve lesion paradigms in diabetic rats induced by the injection of streptozotocin (STZ). We found that lumbrokinase therapy could improve the rats' circulatory blood flow and promote the regeneration of axons in a silicone rubber conduit after nerve transection. Lumbrokinase treatment could also improve the neuromuscular functions with better nerve conductive performances. Immunohistochemical staining showed that lumbrokinase could dramatically promote calcitonin gene-related peptide (CGRP) expression in the lamina I-II regions in the dorsal horn ipsilateral to the injury and cause a marked increase in the number of macrophages recruited within the distal nerve stumps. In addition, the lumbrokinase could stimulate the secretion of interleukin-1 (IL-1), nerve growth factor (NGF), platelet-derived growth factor (PDGF), and transforming growth factor-β (TGF-β) in dissected diabetic sciatic nerve segments. In conclusion, the administration of lumbrokinase after nerve repair surgery in diabetic rats was found to have remarkable effects on promoting peripheral nerve regeneration and functional recovery. PMID:25787300

  11. Laser-activated protein bands for peripheral nerve repair

    NASA Astrophysics Data System (ADS)

    Lauto, Antonio; Trickett, Rodney I.; Malik, Richard; Dawes, Judith M.; Owen, Earl R.

    1996-01-01

    A 100 micrometer core optical fiber-coupled 75 mW diode laser operating at a wavelength of 800 nm has been used in conjunction with a protein solder to stripe weld severed rat tibial nerves, reducing the long operating time required for microsurgical nerve repair. Welding is produced by selective laser denaturation of the protein based solder which contains the dye indocyanine green. Operating time for laser soldering was 10 plus or minus 5 min. (n equals 24) compared to 23 plus or minus 9 min (n equals 13) for microsuturing. The laser solder technique resulted in patent welds with a tensile strength of 15 plus or minus 5 g, while microsutured nerves had a tensile strength of 40 plus or minus 10 g. Histopathology of the laser soldered nerves, conducted immediately after surgery, displayed solder adhesion to the outer membrane with minimal damage to the inner axons of the nerves. An in vivo study, with a total of fifty-seven adult male wistar rats, compared laser solder repaired tibial nerves to conventional microsuture repair. Twenty-four laser soldered nerves and thirteen sutured nerves were characterized at three months and showed successful regeneration with average compound muscle action potentials (CMAP) of 2.4 plus or minus 0.7 mV and 2.7 plus or minus 0.8 mV respectively. Histopathology of the in vivo study, confirmed the comparable regeneration of axons in laser and suture operated nerves. A faster, less damaging and long lasting laser based anastomotic technique is presented.

  12. A Review of Bioactive Release from Nerve Conduits as a Neurotherapeutic Strategy for Neuronal Growth in Peripheral Nerve Injury

    PubMed Central

    Choonara, Yahya E.; Bijukumar, Divya; du Toit, Lisa C.

    2014-01-01

    Peripheral nerve regeneration strategies employ the use of polymeric engineered nerve conduits encompassed with components of a delivery system. This allows for the controlled and sustained release of neurotrophic growth factors for the enhancement of the innate regenerative capacity of the injured nerves. This review article focuses on the delivery of neurotrophic factors (NTFs) and the importance of the parameters that control release kinetics in the delivery of optimal quantities of NTFs for improved therapeutic effect and prevention of dose dumping. Studies utilizing various controlled-release strategies, in attempt to obtain ideal release kinetics, have been reviewed in this paper. Release strategies discussed include affinity-based models, crosslinking techniques, and layer-by-layer technologies. Currently available synthetic hollow nerve conduits, an alternative to the nerve autografts, have proven to be successful in the bridging and regeneration of primarily the short transected nerve gaps in several patient cases. However, current research emphasizes on the development of more advanced nerve conduits able to simulate the effectiveness of the autograft which includes, in particular, the ability to deliver growth factors. PMID:25143934

  13. Near-infrared signals associated with electrical stimulation of peripheral nerves

    NASA Astrophysics Data System (ADS)

    Fantini, Sergio; Chen, Debbie K.; Martin, Jeffrey M.; Sassaroli, Angelo; Bergethon, Peter R.

    2009-02-01

    We report our studies on the optical signals measured non-invasively on electrically stimulated peripheral nerves. The stimulation consists of the delivery of 0.1 ms current pulses, below the threshold for triggering any visible motion, to a peripheral nerve in human subjects (we have studied the sural nerve and the median nerve). In response to electrical stimulation, we observe an optical signal that peaks at about 100 ms post-stimulus, on a much longer time scale than the few milliseconds duration of the electrical response, or sensory nerve action potential (SNAP). While the 100 ms optical signal we measured is not a direct optical signature of neural activation, it is nevertheless indicative of a mediated response to neural activation. We argue that this may provide information useful for understanding the origin of the fast optical signal (also on a 100 ms time scale) that has been measured non-invasively in the brain in response to cerebral activation. Furthermore, the optical response to peripheral nerve activation may be developed into a diagnostic tool for peripheral neuropathies, as suggested by the delayed optical signals (average peak time: 230 ms) measured in patients with diabetic neuropathy with respect to normal subjects (average peak time: 160 ms).

  14. Current progress in use of adipose derived stem cells in peripheral nerve regeneration

    PubMed Central

    Zack-Williams, Shomari DL; Butler, Peter E; Kalaskar, Deepak M

    2015-01-01

    Unlike central nervous system neurons; those in the peripheral nervous system have the potential for full regeneration after injury. Following injury, recovery is controlled by schwann cells which replicate and modulate the subsequent immune response. The level of nerve recovery is strongly linked to the severity of the initial injury despite the significant advancements in imaging and surgical techniques. Multiple experimental models have been used with varying successes to augment the natural regenerative processes which occur following nerve injury. Stem cell therapy in peripheral nerve injury may be an important future intervention to improve the best attainable clinical results. In particular adipose derived stem cells (ADSCs) are multipotent mesenchymal stem cells similar to bone marrow derived stem cells, which are thought to have neurotrophic properties and the ability to differentiate into multiple lineages. They are ubiquitous within adipose tissue; they can form many structures resembling the mature adult peripheral nervous system. Following early in vitro work; multiple small and large animal in vivo models have been used in conjunction with conduits, autografts and allografts to successfully bridge the peripheral nerve gap. Some of the ADSC related neuroprotective and regenerative properties have been elucidated however much work remains before a model can be used successfully in human peripheral nerve injury (PNI). This review aims to provide a detailed overview of progress made in the use of ADSC in PNI, with discussion on the role of a tissue engineered approach for PNI repair. PMID:25621105

  15. Sonographic Tracking of the Lower Limb Peripheral Nerves: A Pictorial Essay and Video Demonstration.

    PubMed

    Hung, Chen-Yu; Hsiao, Ming-Yen; Özçakar, Levent; Chang, Ke-Vin; Wu, Chueh-Hung; Wang, Tyng-Guey; Chen, Wen-Shiang

    2016-09-01

    Compared with the upper limbs, sonographic tracking of peripheral nerves in the lower limbs is more challenging. The overlying muscles are larger, hindering visualization of the deeply embedded nerves by using a linear transducer. The use of a curvilinear transducer-providing an extended view with better penetration for the field of interest-may be useful for scanning the nerves in the hip and thigh. Application of the Doppler mode helps localization of the target nerve by identifying the accompanying vessels. Aiming to demonstrate the relevant tracking techniques, the present article comprises a series of ultrasound images and videos showing how to scan the nerves in the lower limb, that is, femoral, obturator, pudendal, lateral femoral cutaneous, sciatic, saphenous, sural, tibial, and peroneal nerves. PMID:26945217

  16. Custom prefabrication of silicone tubes from urinary catheters for experimental peripheral nerve surgery.

    PubMed

    Saray, Aydin

    2004-01-01

    The entubulation principle represents a neurobiological approach to nerve surgery in which the role of the surgeon is limited and intrinsic healing capabilities of the nerve play the primary role. Herein, a technique for fabricating custom-made silicone tubes from a silicone urinary catheter is described. Silicone tubes with varying size and dimensions can be tailored depending on the diameter of the silicone urinary catheter (14 F to 18 F). Tubes crafted from silicone urinary catheters were used either as a nerve conduit to facilitate regeneration or as compressive nerve banding to simulate compressive neuropathy in the rat sciatic nerve. Custom-made silicone tubes have similar pros and cons to the commercially available silicone tubes regarding the capsule and foreign body reaction. It can be concluded that these cost effective tubes can be easily cut and used in experimental peripheral nerve surgery in developing countries where the cost of such materials becomes an important issue for the researchers. PMID:24115867

  17. Novel use of biodegradable casein conduits for guided peripheral nerve regeneration

    PubMed Central

    Hsiang, Shih-Wei; Tsai, Chin-Chuan; Tsai, Fuu-Jen; Ho, Tin-Yun; Yao, Chun-Hsu; Chen, Yueh-Sheng

    2011-01-01

    Recent advances in nerve repair technology have focused on finding more biocompatible, non-toxic materials to imitate natural peripheral nerve components. In this study, casein protein cross-linked with naturally occurring genipin (genipin-cross-linked casein (GCC)) was used for the first time to make a biodegradable conduit for peripheral nerve repair. The GCC conduit was dark blue in appearance with a concentric and round lumen. Water uptake, contact angle and mechanical tests indicated that the conduit had a high stability in water and did not collapse and cramped with a sufficiently high level of mechanical properties. Cytotoxic testing and terminal deoxynucleotidyl transferase dUTP nick-end labelling assay showed that the GCC was non-toxic and non-apoptotic, which could maintain the survival and outgrowth of Schwann cells. Non-invasive real-time nuclear factor-κB bioluminescence imaging accompanied by histochemical assessment showed that the GCC was highly biocompatible after subcutaneous implantation in transgenic mice. Effectiveness of the GCC conduit as a guidance channel was examined as it was used to repair a 10 mm gap in the rat sciatic nerve. Electrophysiology, labelling of calcitonin gene-related peptide in the lumbar spinal cord, and histology analysis all showed a rapid morphological and functional recovery for the disrupted nerves. Therefore, we conclude that the GCC can offer great nerve regeneration characteristics and can be a promising material for the successful repair of peripheral nerve defects. PMID:21525148

  18. Spatial and Functional Selectivity of Peripheral Nerve Signal Recording With the Transversal Intrafascicular Multichannel Electrode (TIME).

    PubMed

    Badia, Jordi; Raspopovic, Stanisa; Carpaneto, Jacopo; Micera, Silvestro; Navarro, Xavier

    2016-01-01

    The selection of suitable peripheral nerve electrodes for biomedical applications implies a trade-off between invasiveness and selectivity. The optimal design should provide the highest selectivity for targeting a large number of nerve fascicles with the least invasiveness and potential damage to the nerve. The transverse intrafascicular multichannel electrode (TIME), transversally inserted in the peripheral nerve, has been shown to be useful for the selective activation of subsets of axons, both at inter- and intra-fascicular levels, in the small sciatic nerve of the rat. In this study we assessed the capabilities of TIME for the selective recording of neural activity, considering the topographical selectivity and the distinction of neural signals corresponding to different sensory types. Topographical recording selectivity was proved by the differential recording of CNAPs from different subsets of nerve fibers, such as those innervating toes 2 and 4 of the hindpaw of the rat. Neural signals elicited by sensory stimuli applied to the rat paw were successfully recorded. Signal processing allowed distinguishing three different types of sensory stimuli such as tactile, proprioceptive and nociceptive ones with high performance. These findings further support the suitability of TIMEs for neuroprosthetic applications, by exploiting the transversal topographical structure of the peripheral nerves. PMID:26087496

  19. Fluorescently-tagged anti-ganglioside antibody selectively identifies peripheral nerve in living animals

    PubMed Central

    Massaad, Cynthia A.; Zhang, Gang; Pillai, Laila; Azhdarinia, Ali; Liu, Weiqiang; Sheikh, Kazim A.

    2015-01-01

    Selective in vivo delivery of cargo to peripheral nervous system (PNS) has broad clinical and preclinical applications. An important applicability of this approach is systemic delivery of fluorescently conjugated ligands that selectively label PNS, which could allow visualization of peripheral nerves during any surgery. We examine the use of an anti-ganglioside monoclonal antibody (mAb) as selective neuronal delivery vector for surgical imaging of peripheral nerves. Systemic delivery of an anti-ganglioside mAb was used for selective intraneuronal/axonal delivery of fluorescent agents to visualize nerves by surgical imaging in living mice. In this study, we show that intact motor, sensory, and autonomic nerve fibers/paths are distinctly labeled following a single nanomolar systemic injection of fluorescently labeled anti-ganglioside mAb. Tissue biodistribution studies with radiolabeled mAb were used to validate neuronal uptake of fluorescently labeled mAb. Implications of this proof of concept study are that fluorescent conjugates of anti-ganglioside mAbs are valuable delivery vectors to visualize nerves during surgery to avoid nerve injury and monitor nerve degeneration and regeneration after injury. These findings support that antibodies, and their derivatives/fragments, can be used as selective neuronal delivery vector for transport of various cargos to PNS in preclinical and clinical settings. PMID:26514366

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

    ERIC Educational Resources Information Center

    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…

  1. Peripheral nerve stimulation for treatment of chronic headache: a case report.

    PubMed

    Green, Adam; Issa, Mohammed A; Kim, Chong H

    2013-01-01

    Chronic daily headaches can be debilitating. Multiple treatments have been suggested with varying degrees of success. We present a case of a 27-year-old female with greater than ten years of chronic daily headaches. The patient was evaluated at the headache clinic where she was diagnosed with complex migraine with components of occipital neuralgia. Multiple medication regimens were tried without significant benefit. The patient also underwent bilateral occipital blocks along with trigger point injections of various muscles including the semispinalis capitis with significant but limited duration of benefit. After other treatments were unsuccessful, the patient was referred to the Pain Management Center and underwent a trial of peripheral nerve stimulation with significant pain relief without complications. She then proceeded with permanent implantation of the peripheral nerve stimulator with continued pain relief. This case demonstrates the utility of peripheral nerve stimulation for the treatment of refractory chronic daily headaches and should be part of our armamentarium. PMID:24371861

  2. Malignant Peripheral Nerve Sheath Tumor in Neurofibromatosis Type I : Unusual Presentation of Intraabdominal or Intrathoracic Mass

    PubMed Central

    Kim, Jong Gwang; Sung, Woo Jin; Kim, Dong Hwan; Kim, Young Hwan; Lee, Kyu Bo

    2005-01-01

    A malignant peripheral nerve sheath tumor (MPNST) is an extremely rare soft tissue tumor in the general population. On the other hand, there is a higher incidence of MPNST in patients with neurofibromatosis type I (von Recklinghausen's disease). The common sites are the extremities, trunk, head and neck. However, an intraabdominal or intrathoracic manifestation is uncommon. This paper reports two patients, a 31 year-old woman with multiple neurofibromatosis presenting as an intraabdominal malignant peripheral nerve sheath tumor, and a 33 year-old woman with an intrathoracic malignant peripheral nerve sheath tumor. The patients were treated with chemotherapy followed by radiotherapy. However, one patient died as a result of disease progression 21 months after the diagnosis and the other patient is currently being treated with radiotherapy. PMID:15906964

  3. Conductive PPY/PDLLA conduit for peripheral nerve regeneration

    PubMed Central

    Xu, Haixing; Holzwarth, Jeremy M.; Yan, Yuhua; Xu, Peihu; Zheng, Hua; Yin, Yixia; Li, Shipu; Ma, Peter X.

    2013-01-01

    The significant drawbacks and lack of success associated with current methods to treat critically sized nerve defects have led to increased interest in neural tissue engineering. Conducting polymers show great promise due to their electrical properties, and in the case of polypyrrole (PPY), its cell compatibility as well. Thus, the goal of this study is to synthesize a conducting composite nerve conduit with PPY and poly(D, L-lactic acid) (PDLLA), assess its ability to support the differentiation of rat pheochromocytoma 12 (PC12) cells in vitro, and determine its ability to promote nerve regeneration in vivo. Different amounts of PPY (5%, 10%, and 15%) are used to synthesize the conduits resulting in different conductivities (5.65, 10.40, and 15.56 ms/cm, respectively). When PC12 cells are seeded on these conduits and stimulated with 100 mV for 2 h, there is a marked increase in both the percentage of neurite-bearing cells and the median neurite length as the content of PPY increased. More importantly, when the PPY/PDLLA nerve conduit was used to repair a rat sciatic nerve defect it performed similarly to the gold standard autologous graft. These promising results illustrate the potential that this PPY/PDLLA conducting composite conduit has for neural tissue engineering. PMID:24138830

  4. Biosynthesis and transport of gangliosides in peripheral nerve

    SciTech Connect

    Yates, A.J.; Tipnis, U.R.; Hofteig, J.H.; Warner, J.K.

    1984-01-01

    Radiolabelled glucosamine was injected into L-7 dorsal root ganglion (DRG) of rabbits. At several different times after injection DRG, lumbosacral trunks (LST) and sciatic nerves (SN) were removed and gangliosides extracted. Two and 3 weeks after injection the amounts of radioactivity in the ganglioside fractions of LST and SN were significantly higher than at days 1 and 2. The TCA soluble radioactivity decreased dramatically over the same time period. Colchicine prevented the appearance of radiolabelled lipid in LST and SN. From these experiments the authors conclude that some ganglioside is synthesized in the neuronal cell bodies of DRG and transported in the axons of the sciatic nerve. In another experiment the sciatic nerve was transected and ends separated to prevent regeneration. There was no difference in the amount of radiolabelled ganglioside that was isolated from DRG or LST of transected nerves compared with control nerves. The behavior of several potential acid soluble contaminants was studied in several steps used to isolate gangliosides. Of those studied only CMP-NeuAc could cause significant contamination of the final ganglioside preparation.

  5. [Neuropathic pain intensity depends on the degree of peripheral nerve injury in the rat].

    PubMed

    Abuduhadeer, Tayier

    2004-12-01

    Partial peripheral nerve injury produces a persistent neuropathic pain which is difficult to relieve. In order to determine whether different degrees of peripheral nerve injury are related with the severity of neuropathic pain, we examined pain-related behaviors, histological changes and NGF in the skin in rats treated with different types of spinal nerve injury: tight ligation of the left L5 spinal nerve, incomplete ligation of the left L4 and L5 spinal nerves and incomplete crush of the left L4 and L5 spinal nerves. In all model rats, the thresholds of paw withdrawal in response to mechanical and heat stimuli began to decrease on the injured side 1 day after the operation, and the decreases in the thresholds persisted for more than 1 month. Incomplete ligation and incomplete crush of the left L4 and L5 spinal nerves caused more severe allodynia and hyperalgesia than tight ligation of the left L5 spinal nerve on the injured side. In rats treated with incomplete crush, the threshold of withdrawal response to mechanical or heat stimuli was improved on day 32 after the operation as compared with that on day 15. Histological analysis revealed that about 80% of the fibers in the sciatic nerve were injured after incomplete ligation and incomplete crush of the left L4 and L5 spinal nerves on day 15, while about 50% of the fibers were damaged by tight ligation of the left L5 spinal nerve. In accordance with pain-relieving, the sciatic nerve fibers regenerated to about 50% of the number of the intact sciatic nerve fibers on day 32 in the crush model. Nerve growth factor (NGF) in the skin of the hindpaw on the injured side was accumulated after incomplete ligation and incomplete crush of the left L4 and L5 spinal nerves, but not tight ligation of the left L5 spinal nerve, on day 15 after the operation, possibly due to impairment of transport via unmyelinated primary afferents. Regeneration of the sciatic nerve alleviated the accumulation of NGF in the injured side hindpaw

  6. Using Eggshell Membrane as Nerve Guide Channels in Peripheral Nerve Regeneration

    PubMed Central

    Farjah, Gholam Hossein; Heshmatian, Behnam; Karimipour, Mojtaba; Saberi, Ali

    2013-01-01

    Objective(s): The aim of this study was to evaluate the final outcome of nerve regeneration across the eggsell membrane (ESM) tube conduit in comparison with autograft. Materials and Methods: Thirty adult male rats (250-300 g) were randomized into (1) ESM conduit, (2) autograft, and (3) sham surgery groups. The eggs submerged in 5% acetic acid. The decalcifying membranes were cut into four pieces, rotated over the teflon mandrel and dried at 37°C. The left sciatic nerve was surgically cut. A 10-mm nerve segment was cut and removed. In the ESM group, the proximal and distal cut ends of the sciatic nerve were telescoped into the nerve guides. In the autograft group, the 10 mm nerve segment was reversed and used as an autologous nerve graft. All animals were evaluated by sciatic functional index (SFI) and electrophysiology testing. Results: The improvement in SFI from the first to the last evalution in ESM and autograft groups were evaluated. On days 49 and 60 post-operation, the mean SFI of ESM group was significantly greater than the autograft group (P< 0.05). On day 90, the mean nerve conduction velocity (NCV) of ESM group was greater than autograft group, although the difference was not statistically significant (P> 0.05). Conclusion: These findings demonstrate that ESM effectively enhances nerve regeneration and promotes functional recovery in injured sciatic nerve of rat. PMID:24106593

  7. Preoperative evaluation of peripheral nerve injuries: What is the place for ultrasound?

    PubMed

    Toia, Francesca; Gagliardo, Andrea; D'Arpa, Salvatore; Gagliardo, Cesare; Gagliardo, Giuseppe; Cordova, Adriana

    2016-09-01

    OBJECTIVE The purpose of this study was to evaluate the usefulness of ultrasound in the preoperative workup of peripheral nerve lesions and illustrate how nerve ultrasonography can be integrated in routine clinical and neurophysiological evaluation and in the management of focal peripheral nerve injuries. The diagnostic role and therapeutic implications of ultrasonography for different neuropathies are described. METHODS The authors analyzed the use of ultrasound in 119 entrapment, tumoral, posttraumatic, or postsurgical nerve injuries of limbs evaluated in 108 patients during 2013 and 2014. All patients were candidates for surgery, and in all cases the evaluation included clinical examination, electrodiagnostic studies (nerve conduction study and electromyography), and ultrasound nerve study. Ultrasound was used to explore the nerve fascicular echotexture, continuity, and surrounding tissues. The maximum cross-sectional area (CSA) and the presence of epineurial hyperechogenicity or intraneural hyper- or hypoechogenicity, of anatomical anomalies, dynamic nerve dislocations, or compressions were recorded. The concordance rate of neurophysiological and ultrasonographic data was analyzed, classifying ultrasound findings as confirming, contributive, or nonconfirming with respect to electrodiagnostic data. The correlation between maximum nerve CSA and neurophysiological severity degree in entrapment syndromes was statistically analyzed. RESULTS Ultrasonography confirmed electrodiagnostic findings in 36.1% of cases and showed a contributive role in the diagnosis and surgical planning in 53.8% of all cases; the findings were negative ("nonconfirming") in only 10.1% of the patients. In 16% of cases, ultrasound was not only contributive, but had a key diagnostic role in the presence of doubtful electrodiagnostic findings. The contributive role differed according to etiology, being higher for tumors (100%) and for posttraumatic or postsurgical neuropathies (72.2%) than for

  8. Cold and post-traumatic pain: modeling of the peripheral nerve message.

    PubMed

    de Medinaceli, L; Hurpeau, J; Merle, M; Begorre, H

    1997-01-01

    Hypersensitivity to cold is a relatively frequent sequel of peripheral nerve injuries but its mechanism is not well understood. We suggested that incomplete recovery of diameter of regenerated fibers is one of the factors involved in cold intolerance after nerve damage. Conduction velocity is correlated to fiber diameter, and is slowed down by cold. In normal subjects, cold does not desynchronize the volleys of sensory impulses sufficiently to change the intelligibility of the peripheral 'messages'. Sensory perceptions remain accurate although they acquire a characteristic numbness. On the other hand, post-traumatic reduction in fiber diameters causes a permanent distortion of the messages. We considered that when the distortion is severe, the resulting messages may be perceived by the centers as containing nociceptive components. We further hypothesized that, even in cases of moderate permanent distortion, cold acts by increasing the post-traumatic abnormalities of impulse synchronization. In winter, decompensation is observed when a threshold of desynchronization is reached. We constructed a model of peripheral nerve messages in an attempt to represent and quantitate the desynchronizations produced by cold and crush damage lesions in peripheral nerve messages. A number of parameters concerning fiber anatomy, exposure to cold, and type of nerve damage were taken into consideration. Four elementary types of desynchronization could be recognized by considering the times of arrival of pairs of impulses at the nervous centers. The difference between a normal and a distorted message could be expressed by eight variables. Thus, although our model was quite simple, a large amount of data was obtained and a preliminary statistical study was necessary in order to orient the final analysis. Then, we used factor analysis in an attempt to obtain a satisfactory interpretation of the data. The results indicated that peripheral desynchronization might explain, at least in part

  9. [Repair and revision 9. Peripheral trigeminal nerve injury].

    PubMed

    Vriens, J P M; van der Glas, H W; Koole, R

    2002-03-01

    A review is given about long-term incidence of sensory disturbance in the areas of innervation of the n. trigeminus for different types of trauma and/or treatment. Diagnosis, clinical course and possible types of treatment are in addition reviewed. Regarding diagnosis, the outcome of a test on sensory function is not always related to the degree of nerve damage because methods differ in the type of afferent nerve fibers of which function is tested, and some specificity might occur in nerve damage, i.e. either thick or thin afferent fibers might be predominantly affected at a particular time. An initial quick testing of sensory function is recommended. This testing includes examining two sensory modalities, which are related to functioning of thick and thin afferent fibers respectively and which have a dichotomous yes/no outcome on the incidence of a pronounced sensory disturbance. PMID:11933529

  10. Loss of H3K27 trimethylation distinguishes malignant peripheral nerve sheath tumors from histologic mimics.

    PubMed

    Schaefer, Inga-Marie; Fletcher, Christopher Dm; Hornick, Jason L

    2016-01-01

    The diagnosis of malignant peripheral nerve sheath tumor is challenging, particularly in the sporadic setting. Inactivation of the polycomb repressive complex 2 (PRC2), resulting from inactivating mutations of its constituents SUZ12 or EED1, has recently been identified in 70-90% of malignant peripheral nerve sheath tumors. Homozygous PRC2 inactivation results in loss of histone H3K27 trimethylation (H3K27me3). PRC2 inactivation promotes tumor progression and may render patients sensitive to epigenetic-based targeted therapies. H3K27me3 loss has not yet been validated as a diagnostic marker. We evaluated immunohistochemistry for H3K27me3 in 100 malignant peripheral nerve sheath tumors (70 sporadic, 10 neurofibromatosis type 1-associated, 10 radiation-associated, 10 epithelioid) and 200 other spindle cell neoplasms representing potential mimics (20 each monophasic synovial sarcoma, leiomyosarcoma, dedifferentiated liposarcoma, malignant solitary fibrous tumor, low-grade fibromyxoid sarcoma, cellular schwannoma, spindle cell melanoma, unclassified postradiation sarcoma; 10 each atypical neurofibroma, spindle cell rhabdomyosarcoma, gastrointestinal stromal tumor, fibrosarcomatous dermatofibrosarcoma protuberans). In total, 51 (51%) malignant peripheral nerve sheath tumors, including 34 (49%) sporadic, 7 (70%) neurofibromatosis type 1-associated, and 10 (100%) radiation-associated, but no epithelioid malignant peripheral nerve sheath tumors, were negative for H3K27me3. An additional 6 (6%) tumors showed heterogeneous H3K27me3 expression. Among the 90 sporadic, neurofibromatosis type 1-associated, and radiation-associated malignant peripheral nerve sheath tumors, complete H3K27me3 loss was observed in 29% of low-grade, 59% of intermediate-grade, and 83% of high-grade tumors (low vs intermediate/high grade, P=0.0003). Among other tumor types, 4 (20%) unclassified postradiation sarcomas were negative for H3K27me3, whereas all other neoplasms were positive. Loss of H3K27me

  11. The coexistence of peripheral nerve sheath tumors and vitiligo: more than coincidence?

    PubMed

    Elsherif, Mohamed A; Spinner, Robert J; Miest, Rachel Y

    2016-01-01

    Neurocristopathies arise from abnormal migration, differentiation, or proliferation of neural crest derivatives, leading to diverse clinical and pathological features. They are classified into dysgenetic or neoplastic, and can affect single or multiple sites (simple versus complex). Examples include congenital melanocytic nevi, neuroblastoma, Hirshsprung's disease, Waardenburg's syndrome, neurofibromatosis (NF) 1 and multiple endocrine neoplasia (MEN) 2A and 2B. We report two cases of peripheral nerve sheath tumors associated with vitiligo and discuss the possible implicated embryologic, genetic and molecular mechanisms. To our knowledge, we also report the first case of de novo malignant peripheral nerve sheath tumor (MPNST) associated with vitiligo. PMID:26607956

  12. Decellular biological scaffold polymerized with PEDOT for improving peripheral nerve interface charge transfer.

    PubMed

    Frost, Christopher M; Cederna, Paul S; Martin, David C; Shim, Bong Sup; Urbanchek, Melanie G

    2014-01-01

    Regenerative peripheral nerve interfaces (RPNIs) are for signal transfer between peripheral nerves inside the body to controllers for motorized prosthetics external to the body. Within the residual limb of an amputee, surgical construction of a RPNI connects a remaining peripheral nerve and spare muscle. Nerve signals become concentrated within the RPNI. Currently metal electrodes implanted on the RPNI muscle transfer signals but scarring around metal electrodes progressively diminishes charge transfer. Engineered materials may benefit RPNI signal transfer across the neural interface if they lower the power and charge density of the biologically meaningful signals. Poly3,4-ethylenedioxythiophene (PEDOT) is known to mediate ionic potentials allowing excitation across a critical nerve gap. We hypothesize that the capacity of an interface material to conduct electron mediated current is significantly increased by polymerized coating of PEDOT. SIS was either used plain or after PEDOT coating by electrochemical polymerization. Muscle forces are a direct representation of stimulating current distribution within an RPNI. In situ muscle forces were measured for the same muscle by electrically stimulating: a) the muscle's innervating nerve, b) directly on the muscle, c) on plain SIS laid on the muscle, and d) on SIS polymerized with PEDOT laid on the muscle. Electro-chemically coating PEDOT on SIS resulted in a thin, flexible material. PEDOT coated SIS distributed electrical stimulation more efficiently than SIS alone. Conductive polymer containing biological material allowed ionic signal distribution within the RPNI like muscle at lower charge density. PMID:25569986

  13. Strategies to promote peripheral nerve regeneration: electrical stimulation and/or exercise.

    PubMed

    Gordon, Tessa; English, Arthur W

    2016-02-01

    Enhancing the regeneration of axons is often considered to be a therapeutic target for improving functional recovery after peripheral nerve injury. In this review, the evidence for the efficacy of electrical stimulation (ES), daily exercise and their combination in promoting nerve regeneration after peripheral nerve injuries in both animal models and in human patients is explored. The rationale, effectiveness and molecular basis of ES and exercise in accelerating axon outgrowth are reviewed. In comparing the effects of ES and exercise in enhancing axon regeneration, increased neural activity, neurotrophins and androgens are considered to be common requirements. Similarly, there are sex-specific requirements for exercise to enhance axon regeneration in the periphery and for sustaining synaptic inputs onto injured motoneurons. ES promotes nerve regeneration after delayed nerve repair in humans and rats. The effectiveness of exercise is less clear. Although ES, but not exercise, results in a significant misdirection of regenerating motor axons to reinnervate different muscle targets, the loss of neuromuscular specificity encountered has only a very small impact on resulting functional recovery. Both ES and exercise are promising experimental treatments for peripheral nerve injury that seem to be ready to be translated to clinical use. PMID:26121368

  14. Peripheral nerve regeneration through a silicone chamber implanted with negative carbon ions: Possibility to clinical application

    NASA Astrophysics Data System (ADS)

    Ikeguchi, Ryosuke; Kakinoki, Ryosuke; Tsuji, Hiroshi; Yasuda, Tadashi; Matsuda, Shuichi

    2014-08-01

    We investigated whether a tube with its inner surface implanted with negative-charged carbon ions (C- ions) would enable axons to extend over a distance greater than 10 mm. The tube was found to support nerves regenerating across a 15-mm-long inter-stump gap. We also investigated whether a C- ion-implanted tube pretreated with basic fibroblast growth factor (bFGF) promotes peripheral nerve regeneration. The C- ion implanted tube accelerated nerve regeneration, and this effect was enhanced by bFGF. Silicone treated with C- ions showed increased hydrophilic properties and cellular affinity, and axon regeneration was promoted with this increased biocompatibility.

  15. Methylprednisolone microsphere sustained-release membrane inhibits scar formation at the site of peripheral nerve lesion.

    PubMed

    Li, Qiang; Li, Teng; Cao, Xiang-Chang; Luo, De-Qing; Lian, Ke-Jian

    2016-05-01

    Corticosteroids are widely used for the treatment of acute central nervous system injury. However, their bioactivity is limited by their short half-life. Sustained release of glucocorticoids can prolong their efficacy and inhibit scar formation at the site of nerve injury. In the present study, we wrapped the anastomotic ends of the rat sciatic nerve with a methylprednisolone sustained-release membrane. Compared with methylprednisone alone or methylprednisone microspheres, the methylprednisolone microsphere sustained-release membrane reduced tissue adhesion and inhibited scar tissue formation at the site of anastomosis. It also increased sciatic nerve function index and the thickness of the myelin sheath. Our findings show that the methylprednisolone microsphere sustained-release membrane effectively inhibits scar formation at the site of anastomosis of the peripheral nerve, thereby promoting nerve regeneration. PMID:27335571

  16. Methylprednisolone microsphere sustained-release membrane inhibits scar formation at the site of peripheral nerve lesion

    PubMed Central

    Li, Qiang; Li, Teng; Cao, Xiang-chang; Luo, De-qing; Lian, Ke-jian

    2016-01-01

    Corticosteroids are widely used for the treatment of acute central nervous system injury. However, their bioactivity is limited by their short half-life. Sustained release of glucocorticoids can prolong their efficacy and inhibit scar formation at the site of nerve injury. In the present study, we wrapped the anastomotic ends of the rat sciatic nerve with a methylprednisolone sustained-release membrane. Compared with methylprednisone alone or methylprednisone microspheres, the methylprednisolone microsphere sustained-release membrane reduced tissue adhesion and inhibited scar tissue formation at the site of anastomosis. It also increased sciatic nerve function index and the thickness of the myelin sheath. Our findings show that the methylprednisolone microsphere sustained-release membrane effectively inhibits scar formation at the site of anastomosis of the peripheral nerve, thereby promoting nerve regeneration. PMID:27335571

  17. Design of barrier coatings on kink-resistant peripheral nerve conduits.

    PubMed

    Clements, Basak Acan; Bushman, Jared; Murthy, N Sanjeeva; Ezra, Mindy; Pastore, Christopher M; Kohn, Joachim

    2016-01-01

    Here, we report on the design of braided peripheral nerve conduits with barrier coatings. Braiding of extruded polymer fibers generates nerve conduits with excellent mechanical properties, high flexibility, and significant kink-resistance. However, braiding also results in variable levels of porosity in the conduit wall, which can lead to the infiltration of fibrous tissue into the interior of the conduit. This problem can be controlled by the application of secondary barrier coatings. Using a critical size defect in a rat sciatic nerve model, the importance of controlling the porosity of the nerve conduit walls was explored. Braided conduits without barrier coatings allowed cellular infiltration that limited nerve recovery. Several types of secondary barrier coatings were tested in animal studies, including (1) electrospinning a layer of polymer fibers onto the surface of the conduit and (2) coating the conduit with a cross-linked hyaluronic acid-based hydrogel. Sixteen weeks after implantation, hyaluronic acid-coated conduits had higher axonal density, displayed higher muscle weight, and better electrophysiological signal recovery than uncoated conduits or conduits having an electrospun layer of polymer fibers. This study indicates that braiding is a promising method of fabrication to improve the mechanical properties of peripheral nerve conduits and demonstrates the need to control the porosity of the conduit wall to optimize functional nerve recovery. PMID:26977288

  18. Histological Study of Bone Marrow and Umbilical Cord Stromal Cell Transplantation in Regenerating Rat Peripheral Nerve

    PubMed Central

    Zarbakhsh, Sam; Goudarzi, Nasim; Shirmohammadi, Maryam; Safari, Manouchehr

    2016-01-01

    Objective Bone marrow and umbilical cord stromal cells are multipotential stem cells that have the ability to produce growth factors that play an important role in survival and generation of axons. The goal of this study was to evaluate the effects of the two different mesenchymal stem cells on peripheral nerve regeneration. Materials and Methods In this experimental study, a 10 mm segment of the left sciatic nerve of male Wistar rats (250-300 g) was removed with a silicone tube interposed into this nerve gap. Bone marrow stromal cells (BMSCs) and human umbilical cord stromal cells (HUCSCs) were respectively obtained from rat and human. The cells were sepa- rately cultured and transplanted into the nerve gap. The sciatic nerve regeneration was evaluated by immunohistochemistry, and light and electron microscopy. Moreover, histo- morphology of the gastrocnemius muscle was observed. Results The nerve regeneration in the BMSCs and HUCSCs groups that had received the stem cells was significantly more favorable than the control group. In addition, the BM- SCs group was significantly more favorable than the HUCSCs group (P<0.05). Conclusion The results of this study suggest that both homograft BMSCs and het- erograft HUCSCs may have the potential to regenerate peripheral nerve injury and transplantation of BMSCs may be more effective than HUCSCs in rat. PMID:26862526

  19. Design of barrier coatings on kink-resistant peripheral nerve conduits

    PubMed Central

    Clements, Basak Acan; Bushman, Jared; Murthy, N Sanjeeva; Ezra, Mindy; Pastore, Christopher M; Kohn, Joachim

    2016-01-01

    Here, we report on the design of braided peripheral nerve conduits with barrier coatings. Braiding of extruded polymer fibers generates nerve conduits with excellent mechanical properties, high flexibility, and significant kink-resistance. However, braiding also results in variable levels of porosity in the conduit wall, which can lead to the infiltration of fibrous tissue into the interior of the conduit. This problem can be controlled by the application of secondary barrier coatings. Using a critical size defect in a rat sciatic nerve model, the importance of controlling the porosity of the nerve conduit walls was explored. Braided conduits without barrier coatings allowed cellular infiltration that limited nerve recovery. Several types of secondary barrier coatings were tested in animal studies, including (1) electrospinning a layer of polymer fibers onto the surface of the conduit and (2) coating the conduit with a cross-linked hyaluronic acid-based hydrogel. Sixteen weeks after implantation, hyaluronic acid-coated conduits had higher axonal density, displayed higher muscle weight, and better electrophysiological signal recovery than uncoated conduits or conduits having an electrospun layer of polymer fibers. This study indicates that braiding is a promising method of fabrication to improve the mechanical properties of peripheral nerve conduits and demonstrates the need to control the porosity of the conduit wall to optimize functional nerve recovery. PMID:26977288

  20. Polyethylene glycol fusion repair prevents reinnervation accuracy in rat peripheral nerve.

    PubMed

    Robinson, Grant A; Madison, Roger D

    2016-07-01

    Functional recovery following a peripheral nerve injury is made easier when regenerating axons correctly reinnervate their original targets. Polyethylene glycol (PEG) has recently been used in attempts to fuse severed peripheral axons during suture-based repair, but an analysis of target selectivity following such repair has not been undertaken. The rat femoral nerve (in which muscle and cutaneous pathways comingle proximally but segregate distally into separate terminal nerve branches) is a convenient in vivo model for assessing motor neuron regeneration accuracy. The present study uses retrograde labeling of motor neurons to compare reinnervation accuracy after suture-based nerve repair with and without PEG fusion. The results show that adding PEG to the suture repair site blocked the preference of motor neurons to reinnervate correctly the distal terminal nerve branch to muscle that was seen with suture repair. Retrograde transport and diffusion studies also determined that PEG fusion allowed passage of probes across the repair site, as has previously been seen, but did not result in motor neuron labeling in the spinal cord. The results suggest that PEG fusion disrupts the beneficial trophic influence of muscle on motor neuron reinnervation accuracy normally seen after suture repair and that such fusion-based approaches may be best suited to nerve injuries in which accurate target reinnervation at the terminal nerve branch level is not a priority. © 2016 Wiley Periodicals, Inc. PMID:26994857

  1. Peripheral Nerve Regeneration Through Hydrogel-Enriched Chitosan Conduits Containing Engineered Schwann Cells for Drug Delivery.

    PubMed

    Meyer, Cora; Wrobel, Sandra; Raimondo, Stefania; Rochkind, Shimon; Heimann, Claudia; Shahar, Abraham; Ziv-Polat, Ofra; Geuna, Stefano; Grothe, Claudia; Haastert-Talini, Kirsten

    2016-01-01

    Critical length nerve defects in the rat sciatic nerve model were reconstructed with chitosan nerve guides filled with Schwann cells (SCs) containing hydrogel. The transplanted SCs were naive or had been genetically modified to overexpress neurotrophic factors, thus providing a cellular neurotrophic factor delivery system. Prior to the assessment in vivo, in vitro studies evaluating the properties of engineered SCs overexpressing glial cell line-derived neurotrophic factor (GDNF) or fibroblast growth factor 2 (FGF-2(18kDa)) demonstrated their neurite outgrowth inductive bioactivity for sympathetic PC-12 cells as well as for dissociated dorsal root ganglion cell drop cultures. SCs within NVR-hydrogel, which is mainly composed of hyaluronic acid and laminin, were delivered into the lumen of chitosan hollow conduits with a 5% degree of acetylation. The viability and neurotrophic factor production by engineered SCs within NVR-Gel inside the chitosan nerve guides was further demonstrated in vitro. In vivo we studied the outcome of peripheral nerve regeneration after reconstruction of 15-mm nerve gaps with either chitosan/NVR-Gel/SCs composite nerve guides or autologous nerve grafts (ANGs). While ANGs did guarantee for functional sensory and motor regeneration in 100% of the animals, delivery of NVR-Gel into the chitosan nerve guides obviously impaired sufficient axonal outgrowth. This obstacle was overcome to a remarkable extent when the NVR-Gel was enriched with FGF-2(18kDa) overexpressing SCs. PMID:25876520

  2. Peripheral nerve repair using a poly(organo)phosphazene tubular prosthesis.

    PubMed

    Langone, F; Lora, S; Veronese, F M; Caliceti, P; Parnigotto, P P; Valenti, F; Palma, G

    1995-03-01

    Nerve regeneration experiments were carried out using tubular nerve guides of poly[(ethylalanato)1.4(imidazolyl)0.6phosphazene] (PEIP). By means of in vivo tests, this polymer was found to be biodegradable and transformed into harmless products. The tubular nerve guides were prepared by deposition of the dissolved polymer on a glass capillary tube, followed by evaporation of the solvent (methylene dichloride). After transectioning, rat sciatic nerve stumps were immediately sutured into the ends of 10-mm-long polymer tubes. On removal of the prosthesis, after implantation for 45 d, a tissue cable was found bridging the nerve stumps in all cases. Histological analysis revealed that the tissue cable was essentially composed of a regenerated nerve fibre bundle. A parallel series of experiments was undertaken to compare the use of silicone tubes that are not biodegradable and are most frequently used for studies of nerve regeneration with tubulization techniques. The advantages of biodegradable PEIP tubular nerve guides used for peripheral nerve repair are discussed. PMID:7662819

  3. Mobility-Related Consequences of Reduced Lower-Extremity Peripheral Nerve Function with Age: A Systematic Review

    PubMed Central

    Ward, Rachel E.; Caserotti, Paolo; Cauley, Jane A.; Boudreau, Robert M.; Goodpaster, Bret H.; Vinik, Aaron I.; Newman, Anne B.; Strotmeyer, Elsa S.

