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Sample records for suspect peripheral nerve

  1. Large Extremity Peripheral Nerve Repair

    Science.gov (United States)

    2016-12-01

    rodents as a function of time after surgery. As predicted, those animals in the negative control group (no repair following nerve deficit injury ...80% of penetrating injuries being associated with peripheral nerve damage, typically involve large segmental nerve deficits. Standard repair uses...technology for repair of peripheral nerve injuries involving significant neural deficit with improved functional outcomes for the wounded warrior. The

  2. Neurophysiological approach to disorders of peripheral nerve

    DEFF Research Database (Denmark)

    Crone, Clarissa; Krarup, Christian

    2013-01-01

    Disorders of the peripheral nerve system (PNS) are heterogeneous and may involve motor fibers, sensory fibers, small myelinated and unmyelinated fibers and autonomic nerve fibers, with variable anatomical distribution (single nerves, several different nerves, symmetrical affection of all nerves...

  3. Peripheral Nerve Injury: Stem Cell Therapy and Peripheral Nerve Transfer.

    Science.gov (United States)

    Sullivan, Robert; Dailey, Travis; Duncan, Kelsey; Abel, Naomi; Borlongan, Cesario V

    2016-12-14

    Peripheral nerve injury can lead to great morbidity in those afflicted, ranging from sensory loss, motor loss, chronic pain, or a combination of deficits. Over time, research has investigated neuronal molecular mechanisms implicated in nerve damage, classified nerve injury, and developed surgical techniques for treatment. Despite these advancements, full functional recovery remains less than ideal. In this review, we discuss historical aspects of peripheral nerve injury and introduce nerve transfer as a therapeutic option, as well as an adjunct therapy to transplantation of Schwann cells and their stem cell derivatives for repair of the damaged nerve. This review furthermore, will provide an elaborated discussion on the sources of Schwann cells, including sites to harvest their progenitor and stem cell lines. This reflects the accessibility to an additional, concurrent treatment approach with nerve transfers that, predicated on related research, may increase the efficacy of the current approach. We then discuss the experimental and clinical investigations of both Schwann cells and nerve transfer that are underway. Lastly, we provide the necessary consideration that these two lines of therapeutic approaches should not be exclusive, but conversely, should be pursued as a combined modality given their mutual role in peripheral nerve regeneration.

  4. Peripheral Nerve Injury: Stem Cell Therapy and Peripheral Nerve Transfer

    Directory of Open Access Journals (Sweden)

    Robert Sullivan

    2016-12-01

    Full Text Available Peripheral nerve injury can lead to great morbidity in those afflicted, ranging from sensory loss, motor loss, chronic pain, or a combination of deficits. Over time, research has investigated neuronal molecular mechanisms implicated in nerve damage, classified nerve injury, and developed surgical techniques for treatment. Despite these advancements, full functional recovery remains less than ideal. In this review, we discuss historical aspects of peripheral nerve injury and introduce nerve transfer as a therapeutic option, as well as an adjunct therapy to transplantation of Schwann cells and their stem cell derivatives for repair of the damaged nerve. This review furthermore, will provide an elaborated discussion on the sources of Schwann cells, including sites to harvest their progenitor and stem cell lines. This reflects the accessibility to an additional, concurrent treatment approach with nerve transfers that, predicated on related research, may increase the efficacy of the current approach. We then discuss the experimental and clinical investigations of both Schwann cells and nerve transfer that are underway. Lastly, we provide the necessary consideration that these two lines of therapeutic approaches should not be exclusive, but conversely, should be pursued as a combined modality given their mutual role in peripheral nerve regeneration.

  5. Nanofiber Nerve Guide for Peripheral Nerve Repair and Regeneration

    Science.gov (United States)

    2016-04-01

    project was to develop an alternative to autologous nerve grafts used in repair of peripheral nerve injuries in war and civilian life. Based on our...gradient compositions tested in Aim 1 in preparation to studies in the large animal model of peripheral nerve injury and repair . As it was not...this specific aim was to test the efficacy of optimized nanofiber nerve guide in a canine model of peripheral nerve injury and repair . Peripheral nerve

  6. [Development of peripheral nerve surgery].

    Science.gov (United States)

    Sames, M

    1998-03-01

    In the submitted review the author deals with the development of peripheral nerve surgery (PN) from ancient times to the present time incl. hithero unpublished details. He analyses in great detail the period of the last 40 years which is divided into three stages--the mechanical, biological period and the period of neurotrophism. From the Second World War to the sixties the period bears the term mechanical. The results of reinnervation during this period were not satisfactory as the nerves were connected without the use of a microscope, in major defects they were connected under considerable traction and the only criterion was the resistance against dehiscence. Significant improvement of results of regeneration of PN was recorded during the biological period. Mechanical ideas were overcome and biological and physiological reactions of the peripheral nerves were taken into account. Suture of nerves under traction was refuted and into clinical practice the surgical microscope, microsurgical technique and microsurgical autotransplantation with a nervous graft were introduced. The anatomical structure of the nerve with a plexiform pattern of the fascicles became however the limitation of surgical methods. After discovery of NGF (nerve growth factor) we can speak of the onset of a new period, neurotrophism. In laboratory experiments many substances are studied and theoretically new non-surgical possibilities how to promote regeneration lie ahead. However they cannot be applied yet in clinical practice. In injuries of peripheral nerves the only correct reconstruction method is still microsuture of the nerve and in case of losses microsurgical autotransplantation using a nerve graft.

  7. Peripheral nerve conduits: technology update

    Directory of Open Access Journals (Sweden)

    Arslantunali D

    2014-12-01

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

  8. Side Effects: Nerve Problems (Peripheral Neuropathy)

    Science.gov (United States)

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

  9. Transdermal optogenetic peripheral nerve stimulation

    Science.gov (United States)

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

    2017-06-01

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

  10. Peripheral Facial Nerve Palsy after Therapeutic Endoscopy

    OpenAIRE

    Kim, Eun Jeong; Lee, Jun; Lee, Ji Woon; Lee, Jun Hyung; Park, Chol Jin; Kim, Young Dae; Lee, Hyun Jin

    2015-01-01

    Peripheral facial nerve palsy (FNP) is a mononeuropathy that affects the peripheral part of the facial nerve. Primary causes of peripheral FNP remain largely unknown, but detectable causes include systemic infections (viral and others), trauma, ischemia, tumor, and extrinsic compression. Peripheral FNP in relation to extrinsic compression has rarely been described in case reports. Here, we report a case of a 71-year-old man who was diagnosed with peripheral FNP following endoscopic submucosal...

  11. Diabetes and the peripheral nerve.

    Science.gov (United States)

    Obrosova, Irina G

    2009-10-01

    Diabetes-induced damage to peripheral nerve culminates in development of peripheral diabetic neuropathy (PDN), one of the most devastating complications of diabetes mellitus and a leading cause of foot amputation. The pathogenesis of PDN occurs as a consequence of complex interactions among multiple hyperglycemia-initiated mechanisms, impaired insulin signaling, inflammation, hypertension, and disturbances of fatty acid and lipid metabolism. This review describes experimental new findings in animal and cell culture models as well as clinical data suggesting the importance of 1) previously established hyperglycemia-initiated mechanisms such as increased aldose reductase activity, non-enzymatic glycation/glycooxidation, activation of protein kinase C, 2) oxidative-nitrosative stress and poly(ADP-ribose) polymerase activation; 3) mitogen-activated protein kinase and cyclooxygenase-2 activation, impaired Ca(++) homeostasis and signaling, and several other mechanisms, in PDN.

  12. The surgery of peripheral nerves (including tumors)

    DEFF Research Database (Denmark)

    Fugleholm, Kåre

    2013-01-01

    Surgical pathology of the peripheral nervous system includes traumatic injury, entrapment syndromes, and tumors. The recent significant advances in the understanding of the pathophysiology and cellular biology of peripheral nerve degeneration and regeneration has yet to be translated into improved...

  13. Peripheral facial nerve palsy after therapeutic endoscopy.

    Science.gov (United States)

    Kim, Eun Jeong; Lee, Jun; Lee, Ji Woon; Lee, Jun Hyung; Park, Chol Jin; Kim, Young Dae; Lee, Hyun Jin

    2015-03-01

    Peripheral facial nerve palsy (FNP) is a mononeuropathy that affects the peripheral part of the facial nerve. Primary causes of peripheral FNP remain largely unknown, but detectable causes include systemic infections (viral and others), trauma, ischemia, tumor, and extrinsic compression. Peripheral FNP in relation to extrinsic compression has rarely been described in case reports. Here, we report a case of a 71-year-old man who was diagnosed with peripheral FNP following endoscopic submucosal dissection. This case is the first report of the development of peripheral FNP in a patient undergoing therapeutic endoscopy. We emphasize the fact that physicians should be attentive to the development of peripheral FNP following therapeutic endoscopy.

  14. Nerve conduction and excitability studies in peripheral nerve disorders

    DEFF Research Database (Denmark)

    Krarup, Christian; Moldovan, Mihai

    2009-01-01

    PURPOSE OF REVIEW: The review is aimed at providing information about the role of nerve excitability studies in peripheral nerve disorders. It has been known for many years that the insight into peripheral nerve pathophysiology provided by conventional nerve conduction studies is limited. Nerve....... Studies of different metabolic neuropathies have assessed the influence of uremia, diabetes and ischemia, and the use of these methods in toxic neuropathies has allowed pinpointing damaging factors. Various mutations in ion channels associated with central nervous system disorders have been shown to have...

  15. Peripheral nerve lesions in Zimbabwe: a retrospective

    African Journals Online (AJOL)

    Tests of nerve function carried out in this laboratory include sensory and motor nerve conduction measurements, electromyography and somatosensory evoked potentials. Their application has been reviewed previously1. Peripheral nerves are common sites of injury. The consequences can be debilitating to the individual.

  16. Peripheral nerve involvement in Bell's palsy

    Directory of Open Access Journals (Sweden)

    J. A. Bueri

    1984-12-01

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

  17. Beta secretase activity in peripheral nerve regeneration

    Directory of Open Access Journals (Sweden)

    Carolyn Tallon

    2017-01-01

    Full Text Available While the peripheral nervous system has the capacity to regenerate following a nerve injury, it is often at a slow rate and results in unsatisfactory recovery, leaving patients with reduced function. Many regeneration associated genes have been identified over the years, which may shed some insight into how we can manipulate this intrinsic regenerative ability to enhance repair following peripheral nerve injuries. Our lab has identified the membrane bound protease beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1, or beta secretase, as a potential negative regulator of peripheral nerve regeneration. When beta secretase activity levels are abolished via a null mutation in mice, peripheral regeneration is enhanced following a sciatic nerve crush injury. Conversely, when activity levels are greatly increased by overexpressing beta secretase in mice, nerve regeneration and functional recovery are impaired after a sciatic nerve crush injury. In addition to our work, many substrates of beta secretase have been found to be involved in regulating neurite outgrowth and some have even been identified as regeneration associated genes. In this review, we set out to discuss BACE1 and its substrates with respect to axonal regeneration and speculate on the possibility of utilizing BACE1 inhibitors to enhance regeneration following acute nerve injury and potential uses in peripheral neuropathies.