    2016-01-01

    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 articles were identified, including 6 cross-sectional and 2 longitudinal studies. These articles investigated 6 elderly cohorts (4 from the U.S. and 2 from Italy): 3 community-dwelling (including 1 with only disabled women and 1 without mobility limitations at baseline), 1 with both community-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); and a combination of both sensory measures and motor nerve conduction (n=3). Each study found that worse peripheral nerve function was related to poor mobility, although relationships varied based on the nerve function measure and mobility domain assessed. Six studies found that the association between nerve function and mobility persisted despite adjustment for diabetes. Evidence suggests that peripheral nerve function impairment at various levels of severity is related to poor mobility independent of diabetes. Relationships varied depending on peripheral nerve measure, which may be particularly important when investigating specific biological mechanisms. Future research needs to identify risk factors for peripheral nerve decline beyond diabetes, especially those

  4. Mobility-Related Consequences of Reduced Lower-Extremity Peripheral Nerve Function with Age: A Systematic Review.

    PubMed

    Ward, Rachel E; Caserotti, Paolo; Cauley, Jane A; Boudreau, Robert M; Goodpaster, Bret H; Vinik, Aaron I; Newman, Anne B; Strotmeyer, Elsa S

    2016-08-01

    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 articles were identified, including 6 cross-sectional and 2 longitudinal studies. These articles investigated 6 elderly cohorts (4 from the U.S. and 2 from Italy): 3 community-dwelling (including 1 with only disabled women and 1 without mobility limitations at baseline), 1 with both community-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); and a combination of both sensory measures and motor nerve conduction (n=3). Each study found that worse peripheral nerve function was related to poor mobility, although relationships varied based on the nerve function measure and mobility domain assessed. Six studies found that the association between nerve function and mobility persisted despite adjustment for diabetes. Evidence suggests that peripheral nerve function impairment at various levels of severity is related to poor mobility independent of diabetes. Relationships varied depending on peripheral nerve measure, which may be particularly important when investigating specific biological mechanisms. Future research needs to identify risk factors for peripheral nerve decline beyond diabetes, especially those

  5. Electrical stimulation accelerates axonal and functional peripheral nerve regeneration across long gaps.

    PubMed

    Haastert-Talini, Kirsten; Schmitte, Ruth; Korte, Nele; Klode, Dorothee; Ratzka, Andreas; Grothe, Claudia

    2011-04-01

    Short-term low-frequency electrical stimulation (ESTIM) of proximal peripheral nerve stumps prior to end-to-end coaptation or tubular bridging of small distances has been reported to increase preferential motor reinnervation and functional motor recovery in animal models and human patients undergoing carpal tunnel release surgery. We investigated the effects of ESTIM on regeneration across rat sciatic nerve gaps, which exceed distances that allow spontaneous regeneration. Three different reconstruction approaches were combined with ESTIM in the experimental groups. Nerve gaps (13 mm) were bridged using (I) nerve autotransplantation, (II) transplantation of differentially filled silicone tubes, or (III) transplantation of tubular grafts containing fibroblast growth factor-2 overexpressing Schwann cells (SCs) for gene therapy. The regeneration outcome was followed for up to 8 weeks, and functionally as well as histomorphometrically analyzed in comparison to non-stimulated control groups. Combining ESTIM with nerve autotransplantation significantly increased the nerve fiber density in the regenerated nerve, and the grade of functional recovery as detected by electrodiagnostic recordings from the gastrocnemius muscle. The combination of ESTIM with transplantation of naïve SCs increased the regeneration of gap-bridging nerve tissue. Although macroscopic tissue regeneration was not further improved after combining ESTIM with FGF-2(21/23-kD) gene therapy, the latter resulted in a high rate of regenerated nerves that functionally reconnected to the target muscle. Based on our results, brief ESTIM shows high potential to accelerate axonal as well as functional (motor and sensory) outcomes in the clinical setting of peripheral nerve gap reconstruction in human patients. PMID:21265597

  6. A Biosynthetic Nerve Guide Conduit Based on Silk/SWNT/Fibronectin Nanocomposite for Peripheral Nerve Regeneration

    PubMed Central

    Mottaghitalab, Fatemeh; Farokhi, Mehdi; Zaminy, Arash; Kokabi, Mehrdad; Soleimani, Masoud; Mirahmadi, Fereshteh

    2013-01-01

    As a contribution to the functionality of nerve guide conduits (NGCs) in nerve tissue engineering, here we report a conduit processing technique through introduction and evaluation of topographical, physical and chemical cues. Porous structure of NGCs based on freeze-dried silk/single walled carbon nanotubes (SF/SWNTs) has shown a uniform chemical and physical structure with suitable electrical conductivity. Moreover, fibronectin (FN) containing nanofibers within the structure of SF/SWNT conduits produced through electrospinning process have shown aligned fashion with appropriate porosity and diameter. Moreover, fibronectin remained its bioactivity and influenced the adhesion and growth of U373 cell lines. The conduits were then implanted to 10 mm left sciatic nerve defects in rats. The histological assessment has shown that nerve regeneration has taken places in proximal region of implanted nerve after 5 weeks following surgery. Furthermore, nerve conduction velocities (NCV) and more myelinated axons were observed in SF/SWNT and SF/SWNT/FN groups after 5 weeks post implantation, indicating a functional recovery for the injured nerves. With immunohistochemistry, the higher S-100 expression of Schwann cells in SF/SWNT/FN conduits in comparison to other groups was confirmed. In conclusion, an oriented conduit of biocompatible SF/SWNT/FN has been fabricated with acceptable structure that is particularly applicable in nerve grafts. PMID:24098649

  7. Interfaces with the peripheral nerve for the control of neuroprostheses.

    PubMed

    del Valle, Jaume; Navarro, Xavier

    2013-01-01

    Nervous system injuries lead to loss of control of sensory, motor, and autonomic functions of the affected areas of the body. Provided the high amount of people worldwide suffering from these injuries and the impact on their everyday life, numerous and different neuroprostheses and hybrid bionic systems have been developed to restore or partially mimic the lost functions. A key point for usable neuroprostheses is the electrode that interfaces the nervous system and translates not only motor orders into electrical outputs that activate the prosthesis but is also able to transform sensory information detected by the machine into signals that are transmitted to the central nervous system. Nerve electrodes have been classified with regard to their invasiveness in extraneural, intraneural, and regenerative. The more invasive is the implant the more selectivity of interfacing can be reached. However, boosting invasiveness and selectivity may also heighten nerve damage. This chapter provides a general overview of nerve electrodes as well as the state-of-the-art of their biomedical applications in neuroprosthetic systems. PMID:24093606

  8. 3D-engineering of Cellularized Conduits for Peripheral Nerve Regeneration.

    PubMed

    Hu, Yu; Wu, Yao; Gou, Zhiyuan; Tao, Jie; Zhang, Jiumeng; Liu, Qianqi; Kang, Tianyi; Jiang, Shu; Huang, Siqing; He, Jiankang; Chen, Shaochen; Du, Yanan; Gou, Maling

    2016-01-01

    Tissue engineered conduits have great promise for bridging peripheral nerve defects by providing physical guiding and biological cues. A flexible method for integrating support cells into a conduit with desired architectures is wanted. Here, a 3D-printing technology is adopted to prepare a bio-conduit with designer structures for peripheral nerve regeneration. This bio-conduit is consisted of a cryopolymerized gelatin methacryloyl (cryoGelMA) gel cellularized with adipose-derived stem cells (ASCs). By modeling using 3D-printed "lock and key" moulds, the cryoGelMA gel is structured into conduits with different geometries, such as the designed multichannel or bifurcating and the personalized structures. The cryoGelMA conduit is degradable and could be completely degraded in 2-4 months in vivo. The cryoGelMA scaffold supports the attachment, proliferation and survival of the seeded ASCs, and up-regulates the expression of their neurotrophic factors mRNA in vitro. After implanted in a rat model, the bio-conduit is capable of supporting the re-innervation across a 10 mm sciatic nerve gap, with results close to that of the autografts in terms of functional and histological assessments. The study describes an indirect 3D-printing technology for fabricating cellularized designer conduits for peripheral nerve regeneration, and could lead to the development of future nerve bio-conduits for clinical use. PMID:27572698

  9. 3D-engineering of Cellularized Conduits for Peripheral Nerve Regeneration

    PubMed Central

    Hu, Yu; Wu, Yao; Gou, Zhiyuan; Tao, Jie; Zhang, Jiumeng; Liu, Qianqi; Kang, Tianyi; Jiang, Shu; Huang, Siqing; He, Jiankang; Chen, Shaochen; Du, Yanan; Gou, Maling

    2016-01-01

    Tissue engineered conduits have great promise for bridging peripheral nerve defects by providing physical guiding and biological cues. A flexible method for integrating support cells into a conduit with desired architectures is wanted. Here, a 3D-printing technology is adopted to prepare a bio-conduit with designer structures for peripheral nerve regeneration. This bio-conduit is consisted of a cryopolymerized gelatin methacryloyl (cryoGelMA) gel cellularized with adipose-derived stem cells (ASCs). By modeling using 3D-printed “lock and key” moulds, the cryoGelMA gel is structured into conduits with different geometries, such as the designed multichannel or bifurcating and the personalized structures. The cryoGelMA conduit is degradable and could be completely degraded in 2-4 months in vivo. The cryoGelMA scaffold supports the attachment, proliferation and survival of the seeded ASCs, and up-regulates the expression of their neurotrophic factors mRNA in vitro. After implanted in a rat model, the bio-conduit is capable of supporting the re-innervation across a 10 mm sciatic nerve gap, with results close to that of the autografts in terms of functional and histological assessments. The study describes an indirect 3D-printing technology for fabricating cellularized designer conduits for peripheral nerve regeneration, and could lead to the development of future nerve bio-conduits for clinical use. PMID:27572698

  10. Peripheral nerve blocks as the sole anesthetic technique in a patient with severe Duchenne muscular dystrophy.

    PubMed

    Bang, Seung Uk; Kim, Yee Suk; Kwon, Woo Jin; Lee, Sang Mook; Kim, Soo Hyang

    2016-04-01

    General anesthesia and central neuraxial blockades in patients with severe Duchenne muscular dystrophy are associated with high risks of complications, including rhabdomyolysis, malignant hyperthermia, hemodynamic instability, and postoperative mechanical ventilation. Here, we describe peripheral nerve blocks as a safe approach to anesthesia in a patient with severe Duchenne muscular dystrophy who was scheduled to undergo surgery. A 22-year-old male patient was scheduled to undergo reduction and internal fixation of a left distal femur fracture. He had been diagnosed with Duchenne muscular dystrophy at 5 years of age, and had no locomotive capability except for that of the finger flexors and toe extensors. He had developed symptoms associated with dyspnea 5 years before and required intermittent ventilation. We blocked the femoral nerve, lateral femoral cutaneous nerve, and parasacral plexus under ultrasound on the left leg. The patient underwent a successful operation using peripheral nerve blocks with no complications. In conclusion general anesthesia and central neuraxial blockades in patients with severe Duchenne muscular dystrophy are unsafe approaches to anesthesia because of hemodynamic instability and respiratory depression. Peripheral nerve blocks are the best way to reduce the risks of critical complications, and are a safe and feasible approach to anesthesia in patients with severe Duchenne muscular dystrophy. PMID:26721827

  11. Regulation of Peripheral Nerve Myelin Maintenance by Gene Repression through Polycomb Repressive Complex 2.

    PubMed

    Ma, Ki H; Hung, Holly A; Srinivasan, Rajini; Xie, Huafeng; Orkin, Stuart H; Svaren, John

    2015-06-01

    Myelination of peripheral nerves by Schwann cells requires coordinate regulation of gene repression as well as gene activation. Several chromatin remodeling pathways critical for peripheral nerve myelination have been identified, but the functions of histone methylation in the peripheral nerve have not been elucidated. To determine the role of histone H3 Lys27 methylation, we have generated mice with a Schwann cell-specific knock-out of Eed, which is an essential subunit of the polycomb repressive complex 2 (PRC2) that catalyzes methylation of histone H3 Lys27. Analysis of this mutant revealed no significant effects on early postnatal development of myelin. However, its loss eventually causes progressive hypermyelination of small-diameter axons and apparent fragmentation of Remak bundles. These data identify the PRC2 complex as an epigenomic modulator of mature myelin thickness, which is associated with changes in Akt phosphorylation. Interestingly, we found that Eed inactivation causes derepression of several genes, e.g., Sonic hedgehog (Shh) and Insulin-like growth factor-binding protein 2 (Igfbp2), that become activated after nerve injury, but without activation of a primary regulator of the injury program, c-Jun. Analysis of the activated genes in cultured Schwann cells showed that Igfbp2 regulates Akt activation. Our results identify an epigenomic pathway required for establishing thickness of mature myelin and repressing genes that respond to nerve injury. PMID:26041929

  12. Augmenting peripheral nerve regeneration using stem cells: A review of current opinion

    PubMed Central

    Fairbairn, Neil G; Meppelink, Amanda M; Ng-Glazier, Joanna; Randolph, Mark A; Winograd, Jonathan M

    2015-01-01

    Outcomes following peripheral nerve injury remain frustratingly poor. The reasons for this are multifactorial, although maintaining a growth permissive environment in the distal nerve stump following repair is arguably the most important. The optimal environment for axonal regeneration relies on the synthesis and release of many biochemical mediators that are temporally and spatially regulated with a high level of incompletely understood complexity. The Schwann cell (SC) has emerged as a key player in this process. Prolonged periods of distal nerve stump denervation, characteristic of large gaps and proximal injuries, have been associated with a reduction in SC number and ability to support regenerating axons. Cell based therapy offers a potential therapy for the improvement of outcomes following peripheral nerve reconstruction. Stem cells have the potential to increase the number of SCs and prolong their ability to support regeneration. They may also have the ability to rescue and replenish populations of chromatolytic and apoptotic neurons following axotomy. Finally, they can be used in non-physiologic ways to preserve injured tissues such as denervated muscle while neuronal ingrowth has not yet occurred. Aside from stem cell type, careful consideration must be given to differentiation status, how stem cells are supported following transplantation and how they will be delivered to the site of injury. It is the aim of this article to review current opinions on the strategies of stem cell based therapy for the augmentation of peripheral nerve regeneration. PMID:25621102

  13. Interest of Electrostimulation of Peripheral Motor Nerves during Percutaneous Thermal Ablation

    SciTech Connect

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

    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.

  14. [Physiological approach to peripheral neuropathy. Conventional nerve conduction studies and magnetic motor root stimulation].

    PubMed

    Ugawa, Yoshikazu

    2004-11-01

    In this communication, I first show some points we should mind in the conventional peripheral nerve conduction studies and later present clinical usefulness of motor root stimulation for peripheral neuropathy. CONVENTIONAL NERVE CONDUCTION STUDIES (NCS): The most important point revealed by the conventional NCSs is whether neuropathy is due to axonal degeneration or demyelinating process. Precise clinical examination with this neurophysiological information leads us to a diagnosis and treatment. Poor clinical examination makes these findings useless. Long standing axonal degeneration sometimes induces secondary demyelination at the most distal part of involved nerves. On the other hand, severe segmental demyelination often provokes secondary axonal degeneration at distal parts to the site of demyelination. These secondary changes show the same abnormal neurophysiological findings as those of the primary involvement. We should be careful of this possibility when interpreting the results of NCS. NCS of sensory nerves is not good at revealing demyelinating process. Mild temporal dispersion of potentials often reduces an amplitude of SNAP or loss of responses, which usually suggests axonal degeneration, because of short duration of sensory nerve potentials. MOTOR ROOT STIMULATION IN PERIPHERAL NEUROPATHY: Magnetic stimulation with a coil placed over the spine activates motor roots and evokes EMG responses from upper and lower limb muscles. The site of activation with this method was determined to be where the motor roots exit from the spinal canal (intervertebral foramina) (J Neurol Neurosurg Psychiatry 52 (9): 1025-1032, 1989) because induced currents are very dense at such a foramen made by electric resistant bones. In several kinds of peripheral neuropathy, this method has been used to detect a lesion at a proximal part of the peripheral nerves which can not be detected by the conventional NCSs. I present a few cases in whom motor root stimulation had a clinical

  15. Ginkgo biloba extract (EGb 761) promotes peripheral nerve regeneration and neovascularization after acellular nerve allografts in a rat model.

    PubMed

    Zhu, Zhaowei; Zhou, Xiang; He, Bo; Dai, Ting; Zheng, Canbin; Yang, Chuang; Zhu, Shuang; Zhu, Jiakai; Zhu, Qingtang; Liu, Xiaolin

    2015-03-01

    This study aimed to investigate whether or not ginkgo biloba extract (EGb 761) enhances peripheral nerve regeneration and vascularization after repair using acellular nerve allografts (ANA). Seventy-two Sprague-Dawley rats were randomly divided into three experimental groups: a unilateral 15-mm sciatic nerve defect was created and repaired with an autologous graft (autograft group); the same defect was repaired with an 18 mm ANA with an i.p. injection of normal saline for 10 days (saline group); and in the final group, the same defect was repaired with an 18 mm ANA with an i.p. injection of EGb 761 for 10 days (EGb 761 group). Axon outgrowth and vascularization were evaluated by immunocytochemistry 14 days post-implantation. The expression of genes associated with angiogenesis was analyzed by real-time polymerase chain reaction (PCR) seven days post-implantation. Compared with the saline group, rats in the EGb 761 group significantly increased the number of myelinated fibers and the average diameter of the nerves within the graft. There is no significant difference between the EGb 761 group and the autograft group. The expression of CD34 and NF200 was significantly higher in the EGb 761 group than in the saline group. Additionally, EGb 761 treatment increased the expression of several angiogenesis-related genes, including Vegf, SOX18, Prom 1, and IL-6. In conclusion, ANA repair with EGb 761 treatment demonstrates effects on peripheral nerve regeneration and vascularization that are equal to those of autologous graft repair, and that are superior to ANA repair alone. PMID:25319407

  16. Factors predicting sensory and motor recovery after the repair of upper limb peripheral nerve injuries

    PubMed Central

    He, Bo; Zhu, Zhaowei; Zhu, Qingtang; Zhou, Xiang; Zheng, Canbin; Li, Pengliang; Zhu, Shuang; Liu, Xiaolin; Zhu, Jiakai

    2014-01-01

    OBJECTIVE: To investigate the factors associated with sensory and motor recovery after the repair of upper limb peripheral nerve injuries. DATA SOURCES: The online PubMed database was searched for English articles describing outcomes after the repair of median, ulnar, radial, and digital nerve injuries in humans with a publication date between 1 January 1990 and 16 February 2011. STUDY SELECTION: The following types of article were selected: (1) clinical trials describing the repair of median, ulnar, radial, and digital nerve injuries published in English; and (2) studies that reported sufficient patient information, including age, mechanism of injury, nerve injured, injury location, defect length, repair time, repair method, and repair materials. SPSS 13.0 software was used to perform univariate and multivariate logistic regression analyses and to investigate the patient and intervention factors associated with outcomes. MAIN OUTCOME MEASURES: Sensory function was assessed using the Mackinnon-Dellon scale and motor function was assessed using the manual muscle test. Satisfactory motor recovery was defined as grade M4 or M5, and satisfactory sensory recovery was defined as grade S3+ or S4. RESULTS: Seventy-one articles were included in this study. Univariate and multivariate logistic regression analyses showed that repair time, repair materials, and nerve injured were independent predictors of outcome after the repair of nerve injuries (P < 0.05), and that the nerve injured was the main factor affecting the rate of good to excellent recovery. CONCLUSION: Predictors of outcome after the repair of peripheral nerve injuries include age, gender, repair time, repair materials, nerve injured, defect length, and duration of follow-up. PMID:25206870

  17. Inhibition of Peripheral Nerve Scarring by Calcium Antagonists, Also Known as Calcium Channel Blockers.

    PubMed

    Xue, Jin-Wei; Jiao, Jian-Bao; Liu, Xiao-Feng; Jiang, Yuan-Tao; Yang, Guang; Li, Chun-Yu; Yin, Wei-Tian; Ling, Li

    2016-05-01

    The aim of this research was to investigate the impact of calcium channel blockers (verapamil) on the formation of scars in the sciatic nerve anastomosis after peripheral nerve injury. One hundred twenty healthy, male Sprague-Dawley rats were selected and prepared with right sciatic nerve injury for this study. Samples were selected at the fourth and 12th weeks, respectively, after treatment and observations were made on the nerve anastomosis healing and diameter. Image analysis and statistical processing were carried out relating to the results of the study. The diameter of the anastomosis of the treatment group at weeks 4 and 12 was noticeably smaller than the control group (P < 0.05). In the treatment group at week 4, there were many vesicles observed in the fibroblasts' cytosol and in the control group, the fibroblasts exhibited high number of rough endoplasmic reticulum. The collagen content of the nerve scarring at week 12 in the treatment group was apparently less than the control group (P < 0.01). The calcium channel blocker (verapamil) reduced the axon resistance through the anastomosis during nerve regeneration. It can effectively inhibit the formation of scarring from nerve injury. It also provided an excellent microenvironment for the regeneration of nerve fibers. PMID:26488333

  18. Myelinated sensory and alpha motor axon regeneration in peripheral nerve neuromas

    NASA Technical Reports Server (NTRS)

    Macias, M. Y.; Lehman, C. T.; Sanger, J. R.; Riley, D. A.

    1998-01-01

    Histochemical staining for carbonic anhydrase and cholinesterase (CE) activities was used to analyze sensory and motor axon regeneration, respectively, during neuroma formation in transected and tube-encapsulated peripheral nerves. Median-ulnar and sciatic nerves in the rodent model permitted testing whether a 4 cm greater distance of the motor neuron soma from axotomy site or intrinsic differences between motor and sensory neurons influenced regeneration and neuroma formation 10, 30, and 90 days later. Ventral root radiculotomy confirmed that CE-stained axons were 97% alpha motor axons. Distance significantly delayed axon regeneration. When distance was negligible, sensory axons grew out sooner than motor axons, but motor axons regenerated to a greater quantity. These results indicate regeneration differences between axon subtypes and suggest more extensive branching of motor axons within the neuroma. Thus, both distance from injury site to soma and inherent motor and sensory differences should be considered in peripheral nerve repair strategies.

  19. Treatment of Peripheral Neuropathy in Leprosy: The Case for Nerve Decompression

    PubMed Central

    Wan, Eric L.; Rivadeneira, Andres F.; Jouvin, Renato Martinez

    2016-01-01

    Summary: Plastic surgery has a tradition of caring for patients with facial deformity and hand deformity related to leprosy. The approach, however, to the progressive deformity and disability related to chronic nerve compression is underappreciated in the world today. A cohort of patients with leprous neuropathy from an indigenous area of leprosy in Ecuador was evaluated for the presence of chronic peripheral nerve compression, and 12 patients were chosen for simultaneous upper and lower extremity, unilateral, nerve decompression at multiple levels along the course of each nerve. The results at 1 year of follow-up show that 6 patients improved into the excellent category and 4 patients improved into the good category for improved function. Based on the early results in this small cohort of patients with leprous neuropathy, an approach to peripheral nerve decompression, encompassing the concept of multiple crush at multiple levels of each nerve, seems to offer optimism to improve upper and lower extremity limb function. Long-term studies with quality-of-life outcomes would be welcome. PMID:27257567

  20. Recording sensory and motor information from peripheral nerves with Utah Slanted Electrode Arrays.

    PubMed

    Clark, Gregory A; Ledbetter, Noah M; Warren, David J; Harrison, Reid R

    2011-01-01

    Recording and stimulation via high-count penetrating microelectrode arrays implanted in peripheral nerves may help restore precise motor and sensory function after nervous system damage or disease. Although previous work has demonstrated safety and relatively successful stimulation for long-term implants of 100-electrode Utah Slanted Electrode Arrays (USEAs) in feline sciatic nerve [1], two major remaining challenges were 1) to maintain viable recordings of nerve action potentials long-term, and 2) to overcome contamination of unit recordings by myoelectric (EMG) activity in awake, moving animals. In conjunction with improvements to USEAs themselves, we have redesigned several aspects of our USEA containment and connector systems. Although further increases in unit yield and long-term stability remain desirable, here we report considerable progress toward meeting both of these goals: We have successfully recorded unit activity from USEAs implanted intrafascicularly in sciatic nerve for periods up to 4 months (the terminal experimental time point), and we have developed a containment system that effectively eliminates or substantially reduces EMG contamination of unit recordings in the moving animal. In addition, we used a 100-channel wireless recording integrated circuit attached to implanted USEAs to transmit broadband or spike-threshold data from nerve. Neural data thusly obtained during imposed limb movements were decoded blindly to drive a virtual prosthetic limb in real time. These results support the possibility of using USEAs in peripheral nerves to provide motor control and cutaneous or proprioceptive sensory feedback in individuals after limb loss or spinal cord injury. PMID:22255372

  1. Real time imaging of peripheral nerve vasculature using optical coherence angiography

    NASA Astrophysics Data System (ADS)

    Vasudevan, Srikanth; Kumsa, Doe; Takmakov, Pavel; Welle, Cristin G.; Hammer, Daniel X.

    2016-03-01

    The peripheral nervous system (PNS) carries bidirectional information between the central nervous system and distal organs. PNS stimulation has been widely used in medical devices for therapeutic indications, such as bladder control and seizure cessation. Investigational uses of PNS stimulation include providing sensory feedback for improved control of prosthetic limbs. While nerve safety has been well documented for stimulation parameters used in marketed devices, novel PNS stimulation devices may require alternative stimulation paradigms to achieve maximum therapeutic benefit. Improved testing paradigms to assess the safety of stimulation will expedite the development process for novel PNS stimulation devices. The objective of this research is to assess peripheral nerve vascular changes in real-time with optical coherence angiography (OCA). A 1300-nm OCA system was used to image vasculature changes in the rat sciatic nerve in the region around a surface contacting single electrode. Nerves and vasculature were imaged without stimulation for 180 minutes to quantify resting blood vessel diameter. Walking track analysis was used to assess motor function before and 6 days following experiments. There was no significant change in vessel diameter between baseline and other time points in all animals. Motor function tests indicated the experiments did not impair functionality. We also evaluated the capabilities to image the nerve during electrical stimulation in a pilot study. Combining OCA with established nerve assessment methods can be used to study the effects of electrical stimulation safety on neural and vascular tissue in the periphery.

  2. Global analysis of transcriptome in dorsal root ganglia following peripheral nerve injury in rats.

    PubMed

    Gong, Leilei; Wu, Jiancheng; Zhou, Songlin; Wang, Yaxian; Qin, Jing; Yu, Bin; Gu, Xiaosong; Yao, Chun

    2016-09-01

    Peripheral nervous system has intrinsic regeneration ability after injury, accompanied with the coordination of numerous cells, molecules and signaling pathways. These post-injury biological changes are complex with insufficient understanding. Thus, to obtain a global perspective of changes following nerve injury and to elucidate the mechanisms underlying nerve regeneration are of great importance. By RNA sequencing, we detected transcriptional changes in dorsal root ganglia (DRG) neurons at 0 h, 3 h, 9 h, 1 d, 4 d and 7 d following sciatic nerve crush injury in rats. Differentially expressed genes were then selected and classified into major clusters according to their expression patterns. Cluster 2 (with genes high expressed before 9 h and then down expressed) and cluster 6 (combination of cluster 4 and 5 with genes low expressed before 1 d and then up expressed) were underwent GO annotation and KEGG pathway analysis. Gene act networks were then constructed for these two clusters and the expression of pivotal genes was validated by quantitative real-time PCR. This study provided valuable information regarding the transcriptome changes in DRG neurons following nerve injury, identified potential genes that could be used for improving axon regeneration after nerve injury, and facilitated to elucidate the biological process and molecular mechanisms underlying peripheral nerve injury. PMID:27450809

  3. Peripheral nerve stimulation for the treatment of postamputation pain--a case report.

    PubMed

    Rauck, Richard L; Kapural, Leonardo; Cohen, Steven P; North, James M; Gilmore, Christopher A; Zang, Rosemary H; Boggs, Joseph W

    2012-11-01

    Many amputees suffer from postamputation pain, which can be extremely debilitating, decrease quality of life, increase the risk of depression, and negatively affect interpersonal relationships and the ability to work. Present methods of treatment, including medications, are often unsatisfactory in reducing postamputation pain. Electrical stimulation of the nerve innervating the painful area could reduce the pain, but peripheral nerve stimulation is rarely used to treat postamputation pain because present methods require invasive surgical access and precise placement of the leads in close proximity (≤ 2 mm) with the nerve. The present study investigated a novel approach to peripheral nerve stimulation in which a lead was placed percutaneously a remote distance (> 1 cm) away from the femoral nerve in a patient with severe residual limb pain (RLP) 33 years following a below-knee amputation. Electrical stimulation generated ≥ 75% paresthesia coverage, reduced RLP by > 60%, and improved quality of life outcomes as measured by the pain interference scale of the Brief Pain Inventory-Short Form (100% reduction in pain interference), Pain Disability Index (74% reduction in disability), and the Patient Global Impression of Change (very much improved) during a 2-week home trial. There were no adverse events. The ability to generate significant paresthesia coverage and pain relief with a single lead inserted percutaneously and remotely from the target nerve holds promise for providing relief of postamputation pain. PMID:22548686

  4. Peripheral Nerve Stimulation for Treatment of Post-Amputation Pain – A Case Report

    PubMed Central

    Rauck, Richard L.; Kapural, Leonardo; Cohen, Steven P.; North, James M.; Gilmore, Christopher A.; Zang, Rosemary H.; Boggs, Joseph W.

    2012-01-01

    Many amputees suffer from post-amputation pain, which can be extremely debilitating, decrease quality of life, increase the risk of depression, and negatively affect interpersonal relationships and the ability to work. Present methods of treatment, including medications, are often unsatisfactory in reducing post-amputation pain. Electrical stimulation of the nerve innervating the painful area could reduce the pain, but peripheral nerve stimulation is rarely used to treat post-amputation pain because present methods require invasive surgical access and precise placement of the leads in close proximity (≤ 2 mm) with the nerve. The present study investigated a novel approach to peripheral nerve stimulation in which a lead was placed percutaneously a remote distance (> 1 cm) away from the femoral nerve in a patient with severe residual limb pain 33 years following a below-knee amputation. Electrical stimulation generated ≥ 75% paresthesia coverage, reduced residual limb pain by > 60%, and improved quality of life outcomes as measured by the pain interference scale of the Brief Pain Inventory-Short Form (100% reduction in pain interference), Pain Disability Index (74% reduction in disability), and the Patient Global Impression of Change (Very Much Improved) during a 2-week home trial. There were no adverse events. The ability to generate significant paresthesia coverage and pain relief with a single lead inserted percutaneously and remotely from the target nerve holds promise for providing relief of post-amputation pain. PMID:22548686

  5. Treatment of Peripheral Neuropathy in Leprosy: The Case for Nerve Decompression.

    PubMed

    Wan, Eric L; Rivadeneira, Andres F; Jouvin, Renato Martinez; Dellon, A Lee

    2016-03-01

    Plastic surgery has a tradition of caring for patients with facial deformity and hand deformity related to leprosy. The approach, however, to the progressive deformity and disability related to chronic nerve compression is underappreciated in the world today. A cohort of patients with leprous neuropathy from an indigenous area of leprosy in Ecuador was evaluated for the presence of chronic peripheral nerve compression, and 12 patients were chosen for simultaneous upper and lower extremity, unilateral, nerve decompression at multiple levels along the course of each nerve. The results at 1 year of follow-up show that 6 patients improved into the excellent category and 4 patients improved into the good category for improved function. Based on the early results in this small cohort of patients with leprous neuropathy, an approach to peripheral nerve decompression, encompassing the concept of multiple crush at multiple levels of each nerve, seems to offer optimism to improve upper and lower extremity limb function. Long-term studies with quality-of-life outcomes would be welcome. PMID:27257567

  6. Promotion of peripheral nerve regeneration of a peptide compound hydrogel scaffold

    PubMed Central

    Wei, Guo-Jun; Yao, Meng; Wang, Yan-Song; Zhou, Chang-Wei; Wan, De-Yu; Lei, Peng-Zhen; Wen, Jian; Lei, Hong-Wei; Dong, Da-Ming

    2013-01-01

    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 matrix to maintain the viability, morphology and proliferation of PC12 cells. Electrophysiology demonstrated that the use of the hydrogel scaffold (SF16 or collagen) resulted in a significant improvement in amplitude recovery in the in vivo model compared to physiological saline. Moreover, nerve cells in the SF16 hydrogel group displayed greater axon density, larger average axon diameter and

  7. Short-term peripheral nerve stimulation ameliorates axonal dysfunction after spinal cord injury

    PubMed Central

    Kiernan, Matthew C.; Macefield, Vaughan G.; Lee, Bonne B.; Lin, Cindy S.-Y.

    2015-01-01

    There is accumulating evidence that peripheral motor axons deteriorate following spinal cord injury (SCI). Secondary axonal dysfunction can exacerbate muscle atrophy, contribute to peripheral neuropathies and neuropathic pain, and lead to further functional impairment. In an attempt to ameliorate the adverse downstream effects that developed following SCI, we investigated the effects of a short-term peripheral nerve stimulation (PNS) program on motor axonal excitability in 22 SCI patients. Axonal excitability studies were undertaken in the median and common peroneal nerves (CPN) bilaterally before and after a 6-wk unilateral PNS program. PNS was delivered percutaneously over the median nerve at the wrist and CPN around the fibular head, and the compound muscle action potential (CMAP) from the abductor pollicis brevis and tibialis anterior was recorded. Stimulus intensity was above motor threshold, and pulses (450 μs) were delivered at 100 Hz with a 2-s on/off cycle for 30 min 5 days/wk. SCI patients had consistently high thresholds with a reduced CMAP consistent with axonal loss; in some patients the peripheral nerves were completely inexcitable. Nerve excitability studies revealed profound changes in membrane potential, with a “fanned-in” appearance in threshold electrotonus, consistent with membrane depolarization, and significantly reduced superexcitability during the recovery cycle. These membrane dysfunctions were ameliorated after 6 wk of PNS, which produced a significant hyperpolarizing effect. The contralateral, nonstimulated nerves remained depolarized. Short-term PNS reversed axonal dysfunction following SCI, may provide an opportunity to prevent chronic changes in axonal and muscular function, and may improve rehabilitation outcomes. PMID:25787956

  8. Stereological and somatotopic analysis of the spinal microglial response to peripheral nerve injury

    PubMed Central

    Beggs, Simon; Salter, Michael W.

    2016-01-01

    The involvement of glia, and glia-neuronal signalling in enhancing nociceptive transmission has become an area of intense scientific interest. In particular, a role has emerged for activated microglia in the development and maintenance of neuropathic pain following peripheral nerve injury. Following activation, spinal microglia proliferate and release many substances which are capable of modulating neuronal excitability within the spinal cord. Here, we the investigated the response of spinal microglia to a unilateral spared nerve injury (SNI) in terms of the quantitative increase in cell number and the spatial distribution of the increase. Design-based stereological techniques were combined with iba-1 immunohistochemistry to estimate the total number of microglia in the spinal dorsal horn in naïve and peripheral nerve-injured adult rats. In addition, by mapping the central terminals of hindlimb nerves, the somatotopic distribution of the microglial response was mapped. Following SNI there was a marked increase in the number of spinal microglia: The total number of microglia (mean ± SD) in the dorsal horn sciatic territory of the naïve rat was estimated to be 28,591 ± 2715. Following SNI the number of microglia was 82,034 ± 8828. While the pattern of microglial activation generally followed somatotopic boundaries, with the majority of microglia within the territory occupied by peripherally axotomised primary afferents, some spread was seen into regions occupied by intact, ‘spared’ central projections of the sural nerve. This study provides a reproducible method of assaying spinal microglial dynamics following peripheral nerve injury both quantitatively and spatially. PMID:17267172

  9. Oxidized galectin-1 stimulates macrophages to promote axonal regeneration in peripheral nerves after axotomy.

    PubMed

    Horie, Hidenori; Kadoya, Toshihiko; Hikawa, Naoshi; Sango, Kazunori; Inoue, Hiroko; Takeshita, Kaori; Asawa, Reiko; Hiroi, Tomoko; Sato, Manami; Yoshioka, Tohru; Ishikawa, Yoshihiro

    2004-02-25

    Various neurotrophic factors that promote axonal regeneration have been investigated in vivo, but the signals that prompt neurons to send out processes in peripheral nerves after axotomy are not well understood. Previously, we have shown oxidized galectin-1 (GAL-1/Ox) promotes initial axonal growth after axotomy in peripheral nerves. However, the mechanism by which GAL-1/Ox promotes axonal regeneration remains unclear and is the subject of the present study. To identify possible target cells of GAL-1/Ox, a fluorescently labeled recombinant human GAL-1/Ox (rhGAL-1/Ox) was incubated with DRG neurons, Schwann cells, and intraperitoneal macrophages from adult rats. Only the cell surfaces of intraperitoneal macrophages bound the rhGAL-1/Ox, suggesting that these cells possess a receptor for GAL-1/Ox. Experiments examining tyrosine phosphorylation revealed that rhGAL-1/Ox stimulated changes in signal transduction pathways in these macrophages. These changes caused macrophages to secrete an axonal growth-promoting factor. This was demonstrated when conditioned media of macrophages stimulated with rhGAL-1/Ox in 48 hr culture strongly enhanced axonal regeneration from transected-nerve sites of DRG explants. Furthermore, activated macrophage-conditioned media also improved Schwann cell migration from the transected-nerve sites. From these results, we propose that axonal regeneration occurs in axotomized peripheral nerves as a result of cytosolic reduced galectin-1 being released from Schwann cells and injured axons, which then becomes oxidized in the extracellular space. Oxidized galectin-1 then stimulates macrophages to secrete a factor that promotes axonal growth and Schwann cell migration, thus enhancing peripheral nerve regeneration. PMID:14985427

  10. Promoting plasticity in the spinal cord with chondroitinase improves functional recovery after peripheral nerve repair.

    PubMed

    Galtrey, Clare M; Asher, Richard A; Nothias, Fatiha; Fawcett, James W

    2007-04-01

    Functional recovery after peripheral nerve repair in humans is often disappointing. A major reason for this is the inaccuracy of re-innervation of muscles and sensory structures. We hypothesized that promoting plasticity in the spinal cord, through digestion of chondroitin sulphate proteoglycans (CSPGs) with chondroitinase ABC (ChABC), might allow the CNS to compensate for inaccurate peripheral re-innervation and improve functional recovery. The median and ulnar nerves were injured and repaired to produce three grades of inaccuracy of peripheral re-innervation by (i) crush of both nerves; (ii) correct repair of median to median and ulnar to ulnar; and (iii) crossover of the median and ulnar nerves. Mapping of the motor neuron pool of the flexor carpi radialis muscle showed precise re-innervation after nerve crush, inaccurate regeneration after correct repair, more inaccurate after crossover repair. Recovery of forelimb function, assessed by skilled paw reaching, grip strength and sensory testing varied with accuracy of re-innervation. This was not due to differences in the number of regenerated axons. Single injections of ChABC into the spinal cord led to long-term changes in the extracellular matrix, with hyaluronan and neurocan being removed and not fully replaced after 8 weeks. ChABC treatment produce increased sprouting visualized by MAP1BP staining and improved functional recovery in skilled paw reaching after correct repair and in grip strength after crossover repair. There was no hyperalgesia. Enhanced plasticity in the spinal cord, therefore, allows the CNS to compensate for inaccurate motor and sensory re-innervation of the periphery, and may be a useful adjunct therapy to peripheral nerve repair. PMID:17255150

  11. Insulin Pump Therapy Is Associated with Lower Rates of Retinopathy and Peripheral Nerve Abnormality

    PubMed Central

    Zabeen, Bedowra; Craig, Maria E.; Virk, Sohaib A.; Pryke, Alison; Chan, Albert K. F.; Cho, Yoon Hi; Benitez-Aguirre, Paul Z.; Hing, Stephen; Donaghue, Kim C.

    2016-01-01

    Objective To compare rates of microvascular complications in adolescents with type 1 diabetes treated with continuous subcutaneous insulin infusion (CSII) versus multiple daily injections (MDI). Research Design and Methods Prospective cohort of 989 patients (aged 12–20 years; diabetes duration >5 years) treated with CSII or MDI for >12 months. Microvascular complications were assessed from 2000–14: early retinopathy (seven-field fundal photography), peripheral nerve function (thermal and vibration threshold testing), autonomic nerve abnormality (heart rate variability analysis of electrocardiogram recordings) and albuminuria (albumin creatinine ratio/timed overnight albumin excretion). Generalized estimating equations (GEE) were used to examine the relationship between treatment and complications rates, adjusting for socio-economic status (SES) and known risk factors including HbA1c and diabetes duration. Results Comparing CSII with MDI: HbA1C was 8.6% [70mmol/mol] vs. 8.7% [72 mmol/mol]) (p = 0.7), retinopathy 17% vs. 22% (p = 0.06); microalbuminuria 1% vs. 4% (p = 0.07), peripheral nerve abnormality 27% vs. 33% (p = 0.108) and autonomic nerve abnormality 24% vs. 28% (p = 0.401). In multivariable GEE, CSII use was associated with lower rates of retinopathy (OR 0.66, 95% CI 0.45–0.95, p = 0.029) and peripheral nerve abnormality (OR 0.63, 95% CI 0.42–0.95, p = 0.026), but not albuminuria (OR 0.46, 95% CI 0.10–2.17, p = 0.33). SES was not associated with any of the complication outcomes. Conclusions In adolescents, CSII use is associated with lower rates of retinopathy and peripheral nerve abnormality, suggesting an apparent benefit of CSII over MDI independent of glycemic control or SES. PMID:27050468

  12. Short-term peripheral nerve stimulation ameliorates axonal dysfunction after spinal cord injury.

    PubMed

    Lee, Michael; Kiernan, Matthew C; Macefield, Vaughan G; Lee, Bonne B; Lin, Cindy S-Y

    2015-05-01

    There is accumulating evidence that peripheral motor axons deteriorate following spinal cord injury (SCI). Secondary axonal dysfunction can exacerbate muscle atrophy, contribute to peripheral neuropathies and neuropathic pain, and lead to further functional impairment. In an attempt to ameliorate the adverse downstream effects that developed following SCI, we investigated the effects of a short-term peripheral nerve stimulation (PNS) program on motor axonal excitability in 22 SCI patients. Axonal excitability studies were undertaken in the median and common peroneal nerves (CPN) bilaterally before and after a 6-wk unilateral PNS program. PNS was delivered percutaneously over the median nerve at the wrist and CPN around the fibular head, and the compound muscle action potential (CMAP) from the abductor pollicis brevis and tibialis anterior was recorded. Stimulus intensity was above motor threshold, and pulses (450 μs) were delivered at 100 Hz with a 2-s on/off cycle for 30 min 5 days/wk. SCI patients had consistently high thresholds with a reduced CMAP consistent with axonal loss; in some patients the peripheral nerves were completely inexcitable. Nerve excitability studies revealed profound changes in membrane potential, with a "fanned-in" appearance in threshold electrotonus, consistent with membrane depolarization, and significantly reduced superexcitability during the recovery cycle. These membrane dysfunctions were ameliorated after 6 wk of PNS, which produced a significant hyperpolarizing effect. The contralateral, nonstimulated nerves remained depolarized. Short-term PNS reversed axonal dysfunction following SCI, may provide an opportunity to prevent chronic changes in axonal and muscular function, and may improve rehabilitation outcomes. PMID:25787956

  13. Nanostructured Guidance for Peripheral Nerve Injuries: A Review with a Perspective in the Oral and Maxillofacial Area

    PubMed Central

    Sivolella, Stefano; Brunello, Giulia; Ferrarese, Nadia; Puppa, Alessandro Della; D’Avella, Domenico; Bressan, Eriberto; Zavan, Barbara

    2014-01-01

    Injury to peripheral nerves can occur as a result of various surgical procedures, including oral and maxillofacial surgery. In the case of nerve transaction, the gold standard treatment is the end-to-end reconnection of the two nerve stumps. When it cannot be performed, the actual strategies consist of the positioning of a nerve graft between the two stumps. Guided nerve regeneration using nano-structured scaffolds is a promising strategy to promote axon regeneration. Biodegradable electrospun conduits composed of aligned nanofibers is a new class of devices used to improve neurite extension and axon outgrowth. Self assembled peptide nanofibrous scaffolds (SAPNSs) demonstrated promising results in animal models for central nervous system injuries, and, more recently, for peripheral nerve injury. Aims of this work are (1) to review electrospun and self-assembled nanofibrous scaffolds use in vitro and in vivo for peripheral nerve regeneration; and (2) its application in peripheral nerve injuries treatment. The review focused on nanofibrous scaffolds with a diameter of less than approximately 250 nm. The conjugation in a nano scale of a natural bioactive factor with a resorbable synthetic or natural material may represent the best compromise providing both biological and mechanical cues for guided nerve regeneration. Injured peripheral nerves, such as trigeminal and facial, may benefit from these treatments. PMID:24562333

  14. A novel electrospun nerve conduit enhanced by carbon nanotubes for peripheral nerve regeneration

    NASA Astrophysics Data System (ADS)

    Yu, Wenwen; Jiang, Xinquan; Cai, Ming; Zhao, Wen; Ye, Dongxia; Zhou, Yong; Zhu, Chao; Zhang, Xiuli; Lu, Xiaofeng; Zhang, Zhiyuan

    2014-04-01

    For artificial nerve conduits, great improvements have been achieved in mimicking the structures and components of autologous nerves. However, there are still some problems in conduit construction, especially in terms of mechanical properties, biomimetic surface tomography, electrical conductivity and sustained release of neurotrophic factors or cells. In this study, we designed and fabricated a novel electrospun nerve conduit enhanced by multi-walled carbon nanotubes (MWNTs) on the basis of a collagen/poly(ɛ-caprolactone) (collagen/PCL) fibrous scaffold. Our aim was to provide further knowledge about the mechanical effects and efficacy of MWNTs on nerve conduits as well as the biocompatibility and toxicology of MWNTs when applied in vivo. The results showed that as one component, carboxyl MWNTs could greatly alter the composite scaffold’s hydrophilicity, mechanical properties and degradability. The electrospun fibers enhanced by MWNTs could support Schwann cell adhesion and elongation as a substrate in vitro. In vivo animal studies demonstrated that the MWNT-enhanced collagen/PCL conduit could effectively promote nerve regeneration of sciatic nerve defect in rats and prevent muscle atrophy without invoking body rejection or serious chronic inflammation. All of these results showed that this MWNT-enhanced scaffold possesses good biocompatibility and MWNTs might be excellent candidates as engineered nanocarriers for further neurotrophic factor delivery research.