  18. Case report of a patient with peripheral facial nerve palsy

    OpenAIRE

    Rysová, Jana

    2013-01-01

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

  19. Factors that influence peripheral nerve regeneration

    DEFF Research Database (Denmark)

    Krarup, Christian; Archibald, Simon J; Madison, Roger D

    2002-01-01

    Regeneration in the peripheral nervous system is often incomplete though it is uncertain which factors, such as the type and extent of the injury or the method or timing of repair, determine the degree of functional recovery. Serial electrophysiological techniques were used to follow recovery from...... median nerve lesions (n = 46) in nonhuman primates over 3 to 4 years, a time span comparable with such lesions in humans. Nerve gap distances of 5, 20, or 50mm were repaired with nerve grafts or collagen-based nerve guide tubes, and three electrophysiological outcome measures were followed: (1) compound...... muscle action potentials in the abductor pollicis brevis muscle, (2) the number and size of motor units in reinnervated muscle, and (3) compound sensory action potentials from digital nerve. A statistical model was used to assess the influence of three variables (repair type, nerve gap distance, and time...

  20. Large Extremity Peripheral Nerve Repair

    Science.gov (United States)

    2015-10-01

    decellularized nerve allograft for inferior alveolar nerve reconstruction: a case report. Journal of oral and maxillofacial surgery : official journal of...the American Association of Oral and Maxillofacial Surgeons. 2011 Feb;69(2):550-3. PubMed PMID: 21145638. Epub 2010/12/15. eng. 16. Gunn S, Cosetti M...Massachusetts General Hospital (protocol #2012N000117) and was also granted ACURO approval on 11/19/2012. Task 2b. Rodent surgeries for segmental deficit

  1. Management of peripheral facial nerve palsy

    OpenAIRE

    Finsterer, Josef

    2008-01-01

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

  2. Regenerative scaffold electrodes for peripheral nerve interfacing.

    Science.gov (United States)

    Clements, Isaac P; Mukhatyar, Vivek J; Srinivasan, Akhil; Bentley, John T; Andreasen, Dinal S; Bellamkonda, Ravi V

    2013-07-01

    Advances in neural interfacing technology are required to enable natural, thought-driven control of a prosthetic limb. Here, we describe a regenerative electrode design in which a polymer-based thin-film electrode array is integrated within a thin-film sheet of aligned nanofibers, such that axons regenerating from a transected peripheral nerve are topographically guided across the electrode recording sites. Cultures of dorsal root ganglia were used to explore design parameters leading to cellular migration and neurite extension across the nanofiber/electrode array boundary. Regenerative scaffold electrodes (RSEs) were subsequently fabricated and implanted across rat tibial nerve gaps to evaluate device recording capabilities and influence on nerve regeneration. In 20 of these animals, regeneration was compared between a conventional nerve gap model and an amputation model. Characteristic shaping of regenerated nerve morphology around the embedded electrode array was observed in both groups, and regenerated axon profile counts were similar at the eight week end point. Implanted RSEs recorded evoked neural activity in all of these cases, and also in separate implantations lasting up to five months. These results demonstrate that nanofiber-based topographic cues within a regenerative electrode can influence nerve regeneration, to the potential benefit of a peripheral nerve interface suitable for limb amputees.

  3. Large Extremity Peripheral Nerve Repair

    Science.gov (United States)

    2016-12-01

    the nerve supply to intrinsic musculature in the hind foot and may be exacerbated by the lack of physical rehabilitative measures that would...LM, de Crombrugghe B. Some recent advances in the chemistry and biology of trans- forming growth factor-beta. J Cell Biol 1987;105:1039e45. 12. Hao Y...into strips, wrapped around nitrocellulose paper , and placed in a storage solution containing a 1:1 mix of 100% sterile glycerol and Dulbecco’s

  4. 21 CFR 868.2775 - Electrical peripheral nerve stimulator.

    Science.gov (United States)

    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) is...

  5. Raman spectroscopic detection of peripheral nerves towards nerve-sparing surgery

    Science.gov (United States)

    Minamikawa, Takeo; Harada, Yoshinori; Takamatsu, Tetsuro

    2017-02-01

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

  6. Selective Recovery of Fascicular Peripheral Nerves

    Science.gov (United States)

    Wodlinger, B; Durand, DM

    2011-01-01

    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 5 fascicular-group signals simultaneously with R2=0.7±0.2 at a signal-to-noise ratio of 0dB. This technique accurately separated peripheral neural signals, potentially providing voluntary, natural, and robust command signals needed for advanced prosthetic limbs. PMID:21828890

  7. The Role of Continuous Peripheral Nerve Blocks

    OpenAIRE

    José Aguirre; Alicia Del Moral; Irina Cobo; Alain Borgeat; Stephan Blumenthal

    2012-01-01

    A continuous peripheral nerve block (cPNB) is provided in the hospital and ambulatory setting. The most common use of CPNBs is in the peri- and postoperative period but different indications have been described like the treatment of chronic pain such as cancer-induced pain, complex regional pain syndrome or phantom limb pain. The documented benefits strongly depend on the analgesia quality and include decreasing baseline/dynamic pain, reducing additional analgesic requirements, decrease of po...

  8. The challenges and beauty of peripheral nerve regrowth.

    Science.gov (United States)

    Zochodne, Douglas W

    2012-03-01

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

  9. Management of peripheral facial nerve palsy.

    Science.gov (United States)

    Finsterer, Josef

    2008-07-01

    Peripheral facial nerve palsy (FNP) may (secondary FNP) or may not have a detectable cause (Bell's palsy). Three quarters of peripheral FNP are primary and one quarter secondary. The most prevalent causes of secondary FNP are systemic viral infections, trauma, surgery, diabetes, local infections, tumor, immunological disorders, or drugs. The diagnosis of FNP relies upon the presence of typical symptoms and signs, blood chemical investigations, cerebro-spinal-fluid-investigations, X-ray of the scull and mastoid, cerebral MRI, or nerve conduction studies. Bell's palsy may be diagnosed after exclusion of all secondary causes, but causes of secondary FNP and Bell's palsy may coexist. Treatment of secondary FNP is based on the therapy of the underlying disorder. Treatment of Bell's palsy is controversial due to the lack of large, randomized, controlled, prospective studies. There are indications that steroids or antiviral agents are beneficial but also studies, which show no beneficial effect. Additional measures include eye protection, physiotherapy, acupuncture, botulinum toxin, or possibly surgery. Prognosis of Bell's palsy is fair with complete recovery in about 80% of the cases, 15% experience some kind of permanent nerve damage and 5% remain with severe sequelae.

  10. Multicenter Clinical Trial of Keratin Biomaterial for Peripheral Nerve Regeneration

    Science.gov (United States)

    2015-12-01

    which cause extensive damage to skin, bones , and nerves. The management of damaged peripheral nerves is challenging for patients and surgeons... artificial nerve conduits for digital nerve repair: a prospective cohort study and literature review. J Reconstr Microsurg 2009 Jan;25(1):55-61. Pace

  11. Selective Recovery of Fascicular Peripheral Nerves

    OpenAIRE

    Wodlinger, B; Durand, DM

    2011-01-01

    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 an...

  12. Triple Peripheral Nerve Injury Accompanying to Traumatic Brain Injury: A Case Report

    Directory of Open Access Journals (Sweden)

    Ižlknur Can

    2014-02-01

    Full Text Available Secondary injuries especially extremity fractures may be seen concurrently with traumatic brain injury (TBI. Peripheral nerve damages may accompany to these fractures and may be missed out, especially in acute stage. In this case report; damage of radial, ulnar and median nerves which was developed secondarily to distal humerus fracture that could not be detected in acute stage, in a patient who had motor vehicle accident (MVA. 29-year-old male patient was admitted with weakness in the right upper extremity. 9 months ago, he had traumatic brain injury because of MVA, and fracture of distal humerus was detected in follow-ups. Upon the suspect of the peripheral nerve injury, the diagnosis was confirmed with ENMG. The patient responded well to the rehabilitation program treatment. In a TBI patient, it must be kept in mind that there might be a secondary trauma and therefore peripheral nerve lesions may accompany to TBI.

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

    OpenAIRE

    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 target...

  14. Immunoglobulin deposits in peripheral nerve endings detected by skin biopsy in patients with IgM M proteins and neuropathy

    DEFF Research Database (Denmark)

    Jønsson, V; Jensen, T S; Friis, M L

    1987-01-01

    biopsies provide a simple effective method of detecting immunoglobulin binding to peripheral nerves in patients suspected of having an autoimmune neuropathy. In contrast to sural nerve biopsy, skin biopsy does not cause sensory loss or pain in a denervated area and can easily be repeated....

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

    Directory of Open Access Journals (Sweden)

    Berta Kowalska

    2012-06-01

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

  16. Synovial sarcoma mimicking benign peripheral nerve sheath tumor

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-11-15

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

  17. Retrospective analysis of oral peripheral nerve sheath tumors in Brazilians

    Directory of Open Access Journals (Sweden)

    Juliana Tito Salla

    2009-03-01

    Full Text Available Traumatic neuroma, neurofibroma, neurilemmoma, palisaded encapsulated neuroma and malignant peripheral nerve sheath tumor (MPNST are peripheral nerve sheath tumors and present neural origin. The goal of this study was to describe the epidemiological data of oral peripheral nerve sheath tumors in a sample of the Brazilian population. Biopsies requested from the Oral Pathology Service, School of Dentistry, Federal University of Minas Gerais (MG, Brazil, between 1966 and 2006 were evaluated. Lesions diagnosed as peripheral nerve sheath tumors were submitted to morphologic and to immunohistochemical analyses. All cases were immunopositive to the S-100 protein. Thirty-five oral peripheral nerve sheath tumors were found, representing 0.16% of all lesions archived in the Oral Pathology Service. Traumatic neuroma (15 cases most frequently affected the mental foramen. Solitary neurofibroma (10 cases was more frequently observed in the palate. Neurofibroma associated with neurofibromatosis type I (2 cases was observed in the gingival and alveolar mucosa. Neurilemmoma (4 cases was more commonly observed in the buccal mucosa. Malignant peripheral nerve sheath tumors (3 cases occurred in the mandible, palate, and tongue. Palisaded encapsulated neuroma (1 case occurred in the buccal mucosa. The data confirmed that oral peripheral nerve sheath tumors are uncommon in the oral region, with some lesions presenting a predilection for a specific gender or site. This study may be useful in clinical dentistry and oral pathology practice and may be used as baseline data regarding oral peripheral nerve sheath tumors in other populations.

  18. Detergent-free Decellularized Nerve Grafts for Long-gap Peripheral Nerve Reconstruction

    Directory of Open Access Journals (Sweden)

    Srikanth Vasudevan, PhD

    2014-08-01

    Conclusions: This study describes a detergent-free nerve decellularization technique for reconstruction of long-gap nerve injuries. We compared DFD grafts with an established detergent processing technique and found that DFD nerve grafts are successful in promoting regeneration across long-gap peripheral nerve defects as an alternative to existing strategies.

  19. Therapeutic electrical stimulation of injured peripheral nerve tissue using implantable thin-film wireless nerve stimulators.

    Science.gov (United States)

    MacEwan, Matthew R; Gamble, Paul; Stephen, Manu; Ray, Wilson Z

    2018-02-09

    OBJECTIVE Electrical stimulation of peripheral nerve tissue has been shown to accelerate axonal regeneration. Yet existing methods of applying electrical stimulation to injured peripheral nerves have presented significant barriers to clinical translation. In this study, the authors examined the use of a novel implantable wireless nerve stimulator capable of simultaneously delivering therapeutic electrical stimulation of injured peripheral nerve tissue and providing postoperative serial assessment of functional recovery. METHODS Flexible wireless stimulators were fabricated and implanted into Lewis rats. Thin-film implants were used to deliver brief electrical stimulation (1 hour, 20 Hz) to sciatic nerves after nerve crush or nerve transection-and-repair injuries. RESULTS Electrical stimulation of injured nerves via implanted wireless stimulators significantly improved functional recovery. Brief electrical stimulation was observed to increase the rate of functional recovery after both nerve crush and nerve transection-and-repair injuries. Wireless stimulators successfully facilitated therapeutic stimulation of peripheral nerve tissue and serial assessment of nerve recovery. CONCLUSIONS Implantable wireless stimulators can deliver therapeutic electrical stimulation to injured peripheral nerve tissue. Implantable wireless nerve stimulators might represent a novel means of facilitating therapeutic electrical stimulation in both intraoperative and postoperative settings.

  20. Progress of nerve bridges in the treatment of peripheral nerve disruptions

    Directory of Open Access Journals (Sweden)

    Ao Q

    2016-12-01

    Full Text Available Qiang Ao Department of Tissue Engineering, School of Fundamental Science, China Medical University, Shenyang, Liaoning, Peoples’ Republic of China Abstract: Clinical repair of a nerve defect is one of the most challenging surgical problems. Autologous nerve grafting remains the gold standard treatment in addressing peripheral nerve injuries that cannot be bridged by direct epineural suturing. However, the autologous nerve graft is not readily available, and the process of harvesting autologous nerve graft results in several complications. Thus, it is necessary to explore an alternative to autologous nerve graft. In the last few decades, with significant advances in the life sciences and biotechnology, a lot of artificial nerve grafts have been developed to aim at the treatment of peripheral nerve disruptions. Artificial nerve grafts range from biological tubes to synthetic tubes and from nondegradable tubes to degradable tubes. Among them, acellular nerve allografts and artificial nerve repair conduits are two kinds of the most promising substitutes for nerve autografts. The history, research status, and prospect of acellular nerve allografts and artificial nerve repair conduits are described briefly in this review. Keywords: peripheral nerve injury, repair, acellular nerve graft, nerve conduit

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  3. Optical detection of peripheral nerves: an in vivo human study.

    Science.gov (United States)

    Balthasar, Andrea; Desjardins, Adrien E; van der Voort, Marjolein; Lucassen, Gerald W; Roggeveen, Stefan; Wang, Ke; Bierhoff, Walter; Kessels, Alfons G H; van Kleef, Maarten; Sommer, Micha

    2012-01-01

    A critical challenge encountered in interventional pain medicine procedures is to accurately and efficiently identify transitions to peripheral nerve targets. Current methods, which include ultrasound guidance and nerve stimulation, are not perfect. In this pilot study, we investigated the feasibility of identifying tissue transitions encountered during insertions toward peripheral nerve targets using optical spectroscopy. Using a custom needle stylet with integrated optical fibers, ultrasound-guided insertions toward peripheral nerves were performed in 20 patients, with the stylet positioned in the cannula of a 20-gauge stimulation needle. Six different peripheral nerves were represented in the study, with 1 insertion per patient. During each insertion, optical reflectance spectra were acquired with the needle tip in subcutaneous fat, skeletal muscle, and at the nerve target region. Differences in the spectra were quantified with 2 parameters that provide contrast for lipid and hemoglobin, respectively. The transition of the needle tip from subcutaneous fat to muscle was associated with lower lipid parameter values (P = 0.003) and higher hemoglobin parameter values (P = 0.023). The transition of the needle tip from the muscle to the nerve target region was associated with higher lipid parameter values (P = 0.008). The results indicate that the spectroscopic information provided by the needle stylet could potentially allow for reliable identification of transitions from subcutaneous fat to skeletal muscle and from the muscle to the nerve target region during peripheral nerve blocks.

  4. [Methodological considerations concerning peripheral nerve morphometry].

    Science.gov (United States)

    Cuadras, J; Butí, M; Calvet, S; Verdú, E; Navarro, X

    1995-01-01

    Morphometric studies of the peripheral nerve often present widely varying results which, in part at least, may be attributed to the different methodologies used. Two questions may be of importance with regard to the reliability of such results: the preselection of fibres according to their morphology and the method used in quantifying observations. In this work a morphological study was carried out on the myelinated fibres of the sciatic nerve of a rat in order to evaluate fibre selection criteria. A morphometric analysis was also performed using manual measurements, image digitalisation and surveying, and automatic image analysis. It was shown that morphological variability of transverse section fibres is considerable and that, really, the proportion of circular fibres with homogeneous compact myelin is only 50 to 70%, from which we can conclude that the selection of fibres carried out in some studies wishing to eliminate abnormal fibres is somewhat exaggerated. By analysing the fibres using various methods significant differences appear, some due to the fact that distinct methods may be used to calculate the same parameters in a different way. The most reliable parameters would appear to be those which do not depend on the shape of the fibres and those which automatic or semiautomatic methods can calculate directly such as areas and perimeters. In any case quantifying methods seem hardly discriminatory and the differences between methods disappear if analyses are carried out using random samples. Preselection of fibres appears unnecessary in this context as in no case are the results altered. Finally we suggest finishing quantitative analyses with qualitative studies which would permit getting more information especially useful in cases of ageing, regeneration or pathological studies.

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

    Directory of Open Access Journals (Sweden)

    Berta Kowalska

    2012-06-01

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

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

    African Journals Online (AJOL)

    group B) received train-of-four electrical stimulation using the peripheral nerve stimulator (PNS) immediately prior to spinal anaesthesia until the completion of surgery. Outcome measures: The primary outcome measure was mean arterial ...

  7. a technique to repair peripheral nerve injury

    African Journals Online (AJOL)

    End-to-side nerve suture (ETSNS) has until recently been extensively researched in the laboratory animal (rat and baboon). Lateral sprouting from an intact nerve into an attached nerve does occur, and functional recovery (sensory and motor) has been demonstrated. We have demonstrated conclusively that ETSNS in the ...

  8. High frequency ultrasound evaluation of traumatic peripheral nerve injuries.

    Science.gov (United States)

    Hollister, Anne M; Simoncini, Alberto; Sciuk, Adam; Jordan, Jenee'

    2012-01-01

    Accurate diagnosis and localization of peripheral nerve traumatic injury remains difficult. Early diagnosis and repair of nerve discontinuity lesions lead to better outcome than delayed repair. We used new high frequency ultrasound to evaluate 24 patients with 29 traumatic nerve injuries. There were a variety of causes including gunshot wounds, blunt injuries, burns, stabbings, and motor vehicle accidents. The patients were then either treated surgically with nerve status directly observed or followed clinically for recovery of nerve function. The ultrasound findings correspond with the clinical outcome of 28 of the 29 nerves. While this is a study limited by a small patient number, ultrasound evaluation should be considered in the evaluation of nerve injury and can lead to early diagnosis and treatment of surgical nerve injuries.

  9. Visualizing peripheral nerve regeneration by whole mount staining.

    Directory of Open Access Journals (Sweden)

    Xin-peng Dun

    Full Text Available Peripheral nerve trauma triggers a well characterised sequence of events both proximal and distal to the site of injury. Axons distal to the injury degenerate, Schwann cells convert to a repair supportive phenotype and macrophages enter the nerve to clear myelin and axonal debris. Following these events, axons must regrow through the distal part of the nerve, re-innervate and finally are re-myelinated by Schwann cells. For nerve crush injuries (axonotmesis, in which the integrity of the nerve is maintained, repair may be relatively effective whereas for nerve transection (neurotmesis repair will likely be very poor as few axons may be able to cross between the two parts of the severed nerve, across the newly generated nerve bridge, to enter the distal stump and regenerate. Analysing axon growth and the cell-cell interactions that occur following both nerve crush and cut injuries has largely been carried out by staining sections of nerve tissue, but this has the obvious disadvantage that it is not possible to follow the paths of regenerating axons in three dimensions within the nerve trunk or nerve bridge. To try and solve this problem, we describe the development and use of a novel whole mount staining protocol that allows the analysis of axonal regeneration, Schwann cell-axon interaction and re-vascularisation of the repairing nerve following nerve cut and crush injuries.

  10. The role of exosomes in peripheral nerve regeneration

    Directory of Open Access Journals (Sweden)

    Rosanna C Ching

    2015-01-01

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

  11. Optimal timing for repair of peripheral nerve injuries.

    Science.gov (United States)

    Wang, Eugene; Inaba, Kenji; Byerly, Saskya; Escamilla, Diandra; Cho, Jayun; Carey, Joseph; Stevanovic, Milan; Ghiassi, Alidad; Demetriades, Demetrios

    2017-11-01

    Data regarding outcomes after peripheral nerve injuries is limited, and the optimal management strategy for an acute injury is unclear. The aim of this study was to examine timing of repair and specific factors that impact motor-sensory outcomes after peripheral nerve injury. This was a single-center, retrospective study. Patients with traumatic peripheral nerve injury from January 2010 to June 2015 were included. Patients who died, required amputation, suffered brachial plexus injury, or had missing motor-sensory examinations were excluded. Motor-sensory examinations were graded 0 to 5 by the Modified British Medical Research Council system. Operative repair of peripheral nerves was analyzed for patient characteristics, anatomic nerve injured, level of injury, associated injuries, days until repair, and repair method. Three hundred eleven patients met inclusion criteria. Two hundred fifty-eight (83%) patients underwent operative management, and 53 (17%) underwent nonoperative management. Those who required operative intervention had significantly more penetrating injuries 85.7% versus 64.2% (p undergoing laparotomy (p = 0.257) and days to nerve repair (p = 0.834) did not influence motor-sensory outcome. Outcomes did not differ significantly in patients who underwent repair 24 hours or longer versus those who were repaired later. Outcomes were primarily influenced by patient characteristics and injury level rather than operative characteristics. Peripheral nerve injuries can be repaired after damage control surgery without detriment to outcomes. Prognostic study, level III.