  15. Basic study on the influence of inhibition induced by the magnetic stimulation on the peripheral nerve

    NASA Astrophysics Data System (ADS)

    Sato, Aya; Torii, Tetsuya; Iwahashi, Masakuni; Iramina, Keiji

    2015-05-01

    The purpose of this study is to analyze the inhibition mechanism of magnetic stimulation on motor function. A magnetic stimulator with a flat figure-eight coil was used to stimulate the peripheral nerve of the antebrachium. The intensity of magnetic stimulation was 0.8 T, and the stimulation frequency was 1 Hz. The amplitudes of the motor-evoked potentials (MEPs) at the abductor pollicis brevis muscle and first dorsal interosseous muscle were used to evaluate the effects of magnetic stimulation. The effects of magnetic stimulation were evaluated by analyzing the MEP amplitude before and after magnetic stimulation to the primary motor cortex. The results showed that MEP amplitude after magnetic stimulation compared with before magnetic stimulation decreased. Because there were individual differences in MEP amplitude induced by magnetic stimulation, the MEP amplitude after stimulation was normalized by the amplitude of each participant before stimulation. The MEP amplitude after stimulation decreased by approximately 58% (p < 0.01) on average compared with before stimulation. Previous studies suggested that magnetic stimulation to the primary motor cortex induced an increase or a decrease in MEP amplitude. Furthermore, previous studies have shown that the alteration in MEP amplitude was induced by cortical excitability based on magnetic stimulation. The results of this study showed that MEP amplitude decreased following magnetic stimulation to the peripheral nerve. We suggest that the decrease in MEP amplitude found in this study was obtained via the feedback from a peripheral nerve through an afferent nerve to the brain. This study suggests that peripheral excitement by magnetic stimulation of the peripheral nerve may control the central nervous system via afferent feedback.

  16. Local Anesthetic Peripheral Nerve Block Adjuvants for Prolongation of Analgesia: A Systematic Qualitative Review

    PubMed Central

    Kirksey, Meghan A.; Haskins, Stephen C.; Cheng, Jennifer; Liu, Spencer S.

    2015-01-01

    Background The use of peripheral nerve blocks for anesthesia and postoperative analgesia has increased significantly in recent years. Adjuvants are frequently added to local anesthetics to prolong analgesia following peripheral nerve blockade. Numerous randomized controlled trials and meta-analyses have examined the pros and cons of the use of various individual adjuvants. Objectives To systematically review adjuvant-related randomized controlled trials and meta-analyses and provide clinical recommendations for the use of adjuvants in peripheral nerve blocks. Methods Randomized controlled trials and meta-analyses that were published between 1990 and 2014 were included in the initial bibliographic search, which was conducted using Medline/PubMed, Cochrane Central Register of Controlled Trials, and EMBASE. Only studies that were published in English and listed block analgesic duration as an outcome were included. Trials that had already been published in the identified meta-analyses and included adjuvants not in widespread use and published without an Investigational New Drug application or equivalent status were excluded. Results Sixty one novel clinical trials and meta-analyses were identified and included in this review. The clinical trials reported analgesic duration data for the following adjuvants: buprenorphine (6), morphine (6), fentanyl (10), epinephrine (3), clonidine (7), dexmedetomidine (7), dexamethasone (7), tramadol (8), and magnesium (4). Studies of perineural buprenorphine, clonidine, dexamethasone, dexmedetomidine, and magnesium most consistently demonstrated prolongation of peripheral nerve blocks. Conclusions Buprenorphine, clonidine, dexamethasone, magnesium, and dexmedetomidine are promising agents for use in prolongation of local anesthetic peripheral nerve blocks, and further studies of safety and efficacy are merited. However, caution is recommended with use of any perineural adjuvant, as none have Food and Drug Administration approval, and

  17. Peripheral neuropathy following administration of nerve tissue antirabies vaccine.

    PubMed

    Arega, D; Zenebe, G

    1999-10-01

    In 1997, two patients were admitted to Tikur Anbessa Hospital with complaints of ascending paralysis in all extremities following administration of sheep brain tissue anti-rabies vaccine following a rabies exposure. The paralysis had started after 14 daily subcutaneous injections of the Fermi type nerve tissue vaccine. After an eight week stay in the hospital with supportive care and physiotherapy, the patients showed remarkable improvement. They received a booster dose of vaccine while in the hospital, with no deterioration in their neurological status and were discharged. PMID:11961878

  18. Using Stem Cells to Grow Artificial Tissue for Peripheral Nerve Repair

    PubMed Central

    Bhangra, Kulraj Singh; Busuttil, Francesca

    2016-01-01

    Peripheral nerve injury continues to pose a clinical hurdle despite its frequency and advances in treatment. Unlike the central nervous system, neurons of the peripheral nervous system have a greater ability to regenerate. However, due to a number of confounding factors, this is often both incomplete and inadequate. The lack of supportive Schwann cells or their inability to maintain a regenerative phenotype is a major factor. Advances in nervous system tissue engineering technology have led to efforts to build Schwann cell scaffolds to overcome this and enhance the regenerative capacity of neurons following injury. Stem cells that can differentiate along a neural lineage represent an essential resource and starting material for this process. In this review, we discuss the different stem cell types that are showing promise for nervous system tissue engineering in the context of peripheral nerve injury. We also discuss some of the biological, practical, ethical, and commercial considerations in using these different stem cells for future clinical application. PMID:27212954

  19. Microchannel-based regenerative scaffold for chronic peripheral nerve interfacing in amputees

    PubMed Central

    Srinivasan, Akhil; Tahilramani, Mayank; Bentley, John T.; Gore, Russell K.; Millard, Daniel; Mukhatyar, Vivek J.; Joseph, Anish; Haque, Adel; Stanley, Garrett B.; English, Arthur W.; Bellamkonda, Ravi V.

    2015-01-01

    Neurally controlled prosthetics that cosmetically and functionally mimic amputated limbs remain a clinical need because state of the art neural prosthetics only provide a fraction of a natural limb’s functionality. Here, we report on the fabrication and capability of polydimethylsiloxane (PDMS) and epoxy-based SU-8 photoresist microchannel scaffolds to serve as viable constructs for peripheral nerve interfacing though in vitro and in vivo studies in a sciatic nerve amputee model where the nerve lacks distal reinnervation targets. These studies showed microchannels with 100 μm × 100 μm cross-sectional areas support and direct the regeneration/migration of axons, Schwann cells, and fibroblasts through the microchannels with space available for future maturation of the axons. Investigation of the nerve in the distal segment, past the scaffold, showed a high degree of organization, adoption of the microchannel architecture forming ‘microchannel fascicles’, reformation of endoneurial tubes and axon myelination, and a lack of aberrant and unorganized growth that might be characteristic of neuroma formation. Separate chronic terminal in vivo electrophysiology studies utilizing the microchannel scaffolds with permanently integrated microwire electrodes were conducted to evaluate interfacing capabilities. In all devices a variety of spontaneous, sensory evoked and electrically evoked single and multi-unit action potentials were recorded after five months of implantation. Together, these findings suggest that microchannel scaffolds are well suited for chronic implantation and peripheral nerve interfacing to promote organized nerve regeneration that lends itself well to stable interfaces. Thus this study establishes the basis for the advanced fabrication of large-electrode count, wireless microchannel devices that are an important step towards highly functional, bi-directional peripheral nerve interfaces. PMID:25522974

  20. Localized and Sustained Delivery of Erythropoietin from PLGA Microspheres Promotes Functional Recovery and Nerve Regeneration in Peripheral Nerve Injury

    PubMed Central

    Zhang, Wei; Gao, Yuan; Zhou, Yan; Liu, Jianheng; Zhang, Licheng; Long, Anhua; Zhang, Lihai; Tang, Peifu

    2015-01-01

    Erythropoietin (EPO) has been demonstrated to exert neuroprotective effects on peripheral nerve injury recovery. Though daily intraperitoneal injection of EPO during a long period of time was effective, it was a tedious procedure. In addition, only limited amount of EPO could reach the injury sites by general administration, and free EPO is easily degraded in vivo. In this study, we encapsulated EPO in poly(lactide-co-glycolide) (PLGA) microspheres. Both in vitro and in vivo release assays showed that the EPO-PLGA microspheres allowed sustained release of EPO within a period of two weeks. After administration of such EPO-PLGA microspheres, the peripheral nerve injured rats had significantly better recovery compared with those which received daily intraperitoneal injection of EPO, empty PLGA microspheres, or saline treatments. This was supported by the functional, electrophysiological, and histological evaluations of the recovery done at week 8 postoperatively. We conclude that sustained delivery of EPO could be achieved by using EPO-PLGA microspheres, and such delivery method could further enhance the recovery function of EPO in nerve injury recovery. PMID:25821803

  1. Effect of helium-neon laser irradiation on peripheral sensory nerve latency

    SciTech Connect

    Snyder-Mackler, L.; Bork, C.E.

    1988-02-01

    The purpose of this randomized, double-blind study was to determine the effect of a helium-neon (He-Ne) laser on latency of peripheral sensory nerve. Forty healthy subjects with no history of right upper extremity pathological conditions were assigned to either a Laser or a Placebo Group. Six 1-cm2 blocks along a 12-cm segment of the subjects' right superficial radial nerve received 20-second applications of either the He-Ne laser or a placebo. We assessed differences between pretest and posttest latencies with t tests for correlated and independent samples. The Laser Group showed a statistically significant increase in latency that corresponded to a decrease in sensory nerve conduction velocity. Short-duration He-Ne laser application significantly increased the distal latency of the superficial radial nerve. This finding provides information about the mechanism of the reported pain-relieving effect of the He-Ne laser.

  2. Differential fiber-specific block of nerve conduction in mammalian peripheral nerves using kilohertz electrical stimulation

    PubMed Central

    Patel, Yogi A.

    2015-01-01

    Kilohertz electrical stimulation (KES) has been shown to induce repeatable and reversible nerve conduction block in animal models. In this study, we characterized the ability of KES stimuli to selectively block specific components of stimulated nerve activity using in vivo preparations of the rat sciatic and vagus nerves. KES stimuli in the frequency range of 5–70 kHz and amplitudes of 0.1–3.0 mA were applied. Compound action potentials were evoked using either electrical or sensory stimulation, and block of components was assessed through direct nerve recordings and muscle force measurements. Distinct observable components of the compound action potential had unique conduction block thresholds as a function of frequency of KES. The fast component, which includes motor activity, had a monotonically increasing block threshold as a function of the KES frequency. The slow component, which includes sensory activity, showed a nonmonotonic block threshold relationship with increasing KES frequency. The distinct trends with frequency of the two components enabled selective block of one component with an appropriate choice of frequency and amplitude. These trends in threshold of the two components were similar when studying electrical stimulation and responses of the sciatic nerve, electrical stimulation and responses of the vagus nerve, and sensorimotor stimulation and responses of the sciatic nerve. This differential blocking effect of KES on specific fibers can extend the applications of KES conduction block to selective block and stimulation of neural signals for neuromodulation as well as selective control of neural circuits underlying sensorimotor function. PMID:25878155

  3. Axon-Schwann cell interactions during peripheral nerve regeneration in zebrafish larvae

    PubMed Central

    2014-01-01

    Background Peripheral nerve injuries can severely affect the way that animals perceive signals from the surrounding environment. While damage to peripheral axons generally has a better outcome than injuries to central nervous system axons, it is currently unknown how neurons re-establish their target innervations to recover function after injury, and how accessory cells contribute to this task. Here we use a simple technique to create reproducible and localized injury in the posterior lateral line (pLL) nerve of zebrafish and follow the fate of both neurons and Schwann cells. Results Using pLL single axon labeling by transient transgene expression, as well as transplantation of glial precursor cells in zebrafish larvae, we individualize different components in this system and characterize their cellular behaviors during the regenerative process. Neurectomy is followed by loss of Schwann cell differentiation markers that is reverted after nerve regrowth. We show that reinnervation of lateral line hair cells in neuromasts during pLL nerve regeneration is a highly dynamic process with promiscuous yet non-random target recognition. Furthermore, Schwann cells are required for directional extension and fasciculation of the regenerating nerve. We provide evidence that these cells and regrowing axons are mutually dependant during early stages of nerve regeneration in the pLL. The role of ErbB signaling in this context is also explored. Conclusion The accessibility of the pLL nerve and the availability of transgenic lines that label this structure and their synaptic targets provides an outstanding in vivo model to study the different events associated with axonal extension, target reinnervation, and the complex cellular interactions between glial cells and injured axons during nerve regeneration. PMID:25326036

  4. Finite element modeling of hyper-viscoelasticity of peripheral nerve ultrastructures.

    PubMed

    Chang, Cheng-Tao; Chen, Yu-Hsing; Lin, Chou-Ching K; Ju, Ming-Shaung

    2015-07-16

    The mechanical characteristics of ultrastructures of rat sciatic nerves were investigated through animal experiments and finite element analyses. A custom-designed dynamic testing apparatus was used to conduct in vitro transverse compression experiments on the nerves. The optical coherence tomography (OCT) was utilized to record the cross-sectional images of nerve during the dynamic testing. Two-dimensional finite element models of the nerves were built based on their OCT images. A hyper-viscoelastic model was employed to describe the elastic and stress relaxation response of each ultrastructure of the nerve, namely the endoneurium, the perineurium and the epineurium. The first-order Ogden model was employed to describe the elasticity of each ultrastructure and a generalized Maxwell model for the relaxation. The inverse finite element analysis was used to estimate the material parameters of the ultrastructures. The results show the instantaneous shear modulus of the ultrastructures in decreasing order is perineurium, endoneurium, and epineurium. The FE model combined with the first-order Ogden model and the second-order Prony series is good enough for describing the compress-and-hold response of the nerve ultrastructures. The integration of OCT and the nonlinear finite element modeling may be applicable to study the viscoelasticity of peripheral nerve down to the ultrastructural level. PMID:25912662

  5. A complete model for the evaluation of the magnetic stimulation of peripheral nerves.

    PubMed

    Pisa, Stefano; Apollonio, Francesca; d'Inzeo, Guglielmo

    2014-01-01

    In this paper, a numerical procedure for the analysis of peripheral nerve excitation through magnetic stimulation is presented and used to investigate the physical parameters influencing stimulation. The finite difference technique is used to evaluate the electric field distribution induced inside an arm by the current flowing through a coil, and a nonlinear cable model is used to describe the response of the nerve fiber to the induced electric field. The comparison among several forearm structures has evidenced that the heterogeneous non dispersive forearm model is a good reference condition. With this model, the lowest charging voltage on the stimulator capacitance, able to produce the nerve stimulation, is achieved when the coil is shifted, with respect to the nerve, of a quantity slightly lower than the coil radius but it is also possible to excite the nerve fiber by applying a shift equal to zero. The charging voltage increases when the coil radius is increased and when a three-dimensional coil geometry is considered. Moreover, this voltage is strongly dependent on the nerve position inside the forearm and on the kind of tissue surrounding the nerve. PMID:24511330

  6. A Complete Model for the Evaluation of the Magnetic Stimulation of Peripheral Nerves

    PubMed Central

    Pisa, Stefano; Apollonio, Francesca; d'Inzeo, Guglielmo

    2014-01-01

    In this paper, a numerical procedure for the analysis of peripheral nerve excitation through magnetic stimulation is presented and used to investigate the physical parameters influencing stimulation. The finite difference technique is used to evaluate the electric field distribution induced inside an arm by the current flowing through a coil, and a nonlinear cable model is used to describe the response of the nerve fiber to the induced electric field. The comparison among several forearm structures has evidenced that the heterogeneous non dispersive forearm model is a good reference condition. With this model, the lowest charging voltage on the stimulator capacitance, able to produce the nerve stimulation, is achieved when the coil is shifted, with respect to the nerve, of a quantity slightly lower than the coil radius but it is also possible to excite the nerve fiber by applying a shift equal to zero. The charging voltage increases when the coil radius is increased and when a three-dimensional coil geometry is considered. Moreover, this voltage is strongly dependent on the nerve position inside the forearm and on the kind of tissue surrounding the nerve. PMID:24511330

  7. Comparative study of peripheral neuropathy and nerve regeneration in NOD and ICR diabetic mice.

    PubMed

    Homs, Judit; Ariza, Lorena; Pagès, Gemma; Verdú, Enrique; Casals, Laura; Udina, Esther; Chillón, Miguel; Bosch, Assumpció; Navarro, Xavier

    2011-09-01

    The non-obese diabetic (NOD) mouse was suggested as an adequate model for diabetic autonomic neuropathy. We evaluated sensory-motor neuropathy and nerve regeneration following sciatic nerve crush in NOD males rendered diabetic by multiple low doses of streptozotocin, in comparison with similarly treated Institute for Cancer Research (ICR) mice, a widely used model for type I diabetes. Neurophysiological values for both strains showed a decline in motor and sensory nerve conduction velocity at 7 and 8 weeks after induction of diabetes in the intact hindlimb. However, amplitudes of compound muscle and sensory action potentials (CMAPs and CNAPs) were significantly reduced in NOD but not in ICR diabetic mice. Morphometrical analysis showed myelinated fiber loss in highly hyperglycemic NOD mice, but no significant changes in fiber size. There was a reduction of intraepidermal nerve fibers, more pronounced in NOD than in ICR diabetic mice. Interestingly, aldose reductase and poly(ADP-ribose) polymerase (PARP) activities were increased already at 1 week of hyperglycemia, persisting until the end of the experiment in both strains. Muscle and nerve reinnervation was delayed in diabetic mice following sciatic nerve crush, being more marked in NOD mice. Thus, diabetes of mid-duration induces more severe peripheral neuropathy and slower nerve regeneration in NOD than in ICR mice. PMID:22003936

  8. Calcium regulation in frog peripheral nerve by the blood-nerve barrier

    SciTech Connect

    Wadhwani, K.C.

    1986-01-01

    The objectives of this research were: (a) to investigate the characteristics of calcium transport across the perineurium and the endoneurial capillaries, and (b) to gain a better understanding of the extent of calcium homeostasis in the endoneurial space. To study the nature of calcium transport across the perineurium, the flux of radiotracer /sup 45/Ca was measured through the perineurial cylinder, isolated from the frog sciatic nerve, and through the perineurium into the nerve in situ. To study the nature of calcium transport across the endoneurial capillaries, the permeability-surface area product (PA) of /sup 45/Ca was determined as a function of the calcium concentration in the blood. To study calcium homeostasis, the calcium content of the frog sciatic nerve was determined as a function of chronic changes in plasma (Ca).

  9. Bone Marrow-Derived, Neural-Like Cells Have the Characteristics of Neurons to Protect the Peripheral Nerve in Microenvironment

    PubMed Central

    Guo, Shi-lei; Zhang, Zhi-ying; Zhi, Yun-xia; Han, Chang-jie; Zhou, Yu-hao; Liu, Fang; Lin, Hai-yan; Zhang, Chuan-sen

    2015-01-01

    Effective repair of peripheral nerve defects is difficult because of the slow growth of new axonal growth. We propose that “neural-like cells” may be useful for the protection of peripheral nerve destructions. Such cells should prolong the time for the disintegration of spinal nerves, reduce lesions, and improve recovery. But the mechanism of neural-like cells in the peripheral nerve is still unclear. In this study, bone marrow-derived neural-like cells were used as seed cells. The cells were injected into the distal end of severed rabbit peripheral nerves that were no longer integrated with the central nervous system. Electromyography (EMG), immunohistochemistry, and transmission electron microscopy (TEM) were employed to analyze the development of the cells in the peripheral nerve environment. The CMAP amplitude appeared during the 5th week following surgery, at which time morphological characteristics of myelinated nerve fiber formation were observed. Bone marrow-derived neural-like cells could protect the disintegration and destruction of the injured peripheral nerve. PMID:25861281

  10. Bone marrow-derived, neural-like cells have the characteristics of neurons to protect the peripheral nerve in microenvironment.

    PubMed

    Guo, Shi-Lei; Zhang, Zhi-Ying; Xu, Yan; Zhi, Yun-Xia; Han, Chang-Jie; Zhou, Yu-Hao; Liu, Fang; Lin, Hai-Yan; Zhang, Chuan-Sen

    2015-01-01

    Effective repair of peripheral nerve defects is difficult because of the slow growth of new axonal growth. We propose that "neural-like cells" may be useful for the protection of peripheral nerve destructions. Such cells should prolong the time for the disintegration of spinal nerves, reduce lesions, and improve recovery. But the mechanism of neural-like cells in the peripheral nerve is still unclear. In this study, bone marrow-derived neural-like cells were used as seed cells. The cells were injected into the distal end of severed rabbit peripheral nerves that were no longer integrated with the central nervous system. Electromyography (EMG), immunohistochemistry, and transmission electron microscopy (TEM) were employed to analyze the development of the cells in the peripheral nerve environment. The CMAP amplitude appeared during the 5th week following surgery, at which time morphological characteristics of myelinated nerve fiber formation were observed. Bone marrow-derived neural-like cells could protect the disintegration and destruction of the injured peripheral nerve. PMID:25861281

  11. Characterization of Endoneurial Fibroblast-like Cells from Human and Rat Peripheral Nerves

    PubMed Central

    Richard, Laurence; Védrenne, Nicolas; Vallat, Jean-Michel

    2014-01-01

    Endoneurial fibroblast-like cells (EFLCs) are one of the cell populations present in the peripheral nervous system. The role and immunophenotypic characteristics of EFLCs are not well known and led us to perform a histological and cytological study of EFLCs in normal human and rat peripheral nerves. We found that all EFLCs express CD34, neural/glial antigen 2 (NG2), and prolyl-4-hydrolase-beta. In addition, half of the EFLCs in normal peripheral nerves express platelet-derived growth factor receptor-β (PDGFR-β) and some also express the intermediate filament nestin in vivo (at a lower level than Schwann cells, which express high levels of nestin). Using cell cultures of purified EFLCs, we characterized subpopulations of EFLCs expressing PDGFR-β alone or PDGFR-β and nestin. Experimental nerve lesions in rat resulted in an increase in nestin-positive EFLCs, which returned to normal levels after 8 days. This suggests that some EFLCs could have a different proliferative and/or regenerative potential than others, and these EFLCs may play a role in the initial phase of nerve repair. These “activated” EFLCs share some immunophenotypic similarities with pericytes and Interstitial cells of Cajal, which have progenitor cell potentials. This raises the questions as to whether a proportion of EFLCs have a possible role as endoneurial progenitor cells. PMID:24670794

  12. Construction of nerve guide conduits from cellulose/soy protein composite membranes combined with Schwann cells and pyrroloquinoline quinone for the repair of peripheral nerve defect.

    PubMed

    Luo, Lihua; Gan, Li; Liu, Yongming; Tian, Weiqun; Tong, Zan; Wang, Xiong; Huselstein, Celine; Chen, Yun

    2015-02-20

    Regeneration and functional reconstruction of peripheral nerve defects remained a significant clinical challenge. Nerve guide conduits, with seed cells or neurotrophic factors (NTFs), had been widely used to improve the repair and regeneration of injured peripheral nerve. Pyrroloquinoline quinone (PQQ) was an antioxidant that can stimulate nerve growth factors (NGFs) synthesis and accelerate the Schwann cells (SCs) proliferation and growth. In present study, three kinds of nerve guide conduits were constructed: one from cellulose/SPI hollow tube (CSC), another from CSC combined with SCs (CSSC), and the third one from CSSC combined with PQQ (CSSPC), respectively. And then they were applied to bridge and repair the sciatic nerve defect in rats, using autograft as control. Effects of different nerve guide conduits on the nerve regeneration were comparatively evaluated by general analysis, sciatic function index (SFI) and histological analysis (HE and TEM). Newly-formed regenerative nerve fibers were observed and running through the transparent nerve guide conduits 12 weeks after surgery. SFI results indicated that the reconstruction of motor function in CSSPC group was better than that in CSSC and CSC groups. HE images from the cross-sections and longitudinal-sections of the harvested regenerative nerve indicated that regenerative nerve fibers had been formed and accompanied with new blood vessels and matrix materials in the conduits. TEM images also showed that lots of fresh myelinated and non-myelinated nerve fibers had been formed. Parts of vacuolar, swollen and abnormal axons occurred in CSC and CSSC groups, while the vacuolization and swell of axons was the least serious in CSSPC group. These results indicated that CSSPC group had the most ability to repair and reconstruct the nerve structure and functions due to the comprehensive contributions from hollow CSC tube, SCs and PQQ. As a result, the CSSPC may have the potential for the applications as nerve guide

  13. (-)-Epigallocatechin-3-gallate (EGCG) attenuates peripheral nerve degeneration in rat sciatic nerve crush injury.

    PubMed

    Renno, Waleed M; Al-Maghrebi, May; Alshammari, Ahmad; George, Preethi

    2013-02-01

    Recently, we have shown that green tea (GT) consumption improves both reflexes and sensation in unilateral chronic constriction injury to the sciatic nerve. Considering the substantial neuroprotective properties of GT polyphenols, we sought to investigate whether (-)-epigallocatechin-3-gallate (EGCG) could protect the sciatic nerve and improve functional impairments induced by a crushing injury. We also examined whether neuronal cell apoptosis induced by the crushing injury is affected by EGCG treatment. Histological examination of sciatic nerves from EGCG-treated (50mg/kg; i.p.) showed that axonotmized rats had a remarkable axonal and myelin regeneration with significant decrease in the number of myelinated axonal fibers compared to vehicle-treated crush group. Similarly, ultrastructural evaluation of EGCG-treated nerves displayed normal unmyelinated and myelinated axons with regular myelin sheath thickness and normalized appearance of Schmidt-Lantermann clefts. Extracellular matrix displayed normal collagen fibers appearance with distinctively organized distribution similar to sham animals. Analysis of foot position and extensor postural thrust test showed a progressive and faster recovery in the EGCG-treated group compared to vehicle-treated animals. EGCG-treated rats showed significant increase in paw withdrawal thresholds to mechanical stimulation compared to vehicle-treated crush group. EGCG treatment also restored the mRNA expression of Bax, Bcl-2 and survivin but not that of p53 to sham levels on days 3 and 7 post-injury. Our results demonstrate that EGCG treatment enhanced functional recovery, advanced morphological nerve rescue and accelerated nerve regeneration following crush injury partly due to the down regulation of apoptosis related genes. PMID:23313191

  14. Construction of nerve guide conduits from cellulose/soy protein composite membranes combined with Schwann cells and pyrroloquinoline quinone for the repair of peripheral nerve defect

    SciTech Connect

    Luo, Lihua; Gan, Li; Liu, Yongming; Tian, Weiqun; Tong, Zan; Wang, Xiong; Huselstein, Celine; Chen, Yun

    2015-02-20

    Regeneration and functional reconstruction of peripheral nerve defects remained a significant clinical challenge. Nerve guide conduits, with seed cells or neurotrophic factors (NTFs), had been widely used to improve the repair and regeneration of injured peripheral nerve. Pyrroloquinoline quinone (PQQ) was an antioxidant that can stimulate nerve growth factors (NGFs) synthesis and accelerate the Schwann cells (SCs) proliferation and growth. In present study, three kinds of nerve guide conduits were constructed: one from cellulose/SPI hollow tube (CSC), another from CSC combined with SCs (CSSC), and the third one from CSSC combined with PQQ (CSSPC), respectively. And then they were applied to bridge and repair the sciatic nerve defect in rats, using autograft as control. Effects of different nerve guide conduits on the nerve regeneration were comparatively evaluated by general analysis, sciatic function index (SFI) and histological analysis (HE and TEM). Newly-formed regenerative nerve fibers were observed and running through the transparent nerve guide conduits 12 weeks after surgery. SFI results indicated that the reconstruction of motor function in CSSPC group was better than that in CSSC and CSC groups. HE images from the cross-sections and longitudinal-sections of the harvested regenerative nerve indicated that regenerative nerve fibers had been formed and accompanied with new blood vessels and matrix materials in the conduits. TEM images also showed that lots of fresh myelinated and non-myelinated nerve fibers had been formed. Parts of vacuolar, swollen and abnormal axons occurred in CSC and CSSC groups, while the vacuolization and swell of axons was the least serious in CSSPC group. These results indicated that CSSPC group had the most ability to repair and reconstruct the nerve structure and functions due to the comprehensive contributions from hollow CSC tube, SCs and PQQ. As a result, the CSSPC may have the potential for the applications as nerve guide

  15. Nerve Demyelination Increases Metabotropic Glutamate Receptor Subtype 5 Expression in Peripheral Painful Mononeuropathy

    PubMed Central

    Ko, Miau-Hwa; Hsieh, Yu-Lin; Hsieh, Sung-Tsang; Tseng, To-Jung

    2015-01-01

    Wallerian degeneration or nerve demyelination, arising from spinal nerve compression, is thought to bring on chronic neuropathic pain. The widely distributed metabotropic glutamate receptor subtype 5 (mGluR5) is involved in modulating nociceptive transmission. The purpose of this study was to investigate the potential effects of mGluR5 on peripheral hypersensitivities after chronic constriction injury (CCI). Sprague-Dawley rats were operated on with four loose ligatures around the sciatic nerve to induce thermal hyperalgesia and mechanical allodynia. Primary afferents in dermis after CCI exhibited progressive decreases, defined as partial cutaneous denervation; importantly, mGluR5 expressions in primary afferents were statistically increased. CCI-induced neuropathic pain behaviors through the intraplantar injections of 2-methyl-6-(phenylethynyl)-pyridine (MPEP), a selective mGluR5 antagonist, were dose-dependently attenuated. Furthermore, the most increased mGluR5 expressions in primary afferents surrounded by reactive Schwann cells were observed at the distal CCI stumps of sciatic nerves. In conclusion, these results suggest that nerve demyelination results in the increases of mGluR5 expression in injured primary afferents after CCI; and further suggest that mGluR5 represents a main therapeutic target in developing pharmacological strategies to prevent peripheral hypersensitivities. PMID:25739080

  16. Earthworm extracts facilitate PC12 cell differentiation and promote axonal sprouting in peripheral nerve injury.

    PubMed

    Chen, Chao-Tsung; Lin, Jaung-Geng; Lu, Tung-Wu; Tsai, Fuu-Jen; Huang, Chih-Yang; Yao, Chun-Hsu; Chen, Yueh-Sheng

    2010-01-01

    The present study provides in vitro and in vivo evaluations of earthworm (Pheretima aspergilum) on peripheral nerve regeneration. In the in vitro study, we found the earthworm (EW) water extracts caused a marked enhancement of the nerve growth factor-mediated neurite outgrowth from PC12 cells as well as the expressions of growth associated protein 43 and synapsin I. In the in vivo study, silicone rubber chambers filled with EW extracts were used to bridge a 10 mm sciatic nerve defect in rats. Eight weeks after implantation, the group receiving EW extracts had a much higher success percentage of regeneration (90%) compared to the control (60%) receiving the saline. In addition, quantitative histology of the successfully regenerated nerves revealed that myelinated axons in EW group at 31.25 microg/ml was significantly more than those in the controls (p < 0.05). These results showed that EW extracts can be a potential growth-promoting factor on regenerating peripheral nerves. PMID:20503471

  17. Reversal of Peripheral Nerve Injury-induced Hypersensitivity in the Postpartum Period: Role of Spinal Oxytocin

    PubMed Central

    Gutierrez, Silvia; Liu, Baogang; Hayashida, Ken-ichiro; Houle, Timothy T.; Eisenach, James C.

    2012-01-01

    Background Physical injury, including surgery, can result in chronic pain; yet chronic pain following childbirth, including cesarean delivery in women, is rare. The mechanisms involved in this protection by pregnancy or delivery have not been explored. Methods We examined the effect of pregnancy and delivery on hypersensitivity to mechanical stimuli of the rat hindpaw induced by peripheral nerve injury (spinal nerve ligation) and after intrathecal oxytocin, atosiban and naloxone. Additionally, oxytocin concentration in lumbar spinal cerebrospinal fluid was determined. Results Spinal nerve ligation performed at mid-pregnancy resulted in similar hypersensitivity to nonpregnant controls, but hypersensitivity partially resolved beginning after delivery. Removal of pups after delivery prevented this partial resolution. Cerebrospinal fluid concentrations of oxytocin were greater in normal postpartum rats prior to weaning. To examine the effect of injury at the time of delivery rather than during pregnancy, spinal nerve ligation was performed within 24 h of delivery. This resulted in acute hypersensitivity that partially resolved over the next 2–3 weeks. Weaning of pups resulted only in a temporary return of hypersensitivity. Intrathecal oxytocin effectively reversed the hypersensitivity following separation of the pups. Postpartum resolution of hypersensitivity was transiently abolished by intrathecal injection of the oxytocin receptor antagonist, atosiban. Conclusions These results suggest that the postpartum period rather than pregnancy protects against chronic hypersensitivity from peripheral nerve injury and that this protection may reflect sustained oxytocin signaling in the central nervous system during this period. PMID:23249932

  18. Identification of the effects of peripheral nerves injury on the muscle control - A review

    NASA Astrophysics Data System (ADS)

    Cabaj, Anna; Zmyslowski, Wojciech

    2011-01-01

    Impairment of motor function following peripheral nerve injury is a serious clinical problem. Generally nerve injury leads to erroneous control of muscle activity that results in gait and voluntary movement abnormalities followed by muscle atrophy. This article presents a review of studies on the effects of peripheral nerve injury on the motor system performed on animal models. We focused our attention on the results that are fundamental for better understanding of the degenerative and regenerative processes induced by nerve injury as well as of the mechanisms of structural changes in neuronal networks controlling movement. Quoted results are also important for clinical applications because they allow to develop new diagnostic and therapeutic techniques that can be used after nerve injury inducing motor deficits. However, till now no efficient therapy inducing satisfactory recovery was found. There is still a need to continue an advanced basic research directed to develop effective therapies. Thus the aim of this review is to compare the results of recent studies performed on various animal models in order to propose new methods for identification of mechanisms responsible for muscle deficits and propose targets for new pharmacological therapies.

  19. Anaesthetic Management of a Patient with Thyrotoxicosis for Nonthyroid Surgery with Peripheral Nerve Blockade

    PubMed Central

    Buget, Mehmet I.; Sencan, Bilge; Varansu, Giray; Kucukay, Suleyman

    2016-01-01

    Thyrotoxicosis is a hypermetabolic condition caused by an elevation in thyroid hormone levels. The disorder has a variety of causes, manifestations, and therapies. Several clinical features of thyrotoxicosis are due to sympathetic stimulation with increased beta-adrenoreceptor upregulation and sensitization to catecholamine. Anaesthetic management of thyrotoxicosis patients using neuraxial block has been described in literature; however, to our knowledge, there are no reports of peripheral nerve block utilization. Here, we report on the anaesthetic management of a patient with thyroiditis-associated thyrotoxicosis undergoing emergency surgery via a femoral and sciatic nerve block. PMID:26885409

  20. Peripheral nerve and neuromuscular junction pathology in Pompe disease

    PubMed Central

    Falk, Darin J.; Todd, Adrian Gary; Lee, Sooyeon; Soustek, Meghan S.; ElMallah, Mai K.; Fuller, David D.; Notterpek, Lucia; Byrne, Barry J.

    2015-01-01

    Pompe disease is a systemic metabolic disorder characterized by lack of acid-alpha glucosidase (GAA) resulting in ubiquitous lysosomal glycogen accumulation. Respiratory and ambulatory dysfunction are prominent features in patients with Pompe yet the mechanism defining the development of muscle weakness is currently unclear. Transgenic animal models of Pompe disease mirroring the patient phenotype have been invaluable in mechanistic and therapeutic study. Here, we demonstrate significant pathological alterations at neuromuscular junctions (NMJs) of the diaphragm and tibialis anterior muscle as prominent features of disease pathology in Gaa knockout mice. Postsynaptic defects including increased motor endplate area and fragmentation were readily observed in Gaa−/− but not wild-type mice. Presynaptic neuropathic changes were also evident, as demonstrated by significant reduction in the levels of neurofilament proteins, and alterations in axonal fiber diameter and myelin thickness within the sciatic and phrenic nerves. Our data suggest the loss of NMJ integrity is a primary contributor to the decline in respiratory and ambulatory function in Pompe and arises from both pre- and postsynaptic pathology. These observations highlight the importance of systemic phenotype correction, specifically restoration of GAA to skeletal muscle and the nervous system for treatment of Pompe disease. PMID:25217571

  1. Low-power laser efficacy in peripheral nerve lesion treatment

    NASA Astrophysics Data System (ADS)

    Antipa, Ciprian; Nacu, Mihaela; Bruckner, Ion I.; Bunila, Daniela; Vlaiculescu, Mihaela; Pascu, Mihail-Lucian; Ionescu, Elena

    1998-07-01

    In order to establish the low energy laser (LEL) effects on nervous tissue regeneration in clinical practice, we evaluated in double blind, placebo controlled study, the efficacy of LEL in the functional recovery of 46 patients with distal forearm post- traumatic nerve lesion, after surgical suture. The patients were divided into two groups: A-26 patients were treated with LEL; B- 20 patients, as control, were treated with placebo lasers and classical medical and physical therapy. Lasers used were: HeNe, 632.5 nm wavelength, 2 mW power, and GaAlAs diode laser, 880 nm wavelength, pulsed emission with an output power about 3 mW. Before, during and after the treatment, electromyography (EMG) and electroneurography (ENG) were done in order to measure objectively the efficacy of the treatment. We obtained good results after 4 - 5 months at 80.7% patients from group A and about the same results at 70% patients from group B, but after at least 8 months. The good results were noticed concerning the improvement of EMG and ENG registrations and on the involution of pain, inflammations, movements and force of the fingers. Finally we can say that the favorable results were obtained in at least half the time with LEL treatment faster than with classical therapy.

  2. Use of Peripheral Nerve Blocks with Sedation for Total Knee Arthroplasty in a Patient with Contraindication for General Anesthesia

    PubMed Central

    Kamenetsky, Eric; Nader, Antoun; Kendall, Mark C.

    2015-01-01

    Although peripheral nerve blocks are commonly used to provide postoperative analgesia after total knee arthroplasty (TKA) and other lower extremity procedures, these blocks are rarely used for intraoperative anesthesia. Most TKAs are performed under general anesthesia (GA) or neuraxial anesthesia (NA). The knee has a complex sensory innervation that makes surgical anesthesia difficult with peripheral nerve blocks alone. Rarely are both GA and NA relatively contraindicated and alternatives are considered. We present a patient who underwent TKA performed under peripheral nerve block and sedation alone. PMID:26587290

  3. Suppression of scarring in peripheral nerve implants by drug elution

    NASA Astrophysics Data System (ADS)

    FitzGerald, James J.

    2016-04-01

    Objective. Medical implants made of non-biological materials provoke a chronic inflammatory response, resulting in the deposition of a collagenous scar tissue (ST) layer on their surface, that gradually thickens over time. This is a critical problem for neural interfaces. Scar build-up on electrodes results in a progressive decline in signal level because the scar tissue gradually separates axons away from the recording contacts. In regenerative sieves and microchannel electrodes, progressive scar deposition will constrict and may eventually choke off the sieve hole or channel lumen. Interface designs need to address this issue if they are to be fit for long term use. This study examines a novel method of inhibiting the formation and thickening of the fibrous scar. Approach. Research to date has mainly focused on methods of preventing stimulation of the foreign body response by implant surface modification. In this paper a pharmacological approach using drug elution to suppress chronic inflammation is introduced. Microchannel implants made of silicone doped with the steroid drug dexamethasone were implanted in the rat sciatic nerve for periods of up to a year. Tissue from within the microchannels was compared to that from control devices that did not release any drug. Main results. In the drug eluting implants the scar layer was significantly thinner at all timepoints, and unlike the controls it did not continue to thicken after 6 months. Control implants supported axon regeneration well initially, but axon counts fell rapidly at later timepoints as scar thickened. Axon counts in drug eluting devices were initially much lower, but increased rather than declined and by one year were significantly higher than in controls. Significance. Drug elution offers a potential long term solution to the problem of performance degradation due to scarring around neural implants.

  4. Cortical Brain Mapping of Peripheral Nerves Using Functional Magnetic Resonance Imaging in a Rodent Model

    PubMed Central

    Cho, Younghoon R.; Jones, Seth R.; Pawela, Christopher P.; Li, Rupeng; Kao, Dennis S.; Schulte, Marie L.; Runquist, Matthew L.; Yan, Ji-Geng; Hudetz, Anthony G.; Jaradeh, Safwan S.; Hyde, James S.; Matloub, Hani S.

    2008-01-01

    The regions of the body have cortical and subcortical representation in proportion to their degree of innervation. The rat forepaw has been studied extensively in recent years using functional magnetic resonance imaging (fMRI)—typically by stimulation using electrodes directly inserted into the skin of the forepaw. Here, we stimulate using surgically implanted electrodes. A major distinction is that stimulation of the skin of the forepaw is mostly sensory, whereas direct nerve stimulation reveals not only the sensory system but also deep brain structures associated with motor activity. In this paper, we seek to define both the motor and sensory cortical and subcortical representations associated with the four major nerves of the rodent upper extremity. We electrically stimulated each nerve (median, ulnar, radial, and musculocutaneous) during fMRI acquisition using a 9.4T Bruker scanner. A current level of 0.5-1.0 mA and a frequency of 5 Hz were used while keeping the duration constant. A distinct pattern of cortical activation was found for each nerve that can be correlated with known sensorimotor afferent and efferent pathways to the rat forepaw. This direct nerve stimulation rat model can provide insight into peripheral nerve injury. PMID:18924070

  5. Potential risk of mitomycin C at high concentrations on peripheral nerve structure.

    PubMed

    Sui, Tao; Zhang, Jinhong; Du, Shihao; Su, Changhui; Que, Jun; Cao, Xiaojian

    2014-04-15

    Although the local application of mitomycin C may prevent epidural adhesion after laminectomy, mitomycin C can induce neurotoxicity in optic and acoustic nerves at high concentrations. To determine the safe concentration range for mitomycin C, cotton pads soaked with mitomycin C at different concentrations (0.1, 0.3, 0.5, and 0.7 mg/mL) were immediately applied for 5 minutes to the operation area of rats that had undergone laminectomy at L1. Rat sciatic nerves, instead of dorsal nerves, were used in this study. The results showed that mitomycin C at 0.1-0.5 mg/mL did not damage the structure and function of the sciatic nerve, while at 0.7 mg/mL, mitomycin C significantly reduced the thickness of the sciatic nerve myelin sheath compared with lower concentrations, though no functional change was found. These experimental findings indicate that the local application of mitomycin C at low concentrations is safe to prevent scar adhesion following laminectomy, but that mitomycin C at high concentrations (> 0.7 mg/mL) has potential safety risks to peripheral nerve structures. PMID:25206895

  6. Malignant peripheral nerve sheath tumor in a cat with nodal and pulmonary metastases.

    PubMed

    Buza, Elizabeth L; Menzies, Robert A; Goldschmidt, Michael H; Durham, Amy C

    2012-07-01

    Peripheral nerve sheath tumors in domestic cats are infrequently reported and are often locally invasive. An 11-year-old Domestic Shorthair cat was originally diagnosed with a right maxillary benign peripheral nerve sheath tumor at incisional biopsy. At necropsy, the neoplasm had features of malignancy including metastases to the regional lymph nodes and lung. Histologically, the neoplasm contained 2 distinct regions: spindle cells arranged in dense interwoven bundles with Antoni A areas and Verocay bodies and Antoni B regions with loosely arranged spindle cells separated by a mucinous matrix. Immunohistochemically, the neoplastic cells in the primary mass and right mandibular lymph node were strongly positive for vimentin, S-100, and glial fibrillar acidic protein. The neoplastic cells within the lung were strongly positive for vimentin and weakly positive for S-100 and glial fibrillar acidic protein. PMID:22604770

  7. Evaluating the effect of polytetrafluoroethylene and extractum cepae-heparin-allantoin gel in peripheral nerve injuries in a rat model

    PubMed Central

    Kahraman, Ahmet; Kahveci, Ramazan

    2015-01-01

    BACKGROUND: Peripheral nerves can be injured by congenital, mechanical, thermal or chemical causes. Peripheral nerve injuries are increasing in frequency, particularly in countries that are becoming more industrialized. Nerve and extremity injuries result in work loss and high treatment costs, and can lead to separation of patients from their social environment. Failure of nerve repair causes muscle functional losses, sensory losses and painful neuropathies. OBJECTIVES: To compare the effects of condensed polytetrafluoroethylene (cPTFE) and cPTFE-extractum cepae-heparin-allantoin (cPTFE-EHA) gel compound on nerve and functional recovery, and the prevention of adhesion and scar tissue formation after total peripheral nerve injury repaired by primary suture in a rat model. RESULTS: cPTFE alone and cPTFE-EHA gel was found to provide better functional recovery and nerve regeneration compared with primary repair only. In the macroscopic evaluation, the cPTFE-EHA gel was found to have no negative effect on wound healing and, despite increasing extra-neural scar tissue and adhesions, it had no negative effect on nerve function; in addition, it facilitated functional recovery. CONCLUSIONS: Compared with the cPTFE application alone, the application of perineural cPTFE-EHA gel during peripheral nerve surgery appeared to provide better functional recovery without causing any significant changes in epineural and extraneural scar tissue formation. PMID:25821766

  8. Methylation-based classification of benign and malignant peripheral nerve sheath tumors.

    PubMed

    Röhrich, Manuel; Koelsche, Christian; Schrimpf, Daniel; Capper, David; Sahm, Felix; Kratz, Annekathrin; Reuss, Jana; Hovestadt, Volker; Jones, David T W; Bewerunge-Hudler, Melanie; Becker, Albert; Weis, Joachim; Mawrin, Christian; Mittelbronn, Michel; Perry, Arie; Mautner, Victor-Felix; Mechtersheimer, Gunhild; Hartmann, Christian; Okuducu, Ali Fuat; Arp, Mirko; Seiz-Rosenhagen, Marcel; Hänggi, Daniel; Heim, Stefanie; Paulus, Werner; Schittenhelm, Jens; Ahmadi, Rezvan; Herold-Mende, Christel; Unterberg, Andreas; Pfister, Stefan M; von Deimling, Andreas; Reuss, David E

    2016-06-01

    The vast majority of peripheral nerve sheath tumors derive from the Schwann cell lineage and comprise diverse histological entities ranging from benign schwannomas and neurofibromas to high-grade malignant peripheral nerve sheath tumors (MPNST), each with several variants. There is increasing evidence for methylation profiling being able to delineate biologically relevant tumor groups even within the same cellular lineage. Therefore, we used DNA methylation arrays for methylome- and chromosomal profile-based characterization of 171 peripheral nerve sheath tumors. We analyzed 28 conventional high-grade MPNST, three malignant Triton tumors, six low-grade MPNST, four epithelioid MPNST, 33 neurofibromas (15 dermal, 8 intraneural, 10 plexiform), six atypical neurofibromas, 43 schwannomas (including 5 NF2 and 5 schwannomatosis associated cases), 11 cellular schwannomas, 10 melanotic schwannomas, 7 neurofibroma/schwannoma hybrid tumors, 10 nerve sheath myxomas and 10 ganglioneuromas. Schwannomas formed different epigenomic subgroups including a vestibular schwannoma subgroup. Cellular schwannomas were not distinct from conventional schwannomas. Nerve sheath myxomas and neurofibroma/schwannoma hybrid tumors were most similar to schwannomas. Dermal, intraneural and plexiform neurofibromas as well as ganglioneuromas all showed distinct methylation profiles. Atypical neurofibromas and low-grade MPNST were indistinguishable with a common methylation profile and frequent losses of CDKN2A. Epigenomic analysis finds two groups of conventional high-grade MPNST sharing a frequent loss of neurofibromin. The larger of the two groups shows an additional loss of trimethylation of histone H3 at lysine 27 (H3K27me3). The smaller one retains H3K27me3 and is found in spinal locations. Sporadic MPNST with retained neurofibromin expression did not form an epigenetic group and most cases could be reclassified as cellular schwannomas or soft tissue sarcomas. Widespread immunohistochemical loss

  9. Lentiviral Vector-Mediated Gradients of GDNF in the Injured Peripheral Nerve: Effects on Nerve Coil Formation, Schwann Cell Maturation and Myelination

    PubMed Central

    Eggers, Ruben; de Winter, Fred; Hoyng, Stefan A.; Roet, Kasper C. D.; Ehlert, Erich M.; Malessy, Martijn J. A.; Verhaagen, Joost; Tannemaat, Martijn R.

    2013-01-01

    Although the peripheral nerve is capable of regeneration, only a small minority of patients regain normal function after surgical reconstruction of a major peripheral nerve lesion, resulting in a severe and lasting negative impact on the quality of life. Glial cell-line derived neurotrophic factor (GDNF) has potent survival- and outgrowth-promoting effects on motoneurons, but locally elevated levels of GDNF cause trapping of regenerating axons and the formation of nerve coils. This phenomenon has been called the “candy store” effect. In this study we created gradients of GDNF in the sciatic nerve after a ventral root avulsion. This approach also allowed us to study the effect of increasing concentrations of GDNF on Schwann cell proliferation and morphology in the injured peripheral nerve. We demonstrate that lentiviral vectors can be used to create a 4 cm long GDNF gradient in the intact and lesioned rat sciatic nerve. Nerve coils were formed throughout the gradient and the number and size of the nerve coils increased with increasing GDNF levels in the nerve. In the nerve coils, Schwann cell density is increased, their morphology is disrupted and myelination of axons is severely impaired. The total number of regenerated and surviving motoneurons is not enhanced after the distal application of a GDNF gradient, but increased sprouting does result in higher number of motor axon in the distal segment of the sciatic nerve. These results show that lentiviral vector mediated overexpression of GDNF exerts multiple effects on both Schwann cells and axons and that nerve coil formation already occurs at relatively low concentrations of exogenous GDNF. Controlled expression of GDNF, by using a viral vector with regulatable GDNF expression, may be required to avoid motor axon trapping and to prevent the effects on Schwann cell proliferation and myelination. PMID:23951085

  10. Ethanol Ablation of a Peripheral Nerve Sheath Tumor Presenting as a Small Bowel Obstruction.

    PubMed

    Chin, Matthew; Chen, Chien-Lin; Chang, Kenneth; Lee, John; Samarasena, Jason

    2015-10-01

    Ethanol has historically been used as an ablative agent for a variety of lesions. One of the more common applications of this technique is celiac plexus neurolysis; however, recent reports have suggested a role for the endoscopic alcohol ablation of a variety of solid and cystic lesions. We report a novel case of endoscopic ethanol ablation of a peripheral nerve sheath tumor presenting as a small bowel obstruction. PMID:26504873

  11. Observations on the migratory behaviour of Schwann cells from adult peripheral nerve explant cultures.

    PubMed

    Crang, A J; Blakemore, W F

    1987-06-01

    The migration of Schwann cells from adult sciatic nerve explant cultures has been examined by time-lapse photomicrography. Analysis of Schwann cell migratory behaviour indicates that the initial outwandering by individual Schwann cells was random. Although chance cell-cell contacts resulted in temporary immobilization of pairs of cells, stable multicellular structures did not form during this initial phase. As local cell densities increased, Schwann cells assembled networks within which Schwann cell movement continued to be observed. A second form of Schwann cell outgrowth was observed from degenerating fibres in which arrays of highly oriented Schwann cells migrated away from their basal lamina tubes onto the culture dish. These observations of Schwann cell random migration, network self-assembly and coordinated extratubal migration are considered to highlight aspects of Schwann cell behaviour, independent of axonal influences, which may have relevance to their role in peripheral nerve repair following nerve section. PMID:3612187

  12. Changes induced by peripheral nerve injury in the morphology and nanomechanics of sensory neurons

    NASA Astrophysics Data System (ADS)

    Benzina, Ouafa; Szabo, Vivien; Lucas, Olivier; Saab, Marie-belle; Cloitre, Thierry; Scamps, Frédérique; Gergely, Csilla; Martin, Marta

    2013-06-01

    Peripheral nerve injury in vivo promotes a regenerative growth in vitro characterized by an improved neurite regrowth. Knowledge of the conditioning injury effects on both morphology and mechanical properties of live sensory neurons could be instrumental to understand the cellular and molecular mechanisms leading to this regenerative growth. In the present study, we use differential interference contrast microscopy, fluorescence microscopy and atomic force microscopy (AFM) to show that conditioned axotomy, induced by sciatic nerve injury, does not increase somatic size of sensory neurons from adult mice lumbar dorsal root ganglia but promotes the appearance of longer and larger neurites and growth cones. AFM on live neurons is also employed to investigate changes in morphology and membrane mechanical properties of somas of conditioned neurons following sciatic nerve injury. Mechanical analysis of the soma allows distinguishing neurons having a regenerative growth from control ones, although they show similar shapes and sizes.

  13. [METABOLIC CHANGES OF SKELETAL MUSCLES IN TRAUMATIC INJURY OF PERIPHERAL NERVE AND AUTOPLASTY IN EXPERIMENT].

    PubMed

    Gayovych, V V; Magomedov, A M; Makarenko, O M; Savohsko, S I

    2016-03-01

    The changes in metabolism of the amine acids, enzymes, electrolytes, fat acids (FA) in skeletal muscles of anterior and posterior extremities of rats in significant defects of peripheral nerve and its autoplasty were studied in experimental investigation. Metabolic changes in skeletal muscles are accompanied by significant intensity of proteolysis, lowering of the enzymes activity, energetic metabolism and in a less extent of the electrolytes balance and the FA metabolism. After autoplasty of big defects in the traumatized nerve the proteins' synthesis and restoration of activity of lactate dehydrogenase and creatine phosphokinase constitute the markers of muscular tissue restoration. Surgical restoration of the nerve is accompanied by a protein synthesis activation in muscles, but normalization of the enzyme systems indices, the lipids metabolism and the electrolytes balance was not observed. Metabolic dysbalance needs a certain pharmacological correction and prevention of a progress of pathological process in skeletal muscles. PMID:27514098

  14. Neurobiological assessment of regenerative electrodes for bidirectional interfacing injured peripheral nerves.

    PubMed

    Lago, Natalia; Udina, Esther; Ramachandran, Anup; Navarro, Xavier

    2007-06-01

    Regenerative electrodes are designed to interface regenerated axons from a sectioned peripheral nerve. Applicability of regenerative electrodes depends on biocompatibility, success of axonal regeneration, secondary nerve damage, and adequacy of interface electronics. Polyimide sieve electrodes with 281 holes were chronically implanted in the severed sciatic nerve of 30 rats. Regeneration was successful in all the animals, with increasing numbers of regenerated myelinated fibers from 2 to 6 mo. However, constrictive axonopathy affected a few cases from 6 to 12 mo. postimplantation. A second electrode design with 571 holes and 27 ring electrodes was developed. The number of regenerated axons increased thanks to the larger open area. Recordings were obtained from a low proportion of electrodes on the sieve in response to distal stimulation. Difficulties for recording impulses with regenerative electrodes include the small size of regenerated axons, changes in membrane excitability and in target reconnection. PMID:17554832

  15. Large-Scale Functional Reorganization in Adult Monkey Cortex after Peripheral Nerve Injury

    NASA Astrophysics Data System (ADS)

    Garraghty, Preston E.; Kaas, Jon H.

    1991-08-01

    In adult monkeys, peripheral nerve injuries induce dramatic examples of neural plasticity in somatosensory cortex. It has been suggested that a cortical distance limit exists and that the amount of plasticity that is possible after injury is constrained by this limit. We have investigated this possibility by depriving a relatively large expanse of cortex by transecting and ligating both the median and the ulnar nerves to the hand. Electrophysiological recording in cortical areas 3b and 1 in three adult squirrel monkeys no less than 2 months after nerve transection has revealed that cutaneous responsiveness is regained throughout the deprived cortex and that a roughly normal topographic order is reestablished for the reorganized cortex.

  16. Design, fabrication and evaluation of a conforming circumpolar peripheral nerve cuff electrode for acute experimental use

    PubMed Central

    Foldes, Emily L.; Ackermann, D. Michael; Bhadra, Niloy; Kilgore, Kevin L.; Bhadra, Narendra

    2011-01-01

    Nerve cuff electrodes are a principle tool of basic and applied electro-neurophysiology studies and are championed for their ability to achieve good nerve recruitment with low thresholds. We describe the design and method of fabrication for a novel circumpolar peripheral nerve electrode for acute experimental use. This cylindrical cuff-style electrode provides approximately 270 degrees of radial electrode contact with a nerve for each of an arbitrary number of contacts, has a profile that allows for simple placement and removal in an acute nerve preparation, and is designed for adjustment of the cylindrical diameter to ensure a close fit on the nerve. For each electrode, the electrical contacts were cut from 25 µm platinum foil as an array so as to maintain their positions relative to each other within the cuff. Lead wires were welded to each intended contact. The structure was then molded in silicone elastomer, after which the individual contacts were electrically isolated. The final electrode was curved into a cylindrical shape with an inner diameter corresponding to that of the intended target nerve. The positions of these contacts were well maintained during the molding and shaping process and failure rates during fabrication due to contact displacements were very low. Established electrochemical measurements were made on one electrode to confirm expected behavior for a platinum electrode and to measure the electrode impedance to applied voltages at different frequencies. These electrodes have been successfully used for nerve stimulation, recording, and conduction block in a number of different acute animal experiments by several investigators. PMID:21187115

  17. Allotransplanted Neurons Used to Repair Peripheral Nerve Injury Do Not Elicit Overt Immunogenicity

    PubMed Central

    Liu, Weimin; Ren, Yi; Bossert, Adam; Wang, Xiaowei; Dayawansa, Samantha; Tong, Jing; He, Xiaoshen; Smith, Douglas H.; Gelbard, Harris A.; Huang, Jason H.

    2012-01-01

    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 standard of

  18. Activity dependent therapies modulate the spinal changes that motoneurons suffer after a peripheral nerve injury.

    PubMed

    Arbat-Plana, Ariadna; Torres-Espín, Abel; Navarro, Xavier; Udina, Esther

    2015-01-01

    Injury of a peripheral nerve not only leads to target denervation, but also induces massive stripping of spinal synapses on axotomized motoneurons, with disruption of spinal circuits. Even when regeneration is successful, unspecific reinnervation and the limited reconnection of the spinal circuits impair functional recovery. The aim of this study was to describe the changes that axotomized motoneurons suffer after peripheral nerve injury and how activity-dependent therapies and neurotrophic factors can modulate these events. We observed a marked decrease in glutamatergic synapses, with a maximum peak at two weeks post-axotomy, which was only partially reversed with time. This decrease was accompanied by an increase in gephyrin immunoreactivity and a disintegration of perineuronal nets (PNNs) surrounding the motoneurons. Direct application of neurotrophins at the proximal stump was not able to reverse these effects. In contrast, activity-dependent treatment, in the form of treadmill running, reduced the observed destructuring of perineuronal nets and the loss of glutamatergic synapses two weeks after injury. These changes were proportional to the intensity of the exercise protocol. Blockade of sensory inputs from the homolateral hindlimb also reduced PNN immunoreactivity around intact motoneurons, and in that case treadmill running did not reverse that loss, suggesting that the effects of exercise on motoneuron PNN depend on increased sensory activity. Preservation of motoneuron PNN and reduction of synaptic stripping by exercise could facilitate the maintenance of the spinal circuitry and benefit functional recovery after peripheral nerve injury. PMID:25448160

  19. Supplementary motor area deactivation impacts the recovery of hand function from severe peripheral nerve injury

    PubMed Central

    Lu, Ye-chen; Liu, Han-qiu; Hua, Xu-yun; Shen, Yun-dong; Xu, Wen-dong; Xu, Jian-guang; Gu, Yu-dong

    2016-01-01

    Although some patients have successful peripheral nerve regeneration, a poor recovery of hand function often occurs after peripheral nerve injury. It is believed that the capability of brain plasticity is crucial for the recovery of hand function. The supplementary motor area may play a key role in brain remodeling after peripheral nerve injury. In this study, we explored the activation mode of the supplementary motor area during a motor imagery task. We investigated the plasticity of the central nervous system after brachial plexus injury, using the motor imagery task. Results from functional magnetic resonance imaging showed that after brachial plexus injury, the motor imagery task for the affected limbs of the patients triggered no obvious activation of bilateral supplementary motor areas. This result indicates that it is difficult to excite the supplementary motor areas of brachial plexus injury patients during a motor imagery task, thereby impacting brain remodeling. Deactivation of the supplementary motor area is likely to be a serious problem for brachial plexus injury patients in terms of preparing, initiating and executing certain movements, which may be partly responsible for the unsatisfactory clinical recovery of hand function. PMID:27212933

  20. Activation of the unfolded protein response promotes axonal regeneration after peripheral nerve injury.

    PubMed

    Oñate, Maritza; Catenaccio, Alejandra; Martínez, Gabriela; Armentano, Donna; Parsons, Geoffrey; Kerr, Bredford; Hetz, Claudio; Court, Felipe A

    2016-01-01

    Although protein-folding stress at the endoplasmic reticulum (ER) is emerging as a driver of neuronal dysfunction in models of spinal cord injury and neurodegeneration, the contribution of this pathway to peripheral nerve damage remains poorly explored. Here we targeted the unfolded protein response (UPR), an adaptive reaction against ER stress, in mouse models of sciatic nerve injury and found that ablation of the transcription factor XBP1, but not ATF4, significantly delay locomotor recovery. XBP1 deficiency led to decreased macrophage recruitment, a reduction in myelin removal and axonal regeneration. Conversely, overexpression of XBP1s in the nervous system in transgenic mice enhanced locomotor recovery after sciatic nerve crush, associated to an improvement in key pro-regenerative events. To assess the therapeutic potential of UPR manipulation to axonal regeneration, we locally delivered XBP1s or an shRNA targeting this transcription factor to sensory neurons of the dorsal root ganglia using a gene therapy approach and found an enhancement or reduction of axonal regeneration in vivo, respectively. Our results demonstrate a functional role of specific components of the ER proteostasis network in the cellular changes associated to regeneration and functional recovery after peripheral nerve injury. PMID:26906090

  1. Activation of the unfolded protein response promotes axonal regeneration after peripheral nerve injury

    PubMed Central

    Oñate, Maritza; Catenaccio, Alejandra; Martínez, Gabriela; Armentano, Donna; Parsons, Geoffrey; Kerr, Bredford; Hetz, Claudio; Court, Felipe A.

    2016-01-01

    Although protein-folding stress at the endoplasmic reticulum (ER) is emerging as a driver of neuronal dysfunction in models of spinal cord injury and neurodegeneration, the contribution of this pathway to peripheral nerve damage remains poorly explored. Here we targeted the unfolded protein response (UPR), an adaptive reaction against ER stress, in mouse models of sciatic nerve injury and found that ablation of the transcription factor XBP1, but not ATF4, significantly delay locomotor recovery. XBP1 deficiency led to decreased macrophage recruitment, a reduction in myelin removal and axonal regeneration. Conversely, overexpression of XBP1s in the nervous system in transgenic mice enhanced locomotor recovery after sciatic nerve crush, associated to an improvement in key pro-regenerative events. To assess the therapeutic potential of UPR manipulation to axonal regeneration, we locally delivered XBP1s or an shRNA targeting this transcription factor to sensory neurons of the dorsal root ganglia using a gene therapy approach and found an enhancement or reduction of axonal regeneration in vivo, respectively. Our results demonstrate a functional role of specific components of the ER proteostasis network in the cellular changes associated to regeneration and functional recovery after peripheral nerve injury. PMID:26906090

  2. Needle stylet with integrated optical fibers for spectroscopic contrast during peripheral nerve blocks

    NASA Astrophysics Data System (ADS)

    Desjardins, Adrien E.; van der Voort, Marjolein; Roggeveen, Stefan; Lucassen, Gerald; Bierhoff, Walter; Hendriks, Benno H. W.; Brynolf, Marcus; Holmström, Björn

    2011-07-01

    The effectiveness of peripheral nerve blocks is highly dependent on the accuracy at which the needle tip is navigated to the target injection site. Even when electrical stimulation is utilized in combination with ultrasound guidance, determining the proximity of the needle tip to the target region close to the nerve can be challenging. Optical reflectance spectroscopy could provide additional information about tissues that is complementary to these navigation methods. We demonstrate a novel needle stylet for acquiring spectra from tissue at the tip of a commercial 20-gauge needle. The stylet has integrated optical fibers that deliver broadband light to tissue and receive scattered light. Two spectrometers resolve the light that is received from tissue across the wavelength range of 500-1600 nm. In our pilot study, measurements are acquired from a postmortem dissection of the brachial plexus of a swine. Clear differences are observed between spectra acquired from nerves and those acquired from adjacent tissue structures. We conclude that spectra acquired with the stylet have the potential to increase the accuracy with which peripheral nerve blocks are performed.

  3. Peripheral NMDA Receptors Mediate Antidromic Nerve Stimulation-Induced Tactile Hypersensitivity in the Rat

    PubMed Central

    Jang, Jun Ho; Nam, Taick Sang; Jun, Jaebeom; Jung, Se Jung; Kim, Dong-Wook; Leem, Joong Woo

    2015-01-01

    We investigated the role of peripheral NMDA receptors (NMDARs) in antidromic nerve stimulation-induced tactile hypersensitivity outside the skin area innervated by stimulated nerve. Tetanic electrical stimulation (ES) of the decentralized L5 spinal nerve, which induced enlargement of plasma extravasation, resulted in tactile hypersensitivity in the L4 plantar dermatome of the hind-paw. When intraplantar (i.pl.) injection was administered into the L4 dermatome before ES, NMDAR and group-I metabotropic Glu receptor (mGluR) antagonists and group-II mGluR agonist but not AMPA/kainate receptor antagonist prevented ES-induced hypersensitivity. I.pl. injection of PKA or PKC inhibitors also prevented ES-induced hypersensitivity. When the same injections were administered after establishment of ES-induced hypersensitivity, hypersensitivity was partially reduced by NMDAR antagonist only. In naïve animals, i.pl. Glu injection into the L4 dermatome induced tactile hypersensitivity, which was blocked by NMDAR antagonist and PKA and PKC inhibitors. These results suggest that the peripheral release of Glu, induced by antidromic nerve stimulation, leads to the expansion of tactile hypersensitive skin probably via nociceptor sensitization spread due to the diffusion of Glu into the skin near the release site. In addition, intracellular PKA- and PKC-dependent mechanisms mediated mainly by NMDAR activation are involved in Glu-induced nociceptor sensitization and subsequent hypersensitivity. PMID:26770021

  4. High aspect ratio template and method for producing same for central and peripheral nerve repair

    NASA Technical Reports Server (NTRS)

    Sakamoto, Jeff S. (Inventor); Tuszynski, Mark Henry (Inventor); Gros, Thomas (Inventor); Chan, Christina (Inventor); Mehrotra, Sumit (Inventor)

    2011-01-01

    Millimeter to nano-scale structures manufactured using a multi-component polymer fiber matrix are disclosed. The use of dissimilar polymers allows the selective dissolution of the polymers at various stages of the manufacturing process. In one application, biocompatible matrixes may be formed with long pore length and small pore size. The manufacturing process begins with a first polymer fiber arranged in a matrix formed by a second polymer fiber. End caps may be attached to provide structural support and the polymer fiber matrix selectively dissolved away leaving only the long polymer fibers. These may be exposed to another product, such as a biocompatible gel to form a biocompatible matrix. The polymer fibers may then be selectively dissolved leaving only a biocompatible gel scaffold with the pores formed by the dissolved polymer fibers. The scaffolds may be used in, among other applications, the repair of central and peripheral nerves. Scaffolds for the repair of peripheral nerves may include a reservoir for the sustained release of nerve growth factor. The scaffolds may also include a multifunctional polyelectrolyte layer for the sustained release of nerve growth factor and enhance biocompatibility.

  5. On the therapeutic viability of peripheral nerve stimulation for ilioinguinal neuralgia: putative mechanisms and possible utility.

    PubMed

    Rauchwerger, Jacob J; Giordano, James; Rozen, Dima; Kent, Joel L; Greenspan, Joshua; Closson, Carey-Walter F

    2008-01-01

    Injury to the ilioinguinal nerve commonly follows during lower abdominal and pelvic surgery, especially with inguinal hernia repair, appendectomy, and hysterectomy. Other potential causes include low abdominal blunt trauma, iliac crest bone graft, psoas abscess, Pott's disease, and prolonged wearing of abdominally constrictive clothing. The actual incidence of ilioinguinal neuralgia is uncertain, as reported percentage ranges between 12% and 62%. Prompt and accurate diagnosis is critical, and appropriate treatments range from conservative pharmacologic management with nonopioid (eg, gabapentin, topiramate) as well as opioid agents, to surgical neurectomy of the proximal portion of the ilioinguinal nerve. Pharmacological treatment is frequently unsuccessful (particularly if delayed) and while surgery is successful in approximately 73% of cases, it can result in problematic paresthesias, and pain may continue to persist in some patients. Thus, minimally invasive techniques, such as peripheral nerve stimulation, may be viable in those patients who are refractory to pharmacological management, as an option to surgery, and who have not gained satisfactory pain relief through surgical intervention. We present three cases of successful pain control of ilioinguinal neuralgia with peripheral nerve stimulation. These cases demonstrate the potential benefits of neurostimulation including durable effective pain relief and decreased use of medication. Putative mechanisms of effect(s) and caveats for continued research to inform prudent employment of this technique are presented. PMID:18208448

  6. Erythropoietin promotes peripheral nerve regeneration in rats by upregulating expression of insulin-like growth factor-1

    PubMed Central

    Wang, Wei; Li, Dongsheng; Li, Qing; Wang, Lei; Bai, Guang; Yang, Tao; Li, Qiang; Zhu, Zhitu

    2015-01-01

    Introduction Erythropoietin (EPO) has been shown to have beneficial effects on peripheral nerve damage, but its mechanism of action remains incompletely understood. In this study we hypothesized that EPO promotes peripheral nerve repair via neurotrophic factor upregulation. Material and methods Thirty adult male Wistar rats were employed to establish a sciatic nerve injury model. They were then randomly divided into two groups to be subjected to different treatment: 0.9% saline (group A) and 5000 U/kg EPO (group B). The walking behavior of rats was evaluated by footprint analysis, and the nerve regeneration was assessed by electron microscopy. The expression of insulin-like growth factor-1 (IGF-1) in the injured sciatic nerves was detected by immunohistochemical analysis. Results Compared to saline treatment, EPO treatment led to the growth of myelin sheath, the recovery of normal morphology of axons and Schwann cells, and higher density of myelinated nerve fibers. Erythropoietin treatment promoted the recovery of SFI in the injured sciatic nerves. In addition, EPO treatment led to increased IGF-1 expression in the injured sciatic nerves. Conclusions Erythropoietin may promote peripheral nerve repair in a rat model of sciatic nerve injury through the upregulation of IGF-1 expression. These findings reveal a novel mechanism underlying the neurotrophic effects of EPO. PMID:25995763

  7. Autotomy and decreased spinal substance P following peripheral cryogenic nerve lesion.

    PubMed

    Deleo, J A; Coombs, D W

    1991-10-01

    Cryotherapy has been clinically applied to relieve pain by blocking peripheral nerve function. Clinically, analgesia has been successfully achieved but there is suggestion that permanent pain relief may be accompanied by extended motor and sensory deficits. This study was undertaken to determine the effect of a peripheral cryogenic nerve lesion, i.e., of the sciatic nerve, on behavioral effects and substance P content in the dorsal horn of the spinal cord. In rats, the right sciatic nerve was exposed and cryolesioned using one freeze-thaw-refreeze cycle. In an alternate group, the right sciatic nerve was cut and a 3-mm region was excised. Animals were allowed to recover 7 or 21 days during which their behavior was assessed. Autotomy, an animal's tendency to attack the nerve-injured affected limb, occurred in both the cryolesioned and sectioned groups. They were killed by transcardiac perfusion of fixative and segments L4-S1 were processed for immunocytochemistry. The SP-like immunoreactivity (SPLI) in the right and left dorsal horns was compared and quantitated using a microcomputer imaging device. We utilized a fully automated program to digitize and quantitate the staining of the substantia gelatinosa. There was no significant difference in SPLI in the dorsal horns of the sham-operated controls at either time period. At 7 days the sectioned group demonstrated a 40% decrease in SPLI and 76% decrease at 21 days. In the cryolesioned group, there was a 34% decrease at 7 days and by 21 days there was a 68% decrease in immunoreactivity on the operated side.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1721566

  8. Mutation in the Na+ channel subunit SCN1B produces paradoxical changes in peripheral nerve excitability.

    PubMed

    Kiernan, Matthew C; Krishnan, Arun V; Lin, Cindy S-Y; Burke, David; Berkovic, Samuel F

    2005-08-01

    To determine the effect of an established mutation of the beta1 subunit of Na(+) channels on nerve excitability, studies were undertaken in patients diagnosed with generalized epilepsy with febrile seizures plus (GEFS+). Multiple nerve excitability measurements were used to investigate the membrane properties of sensory and motor axons in five patients (aged 18-55 years) who were currently experiencing no seizures and were not on anticonvulsants. There was no history of paraesthesiae, fasciculation or cramps to suggest hyperexcitability of peripheral nerve axons. The median nerve was stimulated at the wrist, and compound muscle action potentials (CMAPs) were recorded from abductor pollicis brevis and the antidromic compound sensory nerve action potential (CSAPs) from digit 2. Stimulus-response behaviour, strength-duration time constant, threshold electrotonus, current-threshold relationship and the recovery of excitability following a supramaximal conditioning stimulus were recorded using threshold tracking. Compared with normal controls (n = 29), the axons of patients were of higher threshold. CMAPs and CSAPs were relatively small, although individual values remained within the normal ranges. Refractoriness and relative refractory period (markers of transient Na(+) channel function) were significantly reduced in GEFS+ patients with established mutations in SCN1B (P < 0.05), and strength-duration time constants (dependent on persistent Na(+) conductances) were reduced. It is suggested that, in peripheral nerve axons, the mutation underlying GEFS+ reduces the number of functioning Na(+) channels at the node of Ranvier and that this rather than any change in gating of individual channels dominates axonal excitability in these patients. PMID:15857929

  9. [Transplanted epidermal neural crest stem cell in a peripheral nerve gap].

    PubMed

    Zhang, Lu; Zhang, Jieyuan; Li, Bingcang; Liu, Zheng; Liu, Bin

    2014-04-01

    Neural crest stem cells originated from hair follicle (epidermal neural crest stem cell, EPI-NCSC) are easy to obtain and have potentials to differentiate into various tissues, which make them eminent seed cells for tissue engineering. EPI-NCSC is now used to repair nerve injury, especially, the spinal cord injury. To investigate their effects on repairing peripheral nerve injury, EPI-NCSC from a GFP-SD rat were primarily cultured on coated dishes and on a poly lactic acid coglycolic acid copolymer (PLGA) membrane. Methyl thiazolyl tetrazolium (MTT) assay showed that the initial adhesion rate of EPI-NCSC was 89.7% on PLGA membrane, and the relative growth rates were 89.3%, 87.6%, 85.6%, and 96.6% on the 1st, 3rd, 5th, 7th day respectively. Cell cycles and DNA ploidy analysis demonstrated that cell cycles and proliferation indexes of cultured EPI-NCSC had the same variation pattern on coated dishes and PLGA membrane. Then cultured EPI-NCSC were mixed with equal amount of extracellular matrix and injected into a PLGA conduit to connect a 10 mm surgery excision gap of rat sciatic nerve, Dulbecco's Modified Eagle's medium (DMEM) was used to substitute EPI-NCSC in the control group. After four weeks of transplantation, the defected sciatic nerve achieved a histological restoration, the sensory function of rat hind limb was partly recovered and the sciatic nerve index was also improved. The above results showed that a PLGA conduit filled with EPI-NCSC has a good repair effect on the peripheral nerve injury. PMID:25195250

  10. Mice Lacking GD3 Synthase Display Morphological Abnormalities in the Sciatic Nerve and Neuronal Disturbances during Peripheral Nerve Regeneration

    PubMed Central

    Ribeiro-Resende, Victor Túlio; Gomes, Tiago Araújo; de Lima, Silmara; Nascimento-Lima, Maiara; Bargas-Rega, Michele; Santiago, Marcelo Felipe; Reis, Ricardo Augusto de Melo; de Mello, Fernando Garcia

    2014-01-01

    The ganglioside 9-O-acetyl GD3 is overexpressed in peripheral nerves after lesioning, and its expression is correlated with axonal degeneration and regeneration in adult rodents. However, the biological roles of this ganglioside during the regenerative process are unclear. We used mice lacking GD3 synthase (Siat3a KO), an enzyme that converts GM3 to GD3, which can be further converted to 9-O-acetyl GD3. Morphological analyses of longitudinal and transverse sections of the sciatic nerve revealed significant differences in the transverse area and nerve thickness. The number of axons and the levels of myelin basic protein were significantly reduced in adult KO mice compared to wild-type (WT) mice. The G-ratio was increased in KO mice compared to WT mice based on quantification of thin transverse sections stained with toluidine blue. We found that neurite outgrowth was significantly reduced in the absence of GD3. However, addition of exogenous GD3 led to neurite growth after 3 days, similar to that in WT mice. To evaluate fiber regeneration after nerve lesioning, we compared the regenerated distance from the lesion site and found that this distance was one-fourth the length in KO mice compared to WT mice. KO mice in which GD3 was administered showed markedly improved regeneration compared to the control KO mice. In summary, we suggest that 9-O-acetyl GD3 plays biological roles in neuron-glia interactions, facilitating axonal growth and myelination induced by Schwann cells. Moreover, exogenous GD3 can be converted to 9-O-acetyl GD3 in mice lacking GD3 synthase, improving regeneration. PMID:25330147

  11. Mice lacking GD3 synthase display morphological abnormalities in the sciatic nerve and neuronal disturbances during peripheral nerve regeneration.

    PubMed

    Ribeiro-Resende, Victor Túlio; Araújo Gomes, Tiago; de Lima, Silmara; Nascimento-Lima, Maiara; Bargas-Rega, Michele; Santiago, Marcelo Felipe; Reis, Ricardo Augusto de Melo; de Mello, Fernando Garcia

    2014-01-01

    The ganglioside 9-O-acetyl GD3 is overexpressed in peripheral nerves after lesioning, and its expression is correlated with axonal degeneration and regeneration in adult rodents. However, the biological roles of this ganglioside during the regenerative process are unclear. We used mice lacking GD3 synthase (Siat3a KO), an enzyme that converts GM3 to GD3, which can be further converted to 9-O-acetyl GD3. Morphological analyses of longitudinal and transverse sections of the sciatic nerve revealed significant differences in the transverse area and nerve thickness. The number of axons and the levels of myelin basic protein were significantly reduced in adult KO mice compared to wild-type (WT) mice. The G-ratio was increased in KO mice compared to WT mice based on quantification of thin transverse sections stained with toluidine blue. We found that neurite outgrowth was significantly reduced in the absence of GD3. However, addition of exogenous GD3 led to neurite growth after 3 days, similar to that in WT mice. To evaluate fiber regeneration after nerve lesioning, we compared the regenerated distance from the lesion site and found that this distance was one-fourth the length in KO mice compared to WT mice. KO mice in which GD3 was administered showed markedly improved regeneration compared to the control KO mice. In summary, we suggest that 9-O-acetyl GD3 plays biological roles in neuron-glia interactions, facilitating axonal growth and myelination induced by Schwann cells. Moreover, exogenous GD3 can be converted to 9-O-acetyl GD3 in mice lacking GD3 synthase, improving regeneration. PMID:25330147

  12. Peripheral nerve injury is accompanied by chronic transcriptome-wide changes in the mouse prefrontal cortex

    PubMed Central

    2013-01-01

    Background Peripheral nerve injury can have long-term consequences including pain-related manifestations, such as hypersensitivity to cutaneous stimuli, as well as affective and cognitive disturbances, suggesting the involvement of supraspinal mechanisms. Changes in brain structure and cortical function associated with many chronic pain conditions have been reported in the prefrontal cortex (PFC). The PFC is implicated in pain-related co-morbidities such as depression, anxiety and impaired emotional decision-making ability. We recently reported that this region is subject to significant epigenetic reprogramming following peripheral nerve injury, and normalization of pain-related structural, functional and epigenetic abnormalities in the PFC are all associated with effective pain reduction. In this study, we used the Spared Nerve Injury (SNI) model of neuropathic pain to test the hypothesis that peripheral nerve injury triggers persistent long-lasting changes in gene expression in the PFC, which alter functional gene networks, thus providing a possible explanation for chronic pain associated behaviors. Results SNI or sham surgery where performed in male CD1 mice at three months of age. Six months after injury, we performed transcriptome-wide sequencing (RNAseq), which revealed 1147 differentially regulated transcripts in the PFC in nerve-injured vs. control mice. Changes in gene expression occurred across a number of functional gene clusters encoding cardinal biological processes as revealed by Ingenuity Pathway Analysis. Significantly altered biological processes included neurological disease, skeletal muscular disorders, behavior, and psychological disorders. Several of the changes detected by RNAseq were validated by RT-QPCR and included transcripts with known roles in chronic pain and/or neuronal plasticity including the NMDA receptor (glutamate receptor, ionotropic, NMDA; grin1), neurite outgrowth (roundabout 3; robo3), gliosis (glial fibrillary acidic protein

  13. Metanx alleviates multiple manifestations of peripheral neuropathy and increases intraepidermal nerve fiber density in Zucker diabetic fatty rats.

    PubMed

    Shevalye, Hanna; Watcho, Pierre; Stavniichuk, Roman; Dyukova, Elena; Lupachyk, Sergey; Obrosova, Irina G

    2012-08-01

    Metanx is a product containing L-methylfolate, pyridoxal 5'-phosphate, and methylcobalamin for management of endothelial dysfunction. Metanx ingredients counteract endothelial nitric oxide synthase uncoupling and oxidative stress in vascular endothelium and peripheral nerve. This study evaluates Metanx on diabetic peripheral neuropathy in ZDF rats, a model of type 2 diabetes. Metanx was administered to 15-week-old ZDF and ZDF lean rats at either 4.87 mg ⋅ kg(-1) ⋅ day(-1) (a body weight-based equivalent of human dose) or 24.35 mg ⋅ kg(-1) ⋅ day(-1) by oral gavage two times a day for 4 weeks. Both doses alleviated hind limb digital sensory, but not sciatic motor, nerve conduction slowing and thermal and mechanical hypoalgesia in the absence of any reduction of hyperglycemia. Low-dose Metanx increased intraepidermal nerve fiber density but did not prevent morphometric changes in distal tibial nerve myelinated fibers. Metanx treatment counteracted endothelial nitric oxide synthase uncoupling, inducible nitric oxide synthase upregulation, and methylglyoxal-derived advanced glycation end product, nitrotyrosine, and nitrite/nitrate accumulation in the peripheral nerve. In conclusion, Metanx, at a body weight-based equivalent of human dose, increased intraepidermal nerve fiber density and improved multiple parameters of peripheral nerve function in ZDF rats. Clinical studies are needed to determine if Metanx finds use in management of diabetic peripheral neuropathy. PMID:22751692

  14. Omega-6 and omega-3 fatty acids predict accelerated decline of peripheral nerve function in older persons

    PubMed Central

    Lauretani, F.; Bandinelli, S.; Benedetta, B.; Cherubini, A.; Iorio, A. D.; Blè, A.; Giacomini, V.; Corsi, A. M.; Guralnik, J. M.; Ferrucci, L.