  12. 21 CFR 882.5870 - Implanted peripheral nerve stimulator for pain relief.

    Science.gov (United States)

    2010-04-01

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

  13. Letter: Transient peripheral facial nerve paralysis after local anesthetic procedure.

    Science.gov (United States)

    Rosmaninho, Aristóteles; Lobo, Inês; Caetano, Mónica; Taipa, Ricardo; Magalhães, Marina; Costa, Virgílio; Selores, Manuela

    2012-04-15

    Complications may arise after laser therapy of the face. The most common ones are bleeding and infections; facial nerve paresis or paralysis is rarely reported. We describe a case of a transient peripheral facial nerve paralysis after laser therapy of an epidermal verrucous nevus localized at the left preauricular area.

  14. Omental pedicle transposition and suture repair of peripheral nerve ...

    African Journals Online (AJOL)

    The peripheral nervous system is able to regenerate after injury. Etiologies of injuries include penetrating injury, crush, traction, and ischemia compression. However, the presence of various nerve injury treatments such as coaptation and another technique to attain functional nerve regeneration are still inadequate.

  15. ELECTRODIAGNOSTIC ASSESSMENT OF PERIPHERAL NERVE INJURIES IN KICK-BOXERS

    Directory of Open Access Journals (Sweden)

    M.R EMAD

    2002-06-01

    Full Text Available Introducti0n. Peripheral nerve injuries are one of the common traumas in various sport fields. Nowadays, thera are a growing tendency to Martial arts among young people. Insufficient knowlodage about the biomechanics and true skills in these sports can expose the athletes to many neuromusculoskeletal injuries including peripheral nerve injuries. The aim of this study was assessment of peripheral nerve injuries among Kick-boxers. Methods. The research was done on 30 male kick-boxers Aged between 17-28 years. Ulnar, tibial and median nerves were studied for the presence of unlar nerve entrapment on elbow, trasal tunnel syndrom and carpal tunnel syndrom. Results. Ulnar neuropathy was observed in 12 cases. Tibial entrapment was detected in 13 cases. No median nerve intrapment of CTS was detected. There was a significant correlation between the age of the participants and nerve entrapment. Discussion. Peripheral nerve injuries should be considered in athletes and should be trained to apply preventive and thrapeutic procedures.

  16. Use of electrospinning to construct biomaterials for peripheral nerve regeneration.

    Science.gov (United States)

    Quan, Qi; Chang, Biao; Meng, Hao Ye; Liu, Ruo Xi; Wang, Yu; Lu, Shi Bi; Peng, Jiang; Zhao, Qing

    2016-10-01

    A number of limitations associated with the use of hollow nerve guidance conduits (NGCs) require further discussion. Most importantly, the functional recovery outcomes after the placement of hollow NGCs are poor even after the successful bridging of peripheral nerve injuries. However, nerve regeneration scaffolds built using electric spinning have several advantages that may improve functional recovery. Thus, the present study summarizes recent developments in this area, including the key cells that are combined with the scaffold and associated with nerve regeneration, the structure and configuration of the electrospinning design (which determines the performance of the electrospinning scaffold), the materials the electrospinning fibers are composed of, and the methods used to control the morphology of a single fiber. Additionally, this study also discusses the processes underlying peripheral nerve regeneration. The primary goals of the present review were to evaluate and consolidate the findings of studies that used scaffolding biomaterials built by electrospinning used for peripheral nerve regeneration support. It is amazing that the field of peripheral nerve regeneration continues to consistently produce such a wide variety of innovative techniques and novel types of equipment, because the introduction of every new process creates an opportunity for advances in materials for nerve repair.

  17. Keratin gel filler for peripheral nerve repair in a rodent sciatic nerve injury model.

    Science.gov (United States)

    Lin, Yen-Chih; Ramadan, Mostafa; Van Dyke, Mark; Kokai, Lauren E; Philips, Brian J; Rubin, J Peter; Marra, Kacey G

    2012-01-01

    Restoration with sufficient functional recovery after long-gap peripheral nerve damage remains a clinical challenge. In vitro, keratins, which are derived from human hair, enhance activity and gene expression of Schwann cells. The specific aim of the authors' study was to examine keratin gel as conduit filler for peripheral nerve regeneration in a rat sciatic nerve injury model. Incorporation of glial cell line-derived, neurotrophic factor, double-walled microspheres into polycaprolactone nerve guides has demonstrated an off-the-shelf product alternative to promote nerve regeneration, and this conduit was filled with keratin gel and examined in a rat 15-mm sciatic nerve defect model. As an indicator of recovery, nerve sections were stained with S100 and protein gene product 9.5 antibody. The keratin-treated groups, compared with both saline and empty polycaprolactone (control) groups (p nerve conduits possess optimal mechanical and degradative properties, rendering the biocompatible conduits potentially useful in peripheral nerve repair. From their studies, the authors conclude that polycaprolactone nerve guides with glial cell line-derived, neurotrophic factor-loaded, double-walled microspheres filled with keratin gel represent a potentially viable guiding material for Schwann cell and axon migration and proliferation in the treatment of peripheral nerve regeneration.

  18. Factors that influence peripheral nerve regeneration

    DEFF Research Database (Denmark)

    Krarup, Christian; Archibald, Simon J; Madison, Roger D

    2002-01-01

    median nerve lesions (n = 46) in nonhuman primates over 3 to 4 years, a time span comparable with such lesions in humans. Nerve gap distances of 5, 20, or 50mm were repaired with nerve grafts or collagen-based nerve guide tubes, and three electrophysiological outcome measures were followed: (1) compound...... predictors. Thus, nerve gap distance and repair type exert their influence through time to muscle reinnervation. These findings emphasize that factors that control early axonal outgrowth influence the final level of recovery attained years later. They also highlight that a time window exists within which...... muscle action potentials in the abductor pollicis brevis muscle, (2) the number and size of motor units in reinnervated muscle, and (3) compound sensory action potentials from digital nerve. A statistical model was used to assess the influence of three variables (repair type, nerve gap distance, and time...

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

    Directory of Open Access Journals (Sweden)

    Tessa Gordon

    2015-01-01

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

  20. Immunoglobulin deposits in peripheral nerve endings detected by skin biopsy in patients with IgM M proteins and neuropathy

    DEFF Research Database (Denmark)

    Jønsson, V; Jensen, T S; Friis, M L

    1987-01-01

    Immunofluorescence studies of sural nerve and skin biopsies from three patients with IgM M proteins and clinical neuropathy showed that IgM M protein was bound to the nerve myelin in two patients and by the peri- and endoneurium in one. It is suggested that immunohistochemical studies of skin...... biopsies provide a simple effective method of detecting immunoglobulin binding to peripheral nerves in patients suspected of having an autoimmune neuropathy. In contrast to sural nerve biopsy, skin biopsy does not cause sensory loss or pain in a denervated area and can easily be repeated....

  1. Spinal myoclonus following a peripheral nerve injury: a case report

    Directory of Open Access Journals (Sweden)

    Erkol Gokhan

    2008-08-01

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

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

    Science.gov (United States)

    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.

  3. Clinical aspects of ballistic peripheral nerve injury: shrapnel versus gunshot.

    Science.gov (United States)

    Rochkind, Shimon; Strauss, Ido; Shlitner, Zvi; Alon, Malvina; Reider, Evgeny; Graif, Moshe

    2014-08-01

    Ballistic injuries to peripheral nerves pose special challenges in terms of indications, timing and type of surgical intervention. The aim of the present work was to analyze our experience in the surgical treatment of peripheral nerve ballistic injuries with respect to the mechanism of injury (gunshot versus shrapnel), and identify common and dissimilar prognostic factors in both types of injury. This study was conducted on 42 patients totaling 58 nerves. Twenty-two patients (32 nerves) were injured by gunshot and 20 patients (26 nerves) by shrapnel. Median postoperative follow-up was 33 months (range 12 months to 14 years). Overall postoperative outcome appears to be more favorable for gunshot-wound (GSW) patients than shrapnel-injured patients, especially in terms of neuropathic pain relief (75 % vs. 58 % respectively, p Nerve graft reconstruction, rather than neurolysis, seems to be the more beneficial treatment for shrapnel-induced neuropathic pain (100 % vs. 47 % in improvement rate, respectively). Early surgical intervention (median 2 months after injury) significantly relieved neuropathic pain in 83 % of shrapnel-injured patients compared to 58 % in patients operated later. This study suggests that shrapnel injury is more destructive for nerve tissue than gunshot injury. Our impression is that early surgical intervention in shrapnel injuries and split nerve grafting (especially when small fragments are recognized in the nerve) significantly improve the patient's functional activity and quality of life.

  4. Epimedium Extract Promotes Peripheral Nerve Regeneration in Rats

    Directory of Open Access Journals (Sweden)

    Yuhui Kou

    2013-01-01

    Full Text Available Effects of Epimedium extract and its constituent icariin on peripheral nerve repair were investigated in a crush injury rat model. Animals were divided into four groups: sham, control, Epimedium extract, and icariin groups. At postoperative weeks 1, 2, 4, and 8, nerve regeneration and functional recovery were evaluated by sciatic functional index (SFI, nerve electrophysiology, nerve pinch test, and muscle wet weight. Results showed that at 2 and 4 weeks after surgery rats in the Epimedium group displayed a better recovery of nerve function than that in the icariin and control groups, with better recovery in the icariin group than in the control group. The nerve pinch test showed that nerve regeneration was greater in the Epimedium group and the icariin group as compared to the control group. In addition, the muscle wet weight in the Epimedium group was significantly improved when compared with the icariin group, and the improvement in the icariin group was better than that in the control group at 8 weeks after operation. Our findings suggest that Epimedium extract effectively promotes peripheral nerve regeneration and improves the function of damaged nerves.

  5. [Postoperative rehabilitation in patients with peripheral nerve lesions].

    Science.gov (United States)

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

    2003-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Jonas Francisco Scopel

    Full Text Available 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.

  7. Novel drug delivering conduit for peripheral nerve regeneration

    Science.gov (United States)

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

    2017-12-01

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

  8. Sonographic identification of peripheral nerves in the forearm

    Directory of Open Access Journals (Sweden)

    Saundra A Jackson

    2016-01-01

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

  9. Use of superficial peroneal nerve graft for treating peripheral nerve injuries

    Directory of Open Access Journals (Sweden)

    Samuel Ribak

    2016-02-01

    Full Text Available ABSTRACT 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.

  10. GLP-1 signals via ERK in peripheral nerve and prevents nerve dysfunction in diabetic mice

    DEFF Research Database (Denmark)

    Jolivalt, CG; Fineman, M; Deacon, Carolyn F.