    2009-01-01

    Pre-clinical studies suggest that both omega-6 and omega-3 fatty acids have beneficial effects on peripheral nerve function. Rats feed a diet rich in polyunsaturated fatty acids (PUFAs) showed modification of phospholipid fatty acid composition in nerve membranes and improvement of sciatic nerve conduction velocity (NCV). We tested the hypothesis that baseline plasma omega-6 and omega-3 fatty acids levels predict accelerated decline of peripheral nerve function. Changes between baseline and the 3-year follow-up in peripheral nerve function was assessed by standard surface ENG of the right peroneal nerve in 384 male and 443 female participants of the InCHIANTI study (age range: 24–97 years). Plasma concentrations of selected fatty acids assessed at baseline by gas chromatography. Independent of confounders, plasma omega-6 fatty acids and linoleic acid were significantly correlated with peroneal NCV at enrollment. Lower plasma PUFA, omega-6 fatty acids, linoleic acid, ratio omega-6/omega-3, arachidonic acid and docosahexanoic acid levels were significantly predicted a steeper decline in nerve function parameters over the 3-year follow-up. Low plasma omega-6 and omega-3 fatty acids levels were associated with accelerated decline of peripheral nerve function with aging. PMID:17594339

  15. Omega-6 and omega-3 fatty acids predict accelerated decline of peripheral nerve function in older persons.

    PubMed

    Lauretani, F; Bandinelli, S; Bartali, B; Benedetta, B; Cherubini, A; Iorio, A D; Blè, A; Giacomini, V; Corsi, A M; Guralnik, J M; Ferrucci, L

    2007-07-01

    Pre-clinical studies suggest that both omega-6 and omega-3 fatty acids have beneficial effects on peripheral nerve function. Rats feed a diet rich in polyunsaturated fatty acids (PUFAs) showed modification of phospholipid fatty acid composition in nerve membranes and improvement of sciatic nerve conduction velocity (NCV). We tested the hypothesis that baseline plasma omega-6 and omega-3 fatty acids levels predict accelerated decline of peripheral nerve function. Changes between baseline and the 3-year follow-up in peripheral nerve function was assessed by standard surface ENG of the right peroneal nerve in 384 male and 443 female participants of the InCHIANTI study (age range: 24-97 years). Plasma concentrations of selected fatty acids assessed at baseline by gas chromatography. Independent of confounders, plasma omega-6 fatty acids and linoleic acid were significantly correlated with peroneal NCV at enrollment. Lower plasma PUFA, omega-6 fatty acids, linoleic acid, ratio omega-6/omega-3, arachidonic acid and docosahexanoic acid levels were significantly predicted a steeper decline in nerve function parameters over the 3-year follow-up. Low plasma omega-6 and omega-3 fatty acids levels were associated with accelerated decline of peripheral nerve function with aging. PMID:17594339

  16. Multiwalled CNT-pHEMA composite conduit for peripheral nerve repair.

    PubMed

    Arslantunali, D; Budak, G; Hasirci, V

    2014-03-01

    A nerve conduit is designed to improve peripheral nerve regeneration by providing guidance to the nerve cells. Conductivity of such guides is reported to enhance this process. In the current study, a nerve guide was constructed from poly(2-hydroxyethyl methacrylate) (pHEMA), which was loaded with multiwalled carbon nanotubes (mwCNT) to introduce conductivity. PHEMA hydrogels were designed to have a porous structure to facilitate the transportation of the compounds needed for cell nutrition and growth and also for waste removal. We showed that when loaded with relatively high concentrations of mwCNTs (6%, w/w in hydrogels), the pHEMA guide was more conductive and more hydrophobic than pristine pHEMA hydrogel. The mechanical properties of the composites were better when they carried mwCNT. Elastic modulus of 6% mwCNT loaded pHEMA was twofold higher (0.32 ± 0.06 MPa) and similar to that of the soft tissues. Electrical conductivity was significantly improved (11.4-fold) from 7 × 10(-3) Ω(-1).cm(-1) (pHEMA) to 8.0 × 10(-2) Ω(-1).cm(-1) (6% mwCNT loaded pHEMA). On application of electrical potential, the SHSY5Y neuroblastoma cells seeded on mwCNTs carrying pHEMA maintained their viability, whereas those on pure pHEMA could not, indicating that mwCNT helped conduct electricity and make them more suitable as nerve conduits. PMID:23554154

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

    PubMed

    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. PMID:26228942

  18. Diabetic peripheral neuropathy assessment through texture based analysis of corneal nerve images

    NASA Astrophysics Data System (ADS)

    Silva, Susana F.; Gouveia, Sofia; Gomes, Leonor; Negrão, Luís; João Quadrado, Maria; Domingues, José Paulo; Morgado, António Miguel

    2015-05-01

    Diabetic peripheral neuropathy (DPN) is one common complication of diabetes. Early diagnosis of DPN often fails due to the non-availability of a simple, reliable, non-invasive method. Several published studies show that corneal confocal microscopy (CCM) can identify small nerve fibre damage and quantify the severity of DPN, using nerve morphometric parameters. Here, we used image texture features, extracted from corneal sub-basal nerve plexus images, obtained in vivo by CCM, to identify DPN patients, using classification techniques. A SVM classifier using image texture features was used to identify (DPN vs. No DPN) DPN patients. The accuracies were 80.6%, when excluding diabetic patients without neuropathy, and 73.5%, when including diabetic patients without diabetic neuropathy jointly with healthy controls. The results suggest that texture analysis might be used as a complementing technique for DPN diagnosis, without requiring nerve segmentation in CCM images. The results also suggest that this technique has enough sensitivity to detect early disorders in the corneal nerves of diabetic patients.

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

    SciTech Connect

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

    1990-12-01

    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.

  20. Preparation and characterization of electrical conductive PVA based materials for peripheral nerve tube-guides.

    PubMed

    Gonçalves, C; Ribeiro, J; Pereira, T; Luís, A L; Mauricio, A C; Santos, J D; Lopes, M A

    2016-08-01

    Peripheral nerve regeneration is a serious clinical problem. Presently, there are several nerve tube-guides available in the market, however with some limitations. The goal of this work was the development of a biomaterial with high electrical conductivity to produce tube-guides for nerve regeneration after neurotmesis injuries whenrver an end-to-end suture without tension is not possible. A matrix of poly(vinyl alcohol) (PVA) was used loaded with the following electrical conductive materials: COOH-functionalized multiwall carbon nanotubes (MWCNTs), poly(pyrrole) (PPy), magnesium chloride (MgCl2 ), and silver nitrate (AgNO3 ). The tube-guide production was carried out by a freezing/thawing process (physical crosslinking) with a final annealing treatment. After producing the tube-guide for nerve regeneration, the physicochemical characterization was performed. The most interesting results were achieved by loading PVA with 0.05% of PPy or COOH- functionalized CNTs. These tubes combined the electrical conductivity of carbon nanotubes (CNTs) and PPy with the biocompatibility of PVA matrix, with potential clinical application for nerve regeneration. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1981-1987, 2016. PMID:27027727

  1. Neuroinflammation in the peripheral nerve: Cause, modulator, or bystander in peripheral neuropathies?

    PubMed Central

    2015-01-01

    The role of innate and adaptive inflammation as a primary driver or modifier of neuropathy in premorbidly normal nerves, and as a critical player in amplifying neuropathies of other known causes (e.g., genetic, metabolic) is incompletely understood and under‐researched, despite unmet clinical need. Also, cellular and humoral components of the adaptive and innate immune system are substantial disease modifying agents in the context of neuropathies and, at least in some neuropathies, there is an identified tight interrelationship between both compartments of the immune system. Additionally, the quadruple relationship between Schwann cell, axon, macrophage, and endoneurial fibroblast, with their diverse membrane bound and soluble signalling systems, forms a distinct focus for investigation in nerve diseases with inflammation secondary to Schwann cell mutations and possibly others. Identification of key immunological effector pathways that amplify neuropathic features and associated clinical symptomatology including pain should lead to realistic and timely possibilities for translatable therapeutic interventions using existing immunomodulators, alongside the development of novel therapeutic targets. GLIA 2016;64:475–486 PMID:26250643

  2. Peripheral neuropathy

    MedlinePlus

    Peripheral neuritis; Neuropathy - peripheral; Neuritis - peripheral; Nerve disease; Polyneuropathy ... Neuropathy is very common. There are many types and causes. Often, no cause can be found. Some ...

  3. Small-molecule trkB agonists promote axon regeneration in cut peripheral nerves

    PubMed Central

    English, Arthur W.; Liu, Kevin; Nicolini, Jennifer M.; Mulligan, Amanda M.; Ye, Keqiang

    2013-01-01

    Treatments with two-small molecule tropomyosin receptor kinase B (trkB) ligands, 7,8 dihydroxyflavone (7,8 DHF) and deoxygedunin, were evaluated for their ability to promote the regeneration of cut axons in injured peripheral nerves in mice in which sensory and motor axons are marked by YFP. Peripheral nerves were cut and repaired with grafts from strain-matched, nonfluorescent donors and secured in place with fibrin glue. Lengths of profiles of regenerating YFP+ axons were measured 2 wk later from confocal images. Axon regeneration was enhanced when the fibrin glue contained dilutions of 500-nM solution of either small-molecule trkB agonist. In mice in which the neurotrophin receptor trkB is knocked out selectively in neurons, axon regeneration is very weak, and topical treatment with 7,8 DHF had no effect on axon regeneration. Similar treatments with deoxygedunin had only a modest effect. In conditional BDNF knockout mice, topical treatments with either 7,8 DHF or deoxygedunin resulted in a reversal of the poor regeneration found in controls and produced significant enhancement of regeneration. In WT mice treated with 2 wk of daily i.p. injections of either 7,8 DHF or deoxygedunin (5 mg/kg), regenerating axon profiles were nearly twice as long as in controls. Restoration of direct muscle responses evoked by sciatic nerve stimulation to pretransection levels over an 8-wk survival period was found only in the treated mice. Treatments with either small-molecule trkB agonist enhanced axon regeneration and muscle reinnervation after peripheral nerve injuries. PMID:24043773

  4. Small-molecule trkB agonists promote axon regeneration in cut peripheral nerves.

    PubMed

    English, Arthur W; Liu, Kevin; Nicolini, Jennifer M; Mulligan, Amanda M; Ye, Keqiang

    2013-10-01

    Treatments with two-small molecule tropomyosin receptor kinase B (trkB) ligands, 7,8 dihydroxyflavone (7,8 DHF) and deoxygedunin, were evaluated for their ability to promote the regeneration of cut axons in injured peripheral nerves in mice in which sensory and motor axons are marked by YFP. Peripheral nerves were cut and repaired with grafts from strain-matched, nonfluorescent donors and secured in place with fibrin glue. Lengths of profiles of regenerating YFP(+) axons were measured 2 wk later from confocal images. Axon regeneration was enhanced when the fibrin glue contained dilutions of 500-nM solution of either small-molecule trkB agonist. In mice in which the neurotrophin receptor trkB is knocked out selectively in neurons, axon regeneration is very weak, and topical treatment with 7,8 DHF had no effect on axon regeneration. Similar treatments with deoxygedunin had only a modest effect. In conditional BDNF knockout mice, topical treatments with either 7,8 DHF or deoxygedunin resulted in a reversal of the poor regeneration found in controls and produced significant enhancement of regeneration. In WT mice treated with 2 wk of daily i.p. injections of either 7,8 DHF or deoxygedunin (5 mg/kg), regenerating axon profiles were nearly twice as long as in controls. Restoration of direct muscle responses evoked by sciatic nerve stimulation to pretransection levels over an 8-wk survival period was found only in the treated mice. Treatments with either small-molecule trkB agonist enhanced axon regeneration and muscle reinnervation after peripheral nerve injuries. PMID:24043773

  5. Enhancement of peripheral nerve regeneration due to treadmill training and electrical stimulation is dependent on androgen receptor signaling.

    PubMed

    Thompson, Nicholas J; Sengelaub, Dale R; English, Arthur W

    2014-05-01

    Moderate exercise in the form of treadmill training and brief electrical nerve stimulation both enhance axon regeneration after peripheral nerve injury. Different regimens of exercise are required to enhance axon regeneration in male and female mice (Wood et al.: Dev Neurobiol 72 (2012) 688-698), and androgens are suspected to be involved. We treated mice with the androgen receptor blocker, flutamide, during either exercise or electrical stimulation, to evaluate the role of androgen receptor signaling in these activity-based methods of enhancing axon regeneration. The common fibular (CF) and tibial (TIB) nerves of thy-1-YFP-H mice, in which axons in peripheral nerves are marked by yellow fluorescent protein (YFP), were transected and repaired using CF and TIB nerve grafts harvested from non-fluorescent donor mice. Silastic capsules filled with flutamide were implanted subcutaneously to release the drug continuously. Exercised mice were treadmill trained 5 days/week for 2 weeks, starting on the third day post-transection. For electrical stimulation, the sciatic nerve was stimulated continuously for 1 h prior to nerve transection. After 2 weeks, lengths of YFP+ profiles of regenerating axons were measured from harvested nerves. Both exercise and electrical stimulation enhanced axon regeneration, but this enhancement was blocked completely by flutamide treatments. Signaling through androgen receptors is necessary for the enhancing effects of treadmill exercise or electrical stimulation on axon regeneration in cut peripheral nerves. PMID:24293191

  6. Dorsal root ganglion myeloid zinc finger protein 1 contributes to neuropathic pain after peripheral nerve trauma

    PubMed Central

    Liang, Lingli; Cao, Jing; Lutz, Brianna Marie; Bekker, Alex; Zhang, Wei; Tao, Yuan-Xiang

    2015-01-01

    Peripheral nerve injury-induced changes in gene transcription and translation in primary sensory neurons of the dorsal root ganglion (DRG) are considered to contribute to neuropathic pain genesis. Transcription factors control gene expression. Peripheral nerve injury increases the expression of myeloid zinc finger protein 1 (MZF1), a transcription factor, and promotes its binding to the voltage-gated potassium 1.2 (Kv1.2) antisense RNA gene in the injured DRG. However, whether DRG MZF1 participates in neuropathic pain is still unknown. Here, we report that blocking the nerve injury-induced increase of DRG MZF1 through microinjection of MZF1 siRNA into the injured DRG attenuated the initiation and maintenance of mechanical, cold, and thermal pain hypersensitivities in rats with chronic constriction injury (CCI) of the sciatic nerve, without affecting locomotor functions and basal responses to acute mechanical, heat, and cold stimuli. Mimicking the nerve injury-induced increase of DRG MZF1 through microinjection of recombinant adeno-associated virus 5 expressing full-length MZF1 into the DRG produced significant mechanical, cold, and thermal pain hypersensitivities in naïve rats. Mechanistically, MZF1 participated in CCI-induced reductions in Kv1.2 mRNA and protein and total Kv current and the CCI-induced increase in neuronal excitability through MZF1-triggered Kv1.2 antisense RNA expression in the injured DRG neurons. MZF1 is likely an endogenous trigger of neuropathic pain and might serve as a potential target for preventing and treating this disorder. PMID:25630025

  7. Investigation of Schwann cell behaviour on RGD-functionalised bioabsorbable nanocomposite for peripheral nerve regeneration.

    PubMed

    Sedaghati, Tina; Jell, Gavin; Seifalian, Alexander

    2014-05-25

    Current commercially available nerve conduits fail to support nerve regeneration gaps larger than 30 mm in length due to the simple intra-luminal design of these conduits which are unable to biomimic the native neural environment. There is, therefore, a major clinical demand for new smart biomaterials, which can stimulate neuronal cell proliferation and migration, and facilitate nerve regeneration across these critical sized defects. In this study, we aimed to investigate Schwann cell (SC) behaviour seeded on the bioabsorbable version of the nanocomposite material, POSS modified poly (caprolactone) urea urethane (PCL), functionalised with arginine-glycine-aspartic acid (RGD) peptide. Successful synthesis of RGD peptide as well as the chemical structure of POSS-PCL nanocomposite film was investigated by Fourier transform infrared spectroscopy. Cell viability assay and morphological assessment were performed to investigate the cytocompatibility of the fabricated constructs. Successful immobilisation of RGD peptide onto the nanocomposite surface was confirmed by water contact angle, Brilliant Blue (BB) staining and thin layer chromatography. Both POSS-PCL and RGD-POSS-PCL nanocomposite scaffolds supported SC attachment, proliferation and morphological differentiation, important aspects for peripheral nerve regeneration. However, a significant increase in SC process length and morphological differentiation towards maturation was observed on the cells grown on RGD-POSS-PCL film. RGD-POSS-PCL nanocomposite demonstrated a significant improvement in SCs spreading and its integrin-dependent process outgrowth (P<0.05). Conduits made by POSS-nanocomposite may be suitable for the next generation of commercially available conduit required to meet current clinical demand in peripheral nerve regeneration and repair as they are currently undergoing in vivo preclinical study. PMID:24503165

  8. Localization of E-cadherin in peripheral glia after nerve injury and repair.

    PubMed

    Hasegawa, M; Seto, A; Uchiyama, N; Kida, S; Yamashima, T; Yamashita, J

    1996-04-01

    Peripheral nerve injury results in histological and histochemical changes in neurons and glia. We have recently found that Ca(2+)-dependent cell adhesion molecule E-cadherin plays an important role in the selective fasciculation of a particular subset of unmyelinated sensory fibers. In the present immunohistochemical and immunoblot analyses, the temporal profile of the subcellular expression of this molecule in spinal nerves was examined after crushing, transecting, or ligaturing the sciatic nerve in mice with special attention paid to E-cadherin expression in glial cells. After axotomy of the sciatic nerve, distal axons of the proximal stump and the fibers of the distal stump degenerated, but E-cadherin was still detectable at the outer mesaxons of the myelinated axons as long as they remained morphologically intact. Subsequently, Schwann cells proliferated and migrated to form Schwann cell columns (Büngner's bands) as initial responses to denervation, and expressed E-cadherin at their site of contact with each other and later with sprouting axons. At the initial stage of myelin formation, slender processes of a single Schwann cell interdigitated with an enveloped axons, and expressed E-cadherin at the contact site elaborated by a single Schwann cell. Immunoblot analysis on day 7 revealed that E-cadherin was detected in both the proximal nerve segments and the regenerative distal segments, but was negative in the degenerative distal segments. On the basis of present data, it is suggested that E-cadherin might be involved in the stabilization of the peripheral glial network which provides the guidance of sprouting axons and myelination. PMID:8786402

  9. Alignment and composition of laminin–polycaprolactone nanofiber blends enhance peripheral nerve regeneration

    PubMed Central

    Neal, Rebekah A.; Tholpady, Sunil S.; Foley, Patricia L.; Swami, Nathan; Ogle, Roy C.; Botchwey, Edward A.

    2012-01-01

    Peripheral nerve transection occurs commonly in traumatic injury, causing deficits distal to the injury site. Conduits for repair currently on the market are hollow tubes; however, they often fail due to slow regeneration over long gaps. To facilitate increased regeneration speed and functional recovery, the ideal conduit should provide biochemically relevant signals and physical guidance cues, thus playing an active role in regeneration. To that end, laminin and laminin–polycaprolactone (PCL) blend nanofibers were fabricated to mimic peripheral nerve basement membrane. In vitro assays established 10% (wt) laminin content is sufficient to retain neurite-promoting effects of laminin. In addition, modified collector plate design to introduce an insulating gap enabled the fabrication of aligned nanofibers. The effects of laminin content and fiber orientation were evaluated in rat tibial nerve defect model. The lumens of conduits were filled with nanofiber meshes of varying laminin content and alignment to assess changes in motor and sensory recovery. Retrograde nerve conduction speed at 6 weeks was significantly faster in animals receiving aligned nanofiber conduits than in those receiving random nanofiber conduits. Animals receiving nanofiber-filled conduits showed some conduction in both anterograde and retrograde directions, whereas in animals receiving hollow conduits, no impulse conduction was detected. Aligned PCL nanofibers significantly improved motor function; aligned laminin blend nanofibers yielded the best sensory function recovery. In both cases, nanofiber-filled conduits resulted in better functional recovery than hollow conduits. These studies provide a firm foundation for the use of natural–synthetic blend electrospun nanofibers to enhance existing hollow nerve guidance conduits. PMID:22106069

  10. Radiosensitizing activity and pharmacokinetics of multiple dose administered KU-2285 in peripheral nerve tissue in mice

    SciTech Connect

    Iwai, Hiroyuki; Matsuno, Etsuko ); Sasai, Keisuke; Abe, Mitsuyuki; Shibamoto, Yuta )

    1994-06-15

    In a clinical trial in which a 2-nitroimidazole radiosensitizer was administered repeatedly, the dose-limiting toxicity was found to be peripheral neuropathy. In the present study, the in vivo radiosensitizing activity of KU-2285 in combination with radiation dose fractionation, and the pharmacokinetics of cumulative dosing of KU-2285 in the peripheral nerves were examined. The ability of three nitroimidazoles, misonidazole (MISO), etanidazole (SR-2508) and KU-2285, to sensitize SCCVII tumors to radiation treatment has been compared for drug doses in the range 0-200 mg/kg. Single radiation doses or two different fractionation schedules (6 Gy/fractions [times] three fractions/48 h or 5 Gy/fractions [times] five fractions/48 h) were used; the tumor cell survival was determined using an in vivo/in vitro colony assay. The pharmacokinetics in the sciatic nerves were undertaken, when KU-2285 or etanidazole were injected at a dose of 200 mg/kg intravenously one, two, three, or four times at 2-h intervals. At less than 100 mg/kg, KU-2285 sensitized SCCVII tumors more than MISO and SR-2508 by fractionated irradiation. Evaluation of pharmacokinetics in the peripheral nerves showed that the apparent biological half-life of SR-2508 increased with the increases in the number of administrations, whereas that of KU-2285 became shorter. Since most clinical radiotherapy is given in small multiple fractions, KU-2285 appears to be a hypoxic cell radiosensitizer that could be useful in such regimens, and that poses no risk of chronic peripheral neurotoxicity. 12 refs., 5 figs., 1 tab.

  11. Cellular reactions of the choroid plexus induced by peripheral nerve injury.

    PubMed

    Joukal, Marek; Klusáková, Ilona; Solár, Peter; Kuklová, Adéla; Dubový, Petr

    2016-08-15

    The choroid plexus (CP) of brain ventricles forms the blood-cerebrospinal fluid (blood-CSF) barrier that is involved in many diseases affecting the central nervous system (CNS). We used ED1 and ED2 immunostaining to investigate epiplexus cell changes in rat CP after chronic constriction injury (CCI). In contrast to naïve CP, the CP of sham-operated rats showed an increase in the number of ED1+ cells of a similar magnitude during all periods of survival up to 3 weeks, while the number of ED2+ increased only at 3 days from operation. In comparison to naïve and sham-operated animals, the number of ED1+ and ED2+ cells in the epiplexus position increased with the duration of nerve compression. We detected no or negligible cell proliferation in the CP after sham- or CCI-operation. This suggests that increased number of ED1+ and ED2+ cells in the epiplexus position of the CP is derived from peripheral monocytes passing through altered blood-CSF barrier. The changes in epiplexus cells indicate that the CP reacts to tissue injury after the surgical approach itself and that the response to peripheral nerve lesion is greater. This suggests a role for an altered blood-CSF barrier allowing for propagation of signal molecules from damaged tissue and nerve to the CNS. PMID:27291457

  12. Traumatic peripheral nerve injuries: epidemiological findings, neuropathic pain and quality of life in 158 patients.

    PubMed

    Ciaramitaro, Palma; Mondelli, Mauro; Logullo, Francesco; Grimaldi, Serena; Battiston, Bruno; Sard, Arman; Scarinzi, Cecilia; Migliaretti, Giuseppe; Faccani, Giuliano; Cocito, Dario

    2010-06-01

    The objectives of this study were (1) epidemiological analysis of traumatic peripheral nerve injuries; (2) assessment of neuropathic pain and quality of life in patients affected by traumatic neuropathies. All consecutive patients with a diagnosis of traumatic neuropathies from four Italian centres were enrolled. Electromyography confirmed clinical level and site diagnosis of peripheral nerve injury. All patients were evaluated by disability scales, pain screening tools, and quality of life tests. 158 consecutive patients for a total of 211 traumatic neuropathies were analysed. The brachial plexus was a frequent site of traumatic injury (36%) and the radial, ulnar, and peroneal were the most commonly involved nerves with 15% of iatrogenic injuries. Seventy-two percent of the traumatic neuropathies were painful. Pain was present in 66% and neuropathic pain in 50% of all patients. Patients had worse quality of life scores than did the healthy Italian population. Moreover, there was a strong correlation between the quality of life and the severity of the pain, particularly neuropathic pain (Short Form-36 [SF-36] p < 0.005; Beck Depression Inventory [BDI] p < 0.0001). Traumatic neuropathies were more frequent in young males after road accidents, mainly in the upper limbs. Severe neuropathic pain and not only disability contributed to worsening the quality of life in patients with traumatic neuropathies. PMID:20626775

  13. Responses to magnetic stimuli recorded in peripheral nerves in the marine nudibranch mollusk Tritonia diomedea.

    PubMed

    Pavlova, Galina A; Glantz, Raymon M; Dennis Willows, A O

    2011-10-01

    Prior behavioral and neurophysiological studies provide evidence that the nudibranch mollusk Tritonia orients to the earth's magnetic field. Earlier studies of electrophysiological responses in certain neurons of the brain to changing ambient magnetic fields suggest that although certain identified brain cells fire impulses when the ambient field is changed, these neuron somata and their central dentritic and axonal processes are themselves not primary magnetic receptors. Here, using semi-intact animal preparations from which the brain was removed, we recorded from peripheral nerve trunks. Using techniques to count spikes in individual nerves and separately also to identify, then count individual axonal spikes in extracellular records, we found both excitatory and inhibitory axonal responses elicited by changes in the direction of ambient earth strength magnetic fields. We found responses in nerves from many locations throughout the body and in axons innervating the body wall and rhinophores. Our results indicate that primary receptors for geomagnetism in Tritonia are not focally concentrated in any particular organ, but appear to be widely dispersed in the peripheral body tissues. PMID:21717186

  14. Solution space reduction in the peripheral nerve source localization problem using forward field similarities

    NASA Astrophysics Data System (ADS)

    Zariffa, José; Popovic, Milos R.

    2008-06-01

    Improving our ability to localize bioelectric sources within a peripheral nerve would help us to monitor the control signals flowing to and from any limb or organ. This technology would provide a useful neuroscience tool, and could perhaps be incorporated into a neuroprosthesis interface. We propose to use measurements from a multi-contact nerve cuff to solve an inverse problem of bioelectric source localization within the peripheral nerve. Before the inverse problem can be addressed, the forward problem is solved using finite element modeling. A fine mesh improves the accuracy of the forward problem solution, but increases the number of variables to be solved for in the inverse problem. To alleviate this problem, variables corresponding to mesh elements that are not distinguishable by the measurement setup are grouped together, thus reducing the dimension of the inverse problem without impacting on the forward problem accuracy. A quantitative criterion for element distinguishability is derived using the columns of the leadfield matrix and information about the uncertainty in the measurements. Our results indicate that the number of variables in the inverse problem can be reduced by more than half using the proposed method, without having a detrimental impact on the quality of the localization.

  15. Cerebrolysin improves sciatic nerve dysfunction in a mouse model of diabetic peripheral neuropathy.

    PubMed

    Dong, Han-Yu; Jiang, Xin-Mei; Niu, Chun-Bo; Du, Lin; Feng, Jun-Yan; Jia, Fei-Yong

    2016-01-01

    To examine the effects of Cerebrolysin on the treatment of diabetic peripheral neuropathy, we first established a mouse model of type 2 diabetes mellitus by administering a high-glucose, high-fat diet and a single intraperitoneal injection of streptozotocin. Mice defined as diabetic in this model were then treated with 1.80, 5.39 or 8.98 mL/kg of Cerebrolysin via intraperitoneal injections for 10 consecutive days. Our results demonstrated that the number, diameter and area of myelinated nerve fibers increased in the sciatic nerves of these mice after administration of Cerebrolysin. The results of several behavioral tests showed that Cerebrolysin dose-dependently increased the slope angle in the inclined plane test (indicating an improved ability to maintain body position), prolonged tail-flick latency and foot-licking time (indicating enhanced sensitivity to thermal and chemical pain, respectively, and reduced pain thresholds), and increased an index of sciatic nerve function in diabetic mice compared with those behavioral results in untreated diabetic mice. Taken together, the anatomical and functional results suggest that Cerebrolysin ameliorated peripheral neuropathy in a mouse model of type 2 diabetes mellitus. PMID:26981106

  16. Extracellular voltage profile for reversing the recruitment order of peripheral nerve stimulation: a simulation study.

    PubMed

    Lertmanorat, Zeng; Durand, Dominique M

    2004-12-01

    Electrical stimulation of peripheral nerve activates large-diameter fibers before small ones. A physiological recruitment order, from small to large-diameter axons, is desirable in many applications. Previous studies using computer simulations showed that selective activation of small fibers could be achieved by reshaping the extracellular voltage profile along the nerve using an array of nine electrodes. In this study, several electrode-array configurations were tested in order to minimize the number of contacts. Electrode arrays of 5, 7, 9, and 11 contacts with 0.75 mm contact separation were performed in computer simulations of dog sacral root (S2). Electrode arrays of 5 and 7 contacts recruited 40% of small axons (<10 microm) when recruiting only 10% of larger axons. Effectiveness of 9- and 11-contact arrays decreased with the presence of epineurium and perineurium. The effectiveness of electrode arrays was independent of stimulation pulsewidth. The biphasic-pulse stimulation with the amplitude of the second phase set as low as possible should be used to prevent the excitation of large axons during the second phase and to minimize the electrode corrosion. Arrays of 5 and 7 contacts also decreased the recruitment curve slope to 26% and 51% of the tripolar electrode, respectively. This modeling study predicts that reversing the recruitment order of peripheral nerve stimulation could be achieved by reshaping the extracellular voltage using electrode arrays of 5 or 7 contacts. PMID:15876640

  17. Cerebrolysin improves sciatic nerve dysfunction in a mouse model of diabetic peripheral neuropathy

    PubMed Central

    Dong, Han-yu; Jiang, Xin-mei; Niu, Chun-bo; Du, Lin; Feng, Jun-yan; Jia, Fei-yong

    2016-01-01

    To examine the effects of Cerebrolysin on the treatment of diabetic peripheral neuropathy, we first established a mouse model of type 2 diabetes mellitus by administering a high-glucose, high-fat diet and a single intraperitoneal injection of streptozotocin. Mice defined as diabetic in this model were then treated with 1.80, 5.39 or 8.98 mL/kg of Cerebrolysin via intraperitoneal injections for 10 consecutive days. Our results demonstrated that the number, diameter and area of myelinated nerve fibers increased in the sciatic nerves of these mice after administration of Cerebrolysin. The results of several behavioral tests showed that Cerebrolysin dose-dependently increased the slope angle in the inclined plane test (indicating an improved ability to maintain body position), prolonged tail-flick latency and foot-licking time (indicating enhanced sensitivity to thermal and chemical pain, respectively, and reduced pain thresholds), and increased an index of sciatic nerve function in diabetic mice compared with those behavioral results in untreated diabetic mice. Taken together, the anatomical and functional results suggest that Cerebrolysin ameliorated peripheral neuropathy in a mouse model of type 2 diabetes mellitus. PMID:26981106

  18. Successful Treatment of Occipital Neuralgia with Implantable Peripheral Nerve Stimulation in a Pacemaker-Dependent Patient

    PubMed Central

    Chaiban, Gassan; Tolba, Reda; Eissa, Hazem; Lirette, Lesley Smallwood; Almualim, Mohammed; Malaty, Adham; Atallah, Joseph

    2014-01-01

    Background Peripheral nerve stimulation has been used to treat patients with occipital nerve–related chronic headaches who have been unsuccessful with less invasive therapeutic approaches. Patients with pacemaker-dependent cardiac conduction abnormalities require unique consideration prior to the implantation of peripheral nerve stimulators because the placement of the devices may lead to failure of the systems secondary to electromagnetic interference or crosstalk between the devices. Case Report An 86-year-old female who suffered from chronic right-sided cervicogenic headaches and neck pain had received only temporary relief from previous treatments. Additional comorbidities included longstanding pacemaker-dependent atrioventricular node conduction disease. Because the extent to which nerve stimulators electrically interact with pacemakers is unclear, we tunneled the leads to the lumbar region of the back and placed the generator on the contralateral side to the pacemaker to minimize the chance that the 2 devices would interfere. The patient has remained pain free for 1 year since implantation. Conclusion Although no current published trials evaluate the degree of interference between medical devices, case reports increasingly suggest that simultaneous implantation of a spinal cord stimulator and pacemaker is safe as long as precautions are taken and the devices are checked periodically, particularly when the devices are adjusted. PMID:24688344

  19. Development of a Regenerative Peripheral Nerve Interface for Control of a Neuroprosthetic Limb

    PubMed Central

    Frost, Christopher M.; Martin, David C.; Larkin, Lisa M.

    2016-01-01

    Background. The purpose of this experiment was to develop a peripheral nerve interface using cultured myoblasts within a scaffold to provide a biologically stable interface while providing signal amplification for neuroprosthetic control and preventing neuroma formation. Methods. A Regenerative Peripheral Nerve Interface (RPNI) composed of a scaffold and cultured myoblasts was implanted on the end of a divided peroneal nerve in rats (n = 25). The scaffold material consisted of either silicone mesh, acellular muscle, or acellular muscle with chemically polymerized poly(3,4-ethylenedioxythiophene) conductive polymer. Average implantation time was 93 days. Electrophysiological tests were performed at endpoint to determine RPNI viability and ability to transduce neural signals. Tissue samples were examined using both light microscopy and immunohistochemistry. Results. All implanted RPNIs, regardless of scaffold type, remained viable and displayed robust vascularity. Electromyographic activity and stimulated compound muscle action potentials were successfully recorded from all RPNIs. Physiologic efferent motor action potentials were detected from RPNIs in response to sensory foot stimulation. Histology and transmission electron microscopy revealed mature muscle fibers, axonal regeneration without neuroma formation, neovascularization, and synaptogenesis. Desmin staining confirmed the preservation and maturation of myoblasts within the RPNIs. Conclusions. RPNI demonstrates significant myoblast maturation, innervation, and vascularization without neuroma formation. PMID:27294122

  20. Genome-wide analysis of EGR2/SOX10 binding in myelinating peripheral nerve.

    PubMed

    Srinivasan, Rajini; Sun, Guannan; Keles, Sunduz; Jones, Erin A; Jang, Sung-Wook; Krueger, Courtney; Moran, John J; Svaren, John

    2012-08-01

    Myelin is essential for the rapidity of saltatory nerve conduction, and also provides trophic support for axons to prevent axonal degeneration. Two critical determinants of myelination are SOX10 and EGR2/KROX20. SOX10 is required for specification of Schwann cells from neural crest, and is required at every stage of Schwann cell development. Egr2/Krox20 expression is activated by axonal signals in myelinating Schwann cells, and is required for cell cycle arrest and myelin formation. To elucidate the integrated function of these two transcription factors during peripheral nerve myelination, we performed in vivo ChIP-Seq analysis of myelinating peripheral nerve. Integration of these binding data with loss-of-function array data identified a range of genes regulated by these factors. In addition, although SOX10 itself regulates Egr2/Krox20 expression, leading to coordinate activation of several major myelin genes by the two factors, there is a large subset of genes that are activated independent of EGR2. Finally, the results identify a set of SOX10-dependent genes that are expressed in early Schwann cell development, but become subsequently repressed by EGR2/KROX20. PMID:22492709

  1. Electrospun and woven silk fibroin/poly(lactic-co-glycolic acid) nerve guidance conduits for repairing peripheral nerve injury.

    PubMed

    Wang, Ya-Ling; Gu, Xiao-Mei; Kong, Yan; Feng, Qi-Lin; Yang, Yu-Min

    2015-10-01

    We have designed a novel nerve guidance conduit (NGC) made from silk fibroin and poly(lactic-co-glycolic acid) through electrospinning and weaving (ESP-NGCs). Several physical and biological properties of the ESP-NGCs were assessed in order to evaluate their biocompatibility. The physical properties, including thickness, tensile stiffness, infrared spectroscopy, porosity, and water absorption were determined in vitro. To assess the biological properties, Schwann cells were cultured in ESP-NGC extracts and were assessed by morphological observation, the MTT assay, and immunohistochemistry. In addition, ESP-NGCs were subcutaneously implanted in the backs of rabbits to evaluate their biocompatibility in vivo. The results showed that ESP-NGCs have high porosity, strong hydrophilicity, and strong tensile stiffness. Schwann cells cultured in the ESP-NGC extract fluids showed no significant differences compared to control cells in their morphology or viability. Histological evaluation of the ESP-NGCs implanted in vivo indicated a mild inflammatory reaction and high biocompatibility. Together, these data suggest that these novel ESP-NGCs are biocompatible, and may thus provide a reliable scaffold for peripheral nerve repair in clinical application. PMID:26692862

  2. Electrospun and woven silk fibroin/poly(lactic-co-glycolic acid) nerve guidance conduits for repairing peripheral nerve injury

    PubMed Central

    Wang, Ya-ling; Gu, Xiao-mei; Kong, Yan; Feng, Qi-lin; Yang, Yu-min

    2015-01-01

    We have designed a novel nerve guidance conduit (NGC) made from silk fibroin and poly(lactic-co-glycolic acid) through electrospinning and weaving (ESP-NGCs). Several physical and biological properties of the ESP-NGCs were assessed in order to evaluate their biocompatibility. The physical properties, including thickness, tensile stiffness, infrared spectroscopy, porosity, and water absorption were determined in vitro. To assess the biological properties, Schwann cells were cultured in ESP-NGC extracts and were assessed by morphological observation, the MTT assay, and immunohistochemistry. In addition, ESP-NGCs were subcutaneously implanted in the backs of rabbits to evaluate their biocompatibility in vivo. The results showed that ESP-NGCs have high porosity, strong hydrophilicity, and strong tensile stiffness. Schwann cells cultured in the ESP-NGC extract fluids showed no significant differences compared to control cells in their morphology or viability. Histological evaluation of the ESP-NGCs implanted in vivo indicated a mild inflammatory reaction and high biocompatibility. Together, these data suggest that these novel ESP-NGCs are biocompatible, and may thus provide a reliable scaffold for peripheral nerve repair in clinical application. PMID:26692862

  3. Altered distribution of juxtaparanodal kv1.2 subunits mediates peripheral nerve hyperexcitability in type 2 diabetes mellitus.

    PubMed

    Zenker, Jennifer; Poirot, Olivier; de Preux Charles, Anne-Sophie; Arnaud, Estelle; Médard, Jean-Jacques; Lacroix, Catherine; Kuntzer, Thierry; Chrast, Roman

    2012-05-30

    Peripheral nerve hyperexcitability (PNH) is one of the distal peripheral neuropathy phenotypes often present in patients affected by type 2 diabetes mellitus (T2DM). Through in vivo and ex vivo electrophysiological recordings in db/db mice, a model of T2DM, we observed that, in addition to reduced nerve conduction velocity, db/db mice also develop PNH. By using pharmacological inhibitors, we demonstrated that the PNH is mediated by the decreased activity of K(v)1-channels. In agreement with these data, we observed that the diabetic condition led to a reduced presence of the K(v)1.2-subunits in juxtaparanodal regions of peripheral nerves in db/db mice and in nerve biopsies from T2DM patients. Together, these observations indicate that the T2DM condition leads to potassium channel-mediated PNH, thus identifying them as a potential drug target to treat some of the DPN related symptoms. PMID:22649228

  4. High Resolution Ultrasound in the Evaluation and Management of Traumatic Peripheral Nerve Injuries: Review of the Literature

    PubMed Central

    Alaqeel, Ahmed; Alshomer, Feras

    2014-01-01

    High-resolution ultrasound has been used as an important tool in the diagnosis, management and monitoring of both acute and chronic peripheral nerve injuries. According to literature, it demonstrated high sensitivity and specificity for the detection of specific pathologies and its ability to differentiate between them. Literature has been reviewed, summarizing the specific finding of such modality in various peripheral neuropathies and with a specific focus over its role in evaluation and management of traumatic peripheral neuropathies. PMID:25337305

  5. Clinical toxicity of peripheral nerve to intraoperative radiotherapy in a canine model

    SciTech Connect

    Johnstone, P.A.S.; DeLuca, A.M.; Terrill, R.E.

    1995-07-15

    The clinical late effects of intraoperative radiotherapy (IORT) on peripheral nerve were investigated in a foxhound model. Between 1982 and 1987, 40 animals underwent laparotomy with intraoperative radiotherapy of doses from 0-75 Gy administered to the right lumbosacral plexus. Subsequently, all animals were monitored closely and sacrificed to assess clinical effects to peripheral nerve. This analysis reports final clinical results of all animals, with follow-up to 5 years. All animals treated with {>=} 25 Gy developed ipsilateral neuropathy. An inverse relationship was noted between intraoperative radiotherapy dose and time to neuropathy, with an effective dose for 50% paralysis (ED{sub 50}) of 17.2 Gy. One of the animals treated with 15 Gy IORT developed paralysis, after a much longer latency than the other animals. Doses of 15 Gy delivered intraoperatively may be accompanied by peripheral neuropathy with long-term follow-up. This threshold is less than that reported with shorter follow-up. The value of ED{sub 50} determined here is in keeping with data from other animal trials, and from clinical trials in humans. 11 refs., 2 figs.

  6. Clinical implications of peripheral myelin protein 22 for nerve compression and neural regeneration: a review.

    PubMed

    Hui-Chou, Helen G; Hashemi, Sharyhar S; Hoke, Ahmet; Dellon, A Lee

    2011-01-01

    Peripheral myelin protein 22 (PMP22) is a major component of the peripheral myelin sheath. The PMP22 gene is located on chromosome 17p11.2, and defects in PMP22 gene have been implicated in several common inherited peripheral neuropathies. Hereditary neuropathy with liability to pressure palsies (HNPP), Charcot-Marie Tooth disease type 1A (CMT1A), Dejerine-Sottas syndrome, and congenital hypomyelinating neuropathy are all associated with defects in PMP22 gene. The disease phenotypes mirror the range of expression of PMP22 due to the corresponding genetic defect. HNPP, characterized by a milder recurrent episodic focal demyelinating neuropathy, is attributed to a deletion leading to PMP22 underexpression. On the other end of the spectrum, CMT1A leads to a more uniform demyelination and axonal loss, resulting in severe progressive distal weakness and paresthesias; it is due to a duplication at 17p11.2 leading to PMP22 overexpression. Additional point mutations result in varying phenotypes due to dysfunction of the resultant PMP22 protein. All inherited neuropathies are diagnosed with a combination of physical findings on examination, electromyography, sural nerve biopsies, and genetic testing. Treatment and management of these disorders differ depending on the underlying genetic defect, nerves involved, and resulting functional impairments. A review of current literature elucidates clinical, microsurgical implications, and management of patients with PMP22-related neuropathy. PMID:20976668

  7. Stimulation of peripheral cholinergic nerves by glutamate indicates a new peripheral glutamate receptor.

    PubMed

    Aas, P; Tansø, R; Fonnum, F

    1989-05-01

    The bronchial smooth muscle of the rat was examined for contractile responses to excitatory amino acids. The nerve-mediated contraction induced by electrical field stimulation was enhanced by exogenous L-glutamate (L-Glu). The apparent affinity (ED50) of L-Glu was 3.5 +/- 0.1 mM. Both tetrodotoxin and hemicholinium-3 completely abolished the electrical field-induced contraction and therefore the potentiation by L-Glu, which indicates that L-Glu has a prejunctional effect. Concentrations of L-Glu higher than 22 mM inhibited the electrical field-induced contractions and enhanced the tonus of the smooth muscle by postjunctional stimulation. The ED50 of exogenous ACh was not altered by L-Glu. High concentrations (62 mM) of L-Glu increased the intrinsic activity (alpha) of ACh, indicating a postjunctional potentiation of ACh-induced contractions. L-Glu did not inhibit the activity of acetylcholinesterase, therefore the postjunctional potentiation was not due to ACh accumulation. Inhibition of the electrical field-induced contraction was seen with high concentrations of D-Glu, L-aspartate (L-Asp), L-alpha-amino adipate and ibotenate. Neither glutamate diethyl ester nor 2-amino-5-phosphonovalerate had any inhibitory effects on the L-Glu- and L-Asp-induced alterations of the electrical field-stimulated contraction or on the L-Glu-enhanced tonus of the bronchial smooth muscle. Kainate, N-methyl-D-aspartate, quisqualate and N-acetyl-aspartyl-glutamate had only minor transient potentiating effects on the electrical field-induced contraction. The results provide evidence for a L-Glu receptor in rat bronchi that has a different specificity for glutamate agonists and antagonists than the L-Glu receptor described in the CNS. The receptor seems to be located prejunctionally and enhances nerve-mediated responses and thereby stimulates the bronchial smooth muscle to contract. The possible involvement of this type of receptor in the 'Chinese restaurant syndrome' is discussed. PMID

  8. NT-3 modulates NPY expression in primary sensory neurons following peripheral nerve injury

    PubMed Central

    STERNE, G. D.; BROWN, R. A.; GREEN, C. J.; TERENGHI, G.