    2011-01-01

    Aim: Glucagon-like peptide-1 (GLP-1) is an incretin hormone that induces glucose-dependent insulin secretion and may have neurotrophic properties. Our aim was to identify the presence and activity of GLP-1 receptors (GLP-1Rs) in peripheral nerve and to assess the impact of GLP-1R agonists on diab...... that the peripheral nerve of diabetic rodents exhibits functional GLP-1R and suggest that GLP-1R-mediated ERK-signalling in sciatic nerve of diabetic rodents may protect large motor fibre function and small C fibre structure by a mechanism independent of glycaemic control....

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

    Directory of Open Access Journals (Sweden)

    Christopher S Crowe

    2015-09-01

    Full Text Available 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.

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

    Directory of Open Access Journals (Sweden)

    Rodrigo Guerra Sabongi

    2015-01-01

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

  13. Laminin-based Nanomaterials for Peripheral Nerve Tissue Engineering

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    Aikeremujiang Muheremu

    2015-01-01

    Full Text Available 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.

  15. Drug Delivery for Peripheral Nerve Regeneration

    Science.gov (United States)

    2015-11-01

    reservoir is designed, fabricated, tested. Devices loaded with nerve growth factor (NGF) are evaluated for sustained drug release and axon growth...life. Unfortunately, current treatments often result in inadequate or untimely repair, which can result in lifelong deficits in muscle function or...interest in learning and careers in science, technology, and the humanities. Nothing to Report What do you plan to do during the next reporting

  16. MRI of pathology-proven peripheral nerve amyloidosis

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-01-15

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

  17. Sulodexide prevents peripheral nerve damage in streptozotocin induced diabetic rats.

    Science.gov (United States)

    Jin, Heung Yong; Lee, Kyung Ae; Song, Sun Kyung; Liu, Wei Jing; Choi, Ji Hae; Song, Chang Ho; Baek, Hong Sun; Park, Tae Sun

    2012-01-15

    We investigated whether sulodexide has additional protective effects against peripheral nerve damage caused by microvascular dysfunction in a rat model of diabetes. Female Sprague-Dawley (SD) rats were divided into the following 4 groups (n=7-9/group): Normal, Normal+Sulodexide (sulodexide 10mg/kg), diabetic group, and diabetic+Sulodexide (sulodexide 10mg/kg). We assessed current perception threshold, skin blood flow, superoxide dismutase, and proteinuria in experimental rats after oral administration of sulodexide for 20 weeks. We also performed morphometric analysis of sciatic nerves and intraepidermal nerve fibers of the foot. Superoxide dismutase activity in the blood and sciatic nerve were increased significantly after sulodexide treatment in the diabetic group. Current perception threshold was reduced at 2000 Hz (633.3 ± 24.15 vs 741.2 ± 23.5 μA, Pdiabetic+Sulodexide group compared with the diabetic group. The mean myelinated axon area was significantly larger (56.6 ± 2.2 vs 49.8 ± 2.7 μm(2), Pnerve fiber density was significantly less reduced (6.27 ± 0.24 vs 5.40 ± 0.25/mm, Pdiabetic+Sulodexide group compared to the diabetic group. Our results demonstrate that sulodexide exhibits protective effects against peripheral nerve damage in a rat experimental model of diabetes. Therefore, these findings suggest that sulodexide is a potential new therapeutic agent for diabetic peripheral neuropathy. Copyright © 2011 Elsevier B.V. All rights reserved.

  18. Malignant Peripheral Nerve Sheath Tumor: MRI and CT Findings

    Directory of Open Access Journals (Sweden)

    K. O. Kragha

    2015-01-01

    important in its diagnosis. A rare case of MPNST that produced urinary retention and bowel incontinence is presented that may aid clinicians in the diagnosis of this rare clinical entity. Motor weakness, central enhancement, and immunohistochemistry may assist in the diagnosis of MPNST and differentiation between benign peripheral nerve sheath tumor (BPNST and MPNST.

  19. Multi-microelectrode devices for intrafascicular use in peripheral nerve

    NARCIS (Netherlands)

    Rutten, Wim

    1996-01-01

    This minisymposium paper gives an overview of experimental, modeling, design and microfabrication steps which lead towards the University of Twente three-dimensional 128-fold silicon microelectrode device. The device is meant for implantation in peripheral nerve for neuromuscular control purposes

  20. Tumors of peripheral nerves; Tumoren der peripheren Nerven

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-03-15

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

  1. Peripheral Nerve Function and Lower Extremity Muscle Power in Older Men

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  2. Peripheral nerve injuries: A retrospective survey of 1124 cases.

    Science.gov (United States)

    Kouyoumdjian, João A; Graça, Carla R; Ferreira, Vanessa F M

    2017-01-01

    Peripheral nerve injuries (PNIs) remain an important health problem often leading to severe motor disabilities predominantly in the younger population. To analyze our experience of clinical and electrodiagnostic evaluation (EDX) of PNIs over a 26-year period. Between 1989 and 2014, 1124 consecutive patients with 1418 PNIs were referred for clinical as well as EDX evaluation. These PNIs involved upper and lower limbs as well as the facial nerves. Patients with iatrogenic lesions and spinal cord/spinal root lesions were excluded from this analysis. Brachial plexus (BP) injuries with associated or not with root avulsions were considered as one particular nerve and was include in the study as BP. The etiological categories of the sustained trauma included vehicular accidents, penetrating injuries, falls, gunshot wounds, car accidents involving pedestrians, sports injuries, and miscellaneous injuries. The mean age of our patients was 34.2 years and most were males (76.7%). Majority (80.9%) of the PNIs were isolated injuries. Combined lesions most commonly involved the ulnar and median nerves. Upper-limb PNIs accounted for 72.6% of our patients. The ulnar nerve was injured most often, either singly or in combination. Vehicular accidents were the most common causes of injury (46.4%), affecting the brachial BP or the radial, fibular, or sciatic nerves. Penetrating trauma (23.9%) commonly affected the ulnar and the median nerves. Falls and gunshot wounds frequently affected the ulnar, radial, and median nerves. Sports injuries, mostly soccer related, affected predominantly the fibular nerves. BP injuries were considerably more common in accidents involving motorcycles than those involving cars (46.1% vs. 17.1%), and root avulsions was more frequently associated in these cases. Most PNIs were caused by vehicular accidents and penetrating trauma, and affected young men. Overall, ulnar nerve, primary BP, and median nerve PNIs were the most prevalent lesions.

  3. Role of metallothioneins in peripheral nerve function and regeneration

    DEFF Research Database (Denmark)

    Ceballos, D; Lago, N; Verdú, E

    2003-01-01

    postlesion (dpl) and electrophysiologically at 14 dpl. The quality of the regeneration was assessed by light microscopy and immunohistochemical methods. The results show that the regeneration distance was greater in the Mt3 KO than in the Mt1+ 2 KO mice, whereas control mice showed intermediate values....... Moreover, the number of regenerating axons in the distal tibial nerve was significantly higher in Mt3KO mice than in the other two strains at 14 dpl. Immunoreactive profiles to protein gene product 9.5 were present in the epidermis and the sweat glands of the plantar skin of the hindpaw of the Mt3 KO group....... The improved regeneration observed with the Mt3 KO mice was confirmed by compound nerve action potentials that were recorded from digital nerves at 14 dpl only in this group. We conclude that Mt3 normally inhibits peripheral nerve regeneration....

  4. Peripheral Nerve Regeneration Strategies: Electrically Stimulating Polymer Based Nerve Growth Conduits

    Science.gov (United States)

    Anderson, Matthew; Shelke, Namdev B.; Manoukian, Ohan S.; Yu, Xiaojun; McCullough, Louise D.; Kumbar, Sangamesh G.

    2017-01-01

    Treatment of large peripheral nerve damages ranges from the use of an autologous nerve graft to a synthetic nerve growth conduit. Biological grafts, in spite of many merits, show several limitations in terms of availability and donor site morbidity, and outcomes are suboptimal due to fascicle mismatch, scarring, and fibrosis. Tissue engineered nerve graft substitutes utilize polymeric conduits in conjunction with cues both chemical and physical, cells alone and or in combination. The chemical and physical cues delivered through polymeric conduits play an important role and drive tissue regeneration. Electrical stimulation (ES) has been applied toward the repair and regeneration of various tissues such as muscle, tendon, nerve, and articular tissue both in laboratory and clinical settings. The underlying mechanisms that regulate cellular activities such as cell adhesion, proliferation, cell migration, protein production, and tissue regeneration following ES is not fully understood. Polymeric constructs that can carry the electrical stimulation along the length of the scaffold have been developed and characterized for possible nerve regeneration applications. We discuss the use of electrically conductive polymers and associated cell interaction, biocompatibility, tissue regeneration, and recent basic research for nerve regeneration. In conclusion, a multifunctional combinatorial device comprised of biomaterial, structural, functional, cellular, and molecular aspects may be the best way forward for effective peripheral nerve regeneration. PMID:27278739

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

    Directory of Open Access Journals (Sweden)

    K. S. Houschyar

    2016-01-01

    Full Text Available 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.

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

    OpenAIRE

    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.

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

    Directory of Open Access Journals (Sweden)

    Marco Andrey Cipriani Frade

    2013-05-01

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

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

    Science.gov (United States)

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

    2018-04-09

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

  9. Peripheral facial nerve palsy: how effective is rehabilitation?

    Science.gov (United States)

    Baricich, Alessio; Cabrio, Claudio; Paggio, Roberto; Cisari, Carlo; Aluffi, Paolo

    2012-09-01

    To review the current literature to assess the effectiveness of rehabilitation treatment for peripheral facial nerve palsy. A review of the literature was conducted using the following database: PubMed, EMBASE, PEDro, and Scopus. All randomized or quasi randomized controlled trials, case control, cohort studies and case series greater than 6 published between 1990 and 2010 in the English language were included. All types of peripheral facial nerve palsy were included. We considered all the exercises or rehabilitation programs provided by a physiotherapy in outpatient or home setting and excluded trials in which a drug therapy or surgical intervention was investigated. Three reviewers independently selected the articles. To rate the methodological quality of the studies the American Academy of Neurology classification of evidence for therapeutic intervention (Classes I-IV) was applied. Peripheral injury of the VIIth cranial nerve can have serious repercussions on the patient's functioning and quality of life. The recovery rate is related to the preservation of the nerve and to the cause of palsy. We obtained a third level of recommendation (level C); mime therapy could be effective to improve functional outcome in these patients. Evidence of specific treatment addressed to specific cause is lacking; likewise, no evidence is available on timing of intervention with respect to time of onset. Well-designed randomized controlled trials are required to evaluate the effect of rehabilitation in patients with facial palsy.

  10. Sensorimotor peripheral nerve function and physical activity in older men

    DEFF Research Database (Denmark)

    Lange-Maia, B. S.; Cauley, J A; Newman, Anne B

    2016-01-01

    We determined whether sensorimotor peripheral nerve (PN) function was associated with physical activity (PA) in older men. The Osteoporotic Fractures in Men Study Pittsburgh, PA, site (n = 328, age 78.8 ± 4.7 years) conducted PN testing, including: peroneal motor and sural sensory nerve conduction...... (latencies, amplitudes: CMAP and SNAP for motor and sensory amplitude, respectively), 1.4g/10g monoflament (dorsum of the great toe), and neuropathy symptoms. ANOVA and multivariate linear regression modeled PN associations with PA (Physical Activity Scale for the Elderly [PASE] and SenseWear Armband). After...

  11. Malignant Peripheral Nerve Sheath Tumor - A Case Report

    Directory of Open Access Journals (Sweden)

    Anju N Duttargi

    2007-01-01

    Full Text Available Malignant Peripheral Nerve Sheath Tumor [MPNST] is an extremely rare tumor affecting the oral cavity. It refers to sarcomas that arise from nerve or display features of neural differentiation. Here we present a case of 30-year old male patient with MPNST of right side of the mandible. There was a family history of neurotibromatosis in this case. Histologically, pleomorphic spindle cells with wavy nuclei, light stained cytoplasm, and mitotic activity were observed. The clinical presentation, radiological findings, and light microscopic findings are described in detail. The criteria for diagnosing these tumors and recent advances for diagnosis have also been highlighted.

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

    Science.gov (United States)

    2016-09-01

    seeded constructs were used to repair critical-sized, large gap nerve injury in rats and their functional recovery was monitored longitudinally using... injuries in non-human primates. These represent a more translational model of peripheral nerve injury and repair . 15. SUBJECT TERMS 16. SECURITY...AWARD NUMBER: W811XWH-13-1-0310 TITLE: Acceleration of Regeneration of Large-Gap Peripheral Nerve Injuries Using Acellular Nerve Allografts

  13. Cortical Reorganization in Dual Innervation by Single Peripheral Nerve.

    Science.gov (United States)

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

    2017-09-21

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

  14. Vascular endothelial growth factor promotes peripheral nerve regeneration after sciatic nerve transection in rat

    Directory of Open Access Journals (Sweden)

    Mohammadi Rahim

    2013-12-01

    Full Text Available 【Abstract】Objective: To evaluate the local effect of vascular endothelial growth factor (VEGF on transected sciatic nerve regeneration. Methods: Sixty male white Wistar rats were divided into four experimental groups randomly (n=15. In transected group the left sciatic nerve was transected and the stump was fixed to adjacent muscle. In treatment group the defect was bridged using a silicone graft filled with 10 µL VEGF. In silicone group the graft was filled with phosphate-buffered saline. In sham-operated group the sciatic nerve was ex- posed and manipulated. Each group was subdivided into three subgroups with five animals in each and nerve fibers were studied 4, 8 and 12 weeks after operation. Results: Behavioral test, functional study of sciatic nerve, gastrocnemius muscle mass and morphometric indi- ces confirmed a faster recovery of regenerated axons in VEGF group than in silicone group (P<0.05. In immunohistochemi- cal assessment, reactions to S-100 in VEGF group were more positive than that in silicone group. Conclusion: Local administration of VEGF will im- prove functional recovery and morphometric indices of sci- atic nerve. Key words: Peripheral nerves; Nerve regeneration; Sciatic nerve; Vascular endothelial growth factor

  15. [Research progress on three-dimensional reconstruction and visualization of peripheral nerve].

    Science.gov (United States)

    Ren, Gaohong; Pei, Guoxian

    2009-02-01

    To review the research progress on the three-dimensional (3D) reconstruction and visualization of peripheral nerve. Literature about the research on the 3D reconstruction and visualization of peripheral nerve both at home and abroad were extensively reviewed and thoroughly analyzed. The application of 3D reconstruction and visualization technology was capable of not only reappearing the 3D outer contour and spatial adjacent relationship of peripheral nerve veritable but also displaying, rotating, zooming, dividing and real-time measuring their 3D internal structure and the delicate pathways in any direction either separately or totally. Preliminary achievements were achieved in terms of brachial plexus, lumbosacral plexus, the functional cluster of nerve trunk, intramuscular nerve distribution pattern, peripheral nerve regeneration and the 3D reconstruction and visualization research of complex tissue including peripheral nerve. However, the research on the visualization of peripheral nerve was still in the initial stage since such problems as recognition, segmentation, registration and fusion of the peripheral nerve information were not resolved yet. Researching 3D reconstruction and visualization of the peripheral nerve is of great value for updating the diagnosis and treatment principle of peripheral nerve injury, improving its diagnosis and treatment method and launching a new way for the studying and teaching, which may be a new growing point for the peripheral nerve surgery.

  16. Selective recovery of fascicular activity in peripheral nerves

    Science.gov (United States)

    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.

  17. Peripheral nerve surgery for the treatment of postherpetic neuralgia.

    Science.gov (United States)

    Ducic, Ivica; Felder, John Matthew

    2013-10-01

    Postherpetic neuralgia is a chronic pain condition that develops in some patients after the resolution of herpes zoster, and has no medical cure. Medications used to treat chronic pain do not hasten resolution of the disorder and may impair function. In this brief case report, we describe our experience with excision and implantation to muscle of peripheral sensory nerves in the affected dermatomes as a novel surgical treatment to reduce pain and improve quality of life for patients with this condition. Of the 3 treated patients, all had resolution of chronic pain after surgery. It is concluded that peripheral nerve surgery offers a promising option to improve pain and quality of life in postherpetic neuralgia patients, without affecting systemic functioning.

  18. Bionic intrafascicular interfaces for recording and stimulating peripheral nerve fibers.

    Science.gov (United States)

    Jung, Ranu; Abbas, James J; Kuntaegowdanahalli, Sathyakumar; Thota, Anil K

    2018-01-01

    The network of peripheral nerves presents extraordinary potential for modulating and/or monitoring the functioning of internal organs or the brain. The degree to which these pathways can be used to influence or observe neural activity patterns will depend greatly on the quality and specificity of the bionic interface. The anatomical organization, which consists of multiple nerve fibers clustered into fascicles within a nerve bundle, presents opportunities and challenges that may necessitate insertion of electrodes into individual fascicles to achieve the specificity that may be required for many clinical applications. This manuscript reviews the current state-of-the-art in bionic intrafascicular interfaces, presents specific concerns for stimulation and recording, describes key implementation considerations and discusses challenges for future designs of bionic intrafascicular interfaces.

  19. An implantable wireless optogenetic stimulation system for peripheral nerve control.

    Science.gov (United States)

    Kang-Il Song; Park, Sunghee E; Myoung-Soo Kim; Chulmin Joo; Yong-Jun Kim; Suh, Jun-Kyo F; Dosik Hwang; Inchan Youn

    2015-08-01

    An implantable wireless optogenetic stimulation system with an LED-based optical stimulation cuff electrode was developed for peripheral nerve control. The proposed system consisted of a battery-powered optical cuff electrode, optical stimulation controller, and wireless communication system. The optical cuff electrode had a polydimethylsiloxane (PDMS) structure was designed to illuminate the entire sciatic nerve. The wireless communication system was designed to comply with medical implant communication service (MICS) regulations. To evaluate the proposed system, optogenetic stimulation was performed in optogenetic transgenic mice (Thy1::ChR2). The optical cuff electrode was implanted on the sciatic nerve, and movement was elicited during optical stimulation. The experimental results show that ankle movement can be generated wirelessly using optical stimulation pulse parameters.

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

    Science.gov (United States)

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

    2010-01-01

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

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

    Science.gov (United States)

    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

  2. Nerve autografts and tissue-engineered materials for the repair of peripheral nerve injuries: a 5-year bibliometric analysis

    Directory of Open Access Journals (Sweden)

    Yuan Gao

    2015-01-01

    Full Text Available With advances in biomedical methods, tissue-engineered materials have developed rapidly as an alternative to nerve autografts for the repair of peripheral nerve injuries. However, the materials selected for use in the repair of peripheral nerve injuries, in particular multiple injuries and large-gap defects, must be chosen carefully. Various methods and materials for protecting the healthy tissue and repairing peripheral nerve injuries have been described, and each method or material has advantages and disadvantages. Recently, a large amount of research has been focused on tissue-engineered materials for the repair of peripheral nerve injuries. Using the keywords "pe-ripheral nerve injury", "autotransplant", "nerve graft", and "biomaterial", we retrieved publications using tissue-engineered materials for the repair of peripheral nerve injuries appearing in the Web of Science from 2010 to 2014. The country with the most total publications was the USA. The institutions that were the most productive in this field include Hannover Medical School (Germany, Washington University (USA, and Nantong University (China. The total number of publications using tissue-engineered materials for the repair of peripheral nerve injuries grad-ually increased over time, as did the number of Chinese publications, suggesting that China has made many scientific contributions to this field of research.

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

    Science.gov (United States)

    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.

  4. Role of Demyelination Efficiency within Acellular Nerve Scaffolds during Nerve Regeneration across Peripheral Defects

    Directory of Open Access Journals (Sweden)

    Meiqin Cai

    2017-01-01

    Full Text Available Hudson’s optimized chemical processing method is the most commonly used chemical method to prepare acellular nerve scaffolds for the reconstruction of large peripheral nerve defects. However, residual myelin attached to the basal laminar tube has been observed in acellular nerve scaffolds prepared using Hudson’s method. Here, we describe a novel method of producing acellular nerve scaffolds that eliminates residual myelin more effectively than Hudson’s method through the use of various detergent combinations of sulfobetaine-10, sulfobetaine-16, Triton X-200, sodium deoxycholate, and peracetic acid. In addition, the efficacy of this new scaffold in repairing a 1.5 cm defect in the sciatic nerve of rats was examined. The modified method produced a higher degree of demyelination than Hudson’s method, resulting in a minor host immune response in vivo and providing an improved environment for nerve regeneration and, consequently, better functional recovery. A morphological study showed that the number of regenerated axons in the modified group and Hudson group did not differ. However, the autograft and modified groups were more similar in myelin sheath regeneration than the autograft and Hudson groups. These results suggest that the modified method for producing a demyelinated acellular scaffold may aid functional recovery in general after nerve defects.