    1998-01-01

    Peripheral nerve transection induces significant changes in neuropeptide expression and content in injured primary sensory neurons, possibly due to loss of target derived neurotrophic support. This study shows that neurotrophin-3 (NT-3) delivery to the injured nerve influences neuropeptide Y (NPY) expression within dorsal root ganglia (DRG) neurons. NT-3 was delivered by grafting impregnated fibronectin (500 ng/ml; NT group) in the axotomised sciatic nerve. Animals grafted with plain fibronectin mats (FN) or nerve grafts (NG) were used as controls. L4 and L5 DRG from operated and contralateral sides were harvested between 5 and 240 d. Using immunohistochemistry and computerised image analysis the percentage, diameter and optical density of neurons expressing calcitonin gene-related peptide (CGRP), substance P (SP), vasoactive intestinal peptide (VIP) and NPY were quantified. Sciatic nerve axotomy resulted in significant reduction in expression of CGRP and SP, and significant upregulation of VIP and NPY (P<0.05 for ipsilateral vs contralateral DRG). By d 30, exogenous NT-3 and nerve graft attenuated the upregulation of NPY (P<0.05 for NT and NG vs FN). However, NT-3 administration did not influence the expression of CGRP, SP or VIP. The mean cell diameter of NPY immunoreactive neurons was significantly smaller in the NT-3 group (P<0.05 for NT vs FN and NG) suggesting a differential influence of NT-3 on larger neurons. The optical densities of NPY immunoreactive neurons of equal size were the same in each group at any time point, indicating that the neurons responding to NT-3 downregulate NPY expression to levels not detectable by immunohistochemistry. These results demonstrate that targeted administration of NT-3 regulates the phenotype of a NPY-immunoreactive neuronal subpopulation in the dorsal root ganglia, a further evidence of the trophic role of neurotrophins on primary sensory neurons. PMID:9827642

  9. Dorsal root ganglion transcriptome analysis following peripheral nerve injury in mice

    PubMed Central

    Wu, Shaogen; Marie Lutz, Brianna; Miao, Xuerong; Liang, Lingli; Mo, Kai; Chang, Yun-Juan; Du, Peicheng; Soteropoulos, Patricia; Tian, Bin; Kaufman, Andrew G.; Bekker, Alex; Hu, Yali

    2016-01-01

    Background Peripheral nerve injury leads to changes in gene expression in primary sensory neurons of the injured dorsal root ganglia. These changes are believed to be involved in neuropathic pain genesis. Previously, these changes have been identified using gene microarrays or next generation RNA sequencing with poly-A tail selection, but these approaches cannot provide a more thorough analysis of gene expression alterations after nerve injury. Methods The present study chose to eliminate mRNA poly-A tail selection and perform strand-specific next generation RNA sequencing to analyze whole transcriptomes in the injured dorsal root ganglia following spinal nerve ligation. Quantitative real-time reverse transcriptase polymerase chain reaction assay was carried out to verify the changes of some differentially expressed RNAs in the injured dorsal root ganglia after spinal nerve ligation. Results Our results showed that more than 50 million (M) paired mapped sequences with strand information were yielded in each group (51.87 M–56.12 M in sham vs. 51.08 M–57.99 M in spinal nerve ligation). Six days after spinal nerve ligation, expression levels of 11,163 out of a total of 27,463 identified genes in the injured dorsal root ganglia significantly changed, of which 52.14% were upregulated and 47.86% downregulated. The largest transcriptional changes were observed in protein-coding genes (91.5%) followed by noncoding RNAs. Within 944 differentially expressed noncoding RNAs, the most significant changes were seen in long interspersed noncoding RNAs followed by antisense RNAs, processed transcripts, and pseudogenes. We observed a notable proportion of reads aligning to intronic regions in both groups (44.0% in sham vs. 49.6% in spinal nerve ligation). Using quantitative real-time polymerase chain reaction, we confirmed consistent differential expression of selected genes including Kcna2, Oprm1 as well as lncRNAs Gm21781 and 4732491K20Rik following spinal nerve

  10. Pulsed electrical stimulation protects neurons in the dorsal root and anterior horn of the spinal cord after peripheral nerve injury

    PubMed Central

    Pei, Bao-an; Zi, Jin-hua; Wu, Li-sheng; Zhang, Cun-hua; Chen, Yun-zhen

    2015-01-01

    Most studies on peripheral nerve injury have focused on repair at the site of injury, but very few have examined the effects of repair strategies on the more proximal neuronal cell bodies. In this study, an approximately 10-mm-long nerve segment from the ischial tuberosity in the rat was transected and its proximal and distal ends were inverted and sutured. The spinal cord was subjected to pulsed electrical stimulation at T10 and L3, at a current of 6.5 mA and a stimulation frequency of 15 Hz, 15 minutes per session, twice a day for 56 days. After pulsed electrical stimulation, the number of neurons in the dorsal root ganglion and anterior horn was increased in rats with sciatic nerve injury. The number of myelinated nerve fibers was increased in the sciatic nerve. The ultrastructure of neurons in the dorsal root ganglion and spinal cord was noticeably improved. Conduction velocity of the sciatic nerve was also increased. These results show that pulsed electrical stimulation protects sensory neurons in the dorsal root ganglia as well as motor neurons in the anterior horn of the spinal cord after peripheral nerve injury, and that it promotes the regeneration of peripheral nerve fibers. PMID:26692864

  11. Pulsed electrical stimulation protects neurons in the dorsal root and anterior horn of the spinal cord after peripheral nerve injury.

    PubMed

    Pei, Bao-An; Zi, Jin-Hua; Wu, Li-Sheng; Zhang, Cun-Hua; Chen, Yun-Zhen

    2015-10-01

    Most studies on peripheral nerve injury have focused on repair at the site of injury, but very few have examined the effects of repair strategies on the more proximal neuronal cell bodies. In this study, an approximately 10-mm-long nerve segment from the ischial tuberosity in the rat was transected and its proximal and distal ends were inverted and sutured. The spinal cord was subjected to pulsed electrical stimulation at T10 and L3, at a current of 6.5 mA and a stimulation frequency of 15 Hz, 15 minutes per session, twice a day for 56 days. After pulsed electrical stimulation, the number of neurons in the dorsal root ganglion and anterior horn was increased in rats with sciatic nerve injury. The number of myelinated nerve fibers was increased in the sciatic nerve. The ultrastructure of neurons in the dorsal root ganglion and spinal cord was noticeably improved. Conduction velocity of the sciatic nerve was also increased. These results show that pulsed electrical stimulation protects sensory neurons in the dorsal root ganglia as well as motor neurons in the anterior horn of the spinal cord after peripheral nerve injury, and that it promotes the regeneration of peripheral nerve fibers. PMID:26692864

  12. Growth-associated protein 43 in differentiating peripheral nerve sheath tumors from other non-neural spindle cell neoplasms.

    PubMed

    Chen, Wei-Shen; Chen, Pei-Ling; Lu, Dongsi; Lind, Anne C; Dehner, Louis P

    2014-02-01

    The malignant peripheral nerve sheath tumor is a relatively uncommon type of soft tissue sarcoma arising from a peripheral nerve or extraneural soft tissues and showing nerve sheath differentiation. The diagnosis of malignant peripheral nerve sheath tumor is one of the most challenging tasks in surgical pathology because of its uncommon type (5-10% soft tissue sarcomas), morphologic resemblance to other spindle cell neoplasms and lack of sensitive and specific immunohistochemical markers. The pathologic diagnosis is more straightforward in the clinical setting of neurofibromatosis-1, but problems are mainly centered on the non-neurofibromatosis-1 malignant peripheral nerve sheath tumors. To date, S100 protein is the most widely applied marker in the case of a suspected malignant peripheral nerve sheath tumor, yet its suboptimal sensitivity and its expression in other spindle cell neoplasms, including spindle cell melanoma, clear-cell sarcoma, leiomyosarcoma and monophasic synovial sarcoma, add to the diagnostic conundrum. Growth-associated protein 43 (GAP43), a membrane-associated phosphoprotein expressed in neuronal growth cones and Schwann cell precursors during neural development and axonal regeneration, was applied to a set of nerve sheath and non-nerve sheath spindle cell neoplasms. The findings in this study indicate that GAP43 is expressed in malignant peripheral nerve sheath tumors (n=18/21; 86%) and demonstrates a sensitivity superior to S100 protein (n=13/21; 62%). GAP43 is also positive in neurofibromas (n=17/18; 94%), schwannomas (n=11/12; 92%) and desmoplastic melanomas (n=7/10; 70%). In contrast, it is negative in the non-desmoplastic spindle cell melanomas (n=20/22; 91%). Of the other non-neural soft tissue sarcomas, GAP43 is non-reactive in most leiomyosarcomas (n=14/16; 88%) and clear-cell sarcomas (n=8/8), and only focally positive in monophasic synovial sarcomas (n=3/7; 43%). GAP43 is seemingly a highly sensitive marker for peripheral nerve

  13. Peripheral neuropathy in chronic liver disease: clinical, electrodiagnostic, and nerve biopsy findings

    PubMed Central

    Knill-Jones, R. P.; Goodwill, C. J.; Dayan, A. D.; Williams, Roger

    1972-01-01

    In a prospective study of 70 unselected patients with chronic liver disease, clinical signs of a peripheral neuropathy were observed in 13 patients. Abnormal nerve conduction was demonstrated in nine of these and in one further patient who had no abnormal neurological signs. The occurrence of a neuropathy (in patients with cryptogenic cirrhosis, haemochromatosis, active chronic hepatitis as well as in alcoholic cirrhosis) could not be related to liver function, although it was associated with higher IgA and IgM values. Clinical diabetes was present in six of the 14 patients with neuropathy but there was no relation in the non-diabetic patients between neuropathy and minor impairment of carbohydrate tolerance. Those with neuropathy had a significantly higher incidence of oesophageal varices and there was also a relationship to a history of previous encephalopathy. Sural nerve biopsy was carried out on 14 patients, eight of whom had clinical or electrodiagnostic evidence of neuropathy. Single nerve fibres were examined by teasing and in all nerves histological evidence was found of an indolent process which had damaged whole Schwann cells and which resulted in demyelination and remyelination. Diabetic angiopathy was not seen and axonal degeneration, which was never severe, was found in all disease groups equally. Images PMID:4337271

  14. Novel TRPM8 antagonist attenuates cold hypersensitivity after peripheral nerve injury in rats.

    PubMed

    Patel, Ryan; Gonçalves, Leonor; Newman, Robert; Jiang, Feng Li; Goldby, Anne; Reeve, Jennifer; Hendrick, Alan; Teall, Martin; Hannah, Duncan; Almond, Sarah; Brice, Nicola; Dickenson, Anthony H

    2014-04-01

    Abnormal cold sensitivity is a common feature of a range of neuropathies. In the murine somatosensory system, multiple aspects of cold sensitivity are dependent on TRPM8, both short term and in response to peripheral nerve injury. The specialized nature of cold-sensitive afferents and the restricted expression of TRPM8 render it an attractive target for the treatment of cold hypersensitivity. This current study examines the effect of a novel TRPM8 antagonist (M8-An) in naive and spinal nerve-ligated rats through behavioral and in vivo electrophysiological approaches. In vitro, M8-An inhibited icilin-evoked Ca(2+) currents in HEK293 cells stably expressing human TRPM8 with an IC(50) of 10.9 nM. In vivo, systemic M8-An transiently decreased core body temperature. Deep dorsal horn recordings were made in vivo from neurons innervating the hind paw. M8-An inhibited neuronal responses to innocuous and noxious cooling of the receptive field in spinal nerve-ligated rats but not in naive rats. No effect on neuronal responses to mechanical and heat stimulation was observed. In addition, M8-An also attenuated behavioral responses to cold but not mechanical stimulation after nerve ligation without affecting the uninjured contralateral response. The data presented here support a contribution of TRPM8 to the pathophysiology of cold hypersensitivity in this model and highlight the potential of the pharmacological block of TRPM8 in alleviating the associated symptoms. PMID:24472724

  15. PGC-1α Mediated Peripheral Nerve Protection of Tongxinluo in STZ-Induced Diabetic Rats

    PubMed Central

    Cui, Xiaopei; Feng, Hua; Xu, Xia; Li, Haijun

    2016-01-01

    Aim. To investigate the effect of Tongxinluo (Txl), a Chinese herbal compound, on diabetic peripheral neuropathy (DPN). Methods and Results. Diabetic rat model was established by peritoneal injection of streptozotocin (STZ). Txl ultrafine powder treatment for 16 weeks from the baseline significantly reversed the impairment of motor nerve conductive velocity (MNCV), mechanical hyperalgesia, and nerve structure. We further proved that Tongxinluo upregulates PGC-1α and its downstream factors including COX IV and SOD, which were involved in mitochondrial biogenesis. Conclusion. Our study indicates that the protective effect of Txl in diabetic neuropathy may be attributed to the induction of PGC-1α and its downstream targets. This finding may further illustrate the pleiotropic effect of the medicine. PMID:27504136

  16. Molecular mechanisms of peripheral nerve regeneration: emerging roles of microRNAs

    PubMed Central

    Wu, Di; Murashov, Alexander K.

    2013-01-01

    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 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 by shifting their physiology from maintaining structure and supporting synaptic transmission towards 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. PMID:23554595

  17. Reference values and clinical application of magnetic peripheral nerve stimulation in cats.

    PubMed

    Van Soens, Iris; Struys, Michel M R F; Bhatti, Sofie F M; Van Ham, Luc M L

    2012-07-01

    Magnetic stimulation of radial (RN) and sciatic (SN) nerves was performed bilaterally in 40 healthy cats. Reference values for onset latency and peak-to-peak amplitude of magnetic motor evoked potentials (MMEPs) were obtained and compared with values of electric motor evoked potentials (EMEPs) in 10/40 cats. Onset latencies and peak-to-peak amplitudes of the MMEPs of three cats with polyneuropathy (PNP) were compared to the reference values. Magnetic motor evoked responses were easily recorded in all normal cats. Significant differences were found in onset latencies between MMEPs and EMEPs, but peak-to-peak amplitudes were equal. The MMEPs of three cats with PNP can be seen as outliers in comparison to the reference values. MMEPs from the RN and SN were easily obtained and reproducible in normal cats. The technique could represent a useful adjunct in the assessment of peripheral nerve disorders. PMID:22070914

  18. Multiple orbital neurofibromas, painful peripheral nerve tumors, distinctive face and marfanoid habitus: a new syndrome.

    PubMed

    Babovic-Vuksanovic, D; Messiaen, Ludwine; Nagel, Christoph; Brems, Hilde; Scheithauer, Bernd; Denayer, Ellen; Mao, Rong; Sciot, Raf; Janowski, Karen M; Schuhmann, Martin U; Claes, Kathleen; Beert, Eline; Garrity, James A; Spinner, Robert J; Stemmer-Rachamimov, Anat; Gavrilova, Ralitza; Van Calenbergh, Frank; Mautner, Victor; Legius, Eric

    2012-06-01

    Four unrelated patients having an unusual clinical phenotype, including multiple peripheral nerve sheath tumors, are reported. Their clinical features were not typical of any known familial tumor syndrome. The patients had multiple painful neurofibromas, including bilateral orbital plexiform neurofibromas, and spinal as well as mucosal neurofibromas. In addition, they exhibited a marfanoid habitus, shared similar facial features, and had enlarged corneal nerves as well as neuronal migration defects. Comprehensive NF1, NF2 and SMARCB1 mutation analyses revealed no mutation in blood lymphocytes and in schwann cells cultured from plexiform neurofibromas. Furthermore, no mutations in RET, PRKAR1A, PTEN and other RAS-pathway genes were found in blood leukocytes. Collectively, the clinical and pathological findings in these four cases fit no known syndrome and likely represent a new disorder. PMID:22258529

  19. Redistribution of Kv2.1 ion channels on spinal motoneurons following peripheral nerve injury.

    PubMed

    Romer, Shannon H; Dominguez, Kathleen M; Gelpi, Marc W; Deardorff, Adam S; Tracy, Robert C; Fyffe, Robert E W

    2014-02-14

    Pathophysiological responses to peripheral nerve injury include alterations in the activity, intrinsic membrane properties and excitability of spinal neurons. The intrinsic excitability of α-motoneurons is controlled in part by the expression, regulation, and distribution of membrane-bound ion channels. Ion channels, such as Kv2.1 and SK, which underlie delayed rectifier potassium currents and afterhyperpolarization respectively, are localized in high-density clusters at specific postsynaptic sites (Deardorff et al., 2013; Muennich and Fyffe, 2004). Previous work has indicated that Kv2.1 channel clustering and kinetics are regulated by a variety of stimuli including ischemia, hypoxia, neuromodulator action and increased activity. Regulation occurs via channel dephosphorylation leading to both declustering and alterations in channel kinetics, thus normalizing activity (Misonou et al., 2004; Misonou et al., 2005; Misonou et al., 2008; Mohapatra et al., 2009; Park et al., 2006). Here we demonstrate using immunohistochemistry that peripheral nerve injury is also sufficient to alter the surface distribution of Kv2.1 channels on motoneurons. The dynamic changes in channel localization include a rapid progressive decline in cluster size, beginning immediately after axotomy, and reaching maximum within one week. With reinnervation, the organization and size of Kv2.1 clusters do not fully recover. However, in the absence of reinnervation Kv2.1 cluster sizes fully recover. Moreover, unilateral peripheral nerve injury evokes parallel, but smaller effects bilaterally. These results suggest that homeostatic regulation of motoneuron Kv2.1 membrane distribution after axon injury is largely independent of axon reinnervation. PMID:24355600

  20. SUCCESSFUL TRANSPLANTATION OF MOTONEURONS INTO THE PERIPHERAL NERVE DEPENDS ON THE NUMBER OF TRANSPLANTED CELLS

    PubMed Central

    KATO, SHUICHI; KURIMOTO, SHIGERU; NAKANO, TOMONORI; YONEDA, HIDEMASA; ISHII, HISAO; MITA-SUGIURA, SATOKA; HIRATA, HITOSHI

    2015-01-01

    ABSTRACT Transplantation of motoneurons (MN) into the peripheral nerve to provide a source of neurons for muscle reinnervation, termed motoneuron integrated striated muscle (MISM), may provide the potential to restore functional muscle activity, when combined with computer-programmed functional electrical stimulation (FES). The number of MNs required to restore innervation to denervated muscles in adult Fischer 344 rats was investigated by comparing two groups, one transplanted with 2 × 105 cells (group A) and the other with 1 × 106 cells (group B). Twelve weeks after transplantation, electrophysiological analysis, muscle function analysis, and tissue analysis were performed. The mean motor nerve conduction velocity was faster (12.4 ± 1.0 m/s vs. 8.5 ± 0.7 m/s, P = 0.011) and the mean amplitude of compound muscle action potential was larger (1.6 ± 0.4 mV vs. 0.7 ± 0.2 mV, P = 0.034) in group B. The dorsiflexed ankle angle was larger in group B (27 ± 5° vs. 75 ± 8°, P = 0.02). The mean myelinated axon number in the peroneal nerve and the proportion of reinnervated motor end plates were also greater in group B (317 ± 33 vs. 104 ± 17, 87.5 ± 3.4% vs. 40.6 ± 7.7%; P < 0.01, respectively). When sufficient MNs are transplanted into the peripheral nerve, MISM forms functional motor units. MISM, in conjunction with FES, provides a new treatment strategy for paralyzed muscles. PMID:25797991

  1. Peripheral Nerve Grafts after Cervical Spinal Cord Injury in Adult Cats

    PubMed Central

    Côté, Marie-Pascale; Hanna, Amgad; Lemay, Michel A.; Ollivier-Lanvin, Karen; Santi, Lauren; Miller, Kassi; Monaghan, Rebecca; Houlé, John D.

    2010-01-01

    Peripheral nerve grafts (PNG) into the rat spinal cord support axon regeneration after acute or chronic injury, with synaptic reconnection across the lesion site and some level of behavioral recovery. Here, we grafted a peripheral nerve into the injured spinal cord of cats as a preclinical treatment approach to promote regeneration for eventual translational use. Adult female cats received a partial hemisection lesion at the cervical level (C7) and immediate apposition of an autologous tibial nerve segment to the lesion site. Five weeks later, a dorsal quadrant lesion was performed caudally (T1), the lesion site treated with Chondroitinase ABC two days later to digest growth inhibiting extracellular matrix molecules, and the distal end of the PNG apposed to the injury site. After 4–20 weeks, the grafts survived in 10/12 animals with several thousand myelinated axons present in each graft. The distal end of 9/10 grafts was well apposed to the spinal cord and numerous axons extended beyond the lesion site. Intraspinal stimulation evoked compound action potentials in the graft with an appropriate latency illustrating normal axonal conduction of the regenerated axons. Although stimulation of the PNG failed to elicit responses in the spinal cord distal to the lesion site, the presence of c-Fos immunoreactive neurons close to the distal apposition site indicates that regenerated axons formed functional synapses with host neurons. This study demonstrates the successful application of a nerve grafting approach to promote regeneration after spinal cord injury in a non-rodent, large animal model. PMID:20599980

  2. An approach to identify microRNAs involved in neuropathic pain following a peripheral nerve injury

    PubMed Central

    Norcini, Monica; Sideris, Alexandra; Martin Hernandez, Lourdes A.; Zhang, Jin; Blanck, Thomas J. J.; Recio-Pinto, Esperanza

    2014-01-01

    Peripheral nerve injury alters the expression of hundreds of proteins in dorsal root ganglia (DRG). Targeting some of these proteins has led to successful treatments for acute pain, but not for sustained post-operative neuropathic pain. The latter may require targeting multiple proteins. Since a single microRNA (miR) can affect the expression of multiple proteins, here, we describe an approach to identify chronic neuropathic pain-relevant miRs. We used two variants of the spared nerve injury (SNI): Sural-SNI and Tibial-SNI and found distinct pain phenotypes between the two. Both models induced strong mechanical allodynia, but only Sural-SNI rats maintained strong mechanical and cold allodynia, as previously reported. In contrast, we found that Tibial-SNI rats recovered from mechanical allodynia and never developed cold allodynia. Since both models involve nerve injury, we increased the probability of identifying differentially regulated miRs that correlated with the quality and magnitude of neuropathic pain and decreased the probability of detecting miRs that are solely involved in neuronal regeneration. We found seven such miRs in L3-L5 DRG. The expression of these miRs increased in Tibial-SNI. These miRs displayed a lower level of expression in Sural-SNI, with four having levels lower than those in sham animals. Bioinformatic analysis of how these miRs could affect the expression of some ion channels supports the view that, following a peripheral nerve injury, the increase of the seven miRs may contribute to the recovery from neuropathic pain while the decrease of four of them may contribute to the development of chronic neuropathic pain. The approach used resulted in the identification of a small number of potentially neuropathic pain relevant miRs. Additional studies are required to investigate whether manipulating the expression of the identified miRs in primary sensory neurons can prevent or ameliorate chronic neuropathic pain following peripheral nerve

  3. Ultrasound-Guided Pain Interventions - A Review of Techniques for Peripheral Nerves

    PubMed Central

    Soneji, Neilesh

    2013-01-01

    Ultrasound has emerged to become a commonly used modality in the performance of chronic pain interventions. It allows direct visualization of tissue structure while allowing real time guidance of needle placement and medication administration. Ultrasound is a relatively affordable imaging tool and does not subject the practitioner or patient to radiation exposure. This review focuses on the anatomy and sonoanatomy of peripheral non-axial structures commonly involved in chronic pain conditions including the stellate ganglion, suprascapular, ilioinguinal, iliohypogastric, genitofemoral and lateral femoral cutaneous nerves. Additionally, the review discusses ultrasound guided intervention techniques applicable to these structures. PMID:23614071

  4. Potential of boron neutron capture therapy (BNCT) for malignant peripheral nerve sheath tumors (MPNST).

    PubMed

    Fujimoto, Takuya; Andoh, Tooru; Sudo, Tamotsu; Fujita, Ikuo; Fukase, Naomasa; Takeuchi, Tamotsu; Sonobe, Hiroshi; Inoue, Masayoshi; Hirose, Tkanori; Sakuma, Toshiko; Moritake, Hiroshi; Sugimoto, Tohru; Kawamoto, Teruya; Fukumori, Yoshinobu; Yamamoto, Satomi; Atagi, Shinji; Sakurai, Yoshinori; Kurosaka, Masahiro; Ono, Koji; Ichikawa, Hideki; Suzuki, Minoru

    2015-12-01

    Malignant peripheral nerve sheath tumors (MPNST) are relatively rare neoplasms with poor prognosis. At present there is no effective treatment for MPNST other than surgical resection. Nonetheless, the anti-tumor effect of boron neutron capture therapy (BNCT) was recently demonstrated in two patients with MPNST. Subsequently, tumor-bearing nude mice subcutaneously transplanted with a human MPNST cell line were injected with p-borono-L-phenylalanine (L-BPA) and subjected to BNCT. Pathological studies then revealed that the MPNST cells were selectively destroyed by BNCT. PMID:26278348

  5. Malignant peripheral nerve sheath tumor of the orbit: case report and literature review.

    PubMed

    Aydin, Mehmet D; Yildirim, Umran; Gundogdu, Cemal; Dursun, Osman; Uysal, Hasan H; Ozdikici, Mete

    2004-05-01

    A 68-year-old woman with progressive visual loss and exophthalmos in her right eye had been operated on for a mass in her right calf 3 years earlier. Imaging showed a huge mass invading the orbital structures and temporal pole. The presumptive diagnosis was a malignant orbital tumor. The tumor was resected totally and eroded tissues such as the lateral rectus muscle and dural compartments were repaired. The histological diagnosis was a malignant peripheral nerve sheath tumor (MPNST). The patient recovered uneventfully and was discharged 8 days after surgery. Two years later she died from a liver tumor. Few MPNSTs involving the orbit have been reported. PMID:16145592

  6. Repair of peripheral nerve defects with chemically extracted acellular nerve allografts loaded with neurotrophic factors-transfected bone marrow mesenchymal stem cells.

    PubMed

    Zhang, Yan-Ru; Ka, Ka; Zhang, Ge-Chen; Zhang, Hui; Shang, Yan; Zhao, Guo-Qiang; Huang, Wen-Hua

    2015-09-01

    Chemically extracted acellular nerve allografts loaded with brain-derived neurotrophic factor-transfected or ciliary neurotrophic factor-transfected bone marrow mesenchymal stem cells have been shown to repair sciatic nerve injury better than chemically extracted acellular nerve allografts alone, or chemically extracted acellular nerve allografts loaded with bone marrow mesenchymal stem cells. We hypothesized that these allografts compounded with both brain-derived neurotrophic factor- and ciliary neurotrophic factor-transfected bone marrow mesenchymal stem cells may demonstrate even better effects in the repair of peripheral nerve injury. We cultured bone marrow mesenchymal stem cells expressing brain-derived neurotrophic factor and/or ciliary neurotrophic factor and used them to treat sciatic nerve injury in rats. We observed an increase in sciatic functional index, triceps wet weight recovery rate, myelin thickness, number of myelinated nerve fibers, amplitude of motor-evoked potentials and nerve conduction velocity, and a shortened latency of motor-evoked potentials when allografts loaded with both neurotrophic factors were used, compared with allografts loaded with just one factor. Thus, the combination of both brain-derived neurotrophic factor and ciliary neurotrophic factor-transfected bone marrow mesenchymal stem cells can greatly improve nerve injury. PMID:26604913

  7. Repair of peripheral nerve defects with chemically extracted acellular nerve allografts loaded with neurotrophic factors-transfected bone marrow mesenchymal stem cells

    PubMed Central

    Zhang, Yan-ru; Ka, Ka; Zhang, Ge-chen; Zhang, Hui; Shang, Yan; Zhao, Guo-qiang; Huang, Wen-hua

    2015-01-01

    Chemically extracted acellular nerve allografts loaded with brain-derived neurotrophic factor-transfected or ciliary neurotrophic factor-transfected bone marrow mesenchymal stem cells have been shown to repair sciatic nerve injury better than chemically extracted acellular nerve allografts alone, or chemically extracted acellular nerve allografts loaded with bone marrow mesenchymal stem cells. We hypothesized that these allografts compounded with both brain-derived neurotrophic factor- and ciliary neurotrophic factor-transfected bone marrow mesenchymal stem cells may demonstrate even better effects in the repair of peripheral nerve injury. We cultured bone marrow mesenchymal stem cells expressing brain-derived neurotrophic factor and/or ciliary neurotrophic factor and used them to treat sciatic nerve injury in rats. We observed an increase in sciatic functional index, triceps wet weight recovery rate, myelin thickness, number of myelinated nerve fibers, amplitude of motor-evoked potentials and nerve conduction velocity, and a shortened latency of motor-evoked potentials when allografts loaded with both neurotrophic factors were used, compared with allografts loaded with just one factor. Thus, the combination of both brain-derived neurotrophic factor and ciliary neurotrophic factor-transfected bone marrow mesenchymal stem cells can greatly improve nerve injury. PMID:26604913

  8. Uptake of nerve growth factor along peripheral and spinal axons of primary sensory neurons

    SciTech Connect

    Richardson, P.M.; Riopelle, R.J.

    1984-07-01

    To investigate the distribution of nerve growth factor (NGF) receptors on peripheral and central axons, (/sup 125/I)NGF was injected into the sciatic nerve or spinal cord of adult rats. Accumulation of (/sup 125/I)NGF in lumbar dorsal root ganglia was monitored by gamma emission counting and radioautography. (/sup 125/I)NGF, injected endoneurially in small quantities, was taken into sensory axons by a saturable process and was transported retrogradely to their cell bodies at a maximal rate of 2.5 to 7.5 mm/hr. Because very little (/sup 125/I)NGF reached peripheral terminals, the results were interpreted to indicate that receptors for NGF are present on nonterminal segments of sensory axons. The specificity and high affinity of NGF uptake were illustrated by observations that negligible amounts of gamma activity accumulated in lumbar dorsal root ganglia after comparable intraneural injection of (/sup 125/I) cytochrome C or (/sup 125/I)oxidized NGF. Similar techniques were used to demonstrate avid internalization and retrograde transport of (/sup 125/I)NGF by intraspinal axons arising from dorsal root ganglia. Following injection of (/sup 125/I)NGF into lumbar or cervical regions of the spinal cord, neuronal perikarya were clearly labeled in radioautographs of lumbar dorsal root ganglia. Sites for NGF uptake on primary sensory neurons in the adult rat are not restricted to peripheral axon terminals but are extensively distributed along both peripheral and central axons. Receptors on axons provide a mechanism whereby NGF supplied by glia could influence neuronal maintenance or axonal regeneration.

  9. Peripheral nerve blocks in patients with Ehlers-Danlos syndrome, hypermobility type: a report of 2 cases.

    PubMed

    Patzkowski, Michael S

    2016-03-01

    Ehlers-Danlos syndrome is an inherited disorder of collagen production that results in multiorgan dysfunction. Patients with hypermobility type display skin hyperextensibility and joint laxity, which can result in chronic joint instability, dislocation, peripheral neuropathy, and severe musculoskeletal pain. A bleeding diathesis can be found in all subtypes of varying severity despite a normal coagulation profile. There have also been reports of resistance to local anesthetics in these patients. Several sources advise against the use of regional anesthesia in these patients citing the 2 previous features. There have been reports of successful neuraxial anesthesia, but few concerning peripheral nerve blocks, none of which describe nerves of the lower extremity. This report describes 2 cases of successful peripheral regional anesthesia in the lower extremity. In case 1, a 16-year-old adolescent girl with hypermobility type presented for osteochondral grafting of tibiotalar joint lesions. She underwent a popliteal sciatic (with continuous catheter) and femoral nerve block under ultrasound guidance. She proceeded to surgery and tolerated the procedure under regional block and intravenous sedation. She did not require any analgesics for the following 15 hours. In case 2, an 18-year-old woman with hypermobility type presented for medial patellofemoral ligament reconstruction for chronic patella instability. She underwent a saphenous nerve block above the knee with analgesia in the distribution of the saphenous nerve lasting for approximately 18 hours. There were no complications in either case. Prohibitions against peripheral nerve blocks in patients with Ehlers-Danlos syndrome, hypermobility type, appear unwarranted. PMID:26897449

  10. Peripheral chemoreflex sensitivity and sympathetic nerve activity are normal in apnea divers during training season.

    PubMed

    Breskovic, Toni; Ivancev, Vladimir; Banic, Ivana; Jordan, Jens; Dujic, Zeljko

    2010-04-19

    Apnea divers are exposed to repeated massive arterial oxygen desaturation, which could perturb chemoreflexes. An earlier study suggested that peripheral chemoreflex regulation of sympathetic vasomotor tone and ventilation may have recovered 4 or more weeks into the off season. Therefore, we tested the hypothesis that peripheral chemoreflex regulation of ventilation and sympathetic vasomotor tone is present during the training season. We determined ventilation, heart rate, blood pressure, cardiac stroke volume, and muscle sympathetic nerve activity (MSNA) during isocapnic hypoxia in 10 breath hold divers and 11 matched control subjects. The study was carried out at the end of the season of intense apnea trainings. Baseline MSNA frequency was 30+/-4bursts/min in control subjects and 25+/-4bursts/min in breath hold divers (P=0.053). During hypoxia burst frequency and total sympathetic activity increased similarly in both groups. Sympathetic activity normalized during the 30-minute recovery. Hypoxia-induced stimulation of minute ventilation was similar in both groups, although in divers it was maintained by higher tidal volumes and lower breathing frequency compared with control subjects. In both groups, hypoxia increased heart rate and cardiac output whereas total peripheral resistance decreased. Blood pressure remained unchanged. We conclude that peripheral chemoreflex regulation of ventilation and sympathetic vasomotor tone is paradoxically preserved in apnea divers, both, during the off and during the training season. The observation suggests that repeated arterial oxygen desaturation may not be sufficient explaining sympathetic reflex abnormalities similar to those in obstructive sleep apnea patients. PMID:19926535

  11. Nerve injury induces a new profile of tactile and mechanical nociceptor input from undamaged peripheral afferents

    PubMed Central

    Gutierrez, Silvia; Aschenbrenner, Carol A.; Houle, Timothy T.; Hayashida, Ken-ichiro; Ririe, Douglas G.; Eisenach, James C.

    2014-01-01

    Chronic pain after nerve injury is often accompanied by hypersensitivity to mechanical stimuli, yet whether this reflects altered input, altered processing, or both remains unclear. Spinal nerve ligation or transection results in hypersensitivity to mechanical stimuli in skin innervated by adjacent dorsal root ganglia, but no previous study has quantified the changes in receptive field properties of these neurons in vivo. To address this, we recorded intracellularly from L4 dorsal root ganglion neurons of anesthetized young adult rats, 1 wk after L5 partial spinal nerve ligation (pSNL) or sham surgery. One week after pSNL, hindpaw mechanical withdrawal threshold in awake, freely behaving animals was decreased in the L4 distribution on the nerve-injured side compared with sham controls. Electrophysiology revealed that high-threshold mechanoreceptive cells of A-fiber conduction velocity in L4 were sensitized, with a seven-fold reduction in mechanical threshold, a seven-fold increase in receptive field area, and doubling of maximum instantaneous frequency in response to peripheral stimuli, accompanied by reductions in after-hyperpolarization amplitude and duration. Only a reduction in mechanical threshold (minimum von Frey hair producing neuronal activity) was observed in C-fiber conduction velocity high-threshold mechanoreceptive cells. In contrast, low-threshold mechanoreceptive cells were desensitized, with a 13-fold increase in mechanical threshold, a 60% reduction in receptive field area, and a 40% reduction in instantaneous frequency to stimulation. No spontaneous activity was observed in L4 ganglia, and the likelihood of recording from neurons without a mechanical receptive field was increased after pSNL. These data suggest massively altered input from undamaged sensory afferents innervating areas of hypersensitivity after nerve injury, with reduced tactile and increased nociceptive afferent response. These findings differ importantly from previous preclinical

  12. Fibre-selective recording from the peripheral nerves of frogs using a multi-electrode cuff

    NASA Astrophysics Data System (ADS)

    Schuettler, Martin; Donaldson, Nick; Seetohul, Vipin; Taylor, John

    2013-06-01

    Objective. We investigate the ability of the method of velocity selective recording (VSR) to determine the fibre types that contribute to a compound action potential (CAP) propagating along a peripheral nerve. Real-time identification of the active fibre types by determining the direction of action potential propagation (afferent or efferent) and velocity might allow future neural prostheses to make better use of biological sensor signals and provide a new and simple tool for use in fundamental neuroscience. Approach. Fibre activity was recorded from explanted Xenopus Laevis frog sciatic nerve using a single multi-electrode cuff that records whole nerve activity with 11 equidistant ring-shaped electrodes. The recorded signals were amplified, delayed against each other with variable delay times, added and band-pass filtered. Finally, the resulting amplitudes were measured. Main Result. Our experiments showed that electrically evoked frog CAP was dominated by two fibre populations, propagating at around 20 and 40 m/s, respectively. The velocity selectivity, i.e. the ability of the system to discriminate between individual populations was increased by applying band-pass filtering. The method extracted an entire velocity spectrum from a 10 ms CAP recording sample in real time. Significance. Unlike the techniques introduced in the 1970s and subsequently, VSR requires only a single nerve cuff and does not require averaging to provide velocity spectral information. This makes it potentially suitable for the generation of highly-selective real-time control-signals for future neural prostheses. In our study, electrically evoked CAPs were analysed and it remains to be proven whether the method can reliably classify physiological nerve traffic. The work presented here was carried out at the laboratories of the Implanted Devices Group, Department of Medical Physics and Bioengineering, University College London, UK.

  13. Peripheral Nerve Diffusion Tensor Imaging: Assessment of Axon and Myelin Sheath Integrity

    PubMed Central

    Heckel, A.; Weiler, M.; Xia, A.; Ruetters, M.; Pham, M.; Bendszus, M.; Heiland, S.; Baeumer, P.

    2015-01-01

    Purpose To investigate the potential of diffusion tensor imaging (DTI) parameters as in-vivo biomarkers of axon and myelin sheath integrity of the median nerve in the carpal tunnel as validated by correlation with electrophysiology. Methods MRI examinations at 3T including DTI were conducted on wrists in 30 healthy subjects. After manual segmentation of the median nerve quantitative analysis of fractional anisotropy (FA) as well as axial, radial and mean diffusivity (AD, RD, and MD) was carried out. Pairwise Pearson correlations with electrophysiological parameters comprising sensory nerve action potential (SNAP) and compound muscle action potential (CMAP) as markers of axon integrity, and distal motor latency (dml) and sensory nerve conduction velocity (sNCV) as markers of myelin sheath integrity were computed. The significance criterion was set at P=0.05, Bonferroni corrected for multiple comparisons. Results DTI parameters showed a distinct proximal-to-distal profile with FA, MD, and RD extrema coinciding in the center of the carpal tunnel. AD correlated with CMAP (r=0.50, p=0.04, Bonf. corr.) but not with markers of myelin sheath integrity. RD correlated with sNCV (r=-0.53, p=0.02, Bonf. corr.) but not with markers of axon integrity. FA correlated with dml (r=-0.63, p=0.002, Bonf. corr.) and sNCV (r=0.68, p=0.001, Bonf. corr.) but not with markers of axon integrity. Conclusion AD reflects axon integrity, while RD (and FA) reflect myelin sheath integrity as validated by correlation with electrophysiology. DTI parameters consistently indicate a slight decrease of structural integrity in the carpal tunnel as a physiological site of median nerve entrapment. DTI is particularly sensitive, since these findings are observed in healthy participants. Our results encourage future studies to evaluate the potential of DTI in differentiating axon from myelin sheath injury in patients with manifest peripheral neuropathies. PMID:26114630

  14. Dynamic Quantification of Host Schwann Cell Migration into Peripheral Nerve Allografts

    PubMed Central

    Whitlock, Elizabeth L.; Myckatyn, Terence M.; Tong, Alice Y.; Yee, Andrew; Yan, Ying; Magill, Christina K.; Johnson, Philip J.; Mackinnon, Susan E.

    2010-01-01

    Host Schwann cell (SC) migration into nerve allografts is the limiting factor in the duration of immunosuppression following peripheral nerve allotransplantation, and may be affected by different immunosuppressive regimens. Our objective was to compare SC migration patterns between clinical and experimental immunosuppression regimens both over time and at the harvest endpoint. Eighty mice that express GFP under the control of the Schwann cell specific S100 promoter were engrafted with allogeneic, nonfluorescent sciatic nerve grafts. Mice received immunosuppression with either tacrolimus (FK506), or experimental T-cell triple costimulation blockade (CSB), consisting of CTLA4-immunoglobulin fusion protein, anti-CD40 monoclonal antibody, and anti-inducible costimulator monoclonal antibody. Migration of GFP-expressing host SCs into wild-type allografts was assessed in vivo every 3 weeks until 15 weeks postoperatively, and explanted allografts were evaluated for immunohistochemical staining patterns to differentiate graft from host SCs. Immunosuppression with tacrolimus exhibited a plateau of SC migration, characterized by significant early migration (< 3 weeks) followed by a constant level of host SCs in the graft (15 weeks). At the endpoint, graft fluorescence was decreased relative to surrounding host nerve, and donor SCs persisted within the graft. CSB-treated mice displayed gradually increasing migration of host SCs into the graft, without the plateau noted in tacrolimus-treated mice, and also maintained a population of donor SCs at the 15-week endpoint. SC migration patterns are affected by immunosuppressant choice, particularly in the immediate postoperative period, and the use of a single treatment of CSB may allow for gradual population of nerve allografts with host SCs. PMID:20633557

  15. Enhancing nerve regeneration in the peripheral nervous system using polymeric scaffolds, stem cell engineering and nanoparticle delivery system

    NASA Astrophysics Data System (ADS)

    Sharma, Anup Dutt

    Peripheral nerve regeneration is a complex biological process responsible for regrowth of neural tissue following a nerve injury. The main objective of this project was to enhance peripheral nerve regeneration using interdisciplinary approaches involving polymeric scaffolds, stem cell therapy, drug delivery and high content screening. Biocompatible and biodegradable polymeric materials such as poly (lactic acid) were used for engineering conduits with micropatterns capable of providing mechanical support and orientation to the regenerating axons and polyanhydrides for fabricating nano/microparticles for localized delivery of neurotrophic growth factors and cytokines at the site of injury. Transdifferentiated bone marrow stromal cells or mesenchymal stem cells (MSCs) were used as cellular replacements for lost native Schwann cells (SCs) at the injured nerve tissue. MSCs that have been transdifferentiated into an SC-like phenotype were tested as a substitute for the myelinating SCs. Also, genetically modified MSCs were engineered to hypersecrete brain- derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) to secrete therapeutic factors which Schwann cell secrete. To further enhance the regeneration, nerve growth factor (NGF) and interleukin-4 (IL4) releasing polyanhydrides nano/microparticles were fabricated and characterized in vitro for their efficacy. Synergistic use of these proposed techniques was used for fabricating a multifunctional nerve regeneration conduit which can be used as an efficient tool for enhancing peripheral nerve regeneration.