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

    LENUS (Irish Health Repository)

    O'Brien, Julie

    2008-12-01

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

  6. Pannexin 1 Modulates Axonal Growth in Mouse Peripheral Nerves

    Directory of Open Access Journals (Sweden)

    Steven M. Horton

    2017-11-01

    Full Text Available The pannexin family of channels consists of three members—pannexin-1 (Panx1, pannexin-2 (Panx2, and pannexin-3 (Panx3 that enable the exchange of metabolites and signaling molecules between intracellular and extracellular compartments. Pannexin-mediated release of intracellular ATP into the extracellular space has been tied to a number of cellular activities, primarily through the activity of type P2 purinergic receptors. Previous work indicates that the opening of Panx1 channels and activation of purinergic receptors by extracellular ATP may cause inflammation and apoptosis. In the CNS (central nervous system and PNS (peripheral nervous system, coupled pannexin, and P2 functions have been linked to peripheral sensitization (pain pathways. Purinergic pathways are also essential for other critical processes in the PNS, including myelination and neurite outgrowth. However, whether such pathways are pannexin-dependent remains to be determined. In this study, we use a Panx1 knockout mouse model and pharmacological inhibitors of the Panx1 and the ATP-mediated signaling pathway to fill gaps in our understanding of Panx1 localization in peripheral nerves, roles for Panx1 in axonal outgrowth and myelination, and neurite extension. Our data show that Panx1 is localized to axonal, myelin, and vascular compartments of the peripheral nerves. Knockout of Panx1 gene significantly increased axonal caliber in vivo and axonal growth rate in cultured dorsal root ganglia (DRG neurons. Furthermore, genetic knockout of Panx1 or inhibition of components of purinergic signaling, by treatment with probenecid and apyrase, resulted in denser axonal outgrowth from cultured DRG explants compared to untreated wild-types. Our findings suggest that Panx1 regulates axonal growth in the peripheral nervous system.

  7. Recovery of Peripheral Nerve with Massive Loss Defect by Tissue Engineered Guiding Regenerative Gel

    Directory of Open Access Journals (Sweden)

    Shimon Rochkind

    2014-01-01

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

  8. Peripheral nerve injury induces glial activation in primary motor cortex

    Directory of Open Access Journals (Sweden)

    Julieta Troncoso

    2015-02-01

    Full Text Available Preliminary evidence suggests that peripheral facial nerve injuries are associated with sensorimotor cortex reorganization. We have characterized facial nerve lesion-induced structural changes in primary motor cortex layer 5 pyramidal neurons and their relationship with glial cell density using a rodent facial paralysis model. First, we used adult transgenic mice expressing green fluorescent protein in microglia and yellow fluorescent protein in pyramidal neurons which were subjected to either unilateral lesion of the facial nerve or sham surgery. Two-photon excitation microscopy was then used for evaluating both layer 5 pyramidal neurons and microglia in vibrissal primary motor cortex (vM1. It was found that facial nerve lesion induced long-lasting changes in dendritic morphology of vM1 layer 5 pyramidal neurons and in their surrounding microglia. Pyramidal cells’ dendritic arborization underwent overall shrinkage and transient spine pruning. Moreover, microglial cell density surrounding vM1 layer 5 pyramidal neurons was significantly increased with morphological bias towards the activated phenotype. Additionally, we induced facial nerve lesion in Wistar rats to evaluate the degree and extension of facial nerve lesion-induced reorganization processes in central nervous system using neuronal and glial markers. Immunoreactivity to NeuN (neuronal nuclei antigen, GAP-43 (growth-associated protein 43, GFAP (glial fibrillary acidic protein, and Iba 1 (Ionized calcium binding adaptor molecule 1 were evaluated 1, 3, 7, 14, 28 and 35 days after either unilateral facial nerve lesion or sham surgery. Patches of decreased NeuN immunoreactivity were found bilaterally in vM1 as well as in primary somatosensory cortex (CxS1. Significantly increased GAP-43 immunoreactivity was found bilaterally after the lesion in hippocampus, striatum, and sensorimotor cortex. One day after lesion GFAP immunoreactivity increased bilaterally in hippocampus, subcortical white

  9. Peripheral nerve magnetic stimulation: influence of tissue non-homogeneity

    Directory of Open Access Journals (Sweden)

    Papazov Sava P

    2003-12-01

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

  10. Biomimetic approaches to bionic touch through a peripheral nerve interface.

    Science.gov (United States)

    Saal, Hannes P; Bensmaia, Sliman J

    2015-12-01

    State-of-the-art prosthetic hands nearly match the dexterity of the human hand, and sophisticated approaches have been developed to control them intuitively. However, grasping and dexterously manipulating objects relies heavily on the sense of touch, without which we would struggle to perform even the most basic activities of daily living. Despite the importance of touch, not only in motor control but also in affective communication and embodiment, the restoration of touch through bionic hands is still in its infancy, a shortcoming that severely limits their effectiveness. Here, we focus on approaches to restore the sense of touch through an electrical interface with the peripheral nerve. First, we describe devices that can be chronically implanted in the nerve to electrically activate nerve fibers. Second, we discuss how these interfaces have been used to convey basic somatosensory feedback. Third, we review what is known about how the somatosensory nerve encodes information about grasped objects in intact limbs and discuss how these natural neural codes can be exploited to convey artificial tactile feedback. Finally, we offer a blueprint for how these codes could be implemented in a neuroprosthetic device to deliver rich, natural, and versatile tactile sensations. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. Primary malignant peripheral nerve sheath tumor at unusual location

    Directory of Open Access Journals (Sweden)

    Souvagya Panigrahi

    2013-01-01

    Full Text Available Malignant peripheral nerve sheath tumor (MPNST is a rare soft tissue sarcoma. Most arise in association with major nerve trunks. Their most common anatomical sites are the proximal portions of the upper and lower extremities and the trunk. MPNSTs have rarely been reported in literature to occur in other unusual body parts. We review all such cases reported till now in terms of site of origin, surgical treatment, adjuvant therapy and outcome and shortly describe our experience with two of these cases. Both of our case presented with lump at unusual sites resembling neurofibroma, one at orbitotemporal area and other in the paraspinal region with characteristic feature of neurofibroma with the exception that both had very short history of progression. They underwent gross total removal of the tumor with adjuvant radiotherapy postoperatively. At 6-month follow-up both are doing well with no evidence of recurrence.

  12. Peripheral nerve disorders and treatment strategies according to Avicenna in his medical treatise, Canon of medicine.

    Science.gov (United States)

    Aciduman, Ahmet; Er, Uygur; Belen, Deniz

    2009-01-01

    The written transmission of knowledge has played a great part in the advancement of medicine, and historical documents hold the key to a full exploration of the history of medicine. Some fields, including disciplines that deal with peripheral nerve disorders, have received little benefit from such valuable material. In particular, peripheral nerve surgery lacks perspectives from historical data. For many years, physicians have obtained positive results in the surgical treatment of peripheral nerve diseases. Relevant documents reveal that the first author who described the surgical repair of damaged peripheral nerves was Avicenna, a leading figure of the medieval era who lived in the Middle East. In his primary medical work, the Canon, he provides a description, albeit sketchy, of a suture procedure for peripheral nerve transection. This treatise influenced physicians for several centuries. In this presentation, we analyze excerpts from the Canon that concern peripheral nerve disorders and strategies for their management.

  13. [Treatment of idiopathic peripheral facial nerve paralysis (Bell's palsy)].

    Science.gov (United States)

    Meyer, Martin Willy; Hahn, Christoffer Holst

    2013-01-28

    Bell's palsy is defined as an idiopathic peripheral facial nerve paralysis of sudden onset. It affects 11-40 persons per 100,000 per annum. Many patients recover without intervention; however, up to 30% have poor recovery of facial muscle control and experience facial disfigurement. The aim of this study was to make an overview of which pharmacological treatments have been used to improve outcomes. The available evidence from randomized controlled trials shows significant benefit from treating Bell's palsy with corticosteroids but shows no benefit from antivirals.

  14. Treating Intractable Post Amputation Phantom Limb Pain with Ambulatory Continuous Peripheral Nerve Blocks

    Science.gov (United States)

    2018-01-01

    Award Number: W81XWH-13-2-0009 TITLE: Treating Intractable Post-Amputation Phantom Limb Pain with Ambulatory Continuous Peripheral Nerve Blocks...26 Dec 2016 – 25 Dec 2017 4. TITLE AND SUBTITLE Treating Intractable Post-Amputation Phantom Limb Pain with Ambulatory Continuous Peripheral Nerve...trial to determine if ambulatory continuous peripheral nerve block (CPNB) is an effective treatment for intractable phantom limb pain following a

  15. Peripheral nerve catheters and local anesthetic infiltration in perioperative analgesia.

    Science.gov (United States)

    Merritt, Christopher K; Mariano, Edward R; Kaye, Alan David; Lissauer, Jonathan; Mancuso, Kenneth; Prabhakar, Amit; Urman, Richard D

    2014-03-01

    Peripheral nerve catheters (PNCs) and local infiltration analgesia (LIA) represent valuable options for controlling perioperative pain. PNCs have been increasingly utilized to provide both surgical anesthesia and prolonged postoperative analgesia for a wide variety of procedures. PNCs can be more technically challenging to place than typical single-injection nerve blocks (SINB), and familiarity with the indications, contraindications, relevant anatomy, and appropriate technical skills is a prerequisite for the placement of any PNC. PNCs include risks of peripheral nerve injury, damage to adjacent anatomic structures, local anesthetic toxicity, intravascular injection, risks associated with motor block, risks of unnoticed injury to the insensate limb, and risks of sedation associated with PNC placement. In addition to these common risks, there are specific risks unique to each PNC insertion site. LIA strategies have emerged that seek to provide the benefit of targeted local anesthesia while minimizing collateral motor block and increasing the applicability of durable local anesthesia beyond the extremities. LIA involves the injection and/or infusion of a local anesthetic near the site of surgical incision to provide targeted analgesia. A wide variety of techniques have been described, including single-injection intraoperative wound infiltration, indwelling wound infusion catheters, and the recent high-volume LIA technique associated with joint replacement surgery. The efficacy of these techniques varies depending on specific procedures and anatomic locations. The recent incorporation of ultra-long-acting liposomal bupivacaine preparations has the potential to dramatically increase the utility of single-injection LIA. LIA represents a promising yet under-investigated method of postoperative pain control. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Expression patterns and role of PTEN in rat peripheral nerve development and injury.

    Science.gov (United States)

    Chen, Hui; Xiang, Jianping; Wu, Junxia; He, Bo; Lin, Tao; Zhu, Qingtang; Liu, Xiaolin; Zheng, Canbin

    2018-04-09

    Studies have suggested that phosphatase and tensin homolog (PTEN) plays an important role in neuroprotection and neuronal regeneration. To better understand the potential role of PTEN with respect to peripheral nerve development and injury, we investigated the expression pattern of PTEN at different stages of rat peripheral nerve development and injury and subsequently assessed the effect of pharmacological inhibition of PTEN using bpV(pic) on axonal regeneration in a rat sciatic nerve crush injury model. During the early stages of development, PTEN exhibits low expression in neuronal cell bodies and axons. From embryonic day (E) 18.5 and postnatal day (P)5 to adult, PTEN protein becomes more detectable, with high expression in the dorsal root ganglia (DRG) and axons. PTEN expression is inhibited in peripheral nerves, preceding myelination during neuronal development and remyelination after acute nerve injury. Low PTEN expression after nerve injury promotes Akt/mammalian target of rapamycin (mTOR) signaling pathway activity. In vivo pharmacological inhibition of PTEN using bpV(pic) promoted axonal regrowth, increased the number of myelinated nerve fibers, improved locomotive recovery and enhanced the amplitude response and nerve conduction velocity following stimulation in a rat sciatic nerve crush injury model. Thus, we suggest that PTEN may play potential roles in peripheral nerve development and regeneration and that inhibition of PTEN expression is beneficial for nerve regeneration and functional recovery after peripheral nerve injury. Copyright © 2018. Published by Elsevier B.V.