  16. The development of military medical care for peripheral nerve injuries during World War I.

    PubMed

    Hanigan, William

    2010-05-01

    Although the clinical and electrical diagnoses and treatments of peripheral nerve injuries (PNIs) had been described prior to World War I, many reports were fragmented and incomplete. Individual physicians' experiences were not extensive, and in 1914 the patient with a PNI remained a subject of medical curiosity, and was hardly a focus of comprehensive care. World War I altered these conditions; casualties with septic wounds and PNIs swamped the general hospitals. By 1915, specialized hospitals or wards were developed to care for neurological injuries. In the United Kingdom, Sir Robert Jones developed the concept of Military Orthopedic Centres, with coordinated specialized care and rehabilitation. Military appointments of neurologists and electrotherapists sharpened clinical diagnoses and examinations. Surgical techniques were introduced, then discarded or accepted as surgeons developed skills to meet the new conditions. The US Surgeon General, William Gorgas, and his consultant in neurosurgery, Charles Frazier, went a step further, with the organization of a research laboratory as well as the establishment of a Peripheral Nerve Commission and Registry. Despite these developments and good intentions, postwar follow-up for PNIs remained incomplete at best. Records were lost, personnel transferred, and patients discharged from the system. The lack of a standardized grading system seriously impaired the ability to record clinical changes and compare outcomes. Nevertheless, specialized treatment of a large number of PNIs during World War I established a foundation for comprehensive care that influenced military medical services in the next world war. PMID:20568941

  17. Bayesian spatial filters for the extraction of source signals, a study in the peripheral nerve

    PubMed Central

    Tang, Yuang; Durand, Dominique M.

    2015-01-01

    The ability to extract physiological source signals to control various prosthetics offer tremendous therapeutic potential to improve the quality of life for patients suffering from motor disabilities. Regardless of the modality, recordings of physiological source signals are contaminated with noise and interference along with crosstalk between the sources. These impediments render the task of isolating potential physiological source signals for control difficult. In this paper, a novel Bayesian Source Filter for signal Extraction (BSFE) algorithm for extracting physiological source signals for control is presented. The BSFE algorithm is based on the source localization method Champagne and constructs spatial filters using Bayesian methods that simultaneously maximize the signal to noise ratio of the recovered source signal of interest while minimizing crosstalk interference between sources. When evaluated over peripheral nerve recordings obtained in-vivo, the algorithm achieved the highest signal to noise interference ratio (>7.00±3.45dB) amongst the group of methodologies compared with average correlation between the extracted source signal and the original source signal > 0.93. The results support the efficacy of the BSFE algorithm for extracting source signals from the peripheral nerve or as a pre-filtering stage for BCI methods. PMID:24608686

  18. Peripheral nerve sheath tumors arising in salivary glands: A clinicopathologic study.

    PubMed

    Guraya, Sahejmeet S; Prayson, Richard A

    2016-08-01

    Primary salivary gland peripheral nerve sheath tumors (PNST) are uncommon. This study is a retrospective, clinicopathologic review of 9 cases of PNST (5 neurofibromas, 3 schwannomas and 1 malignant peripheral nerve sheath tumor (MPNST)) arising from the salivary glands, encountered between 1990 and 2015. All patients with neurofibromas were male (ages 1-62 years) and had a single parotid lesion of which 2 were diffuse, 2 plexiform and one mixed diffuse/plexiform. Four had a history of neurofibromatosis I. Four of 5 presented with symptoms related to mass effect including facial swelling, facial drooping, and dysphagia. All underwent de-bulking surgery and recurred due to continued growth. Of the 3 patients with schwannomas, 1 was male and 2 were female (ages 19, 44 and 56 years). One tumor each arose in the sublingual, submandibular, and parotid glands. Two of 3 presented with soreness and swelling local to the affected gland, especially while chewing. There was no recurrence of these tumors after resection. An MPNST in a male presented as a tender mass in the patient's left parotid; the tumor was resected. There was no evidence of tumor elsewhere in the body. The tumor did not recur in 12 years of follow-up. The most common tumor type in the current series was neurofibroma; most arose in the background of neurofibromatosis type I and all of which recurred after initial subtotal resection. Most PNST arose in the parotid gland. PMID:27402223

  19. [Malignant peripheral sheath nerve tumor: An exceptional mass of the anterior and middle mediastinum].

    PubMed

    Bacha, S; Chaouch, N; Ayadi, A; Zidi, A; Cheikhrouhou, S; Racil, H; Chabbou, A

    2015-12-01

    Malignant peripheral nerve sheath tumors (MPNST) are rare nervous tumors usually located in the posterior mediastinum in the paravertebral gutters. We report the case of a non-smoking 62-year-old man who was admitted with a 4 months history of cough, hoarseness and shortness of breath. Physical examination noted a superior vena cava syndrome. CT scan of the chest revealed a right anterior and middle mediastinal mass compressing the superior vena cava, the ascending aorta, the right pulmonary artery, invading the superior root of the pulmonary vein and the right auricle. Flexible bronchoscopy showed extrinsic compression of the right main bronchus, the right upper lobe bronchus and intermedius bronchus. The patient underwent surgical biopsy of the mass by mediastinoscopy. Histological examination revealed a malignant peripheral nerve sheath tumor. The patient received a single cycle of chemotherapy (ifosfamid-adriamycin). Clinical course was marked by the fast worsening of the dyspnea and the general state. Patient died three weeks after the cure of the chemotherapy. This case is original by the exceptional clinical presentation of MPSNT with a superior vena cava syndrome and the very rare location of this tumor in the anterior and middle mediastinum. PMID:26190334

  20. Breast metastases from a malignant peripheral nerve sheath tumor of the kidney: An unusual presentation

    PubMed Central

    Koppisetty, Shalini; Alessio, Ricardo C.; Rajpurkar, Atul

    2016-01-01

    Malignant peripheral nerve sheath tumors (MPNSTs) are extremely rare soft tissue sarcomas of ectomesenchymal origin. They are commonly seen in association with neurofibromatosis type 1 (NF-1), but can also occur without a history of NF (isolated MPNST). MPNSTs are most commonly located on the extremities (brachial and sacral plexus), head and neck, and trunk regions and are rarely reported in genitourinary organs. These tumors are aggressive, with a high recurrence rate and distant metastases. MPNST involving the kidney is extremely rare, and review of the literature using PubMed from 2001 to 2014 revealed eight cases of MPNST involving the kidney (seven, primarily involving the kidney and one metastatic MPNST of the kidney). Herein, we describe a case of breast metastases from an MPNST of the kidney without a history of NF-1. The patient was initially diagnosed with a spindle cell neoplasm of the kidney with peripheral nerve sheath differentiation. Eventually, the patient developed a right breast mass that was diagnosed as metastatic MPNST. The patient refused any kind of treatment and died 6 months later in hospice care. PMID:27453670

  1. Clinical observation of peripheral nerve injury in 2 patients with cancer after radiotherapy

    PubMed Central

    Liang, Li; Jia, Ting-zhen; Zhang, Shu-lan; Wang, Mo-pei; Ma, Li-Wen; Liu, Qiang

    2013-01-01

    Aim of the study This study aims to analyze the clinical manifestations and sequelae of peripheral nerve radiation damage of two cases of cancer patients after radiotherapy at the corresponding sites in clinical practice and to summarize experiences and lesions in order to provide a reference for future tumor radiotherapy. Material and methods Some data of two cases of patients, such as doses of radiotherapy, clinical manifestations and damage occurrence time, were collected and examinations were conducted to define diagnosis. Afterwards, therapies and follow-up were conducted. Results Case 1 (rectal cancer) was diagnosed as mild left lower extremity nerve damage. After the symptomatic treatment, the disease condition was improved, and there was no tumor recurrence sign. Case 2 (breast cancer) was diagnosed as left brachial plexus damage, and left upper extremity movement function was lost completely. While the analgesic treatment was conducted, anti-tumor relevant treatments were being carried out. Conclusions Radiotherapy can cause different extents of radioactive nerve damage. In practice, it is necessary to constantly improve the radiotherapy technology level and actively prevent the occurrence of complications. Once symptoms appear, the diagnosis and treatment should be conducted as early as possible in order to avoid aggravating damage to cause dysfunction and cause lifetime pain to patients. PMID:23788990

  2. Biologic Basis of Nerve Decompression Surgery for Focal Entrapments in Diabetic Peripheral Neuropathy.

    PubMed

    Sessions, John; Nickerson, D Scott

    2014-02-27

    The most recent (2011) National Diabetes Fact Sheet states the combined diagnosed and undiagnosed number of diabetes cases in the United States is approaching 25 million, and another 79 million are prediabetic. Of the diabetes patients, 60-70% suffer from mild to severe neuropathy. This combined loss of sensory and motor control in diabetic limbs is usually considered an irreversible, progressive process. Patients suffering from these losses are at a significantly higher risk for development of foot ulceration, frequently leading to infection and partial or major limb amputation. However, a review of focal nerve entrapment surgical decompression literature suggests that several diabetic sensorimotor polyneuropathy (DSPN) symptoms and complications are potentially partially reversible or preventable. Decompression surgery represents a paradigm shift in treatment protocols because it both relieves pain and restores protective sensation, while providing significant protection against a cascade of serious foot complications. This review surveys current research regarding the biological basis for diabetic focal entrapment neuropathy. Metabolic dysfunction related to aldose reductase, oxidative stress, and advanced glycation end products are considered and correlated to peripheral nerve enlargement and entrapment. In addition, observational studies correlated to that biological basis are presented as well as surgical outcomes illustrating the effect of decompression on DSPN symptomatic relief, nerve function, and protection against complications. PMID:24876595

  3. Macrophage-Induced Blood Vessels Guide Schwann Cell-Mediated Regeneration of Peripheral Nerves

    PubMed Central

    Cattin, Anne-Laure; Burden, Jemima J.; Van Emmenis, Lucie; Mackenzie, Francesca E.; Hoving, Julian J.A.; Garcia Calavia, Noelia; Guo, Yanping; McLaughlin, Maeve; Rosenberg, Laura H.; Quereda, Victor; Jamecna, Denisa; Napoli, Ilaria; Parrinello, Simona; Enver, Tariq; Ruhrberg, Christiana; Lloyd, Alison C.

    2015-01-01

    Summary The peripheral nervous system has remarkable regenerative capacities in that it can repair a fully cut nerve. This requires Schwann cells to migrate collectively to guide regrowing axons across a ‘bridge’ of new tissue, which forms to reconnect a severed nerve. Here we show that blood vessels direct the migrating cords of Schwann cells. This multicellular process is initiated by hypoxia, selectively sensed by macrophages within the bridge, which via VEGF-A secretion induce a polarized vasculature that relieves the hypoxia. Schwann cells then use the blood vessels as “tracks” to cross the bridge taking regrowing axons with them. Importantly, disrupting the organization of the newly formed blood vessels in vivo, either by inhibiting the angiogenic signal or by re-orienting them, compromises Schwann cell directionality resulting in defective nerve repair. This study provides important insights into how the choreography of multiple cell-types is required for the regeneration of an adult tissue. PMID:26279190

  4. Analysis of nociception, sex and peripheral nerve innervation in the TMEV animal model of multiple sclerosis

    PubMed Central

    Lynch, Jessica L.; Gallus, Nathan J.; Ericson, Marna E.; Beitz, Alvin J.

    2009-01-01

    Although pain was previously not considered an important element of multiple sclerosis (MS), recent evidence indicates that over 50% of MS patients suffer from chronic pain. In the present study, we utilized the Theiler’s murine encephalomyelitis virus (TMEV) model of MS to examine whether changes in nociception occur during disease progression and to investigate whether sex influences the development of nociception or disease-associated neurological symptoms. Using the rotarod assay, TMEV infected male mice displayed increased neurological deficits when compared to TMEV infected female mice, which mimics what is observed in human MS. While both male and female TMEV infected mice exhibited thermal hyperalgesia and mechanical allodynia, female mice developed mechanical allodynia at a faster rate and displayed significantly more mechanical allodynia than male mice. Since neuropathic symptoms have been described in MS patients, we quantified sensory nerve fibers in the epidermis of TMEV-infected and non-infected mice to determine if there were alterations in epidermal nerve density. There was a significantly higher density of PGP9.5 and CGRP immunoreactive axons in the epidermis of TMEV-infected mice versus controls. Collectively these results indicate that the TMEV model is well suited to study the mechanisms of MS-induced nociception and suggest that alterations in peripheral nerve innervation may contribute to MS pain. PMID:17766043

  5. Liposomal Bupivacaine as a Single-Injection Peripheral Nerve Block: A Dose-Response Study

    PubMed Central

    Ilfeld, Brian M.; Malhotra, Nisha; Furnish, Timothy J.; Donohue, Michael C.; Madison, Sarah J.

    2013-01-01

    Background Currently available local anesthetics approved for single-injection peripheral nerve blocks have a maximum duration less than 24 hours. A liposomal bupivacaine formulation (EXPAREL®, Pacira Pharmaceuticals, Inc., San Diego, California), releasing bupivacaine over 96 hours, recently gained Food and Drug Administration approval exclusively for wound infiltration, but not peripheral nerve blocks. Methods Bilateral single-injection femoral nerve blocks were administered in healthy volunteers (n=14). For each block, liposomal bupivacaine (0–80 mg) was mixed with normal saline to produce 30 mL of study fluid. Each subject received two different doses, one on each side, applied randomly in a double-masked fashion. The end points included the maximum voluntary isometric contraction (MVIC) of the quadriceps femoris muscle and tolerance to cutaneous electrical current in the femoral nerve distribution. Measurements were performed from baseline until quadriceps MVIC returned to 80% of baseline bilaterally. Results There were statistically significant dose responses in MVIC (0.09% / mg, SE = 0.03, 95% CI 0.04 to 0.14, p = 0.002) and tolerance to cutaneous current (−0.03 mA / mg, SE = 0.01, 95% CI −0.04 to 0.02, p < 0.001), however, in the opposite direction than expected (the higher the dose, the lower the observed effect). This inverse relationship is biologically implausible, and most likely due to the limited sample size and the subjective nature of the measurement instruments. While peak effects occurred within 24 hours after block administration in 75% of cases (95% CI 43 to 93%), block duration usually lasted much longer: for bupivacaine doses above 40 mg, tolerance to cutaneous current did not return to within 20% above baseline until after 24 h in 100% of subjects (95% CI 56 to 100). MVIC did not consistently return to within 20% of baseline until after 24 hours in 90% of subjects (95% CI 54 to 100%). Motor block duration was not correlated with

  6. Evaluation and use of regenerative multi electrode interfaces in peripheral nerves

    NASA Astrophysics Data System (ADS)

    Desai, Vidhi

    Peripheral nerves offer unique accessibility to the innate motor and sensory pathways that can be interfaced with high degree of selectivity for intuitive and bidirectional control of advanced upper extremity prosthetic limbs. Several peripheral nerve interfaces have been proposed and investigated over the last few decades with significant progress made in the area of sensory feedback. However, clinical translation still remains a formidable challenge due to the lack of long term recordings. Prominent causes include signal degradation, eventual interface failures, and lack of specificity in the low amplitude nerve signals. This dissertation evaluates the capabilities of the newly developed Regenerative Multi-electrode Interface (REMI) by the characterization of signal quality progression, the identification of interfaced axon types, and the demonstration of "functional linkage" between acquired signals and target organs. Chapter 2 details the chronic recording of high quality signals from REMI in sciatic nerve which remained stable over a 120 day implantation period indicative of minimal ongoing tissue response with no detrimental effects on the recording ability. The dominant cause of failures was attributable to abiotic factors pertaining to the connector/wire breakage, observed in 76% of REMI implants. Also, the REMI implants had 20% higher success rate and significantly larger Signal to Noise Ratio (SNR) in comparison to the Utah Slanted Electrode Array (USEA). Chapter 3 describes the successful feasibility of interfacing with motor and sensory axons by REMI implantation in the tibial and sural fascicles of the sciatic nerve. A characteristic sampling bias towards recording signals from medium-to-large diameter axons that are primarily involved in mechanoception and proprioception sensory functions was uncovered. Specific bursting units (Inter Spike Interval of 30-70ms) were observed most frequently from the tibial fascicle during bipedal locomotion. Chapter 4

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

    PubMed Central

    2011-01-01

    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 in other tissues

  8. Evaluation of sural nerve automated nerve conduction study in the diagnosis of peripheral neuropathy in patients with type 2 diabetes mellitus

    PubMed Central

    Chatzikosma, Georgia; Pafili, Kalliopi; Demetriou, Maria; Vadikolias, Konstantinos; Maltezos, Efstratios

    2016-01-01

    Introduction New tests for improved diagnosis of diabetic peripheral neuropathy (DPN) are useful. Material and methods We evaluated the utility of automated nerve conduction study (NCS) of the sural nerve with a new portable device for the diagnosis of DPN in patients with type 2 diabetes mellitus (T2DM). This study included 114 T2DM patients (58 men) with mean age 64.60 ±8.61 years. Exclusion criteria were B12 depletion, alcohol abuse and other causes of peripheral neuropathy. The reference method was the Neuropathy Disability Score (NDS) with a threshold NDS ≥ 3. Sural nerve automated NCS was carried out with the portable NC-stat DPNCheck device. Sensory nerve conduction velocity and sensory nerve action potential amplitude were measured bilaterally. Automated NCS was considered abnormal when ≥ 1 of the two aforementioned neurophysiological parameters was abnormal in at least one leg. Results Examination with NC-stat DPNCheck exhibited 90.48% sensitivity, 86.11% specificity, 79.17% positive predictive value (PPV) and 93.94% negative predictive value (NPV). The positive likelihood ratio (LR+) was 6.51 and the negative likelihood ratio (LR–) was 0.11. Conclusions Sural nerve automated NCS with the NC-stat DPNCheck device exhibits high sensitivity and specificity for the diagnosis of DPN in T2DM. PMID:27186185

  9. Fascicular Ratio: A New Parameter to Evaluate Peripheral Nerve Pathology on Magnetic Resonance Imaging

    PubMed Central

    Tagliafico, Alberto S.; Tagliafico, Giulio

    2014-01-01

    Abstract The objective of the study was to define and quantitatively evaluate the fascicular ratio (FR) on magnetic resonance imaging (MRI) in patients with peripheral neuropathies compared with healthy controls. Forty control subjects (20 women, 20 men; age, 44.6 ± 13.4 years) and 40 patients with peripheral neuropathy (22 women, 18 men; age, 50.3 ± 10.2 years) were examined with a standard 3T MRI protocol. With customized software (with semiautomatic and automatic interface), the hypointense and hyperintense areas of the peripheral nerves corresponding to fascicular and nonfascicular tissue were examined on T1-weighted sequences. The ratio of fascicular pixels to total pixels was called FR. Correlation with FR calculated on high-resolution ultrasound was performed. The statistical analysis included the Mann–Whitney U test of controls versus patients, the receiver operating characteristic (ROC) analysis, and the subgroup analysis of patients according to etiologies of neuropathy. Intraobserver and interobserver agreement was calculated based on the evaluation made by 3 readers. Finally, a complete automatic evaluation was performed. On MRI, FRs were significantly increased in patients compared with controls (FR, 76.7 ± 15.1 vs 56 ± 12.3; P < 0.0001 for the semiautomatic interface; and FR 66.3 ± 17.5 vs 47.8 ± 18.4; P < 0.0001 for the automatic interface). The increase in FR was caused mainly by an increase in the hypointense part of the nerve. This observation was valid for all causes of neuropathies. ROC analysis found an area under the curve of 0.75 (95% confidence interval, 0.44–0.81) for FR to discriminate neuropathy from control. The correlation coefficient between MRI and ultrasound was significant (r = 0.49; 95% confidence interval for r, 0.21–0.70; P = 0.012). With the semiautomated evaluation, the mean intraobserver agreement was good (K = 0.86). The interobserver agreements were also good (reader 1

  10. Low serum magnesium levels are associated with impaired peripheral nerve function in type 2 diabetic patients.

    PubMed

    Chu, Chen; Zhao, Weijing; Zhang, Yinan; Li, Lu; Lu, Jingyi; Jiang, Lan; Wang, Congrong; Jia, Weiping

    2016-01-01

    The aim of this study was to explore the relationship between serum magnesium and peripheral nerve function in patients with type 2 diabetes (T2DM). A total of 978 T2DM patients were included in the study. Patients were divided into tertiles according to serum magnesium concentration (low tertile: ≤0.85 mmol/L; medium tertile: 0.85 to 0.92 mmol/L; and high tertile: >0.92 mmol/L). All participants underwent nerve conduction (NC) studies. Composite z scores of conduction velocity, latency, and amplitude were constructed, respectively. The serum magnesium levels were significantly lower in patients with abnormal NC than in those with normal NC (0.87 [0.82, 0.92] vs. 0.88 [0.83, 0.93] mmol/L, P = 0.048). The composite z score of amplitude significantly increased with increasing tertiles of magnesium (-0.60 ± 0.02 vs. -0.57 ± 0.02 vs. -0.48 ± 0.03, P for trend = 0.001). After adjusting for all potential confounders, lower serum magnesium levels were still associated with lower composite z score of amplitude (β = 0.095, P = 0.014). In patients with T2DM, lower serum magnesium levels were significantly associated with lower composite z score of amplitude, indicating magnesium might affect peripheral nerve function through axonal degeneration. PMID:27601013

  11. Low serum magnesium levels are associated with impaired peripheral nerve function in type 2 diabetic patients

    PubMed Central

    Chu, Chen; Zhao, Weijing; Zhang, Yinan; Li, Lu; Lu, Jingyi; Jiang, Lan; Wang, Congrong; Jia, Weiping

    2016-01-01

    The aim of this study was to explore the relationship between serum magnesium and peripheral nerve function in patients with type 2 diabetes (T2DM). A total of 978 T2DM patients were included in the study. Patients were divided into tertiles according to serum magnesium concentration (low tertile: ≤0.85 mmol/L; medium tertile: 0.85 to 0.92 mmol/L; and high tertile: >0.92 mmol/L). All participants underwent nerve conduction (NC) studies. Composite z scores of conduction velocity, latency, and amplitude were constructed, respectively. The serum magnesium levels were significantly lower in patients with abnormal NC than in those with normal NC (0.87 [0.82, 0.92] vs. 0.88 [0.83, 0.93] mmol/L, P = 0.048). The composite z score of amplitude significantly increased with increasing tertiles of magnesium (−0.60 ± 0.02 vs. −0.57 ± 0.02 vs. −0.48 ± 0.03, P for trend = 0.001). After adjusting for all potential confounders, lower serum magnesium levels were still associated with lower composite z score of amplitude (β = 0.095, P = 0.014). In patients with T2DM, lower serum magnesium levels were significantly associated with lower composite z score of amplitude, indicating magnesium might affect peripheral nerve function through axonal degeneration. PMID:27601013

  12. Experimental composite guidance conduits for peripheral nerve repair: an evaluation of ion release.

    PubMed

    Zhang, X F; Coughlan, A; O'Shea, H; Towler, M R; Kehoe, S; Boyd, D

    2012-08-01

    Poly (lactide-co-glycolide) (PLGA) - Pluronic F127 - glass composites have demonstrated excellent potential, from the perspective of controlled mechanical properties and cytocompatibility, for peripheral nerve regeneration. In addition to controlling the mechanical properties and cytotoxicity for such composite devices, the glass component may mediate specific responses upon implantation via degradation in the physiological environment and release of constituent elements. However, research focused on quantifying the release levels of such therapeutic ions from these experimental medical devices has been limited. To redress the balance, this paper explores the ion release profiles for Si(4+), Ca(2+), Na(+), Zn(2+), and Ce(4+) from experimental composite nerve guidance conduits (CNGC) comprising PLGA (at 12.5, and 20 wt.%), F127 (at 0, 2.5 and 5 wt.%) and various loadings of Si-Ca-Na-Zn-Ce glass (at 20 and 40 wt.%) for incubation periods of up to 28 days. The concentration of each ion, at various time points, was determined using Inductively Coupled Plasma-Atomic Emission Spectrometry (Perkin Elmer Optima 3000). It was observed that the Si(4+), Na(+), Ca(2+), Zn(2+) release from CNGCs in this study ranged from 0.22 to 6.477 ppm, 2.307 to 3.277 ppm, 40 to 119 ppm, and 45 to 51 ppm, respectively. The Ce(4+) concentrations were under the minimum detection limits for the ICP instrument utilized. The results indicate that the ion release levels may be appropriate to mediate therapeutic effects with respect to peripheral nerve regeneration. The data generated in this paper provides requisite evidence to optimize composition for pre-clinical evaluation of the experimental composite. PMID:24364973

  13. Peripheral nerve blocks on the upper extremity: Technique of landmark-based and ultrasound-guided approaches.

    PubMed

    Steinfeldt, T; Volk, T; Kessler, P; Vicent, O; Wulf, H; Gottschalk, A; Lange, M; Schwartzkopf, P; Hüttemann, E; Tessmann, R; Marx, A; Souquet, J; Häger, D; Nagel, W; Biscoping, J; Schwemmer, U

    2015-11-01

    The German Society of Anaesthesiology and Intensive Care Medicine (Deutsche Gesellschaft für Anästhesiologie und Intensivmedizin, DGAI) established an expert panel to develop preliminary recommendations for the application of peripheral nerve blocks on the upper extremity. The present recommendations state in different variations how ultrasound and/or electrical nerve stimulation guided nerve blocks should be performed. The description of each procedure is rather a recommendation than a guideline. The anaesthesiologist should select the variation of block which provides the highest grade of safety according to his individual opportunities. The first section comprises recommendations regarding dosages of local anaesthetics, general indications and contraindications for peripheral nerve blocks and informations about complications. In the following sections most common blocks techniques on the upper extremity are described. PMID:26408023

  14. Ciguatoxin reduces regenerative capacity of axotomized peripheral neurons and delays functional recovery in pre-exposed mice after peripheral nerve injury.

    PubMed

    Au, Ngan Pan Bennett; Kumar, Gajendra; Asthana, Pallavi; Tin, Chung; Mak, Yim Ling; Chan, Leo Lai; Lam, Paul Kwan Sing; Ma, Chi Him Eddie

    2016-01-01

    Ciguatera fish poisoning (CFP) results from consumption of tropical reef fish containing ciguatoxins (CTXs). Pacific (P)-CTX-1 is among the most potent known CTXs and the predominant source of CFP in the endemic region responsible for the majority of neurological symptoms in patients. Chronic and persistent neurological symptoms occur in some CFP patients, which often result in incomplete functional recovery for years. However, the direct effects of exposure to CTXs remain largely unknown. In present study, we exposed mice to CTX purified from ciguatera fish sourced from the Pacific region. P-CTX-1 was detected in peripheral nerves within hours and persisted for two months after exposure. P-CTX-1 inhibited axonal regrowth from axotomized peripheral neurons in culture. P-CTX-1 exposure reduced motor function in mice within the first two weeks of exposure before returning to baseline levels. These pre-exposed animals exhibited delayed sensory and motor functional recovery, and irreversible motor deficits after peripheral nerve injury in which formation of functional synapses was impaired. These findings are consistent with reduced muscle function, as assessed by electromyography recordings. Our study provides strong evidence that the persistence of P-CTX-1 in peripheral nerves reduces the intrinsic growth capacity of peripheral neurons, resulting in delayed functional recovery after injury. PMID:27229176

  15. Ciguatoxin reduces regenerative capacity of axotomized peripheral neurons and delays functional recovery in pre-exposed mice after peripheral nerve injury

    PubMed Central

    Au, Ngan Pan Bennett; Kumar, Gajendra; Asthana, Pallavi; Tin, Chung; Mak, Yim Ling; Chan, Leo Lai; Lam, Paul Kwan Sing; Ma, Chi Him Eddie

    2016-01-01

    Ciguatera fish poisoning (CFP) results from consumption of tropical reef fish containing ciguatoxins (CTXs). Pacific (P)-CTX-1 is among the most potent known CTXs and the predominant source of CFP in the endemic region responsible for the majority of neurological symptoms in patients. Chronic and persistent neurological symptoms occur in some CFP patients, which often result in incomplete functional recovery for years. However, the direct effects of exposure to CTXs remain largely unknown. In present study, we exposed mice to CTX purified from ciguatera fish sourced from the Pacific region. P-CTX-1 was detected in peripheral nerves within hours and persisted for two months after exposure. P-CTX-1 inhibited axonal regrowth from axotomized peripheral neurons in culture. P-CTX-1 exposure reduced motor function in mice within the first two weeks of exposure before returning to baseline levels. These pre-exposed animals exhibited delayed sensory and motor functional recovery, and irreversible motor deficits after peripheral nerve injury in which formation of functional synapses was impaired. These findings are consistent with reduced muscle function, as assessed by electromyography recordings. Our study provides strong evidence that the persistence of P-CTX-1 in peripheral nerves reduces the intrinsic growth capacity of peripheral neurons, resulting in delayed functional recovery after injury. PMID:27229176

  16. Unravelling crucial biomechanical resilience of myelinated peripheral nerve fibres provided by the Schwann cell basal lamina and PMP22

    PubMed Central

    Rosso, Gonzalo; Liashkovich, Ivan; Gess, Burkhard; Young, Peter; Kun, Alejandra; Shahin, Victor

    2014-01-01

    There is an urgent need for the research of the close and enigmatic relationship between nerve biomechanics and the development of neuropathies. Here we present a research strategy based on the application atomic force and confocal microscopy for simultaneous nerve biomechanics and integrity investigations. Using wild-type and hereditary neuropathy mouse models, we reveal surprising mechanical protection of peripheral nerves. Myelinated peripheral wild-type fibres promptly and fully recover from acute enormous local mechanical compression while maintaining functional and structural integrity. The basal lamina which enwraps each myelinated fibre separately is identified as the major contributor to the striking fibre's resilience and integrity. In contrast, neuropathic fibres lacking the peripheral myelin protein 22 (PMP22), which is closely connected with several hereditary human neuropathies, fail to recover from light compression. Interestingly, the structural arrangement of the basal lamina of Pmp22−/− fibres is significantly altered compared to wild-type fibres. In conclusion, the basal lamina and PMP22 act in concert to contribute to a resilience and integrity of peripheral nerves at the single fibre level. Our findings and the presented technology set the stage for a comprehensive research of the links between nerve biomechanics and neuropathies. PMID:25446378

  17. Axon-Schwann cell interaction in degenerating and regenerating peripheral nerve

    SciTech Connect

    Pellegrino, R.G.

    1984-01-01

    Severance of a peripheral nerve stimulates a characteristic sequence of events in the distal stump, including the dissolution of axons and myelin and the proliferation of Schwann cells within their basal lamina. The first part of this thesis employs the cat tibial nerve to examine the relationship between the spatio-temporal pattern of Schwann cell mitosis, loss of the structural and functional properties of axolemma, synthesis of P/sub 0/, the major myelin glycoprotein, and the clearance of morphological myelin. Induction of S phase was measured by determining the uptake of /sup 3/H thymidine into trichloroacetic acid (TCA) precipitates following a 3 hour in vitro incubation in Krebs-Ringers buffer containing /sup 3/H thymidine. Nerve transection stimulated a monophasic increase in /sup 3/H thymidine uptake that peaked at 4 days post-transection throughout an 80 mm length of distal stump. Light microscope autoradiography revealed prominent incorporation into Schwann cells of myelinated fibers. Nerve transection also produced dramatic changes in the intrafascicular binding of /sup 3/H STX which binds to voltage-sensitive sodium channels STX binding fell precipitously to 20% of normal at 4 days post-transection, concurrent with the peak of /sup 3/H thymidine uptake. In conclusion, these studies suggest: (a) Schwann cells divide more or less contemporaneously throughout the distal stump; (b) changes in axons rather than myelin are likely to stimulate the Schwann cell to divide; (c) mitosis regulates other events during Wallerian degeneration, including myelin degeneration and the clearance of sodium channels from nodal axolemma.

  18. Ultrasound assessment of selected peripheral nerves pathologies. Part II: Entrapment neuropathies of the lower limb

    PubMed Central

    Sudoł-Szopińska, Iwona

    2012-01-01

    Similarly to entrapment neuropathies of upper extremities, the ultrasound constitutes a valuable supplementation of diagnostic examinations performed in patients with suspicions of nerve entrapment syndromes of the lower limb. For many years, it was claimed that such pathologies were rare. This probably resulted from the lack of proper diagnostic tools (including high frequency ultrasound transducers) as well as the lack of sufficient knowledge in this area. In relation to the above, the symptoms of compression neuropathies were frequently interpreted as a manifestation of pathologies of the lumbar part of the spine or a other orthopedic disease (degenerative or overuse one). Consequently, many patients were treated ineffectively for many months and even, years which led to irreparable neurological changes and changes in the motor organ. Apart from a clinical examination, the diagnostics of entrapment neuropathies of lower limb is currently based on imaging tests (ultrasound, magnetic resonance) as well as functional assessments (electromyography). Magnetic resonance imaging is characterized by a relatively low resolution (as compared to ultrasound) which results in limited possibilities of morphological evaluation of the visualized pathology. Electromyography allows for the assessment of nerve function, but does not precisely determine the type and degree of change. This article presents examples of the most common entrapment neuropathies of the lower limb concerning the following nerves: sciatic, femoral, lateral femoral cutaneous, obturator, fibular and its branches, tibial and its branches as well as sural. The pathomorphological basis of the neuropathies as well as corresponding ultrasound images are presented in this paper. Attention has been drawn to echogenicity, degree of vascularization and bundle presentation of the trunk of a pathological peripheral nerve. PMID:26673938

  19. Combined Spinal Cord Stimulation and Peripheral Nerve Stimulation for Brachial Plexopathy: A Case Report.

    PubMed

    Choi, Ji Hye; Choi, Shu Chung; Kim, Dong Kyu; Sung, Choon Ho; Chon, Jin Young; Hong, Sung Jin; Lee, Ji Young; Moon, Ho Sik

    2016-03-01

    Brachial plexopathy usually results from an iatrogenic brachial plexus injury and can sometimes cause severe chronic pain and disability. There are a number of possible treatments for this condition, including medication, physical therapy, nerve blocks, and neuromodulation, but they are not always successful. Recently, combined spinal cord stimulation (SCS) and peripheral nerve stimulation (PNS) have been tried for various chronic pain diseases because of their different mechanisms of action.Here, we describe the case of a 54-year-old man who was diagnosed with brachial plexopathy 8 years ago. He underwent video-assisted thoracoscopic surgery to remove a superior mediastinal mass. However, his brachial plexus was damaged during the surgery. Although he had received various treatments, the pain did not improve. For the management of intractable severe pain, he underwent SCS 2 years ago, which initially reduced his pain from numeric rating scale (NRS) 10/10 to NRS 4 - 5/10, but the pain then gradually increased, reaching NRS 8/10, 6 months ago. At that time, he was refractory to other treatments, and we therefore applied PNS in combination with SCS. The PNS electrode was positioned on the radial nerve under ultrasound guidance. After combined PNS and SCS, his background pain disappeared, although a breakthrough pain (NRS 3 - 4/10) was caused intermittently by light touch. Furthermore, the patient's need for analgesics decreased, and he was satisfied with the outcome of this combined treatment. We concluded that combined SCS and PNS is a very useful treatment modality, which can stimulate the target nerve both directly and indirectly, and hence, relieve pain from brachial plexopathy. PMID:27008302

  20. Design and fabrication of a nanofibrous polycaprolactone tubular nerve guide for peripheral nerve tissue engineering using a two-pole electrospinning system.

    PubMed

    Panahi-Joo, Y; Karkhaneh, A; Nourinia, A; Abd-Emami, B; Negahdari, B; Renaud, P; Bonakdar, S

    2016-04-01

    Nerve guidance conduits are considered to be the new generation of scaffolds designed for nerve disorders. A tubular construct with a highly aligned fibrous structure, mimicking the endoneurium layer surrounding inner axons of a nerve fascicle, is a suitable candidate for a nerve guide. In this paper a new approach for the fabrication of 3D tubular nerve guides is introduced using simulation of a two-pole electrospinning system and describing its mechanism. The structure of this scaffold is then optimized using the Taguchi statistical method and after morphological studies by scanning electron microscopy, the crystallinity, tensile strength and protein adsorption of these highly aligned fibres are investigated, comparing them with semi-aligned and random fibres produced via conventional mandrel electrospinning. Cell attachment, proliferation and migration of PC12 neuronal like cells are studied on highly aligned, semi aligned and random structures, and morphological change and elongation are observed in PC12 cells. The results of these studies suggest that conduits fabricated using two-pole electrospinning are a suitable and promising scaffold for peripheral and even spinal nerve regeneration. This nerve guide has a great potential for further advanced modifications and regeneration in higher levels. PMID:27066822

  1. Peripheral innervation patterns of vestibular nerve afferents in the bullfrog utriculus

    NASA Technical Reports Server (NTRS)

    Baird, Richard A.; Schuff, N. R.

    1994-01-01

    Vestibular nerve afferents innervating the bullfrog utriculus differ in their response dynamics and sensitivity to natural stimulation. They also supply hair cells that differ markedly in hair bundle morphology. To examine the peripheral innervation patterns of individual utricular afferents more closely, afferent fibers were labeled by the extracellular injection of horseradish peroxidase (HRP) into the vestibular nerve after sectioning the vestibular nerve medial to Scarpa's ganglion to allow the degeneration of sympathetic and efferent fibers. The peripheral arborizations of individual afferents were then correlated with the diameters of their parent axons, the regions of the macula they innervate, and the number and type of hair cells they supply. The utriculus is divided by the striola, a narrow zone of distinctive morphology, into media and lateral parts. Utiricular afferents were classified as striolar or extrastriolar according to the epithelial entrance of their parent axons and the location of their terminal fields. In general, striolar afferents had thicker parent axons, fewer subepithelial bifurcations, larger terminal fields, and more synaptic endings than afferents in extrstriolar regions. Afferents in a juxtastriolar zone, immediately adjacent to the medial striola, had innervation patterns transitional between those in the striola and more peripheral parts of the medial extrastriola. moast afferents innervated only a single macular zone. The terminal fields of striolar afferents, with the notable exception of a few afferents with thin parent axons, were generally confined to one side of the striola. Hair cells in the bullfrog utriculus have perviously been classified into four types based on hair bundle morphology. Afferents in the extrastriolar and juxtastriolar zones largely or exclusively innervated Type B hair cells, the predominant hair cell type in the utricular macula. Striolar afferents supplied a mixture of four hair cell types, but largely

  2. Brain-derived neurotrophic factor modulates immune reaction in mice with peripheral nerve xenotransplantation

    PubMed Central

    Yu, Xin; Lu, Laijin; Liu, Zhigang; Yang, Teng; Gong, Xu; Ning, Yubo; Jiang, Yanfang

    2016-01-01

    Background Brain-derived neurotrophic factor (BDNF) has been demonstrated to play an important role in survival, differentiation, and neurite outgrowth for many types of neurons. This study was designed to identify the role of BDNF during peripheral nerve xenotransplantation. Materials and methods A peripheral nerve xenotransplantation from rats to mice was performed. Intracellular cytokines were stained for natural killer (NK) cells, natural killer T (NKT) cells, T cells, and B cells and analyzed by flow cytometry in the spleen of the recipient mouse. Serum levels of related cytokines were quantified by cytometric bead array. Results Splenic NK cells significantly increased in the xenotransplanted mice (8.47±0.88×107 cells/mL) compared to that in the control mice (4.66±0.78×107 cells/mL, P=0.0003), which significantly reduced in the presence of BDNF (4.85±0.87×107 cells/mL, P=0.0004). In contrast, splenic NKT cell number was significantly increased in the mice with xenotransplantation plus BDNF (XT + BDNF) compared to that of control group or of mice receiving xenotransplantation only (XT only). Furthermore, the number of CD3+ T cells, CD3+CD4+ T cells, CD3+CD4− T cells, interferon-γ-producing CD3+CD4+ T cells, and interleukin (IL)-17-producing CD3+CD4+ T cells, as well as CD3−CD19+ B cells, was significantly higher in the spleen of XT only mice compared to the control mice (P<0.05), which was significantly reduced by BDNF (P<0.05). The number of IL-4-producing CD3+CD4+ T cells and CD3+CD4+CD25+Foxp3+ T cells was significantly higher in the spleen of XT + BDNF mice than that in the spleen of XT only mice (P<0.05). Serum levels of IL-6, TNF-α, interferon-γ, and IL-17 were decreased, while IL-4 and IL-10 were stimulated by BDNF following xenotransplantation. Conclusion BDNF reduced NK cells but increased NKT cell accumulation in the spleen of xenotransplanted mice. BDNF modulated the number of splenic T cells and its subtype cells in the mice following

  3. Enhanced Immune Response in Immunodeficient Mice Improves Peripheral Nerve Regeneration Following Axotomy

    PubMed Central

    Bombeiro, André L.; Santini, Júlio C.; Thomé, Rodolfo; Ferreira, Elisângela R. L.; Nunes, Sérgio L. O.; Moreira, Bárbara M.; Bonet, Ivan J. M.; Sartori, Cesar R.; Verinaud, Liana; Oliveira, Alexandre L. R.

    2016-01-01

    Injuries to peripheral nerves cause loss of motor and sensory function, greatly affecting life quality. Successful repair of the lesioned nerve requires efficient cell debris removal, followed by axon regeneration and reinnervation of target organs. Such process is orchestrated by several cellular and molecular events in which glial and immune cells actively participate. It is known that tissue clearance is largely improved by macrophages, which activation is potentiated by cells and molecules of the acquired immune system, such as T helper lymphocytes and antibodies, respectively. In the present work, we evaluated the contribution of lymphocytes in the regenerative process of crushed sciatic nerves of immunocompetent (wild-type, WT) and T and B-deficient (RAG-KO) mice. In Knockout animals, we found increased amount of macrophages under basal conditions and during the initial phase of the regenerative process, that was evaluated at 2, 4, and 8 weeks after lesion (wal). That parallels with faster axonal regeneration evidenced by the quantification of neurofilament and a growth associated protein immunolabeling. The motor function, evaluated by the sciatic function index, was fully recovered in both mouse strains within 4 wal, either in a progressive fashion, as observed for RAG-KO mice, or presenting a subtle regression, as seen in WT mice between 2 and 3 wal. Interestingly, boosting the immune response by early adoptive transference of activated WT lymphocytes at 3 days after lesion improved motor recovery in WT and RAG-KO mice, which was not ameliorated when cells were transferred at 2 wal. When monitoring lymphocytes by in vivo imaging, in both mouse strains, cells migrated to the lesion site shortly after transference, remaining in the injured limb up to its complete motor recovery. Moreover, a first peak of hyperalgesia, determined by von-Frey test, was coincident with increased lymphocyte infiltration in the damaged paw. Overall, the present results suggest

  4. Identification of a Peripheral Nerve Neurite Growth-Promoting Activity by Development and Use of an in vitro Bioassay

    NASA Astrophysics Data System (ADS)

    Sandrock, Alfred W.; Matthew, William D.

    1987-10-01

    The effective regeneration of severed neuronal axons in the peripheral nerves of adult mammals may be explained by the presence of molecules in situ that promote the effective elongation of neurites. The absence of such molecules in the central nervous system of these animals may underlie the relative inability of axons to regenerate in this tissue after injury. In an effort to identify neurite growth-promoting molecules in tissues that support effective axonal regeneration, we have developed an in vitro bioassay that is sensitive to substrate-bound factors of peripheral nerve that influence the growth of neurites. In this assay, neonatal rat superior cervical ganglion explants are placed on longitudinal cryostat sections of fresh-frozen sciatic nerve, and the regrowing axons are visualized by catecholamine histofluorescence. Axons are found to regenerate effectively over sciatic nerve tissue sections. When ganglia are similarly explanted onto cryostat sections of adult rat central nervous system tissue, however, axonal regeneration is virtually absent. We have begun to identify the molecules in peripheral nerve that promote effective axonal regeneration by examining the effect of antibodies that interfere with the activity of previously described neurite growth-promoting factors. Axonal elongation over sciatic nerve tissue was found to be sensitive to the inhibitory effects of INO (for inhibitor of neurite outgrowth), a monoclonal antibody that recognizes and inhibits a neurite growth-promoting activity from PC-12 cell-conditioned medium. The INO antigen appears to be a molecular complex of laminin and heparan sulfate proteoglycan. In contrast, a rabbit antiserum that recognizes laminin purified from mouse Engelbreth-Holm-Swarm (EHS) sarcoma, stains the Schwann cell basal lamina of peripheral nerve, and inhibits neurite growth over purified laminin substrata has no detectable effect on the rate of axonal regeneration in our assay.

  5. Evaluation of Tookad-mediated photodynamic effect on peripheral nerve and pelvic nerve in a canine model

    NASA Astrophysics Data System (ADS)

    Hetzel, Fred W.; Chen, Qun; Dole, Kenneth C.; Blanc, Dominique; Whalen, Lawrence R.; Gould, Daniel H.; Huang, Zheng

    2006-02-01

    Photodynamic therapy (PDT) mediated with a novel vascular targeting photosensitizer pd-bacteriopheophorbide (Tookad) has been investigated as an alternative modality for the treatment of prostate cancer and other diseases. This study investigated, for the first time, the vascular photodynamic effects of Tookad-PDT on nerve tissues. We established an in situ canine model using the cutaneous branches of the saphenous nerve to evaluate the effect of Tookad-PDT secondary to vascular damage on compound-action potentials. With Tookad dose of 2 mg/kg, treatment with 50 J/cm2 induced little change in nerve conduction. However, treatment with 100 J/cm2 resulted in decreases in nerve conduction velocities, and treatment with 200 J/cm2 caused a total loss of nerve conduction. Vasculature surrounding the saphenous nerve appeared irritated. The nerve itself looked swollen and individual fibers were not as distinct as they were before PDT treatment. Epineurium had mild hemorrhage, leukocyte infiltration, fibroplasias and vascular hypertrophy. However, the nerve fascicles and nerve fibers were free of lesions. We also studied the effect of Tookad-PDT secondary to vascular damage on the pelvic nerve in the immediate vicinity of the prostate gland. The pelvic nerve and saphenous nerve showed different sensitivity and histopathological responses to Tookad-PDT. Degeneration nerve fibers and necrotic neurons were seen in the pelvic nerve at a dose level of 1 mg/kg and 50 J/cm2. Adjacent connective tissue showed areas of hemorrhage, fibrosis and inflammation. Our preliminary results suggest that possible side effects of interstitial PDT on prostate nerve tissues need to be further investigated.

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

    PubMed Central

    He, Chun-qing; Zhang, Li-hai; Liu, Xian-fei; Tang, Pei-fu

    2015-01-01

    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. PMID:25883624

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

    PubMed

    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

  8. EGFR-STAT3 signaling promotes formation of malignant peripheral nerve sheath tumors

    PubMed Central

    Wu, Jianqiang; Patmore, Deanna M.; Jousma, Edwin; Eaves, David W.; Breving, Kimberly; Patel, Ami V.; Schwartz, Eric B.; Fuchs, James R.; Cripe, Timothy P.; Stemmer-Rachamimov, Anat O.; Ratner, Nancy

    2014-01-01

    Malignant peripheral nerve sheath tumors (MPNSTs) develop sporadically or in the context of neurofibromatosis type 1 (NF1). EGFR overexpression has been implicated in MPNST formation, but its precise role and relevant signaling pathways remain unknown. We found that EGFR overexpression promotes mouse neurofibroma transformation to aggressive MPNST (GEM-PNST). Immunohistochemistry demonstrated phosphorylated STAT3 (Tyr705) in both human MPNST and mouse GEM-PNST. A specific JAK2/STAT3 inhibitor FLLL32 delayed MPNST formation in an MPNST xenograft nude mouse model. STAT3 knockdown by shRNA prevented MPNST formation in vivo. Finally, reducing EGFR activity strongly reduced pSTAT3 in vivo. Thus, an EGFR-STAT3 pathway is necessary for MPNST transformation and establishment of MPNST xenografts growth but not for tumor maintenance. Efficacy of the FLLL32 pharmacological inhibitor in delaying MPNST growth suggests that combination therapies targeting JAK/STAT3 might be useful therapeutics. PMID:23318430

  9. EGFR-STAT3 signaling promotes formation of malignant peripheral nerve sheath tumors.

    PubMed

    Wu, J; Patmore, D M; Jousma, E; Eaves, D W; Breving, K; Patel, A V; Schwartz, E B; Fuchs, J R; Cripe, T P; Stemmer-Rachamimov, A O; Ratner, N

    2014-01-01

    Malignant peripheral nerve sheath tumors (MPNSTs) develop sporadically or in the context of neurofibromatosis type 1. Epidermal growth factor receptor (EGFR) overexpression has been implicated in MPNST formation, but its precise role and relevant signaling pathways remain unknown. We found that EGFR overexpression promotes mouse neurofibroma transformation to aggressive MPNST (GEM-PNST). Immunohistochemistry demonstrated phosphorylated STAT3 (Tyr705) in both human MPNST and mouse GEM-PNST. A specific JAK2/STAT3 inhibitor FLLL32 delayed MPNST formation in an MPNST xenograft nude mouse model. STAT3 knockdown by shRNA prevented MPNST formation in vivo. Finally, reducing EGFR activity strongly reduced pSTAT3 in vivo. Thus, an EGFR-STAT3 pathway is necessary for MPNST transformation and establishment of MPNST xenografts growth but not for tumor maintenance. Efficacy of the FLLL32 pharmacological inhibitor in delaying MPNST growth suggests that combination therapies targeting JAK/STAT3 might be useful therapeutics. PMID:23318430

  10. Malignant peripheral nerve sheath tumor presenting as orbito temporal lump: Case report and review of literature

    PubMed Central

    Panigrahi, Souvagya; Mishra, Sudhansu S.; Mishra, Sanjib; Das, Srikant

    2016-01-01

    Malignant peripheral nerve sheath tumor (MPNST) is a rare soft tissue sarcoma. The most common anatomical sites include the upper and lower extremities and trunk and less commonly the head and neck. To our knowledge, few patients with a cranial or facial MPNST have been reported. We report such a lesion in a 35-year-old woman who presented with left sided rapidly progressive proptosis and visual loss due to an orbital lump extending up to the temporal lobe. Cranial imaging showed a huge mass invading the orbital wall and temporal bone. The presumptive diagnosis was a malignant orbital tumor. Preoperative fine needle aspiration cytology of the orbital mass came to be neurofibroma. Near total resection of the tumor was done. Histopathology revealed MPNST which was subsequently confirmed on the basis of immunopositivity for S-100. The patient recovered uneventfully and was discharged 8 days after surgery with an advice to attend cancer institute for possible radiotherapy. PMID:27057226

  11. Malignant peripheral nerve sheath tumour (MPNST) of mandible: solving the perplexity.

    PubMed

    Patel, Shilpa; Pathak, Jigna; Dekate, Kamlesh; Mohanty, Neeta

    2015-01-01

    We present an extremely rare case of malignant peripheral nerve sheath tumour (MPNST) in a 30-year-old woman without associated neurofibromatosis 1. The patient presented with an 8 cm×4 cm lesion extending from 46 to the retro molar region involving the ramus of the right mandible associated with regional paraesthesia. Incisional biopsy revealed spindle cells with vesicular nuclei arranged in fascicles leading to a diagnosis of spindle cell lesion. Posterior segmental mandibulectomy was performed under general anaesthesia. On excisional biopsy, a definitive diagnosis of low-grade MPNST was established on the basis of immunohistochemistry. The patient was then lost to follow-up. PMID:25762575

  12. Study of the Peripheral Nerve Fibers Myelin Structure Changes during Activation of Schwann Cell Acetylcholine Receptors

    PubMed Central

    Verdiyan, Ekaterina E.; Allakhverdiev, Elvin S.; Maksimov, Georgy V.

    2016-01-01

    In the present paper we consider a new type of mechanism by which neurotransmitter acetylcholine (ACh) regulates the properties of peripheral nerve fibers myelin. Our data show the importance of the relationship between the changes in the number of Schwann cell (SC) acetylcholine receptors (AChRs) and the axon excitation (different intervals between action potentials (APs)). Using Raman spectroscopy, an effect of activation of SC AChRs on the myelin membrane fluidity was investigated. It was found, that ACh stimulates an increase in lipid ordering degree of the myelin lipids, thus providing evidence for specific role of the “axon-SC” interactions at the axon excitation. It was proposed, that during the axon excitation, the SC membrane K+- depolarization and the Ca2+—influx led to phospholipase activation or exocytosis of intracellular membrane vesicles and myelin structure reorganization. PMID:27455410

  13. Lithium Enhances Axonal Regeneration in Peripheral Nerve by Inhibiting Glycogen Synthase Kinase 3β Activation

    PubMed Central

    Su, Huanxing; Yuan, Qiuju; Qin, Dajiang; Yang, Xiaoying; So, Kwok-Fai; Wu, Wutian

    2014-01-01

    Brachial plexus injury often involves traumatic root avulsion resulting in permanent paralysis of the innervated muscles. The lack of sufficient regeneration from spinal motoneurons to the peripheral nerve (PN) is considered to be one of the major causes of the unsatisfactory outcome of various surgical interventions for repair of the devastating injury. The present study was undertaken to investigate potential inhibitory signals which influence axonal regeneration after root avulsion injury. The results of the study showed that root avulsion triggered GSK-3β activation in the injured motoneurons and remaining axons in the ventral funiculus. Systemic application of a clinical dose of lithium suppressed activated GSK-3β in the lesioned spinal cord to the normal level and induced extensive axonal regeneration into replanted ventral roots. Our study suggests that GSK-3β activity is involved in negative regulation for axonal elongation and regeneration and lithium, the specific GSK-3β inhibitor, enhances motoneuron regeneration from CNS to PNS. PMID:24967390

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

    PubMed Central

    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

  15. Effect of silanization on chitosan porous scaffolds for peripheral nerve regeneration.

    PubMed

    Li, Guicai; Zhang, Luzhong; Wang, Caiping; Zhao, Xueying; Zhu, Changlai; Zheng, Yanhong; Wang, Yaling; Zhao, Yahong; Yang, Yumin

    2014-01-30

    The aim of this study was to evaluate the feasibility of using 3-aminopropyltriethoxysilane (APTE) silanization treatment for modification and biocompatibility of lyophilized chitosan porous scaffolds. The process is beneficial for biomaterial development due to its low toxicity and simplicity. The silanization treatment with low APTE concentration showed no significant influence on the morphology of chitosan scaffolds, while a skin-like surface was observed for the silanized scaffolds treated with high APTE concentration. The porosity and surface amino densities were increased after silanization whereas the swelling ratio was reduced, and the degradation ratio in PBS and anti-acid degradation properties of the silanized chitosan scaffolds were significantly improved. The in vitro Schwann cells culture demonstrated that the silanized scaffolds with 8% APTE could obviously facilitate the attachment and proliferation of Schwann cells, indicating great potential for the application in peripheral nerve regeneration. PMID:24299831

  16. The search of the target of promotion: Phenylbenzoate esterase activities in hen peripheral nerve

    SciTech Connect

    Moretto, A. . E-mail: angelo.moretto@icps.it; Nicolli, A.; Lotti, M.

    2007-03-15

    Certain esterase inhibitors, such as carbamates, phosphinates and sulfonyl halides, do not cause neuropathy as some organophosphates, but they may exacerbate chemical or traumatic insults to axons. This phenomenon is called promotion of axonopathies. Given the biochemical and toxicological characteristics of these compounds, the hypothesis was made that the target of promotion is a phenyl valerate (PV) esterase similar to neuropathy target esterase (NTE), the target of organophosphate induced delayed polyneuropathy. However, attempts to identify a PV esterase in hen peripheral nerve have been, so far, unsuccessful. We tested several esters, other than PV, as substrates of esterases from crude homogenate of the hen peripheral nerve. The ideal substrate should be poorly hydrolysed by NTE but extensively by enzyme(s) that are insensitive to non-promoters, such as mipafox, and sensitive to promoters, such as phenyl methane sulfonyl fluoride (PMSF). When phenyl benzoate (PB) was used as substrate, about 65% of total activity was resistant to the non-promoter mipafox (up to 0.5 mM, 20 min, pH 8.0), that inhibits NTE and other esterases. More than 90% of this resistant activity was sensitive to the classical promoter PMSF (1 mM, 20 min, pH 8.0) with an IC{sub 50} of about 0.08 mM (20 min, pH 8.0). On the contrary, the non-promoter p-toluene sulfonyl fluoride caused only about 10% inhibition at 0.5 mM. Several esterase inhibitors including, paraoxon, phenyl benzyl carbamate, di-n-butyl dichlorovinyl phosphate and di-isopropyl fluorophosphate, were tested both in vitro and in vivo for inhibition of this PB activity. Mipafox-resistant PMSF-sensitive PB esterase activity(ies) was inhibited by promoters but not by non promoters and neuropathic compounds.

  17. Nitric Oxide Signaling and Neural Stem Cell Differentiation in Peripheral Nerve Regeneration

    PubMed Central

    Tao Li, Jessica; Somasundaram, Chandra; Bian, Ka; Xiong, Weijun; Mahmooduddin, Faiz; Nath, Rahul K.; Murad, Ferid

    2010-01-01

    Objective: The objective was to examine whether nitric oxide signaling plays a role in human embryonic stem cell differentiation into neural cells. This article reviews current literature on nitric oxide signaling and neural stem cell differentiation for potential therapeutic application to peripheral nerve regeneration. Methods: Human embryonic H9-stem cells were grown, maintained on mitomycin C–treated mouse embryonic fibroblast feeder layer, cultured on Matrigel to be feeder-free, and used for all the experiments. Fluorescent dual-immunolabeling and confocal image analysis were used to detect the presence of the neural precursor cell markers nestin and nitric oxide synthase-1. Fluorescence-activated cell sorting analysis was used to determine the percentage of expression. Results: We have shown the confocal image of stage 1 human embryonic stem cells coexpressing nestin and nitric oxide synthase-1. Fluorescence-activated cell sorting analysis indicated 24.3% positive labeling of nitric oxide synthase-1. Adding retinoic acid (10−6 M) to the culture medium increased the percent of nitric oxide synthase-1 positive cells to 33.9%. Combining retinoic acid (10−6 M) with 8-brom cyclic guanosine monophosphate (10−5 M), the fluorescence-activated cell sorting analysis demonstrated a further increase of nitric oxide synthase-1 positive cells to 45.4%. Our current results demonstrate a prodifferentiation potency of nitric oxide synthase-1, stimulated by retinoic acid with and without cyclic guanosine monophosphate. Conclusion: We demonstrated for the first time how nitric oxide/cyclic guanosine monophosphate signaling contributes to the development of neural precursors derived from human embryonic stem cells and enhances the differentiation of precursors toward functional neurons for peripheral nerve regeneration. PMID:20563304

  18. Squamous cell carcinoma and suspect peripheral nerve sheath tumor in a 10-year-old Paint horse

    PubMed Central

    Reid, Natalie

    2009-01-01

    A round mass 4 cm in diameter was present on the proximal rostro-lateral border of the right pinna of a 10-year-old, gelded, Paint horse. A preliminary histopathological diagnosis of a potential squamous cell carcinoma and peripheral nerve sheath tumor was made, and the lesion was resected at the base of the lateral edge of the ear. PMID:20119546

  19. Malignant peripheral nerve sheath tumour of the renal parenchyma presenting as a fast growing atypical renal cyst.

    PubMed

    Ouellet, Simon; Doueik, Alexandre; Sabbagh, Robert

    2013-01-01

    Malignant peripheral nerve sheath tumours (MPNST) of the kidney are very rare, with only 3 cases reported in the English and French literature. However, we report the first case of fast growing atypical renal cyst where a magnetic resonance imaging was an interesting adjunct to the computed tomography scan in imaging this rare tumour. PMID:24069105

  20. Malignant peripheral nerve sheath tumor of the third eyelid in a 3-year-old Rhodesian Ridgeback

    PubMed Central

    vom Hagen, Franziska; Romkes, Gwendolyna; Kershaw, Olivia; Eule, J Corinna

    2015-01-01

    Key Clinical Message A 3-year-old Rhodesian Ridgeback was presented with conjunctivitis, enlargement of the third eyelid and a dorsotemporal deviation of the right eye. A mass within the third eyelid was detected and excised. The histopathologic examination showed a malignant peripheral nerve sheath tumor, which most likely is a neurofibrosarcoma based on immunohistochemistry. PMID:25678975

  1. Galectin-3 Inhibition Is Associated with Neuropathic Pain Attenuation after Peripheral Nerve Injury.

    PubMed

    Ma, Zhicong; Han, Qi; Wang, Xiaolei; Ai, Zisheng; Zheng, Yongjun

    2016-01-01

    Neuropathic pain remains a prevalent and persistent clinical problem because it is often poorly responsive to the currently used analgesics. It is very urgent to develop novel drugs to alleviate neuropathic pain. Galectin-3 (gal3) is a multifunctional protein belonging to the carbohydrate-ligand lectin family, which is expressed by different cells. Emerging studies showed that gal3 elicits a pro-inflammatory response by recruiting and activating lymphocytes, macrophages and microglia. In the study we investigated whether gal3 inhibition could suppress neuroinflammation and alleviate neuropathic pain following peripheral nerve injury. We found that L5 spinal nerve ligation (SNL) increases the expression of gal3 in dorsal root ganglions at the mRNA and protein level. Intrathecal administration of modified citrus pectin (MCP), a gal3 inhibitor, reduces gal3 expression in dorsal root ganglions. MCP treatment also inhibits SNL-induced gal3 expression in primary rat microglia. SNL results in an increased activation of autophagy that contributes to microglial activation and subsequent inflammatory response. Intrathecal administration of MCP significantly suppresses SNL-induced autophagy activation. MCP also inhibits lipopolysaccharide (LPS)-induced autophagy in cultured microglia in vitro. MCP further decreases LPS-induced expression of proinflammatory mediators including IL-1β, TNF-α and IL-6 by regulating autophagy. Intrathecal administration of MCP results in adecreased mechanical and cold hypersensitivity following SNL. These results demonstrated that gal3 inhibition is associated with the suppression of SNL-induced inflammatory process andneurophathic pain attenuation. PMID:26872020

  2. Medullary metastasis of a malignant peripheral nerve sheath tumor: A case report

    PubMed Central

    Hagi, Tomohito; Nakamura, Tomoki; Yokoji, Ayumu; Matsumine, Akihiko; Sudo, Akihiro

    2016-01-01

    The present study reports a case of medullary metastasis without lung metastasis that occurred as a result of a malignant peripheral nerve sheath tumor (MPNST). An 81-year-old woman presented with a MPNST in the left brachial plexus, arising from the cervical nerve root. The patient underwent carbon ion radiotherapy; however, tumor recurrence was identified in the left shoulder. Subsequently, the patient underwent wide excision. Three weeks subsequent to surgery, imbalance and dysarthria developed suddenly. Dysphagia emerged and left upper limb pain disappeared on the day after symptom development. Magnetic resonance imaging (MRI) revealed that this was due to metastasis to the medulla. Five days subsequent to the onset of dysarthria, the patient succumbed due to respiratory failure. To the best of our knowledge, no previous cases of medullary metastasis arising from a MPNST in the absence of lung metastasis have been reported. MRI is a useful examination tool for the identification of brain metastases; however, the high cost of MRI as a routine examination must be considered due to the rarity of brain metastases. Therefore, methods to detect brain metastasis warrant further investigation.

  3. Fully Implantable Peripheral Nerve Stimulation for the Treatment of Hemiplegic Shoulder Pain: A Case Report

    PubMed Central

    Nguyen, Vu Q. C.; Bock, William C.; Groves, Christine C.; Whitney, Marybeth; Bennett, Maria E.; Lechman, Tina E.; Strother, Robert; Grill, Julie H.; Stager, Kathryn W.; Chae, John

    2014-01-01

    This case report describes the first participant treated with a fully-implantable, single-lead peripheral nerve stimulation (PNS) system for refractory hemiplegic shoulder pain (HSP). During the 6-wk trial-stage, a temporary lead was placed percutaneously near the terminal branches of the axillary nerve to the deltoid. The primary outcome measure was the Brief Pain Inventory-Short Form Question 3 (BPI-3), a 0–10 pain numeric rating scale. The participant experienced 75% pain reduction and proceeded to the implant-stage where he received a single-lead, implantable pulse generator. After 3-wks, the participant became pain-free. However, 7-wks after implantation, the system was turned off due to an unrelated acute medical illness. HSP reemerged with BPI-3 of 9. After 11-wks of recovery, PNS was reinitiated and the participant became pain-free through the 9-months follow-up. At 12-months, BPI-3 was a 1. This case report demonstrates the feasibility of a single-lead, fully-implantable PNS system for refractory HSP. PMID:25251248

  4. Neuroprotective Activity of Thioctic Acid in Central Nervous System Lesions Consequent to Peripheral Nerve Injury

    PubMed Central

    Ghelardini, Carla; Nwankwo, Innocent E.; Pacini, Alessandra

    2013-01-01

    Peripheral neuropathies are heterogeneous disorders presenting often with hyperalgesia and allodynia. This study has assessed if chronic constriction injury (CCI) of sciatic nerve is accompanied by increased oxidative stress and central nervous system (CNS) changes and if these changes are sensitive to treatment with thioctic acid. Thioctic acid is a naturally occurring antioxidant existing in two optical isomers (+)- and (−)-thioctic acid and in the racemic form. It has been proposed for treating disorders associated with increased oxidative stress. Sciatic nerve CCI was made in spontaneously hypertensive rats (SHRs) and in normotensive reference cohorts. Rats were untreated or treated intraperitoneally for 14 days with (+/−)-, (+)-, or (−)-thioctic acid. Oxidative stress, astrogliosis, myelin sheets status, and neuronal injury in motor and sensory cerebrocortical areas were assessed. Increase of oxidative stress markers, astrogliosis, and neuronal damage accompanied by a decreased expression of neurofilament were observed in SHR. This phenomenon was more pronounced after CCI. Thioctic acid countered astrogliosis and neuronal damage, (+)-thioctic acid being more active than (+/−)- or (−)-enantiomers. These findings suggest a neuroprotective activity of thioctic acid on CNS lesions consequent to CCI and that the compound may represent a therapeutic option for entrapment neuropathies. PMID:24527432

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

    PubMed

    Gu, Nan; Peng, Jiyun; Murugan, Madhuvika; Wang, Xi; Eyo, Ukpong B; Sun, Dongming; Ren, Yi; DiCicco-Bloom, Emanuel; Young, Wise; Dong, Hailong; Wu, Long-Jun

    2016-07-19

    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 (CCR2(RFP/+):CX3CR1(GFP/+) and CX3CR1(creER/+):R26(tdTomato/+) 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. PMID:27373153

  6. Saltatory conduction of peripheral nerve impulse in clioquinol-treated rats.

    PubMed

    Homma, S; Kotaki, H; Mizote, M; Nakajima, Y; Tamura, Z

    1984-04-01

    By using a new method, unidimensional latency-topography, which shows the saltatory conduction pattern of an impulse along peripheral nerve fibers, the internodal length, internodal conduction time and conduction velocity were determined from the L5 ventral and/or dorsal root filaments of clioquinol-treated rats (CTR). The saltatory conduction pattern was preserved in most of the CTR fibers tested, but was not seen in some fibers. A positive correlation was seen between the conduction velocity and the internodal length in the nerve fibers of both the normal rats and CTR. Although there was no difference in the internodal length between normal rats and CTR, conduction velocities determined in CTR fibers were lower than those in normal rat fibers. Myelin length was calculated from the saltatory conduction pattern in the topography to represent the functional length of the saltatory conduction. The functional myelin length of the CTR fiber was shorter than that of normal rats. Shortening of the functional myelin length in CTR is due to the widening of the Ranvier node, which corresponds to the exposure of the Ranvier node, i.e. demyelination. It was concluded that the decrease in conduction velocity in CTR fibers was due to exposure which caused delayed excitation at the Ranvier nodes. PMID:6233507

  7. Galectin-3 Inhibition Is Associated with Neuropathic Pain Attenuation after Peripheral Nerve Injury

    PubMed Central

    Ai, Zisheng; Zheng, Yongjun

    2016-01-01

    Neuropathic pain remains a prevalent and persistent clinical problem because it is often poorly responsive to the currently used analgesics. It is very urgent to develop novel drugs to alleviate neuropathic pain. Galectin-3 (gal3) is a multifunctional protein belonging to the carbohydrate-ligand lectin family, which is expressed by different cells. Emerging studies showed that gal3 elicits a pro-inflammatory response by recruiting and activating lymphocytes, macrophages and microglia. In the study we investigated whether gal3 inhibition could suppress neuroinflammation and alleviate neuropathic pain following peripheral nerve injury. We found that L5 spinal nerve ligation (SNL) increases the expression of gal3 in dorsal root ganglions at the mRNA and protein level. Intrathecal administration of modified citrus pectin (MCP), a gal3 inhibitor, reduces gal3 expression in dorsal root ganglions. MCP treatment also inhibits SNL-induced gal3 expression in primary rat microglia. SNL results in an increased activation of autophagy that contributes to microglial activation and subsequent inflammatory response. Intrathecal administration of MCP significantly suppresses SNL-induced autophagy activation. MCP also inhibits lipopolysaccharide (LPS)-induced autophagy in cultured microglia in vitro. MCP further decreases LPS-induced expression of proinflammatory mediators including IL-1β, TNF-α and IL-6 by regulating autophagy. Intrathecal administration of MCP results in adecreased mechanical and cold hypersensitivity following SNL. These results demonstrated that gal3 inhibition is associated with the suppression of SNL-induced inflammatory process andneurophathic pain attenuation. PMID:26872020

  8. A longitudinal study of pain, personality, and brain plasticity following peripheral nerve injury.

    PubMed

    Goswami, Ruma; Anastakis, Dimitri J; Katz, Joel; Davis, Karen D

    2016-03-01

    We do not know precisely why pain develops and becomes chronic after peripheral nerve injury (PNI), but it is likely due to biological and psychological factors. Here, we tested the hypotheses that (1) high Pain Catastrophizing Scale (PCS) scores at the time of injury and repair are associated with pain and cold sensitivity after 1-year recovery and (2) insula gray matter changes reflect the course of injury and improvements over time. Ten patients with complete median and/or ulnar nerve transections and surgical repair were tested ∼3 weeks after surgical nerve repair (time 1) and ∼1 year later for 6 of the 10 patients (time 2). Patients and 10 age-/sex-matched healthy controls completed questionnaires that assessed pain (patients) and personality and underwent quantitative sensory testing and 3T MRI to assess cortical thickness. In patients, pain intensity and neuropathic pain correlated with pain catastrophizing. Time 1 pain catastrophizing trended toward predicting cold pain thresholds at time 2, and at time 1 cortical thickness of the right insula was reduced. At time 2, chronic pain was related to the time 1 pain-PCS relationship and cold sensitivity, pain catastrophizing correlated with cold pain threshold, and insula thickness reversed to control levels. This study highlights the interplay between personality, sensory function, and pain in patients following PNI and repair. The PCS-pain association suggests that a focus on affective or negative components of pain could render patients vulnerable to chronic pain. Cold sensitivity and structural insula changes may reflect altered thermosensory or sensorimotor awareness representations. PMID:26588697

  9. Malignant peripheral nerve sheath tumors of the orbit: a clinicopathologic study of eight cases.

    PubMed Central

    Jakobiec, F A; Font, R L; Zimmerman, L E

    1985-01-01

    Eight adult patients with malignant peripheral nerve sheath tumors of the orbit are described. Only two of the patients were known to have von Recklinghausen's neurofibromatosis. The typical clinical history included the development of a mass in the superonasal quadrant of the orbit, which was palpable immediately beneath the skin of the lid. There was a definite tendency for the lesions to arise in, or grow along, the supraorbital nerve--including posteriorly through the superior orbital fissure to the Gasserian ganglion, and even as far posteriorly along the trigeminal rootlets to the pons. Delays in pathologic diagnosis, which beclouded the true nature of the process, led to multiple recurrences, eventuating in five known fatalities out of the eight patients. In addition to intracranial extension, pulmonary metastases and regional cervical metastases were encountered. Once recognized for their diagnostic value, the histopathologic patterns are highly distinctive: biphasic populations of spindled and epithelioid cells; sheets of epithelioid cells or clusters demarcated by delicate reticulin fibers or thicker collagenous trabeculae; malignant plexiform patterns; and neurotubular patterns. Pure spindle cell populations were encountered only in the two patients with von Recklinghausen's disease, and in each, either a pre-existent benign neurofibroma or a coexistent plexiform neurofibroma was found in the pathology specimens. The best management of this condition depends upon early clinical and pathological recognition, leading to radical surgery, which usually consists of orbital exenteration combined with intracranial extirpation of as much of the trigeminal nerve as possible. Postoperative radiotherapy and chemotherapy after radical surgery might also be advisable. Images FIGURE 16 FIGURE 11 FIGURE 15 FIGURE 14 FIGURE 1 FIGURE 2 FIGURE 3 FIGURE 4 FIGURE 5 FIGURE 6 FIGURE 7 FIGURE 8 FIGURE 9 FIGURE 10 FIGURE 12 FIGURE 13 PMID:3938581

  10. Selective neural activation in a histologically derived model of peripheral nerve

    NASA Astrophysics Data System (ADS)

    Butson, Christopher R.; Miller, Ian O.; Normann, Richard A.; Clark, Gregory A.

    2011-06-01

    Functional electrical stimulation (FES) is a general term for therapeutic methods that use electrical stimulation to aid or replace lost ability. For FES systems that communicate with the nervous system, one critical component is the electrode interface through which the machine-body information transfer must occur. In this paper, we examine the influence of inhomogeneous tissue conductivities and positions of nodes of Ranvier on activation of myelinated axons for neuromuscular control as a function of electrode configuration. To evaluate these effects, we developed a high-resolution bioelectric model of a fascicle from a stained cross-section of cat sciatic nerve. The model was constructed by digitizing a fixed specimen of peripheral nerve, extruding the image along the axis of the nerve, and assigning each anatomical component to one of several different tissue types. Electrodes were represented by current sources in monopolar, transverse bipolar, and longitudinal bipolar configurations; neural activation was determined using coupled field-neuron simulations with myelinated axon cable models. We found that the use of an isotropic tissue medium overestimated neural activation thresholds compared with the use of physiologically based, inhomogeneous tissue medium, even after controlling for mean impedance levels. Additionally, the positions of the cathodic sources relative to the nodes of Ranvier had substantial effects on activation, and these effects were modulated by the electrode configuration. Our results indicate that physiologically based tissue properties cause considerable variability in the neural response, and the inclusion of these properties is an important component in accurately predicting activation. The results are used to suggest new electrode designs to enable selective stimulation of small diameter fibers.

  11. Sonographic evaluation of the peripheral nerves in hereditary neuropathy with liability to pressure palsies: a case report.

    PubMed

    Kim, Se Hwa; Yang, Seung Nam; Yoon, Joon Shik; Park, Bum Jun

    2014-02-01

    Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominantly inherited disorder that affects peripheral nerves by repeated focal pressure. HNPP can be diagnosed by clinical findings, electrodiagnostic studies, histopathological features, and genetic analysis. Ultrasonography is increasingly used for the diagnosis of neuromuscular diseases; however, sonographic features of HNPP have not been clearly defined. We report the sonographic findings and comparative electrodiagnostic data in a 73-year-old woman with HNPP, confirmed by genetic analysis. The cross-sectional areas of peripheral nerves were enlarged at typical nerve entrapment sites, but enlargement at non-entrapment sites was uncommon. These sonographic features may be helpful for diagnosis of HNPP when electrodiagnostic studies are suspicious of HNPP and/or gene study is not compatible. PMID:24639934

  12. Sonographic Evaluation of the Peripheral Nerves in Hereditary Neuropathy With Liability to Pressure Palsies: A Case Report

    PubMed Central

    Kim, Se Hwa; Yoon, Joon Shik; Park, Bum Jun

    2014-01-01

    Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominantly inherited disorder that affects peripheral nerves by repeated focal pressure. HNPP can be diagnosed by clinical findings, electrodiagnostic studies, histopathological features, and genetic analysis. Ultrasonography is increasingly used for the diagnosis of neuromuscular diseases; however, sonographic features of HNPP have not been clearly defined. We report the sonographic findings and comparative electrodiagnostic data in a 73-year-old woman with HNPP, confirmed by genetic analysis. The cross-sectional areas of peripheral nerves were enlarged at typical nerve entrapment sites, but enlargement at non-entrapment sites was uncommon. These sonographic features may be helpful for diagnosis of HNPP when electrodiagnostic studies are suspicious of HNPP and/or gene study is not compatible. PMID:24639934

  13. Effect of local administration of platelet-derived growth factor B on functional recovery of peripheral nerve regeneration: A sciatic nerve transection model

    PubMed Central

    Golzadeh, Atefeh; Mohammadi, Rahim

    2016-01-01

    Background: Effects of platelet-derived growth factor B (PDGF-B) on peripheral nerve regeneration was studied using a rat sciatic nerve transection model. Materials and Methods: Forty-five male, white Wistar rats were divided into three experimental groups (n = 15), randomly: Normal control group (NC), silicon group (SIL), and PDGF-B treated group (SIL/PDGF). In NC group, left sciatic nerve was exposed through a gluteal muscle incision and after homeostasis muscle was sutured. In the SIL group, the left sciatic nerve was exposed in the same way and transected proximal to tibio-peroneal bifurcation leaving a 10-mm gap. Proximal and distal stumps were each inserted into a silicone conduit and filled with 10 μL phosphate buffered solution. In SIL/PDGF group, the silicon conduit was filled with 10 μL PDGF-B (0.5 ng/mL). Each group was subdivided into three subgroups of five and were studied in 4, 8, 12 weeks after surgery. Results: Behavioral testing, sciatic nerve functional study, gastrocnemius muscle mass, and histomorphometric studies showed earlier regeneration of axons in SIL/PDGF than in SIL group (P < 0.05). Conclusion: Local administration of PDGF-B combined with silicon grafting could accelerate functional recovery and may have clinical implications for the surgical management of patients after facial nerve transection. PMID:27274342

  14. Peripheral nerve metabolism and zinc levels in streptozotocin induced diabetic rats. Effect of diets high in fish and corn oil

    SciTech Connect

    Burke, J.P.; Fenton, M.R. )

    1991-03-15

    This study was designed to assess the effects of diets high in fish and corn oil on peripheral nerve metabolism in streptozotocin (STZ) induced diabetic rats. A type I diabetic state was induced in female Sprague-Dawley rats by injection of STZ. Animals were divided into three dietary groups; normal rat chow, high corn oil diet and high fish oil diet. After 4 weeks animals were analyzed for nerve conduction velocity, bled and then sacrificed. Sciatic nerves were removed, processed and several biochemical parameters determined. Plasma zinc levels were elevated in the STZ normal chow group compared to non-diabetic controls. Both corn oil and fish oil diets tended to eliminate the rise in plasma zinc. Differences in subcellular distribution of zinc in sciatic nerves were also observed. Normal chow STZ animals displayed a 20% decrease in nerve conduction velocity compared to control. Dietary supplementation with either fish or corn oil seemed to ameliorate these effects. Biochemical analysis of Na{sup +}-K{sup +}-ATPase and protein kinase C revealed a decrease in activity in normal chow animals compared to control groups. Again, dietary intervention with either fish or corn oil seemed to return these activities back to normal. The results suggest a link between zinc metabolism and peripheral nerve metabolism which can be modified by dietary intervention.

  15. Possible involvement of convergent nociceptive input to medullary dorsal horn neurons in intraoral hyperalgesia following peripheral nerve injury.

    PubMed

    Terayama, Ryuji; Tsuchiya, Hiroki; Omura, Shinji; Maruhama, Kotaro; Mizutani, Masahide; Iida, Seiji; Sugimoto, Tomosada

    2015-04-01

    Previous studies demonstrated that the number of c-Fos protein-like immunoreactive (c-Fos-IR) neurons in the medullary dorsal horn (MDH) evoked by noxious stimulation was increased after peripheral nerve injury, and such increase has been proposed to reflect the development of neuropathic pain state. The aim of this study was to examine the MDH for convergent collateral primary afferent input to second order neurons deafferented by peripheral nerve injury, and to explore a possibility of its contribution to the c-Fos hyperinducibility. Double immunofluorescence labeling for c-Fos and phosphorylated extracellular signal-regulated kinase (p-ERK) was performed to detect convergent synaptic input. c-Fos expression and the phosphorylation of ERK were induced by the intraoral application of capsaicin and by electrical stimulation of the inferior alveolar nerve (IAN), respectively. The number of c-Fos-IR neurons in the MDH induced by the intraoral application of capsaicin was increased after IAN injury, whereas the number of p-ERK immunoreactive neurons remained unchanged. The number of double-labeled neurons, that presumably received convergent primary afferent input from the lingual nerve and the IAN, was significantly increased after IAN injury. These results indicated that convergent primary nociceptive input through neighboring intact nerves may contribute to the c-Fos hyperinducibility in the MDH and the pathogenesis of neuropathic pain following trigeminal nerve injury. PMID:25407627

  16. Treadmill Exercise Induced Functional Recovery after Peripheral Nerve Repair Is Associated with Increased Levels of Neurotrophic Factors

    PubMed Central

    Park, Jae-Sung; Höke, Ahmet

    2014-01-01

    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. PMID:24618564

  17. Value of Nerve Biopsy in Patients With Latent Malignant Hemopathy and Peripheral Neuropathy

    PubMed Central

    Duchesne, Mathilde; Mathis, Stéphane; Corcia, Philippe; Richard, Laurence; Ghorab, Karima; Jaccard, Arnaud; Magy, Laurent; Vallat, Jean-Michel

    2015-01-01

    Abstract Hematological malignancies include several diseases that may affect the peripheral nervous system (PNS) through various mechanisms. A common and challenging situation is represented by the occurrence of an active peripheral neuropathy in a patient with a supposed inactive hematological disorder. We report clinical, electrophysiological, biological, and pathological data of 8 patients with latent malignant hemopathies (most were considered in remission): B-cell chronic lymphocytic leukemia in 3 patients, B-cell lymphoma in 1 patient, low-grade non-Hodgkin's lymphoma in 1 patient, Waldenström's macroglobulinemia in 1 patient, smoldering multiple myeloma in 1 patient, and monoclonal gammopathy of undetermined significance in 1 patient. In all these cases, the nerve biopsy (NB) helped to diagnose the hematological relapse or detect a pathological mechanism linked to the hematological disorder: epineurial lymphocytic infiltration in 5 patients (including one with antimyelin-associated glycoprotein antibodies), cryoglobulin deposits in 1 patient, chronic inflammatory demyelinating polyneuropathy in 1 patient, and necrotizing vasculitis in 1 patient. In each case, pathological findings were crucial to select the adequate treatment, leading to an improvement in the neurological and biological manifestations. These observations illustrate the value of NB and the need for active collaboration between neurologists and hematologists in such cases. PMID:25621682

  18. Therapeutic targets for the management of peripheral nerve injury-induced neuropathic pain.

    PubMed

    Jaggi, Amteshwar Singh; Singh, Nirmal

    2011-08-01

    Neuropathic pain is a debilitating form of treatment resistant chronic pain and responds poorly to the clinically available therapies. Studies from animal models of neuropathic pain have led to understanding of its pathobiology which includes complex interrelated pathways leading to peripheral and central neuronal sensitization. Advancements in the elucidation of neuropathic pain mechanisms have revealed a number of key targets that have been hypothesized to modulate clinical status. The present review discusses these therapeutic targets including noradrenaline and 5-HT reuptake inhibitors; sodium, calcium and potassium channels; inhibitory and excitatory neurotransmitters; neuropeptides including bradykinin, tachykinin, cholecystokinin, neuropeptide Y, vasoactive intestinal peptide, and CGRP; pro-inflammatory cytokines; MAP kinases; PPAR γ; Na(+)/Ca(2+) exchanger; nitric oxide; purinergic receptors; neuronal nicotinic receptors; cation-dependent chloride transporters; oxidative stress; matrix metalloproteinase and plasminogen activators; growth factors; transient receptor potential (TRP) channels; endocannabinoids; histamine receptors; dopamine; sigma receptors, beta adrenergic receptors, endothelins, and D-amino acid oxidase. The exploitation of these targets may provide effective therapeutic agents for the management of peripheral nerve injury-induced neuropathic pain. PMID:21631400

  19. [Old or new medicine? Vitamin B12 and peripheral nerve neuropathy].

    PubMed

    Tanaka, Hiroyuki

    2013-09-01

    Methylcobalamin is a vitamin B12 analog that is necessary for nervous system maintenance. Although methylcobalamin has some positive effects on peripheral nervous system disorders, the mechanism through which it affects neurons are not entirely known. Recent studies have revealed its intracellular signaling pathway and some of its molecular actions on neurons. In this article, I review interactions between methylcobalamin and neurons that have been revealed through in vitro studies, in vivo studies, and clinical use. Methylcobalamin participates in nervous system maintenance through several mechanisms. Methylcobalamin is an active form of vitamin B12, and a coenzyme of methionine synthase, which is required for DNA and protein methylation. In addition, methylcobalamin facilitates neurite outgrowth and inhibits neural apoptosis through the Erk1/2 and Akt signaling pathways. Treatment with high doses of methylcobalamin ameliorates symptoms and negative electrophysiological findings in animal models of peripheral nerve neuropathy and in patients with carpal tunnel syndrome and amyotrophic lateral sclerosis. Thus, high-dose methylcobalamin has great potential for treating nervous system disorders. Further investigations with methylcobalamin may help elucidate its mechanisms of action, which may further enable us to treat many nervous system disorders. PMID:24018744

  20. Peripheral Nerve Dysfunction in Middle-Aged Subjects Born with Thalidomide Embryopathy

    PubMed Central

    Nicotra, Alessia; Newman, Claus; Johnson, Martin; Eremin, Oleg; Friede, Tim; Malik, Omar; Nicholas, Richard

    2016-01-01

    Background Phocomelia is an extremely rare congenital malformation that emerged as one extreme of a range of defects resulting from i