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

    Science.gov (United States)

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

    2017-12-01

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

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

    Science.gov (United States)

    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.

  19. Functional evaluation of peripheral nerve regeneration in the rat : walking track analysis

    NARCIS (Netherlands)

    Varejao, ASP; Meek, MF; Patricio, JAB; Cabrita, AMS

    2001-01-01

    The experimental model of choice for many peripheral nerve investigators is the rat. Walking track analysis is a useful tool in the evaluation of functional peripheral nerve recovery in the rat. This quantitative method of analyzing hind limbs performance by examining footprints, known as the

  20. Malignant peripheral nerve sheath tumor arising from solitary neurofibroma

    Directory of Open Access Journals (Sweden)

    Pei-I Chung

    2014-09-01

    Full Text Available Malignant peripheral nerve sheath tumors (MPNSTs are rare sarcomas that are strongly associated with neurofibromatosis type I (NF-1. We describe a 71-year-old woman with no stigmata of neurofibromatosis, who presented with recurrent subcutaneous tumor on her left upper back. She received two excisional biopsies on the back of her trunk at our hospital and both pathology reports revealed neurofibromas. Three years after the last skin biopsy, a rapidly growing subcutaneous tumor emerged at the same site. This tumor was totally resected and the histopathology showed an ill-defined tumor in the dermis and subcutaneous tissue. The tumor was composed of spindle cells in a myxoid stroma with a transition from the area of typical neurofibroma to the hypercellular area. The hypercellular area consisted of atypical, hyperchromatic spindled cells with frequent mitotic figures. She was therefore diagnosed with MPNST.

  1. Cutaneous benign epithelioid peripheral nerve sheath tumour: A rare entity

    Directory of Open Access Journals (Sweden)

    Anuradha CK Rao

    2013-01-01

    Full Text Available Benign epithelioid peripheral nerve sheath tumor, a rare entity is an umbrella term describing benign, neural origin tumors with epithelioid morphology. Clinically indistinguishable from other benign cutaneous lesions, histopathology offers the only source of accurate diagnosis. Morphologic mimics include many benign and malignant soft tissue lesions. Besides a predominant epithelioid component, the lesion can also show a fair share of spindle cells. A circumscribed nodular tumour of low mitotic activity, it often exhibits areas resembling schwannoma or neurofibroma. An awareness of this entity and its varied morphological aspects helps to arrive at the correct diagnosis and hence avoid unnecessary extensive surgical procedures. This case presents features of this benign tumor which occurred in a 47 years old man.

  2. Functional and Molecular Characterization of a Novel Traumatic Peripheral Nerve-Muscle Injury Model.

    Science.gov (United States)

    Wanner, Renate; Gey, Manuel; Abaei, Alireza; Warnecke, Daniela; de Roy, Luisa; Dürselen, Lutz; Rasche, Volker; Knöll, Bernd

    2017-09-01

    Traumatic injuries to human peripheral nerves are frequently associated with damage to nerve surrounding tissues including muscles and blood vessels. Currently, most rodent models of peripheral nerve injuries (e.g., facial or sciatic nerve) employ surgical nerve transection with scissors or scalpels. However, such an isolated surgical nerve injury only mildly damages neighboring tissues and weakly activates an immune response. In order to provide a rodent nerve injury model accounting for such nerve-associated tissue damage and immune cell activation, we developed a drop tower-based facial nerve trauma model in mice. We compare nerve regeneration in this novel peripheral nerve trauma model with the established surgical nerve injury along several parameters. These include gene expression, histological and functional facial motoneuron (FMN) regeneration, facial nerve degeneration, immune cell activation and muscle damage. Regeneration-associated genes (RAGs; e.g., Atf3) were strongly induced in FMNs subjected to traumatic and surgical injury. Regeneration of FMNs and functional recovery of whisker movement were faster in traumatic versus complete surgical injury, thus cutting down experimentation time. Wallerian degeneration of distal nerve stumps was readily observed in this novel trauma injury model. Importantly, drop tower-inflicted facial nerve injury resulted in muscle damage, activation of muscle satellite cell markers (PAX7) and pronounced infiltration of immune cells to the injury site only in this model but not upon surgical nerve transection. Thus, we provide a novel rodent PNS trauma model that can be easily adopted to other PNS nerves such as the sciatic nerve. Since this nerve trauma model replicates multiple tissue damage frequently encountered in clinical routine, it will be well suited to identify molecular and cellular mechanisms of PNS nerve repair in wild-type and genetically modified rodents.

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

    Directory of Open Access Journals (Sweden)

    Guang-yao Liu

    2015-01-01

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

  4. Neuro-otological and peripheral nerve involvement in Fabry disease

    Directory of Open Access Journals (Sweden)

    Sergio Carmona

    2017-07-01

    Full Text Available Fabry disease (FD is an X-linked lysosomal storage disease, with multisystemic glycosphingolipids deposits. Neuro-otological involvement leading to hearing loss and vestibular dysfunctions has been described, but there is limited information about the frequency, site of lesion, or the relationship with peripheral neuropathy. The aim was to evaluate the presence of auditory and vestibular symptoms, and assess neurophysiological involvement of the VIII cranial nerve, correlating these findings with clinical and neurophysiological features of peripheral neuropathy. We studied 36 patients with FD with a complete neurological and neuro-otological evaluation including nerve conduction studies, quantitative sensory testing (to evaluate small fiber by warm and cold threshold detection and cold and heat pain, vestibular evoked myogenic potentials, videonistagmography, audiometry and brainstem auditory evoked potentials. Neuro-otologic symptoms included hearing loss (22.2%, vertigo (27.8% or both (25%. An involvement of either cochlear or vestibular function was identified in most patients (75%. In 70% of our patients the involvement of both cochlear and vestibular function could not be explained by a neural or vascular mechanism. Small fiber neuropathy was identified in 77.7%. There were no significant associations between neurootological and QST abnormalities. Neuro-otologic involvement is frequent and most likely under-recognized in patients with FD. It lacks a specific neural or vascular pattern, suggesting multi-systemic, end organ damage. Small fiber neuropathy is an earlier manifestation of FD, but there is no correlation between the development of neuropathy and neuro-otological abnormalities.

  5. Experimental immunological demyelination enhances regeneration in autograft-repaired long peripheral nerve gaps

    OpenAIRE

    Jun Ge; Shu Zhu; Yafeng Yang; Zhongyang Liu; Xueyu Hu; Liangliang Huang; Xin Quan; Meng Wang; Jinghui Huang; Yunqing Li; Zhuojing Luo

    2016-01-01

    Peripheral nerve long gap defects are a clinical challenge in the regeneration field. Despite the wide variety of surgical techniques and therapies, autografting is the ?gold standard? for peripheral nerve gap reconstruction. The pathological process of Wallerian degeneration from the time of acute injury to efficient regeneration requires several weeks. Regeneration time is critical for nerve reconstruction. Immunological demyelination induced by anti-galactocerebroside antibodies plus guine...

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

    Directory of Open Access Journals (Sweden)

    Pei-xun Zhang

    2015-01-01

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

  7. Dexamethasone as an adjuvant to peripheral nerve block.

    Science.gov (United States)

    Pehora, Carolyne; Pearson, Annabel Me; Kaushal, Alka; Crawford, Mark W; Johnston, Bradley

    2017-11-09

    Peripheral nerve block (infiltration of local anaesthetic around a nerve) is used for anaesthesia or analgesia. A limitation to its use for postoperative analgesia is that the analgesic effect lasts only a few hours, after which moderate to severe pain at the surgical site may result in the need for alternative analgesic therapy. Several adjuvants have been used to prolong the analgesic duration of peripheral nerve block, including perineural or intravenous dexamethasone. To evaluate the comparative efficacy and safety of perineural dexamethasone versus placebo, intravenous dexamethasone versus placebo, and perineural dexamethasone versus intravenous dexamethasone when added to peripheral nerve block for postoperative pain control in people undergoing surgery. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, DARE, Web of Science and Scopus from inception to 25 April 2017. We also searched trial registry databases, Google Scholar and meeting abstracts from the American Society of Anesthesiologists, the Canadian Anesthesiologists' Society, the American Society of Regional Anesthesia, and the European Society of Regional Anaesthesia. We included all randomized controlled trials (RCTs) comparing perineural dexamethasone with placebo, intravenous dexamethasone with placebo, or perineural dexamethasone with intravenous dexamethasone in participants receiving peripheral nerve block for upper or lower limb surgery. We used standard methodological procedures expected by Cochrane. We included 35 trials of 2702 participants aged 15 to 78 years; 33 studies enrolled participants undergoing upper limb surgery and two undergoing lower limb surgery. Risk of bias was low in 13 studies and high/unclear in 22. Perineural dexamethasone versus placeboDuration of sensory block was significantly longer in the perineural dexamethasone group compared with placebo (mean difference (MD) 6.70 hours, 95% confidence interval (CI) 5.54 to 7.85; participants1625

  8. The glucuronyltransferase GlcAT-P is required for stretch growth of peripheral nerves in Drosophila.

    Directory of Open Access Journals (Sweden)

    Rahul Pandey

    Full Text Available 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.

  9. Changes of medium-latency SEP-components following peripheral nerve lesion

    Directory of Open Access Journals (Sweden)

    Straschill Max

    2006-10-01

    Full Text Available Abstract Background Animal studies have demonstrated complex cortical reorganization following peripheral nerve lesion. Central projection fields of intact nerves supplying skin areas which border denervated skin, extended into the deafferentiated cortical representation area. As a consequence of nerve lesions and subsequent reorganization an increase of the somatosensory evoked potentials (SEPs was observed in cats when intact neighbouring nerves were stimulated. An increase of SEP-components of patients with nerve lesions may indicate a similar process of posttraumatic plastic cortical reorganization. Methods To test if a similar process of post-traumatic plastic cortical reorganization does occur in humans, the SEP of intact neighbouring hand nerves were recorded in 29 patients with hand nerve lesions. To hypothetically explain the observed changes of SEP-components, SEP recording following paired stimulation of the median nerve was performed in 12 healthy subjects. Results Surprisingly 16 of the 29 patients (55.2% showed a reduction or elimination of N35, P45 and N60. Patients with lesions of two nerves showed more SEP-changes than patients with a single nerve lesion (85.7%; 6/7 nerves; vs. 34.2%; 13/38 nerves; Fisher's exact test, p Conclusion The results of the present investigation do not provide evidence of collateral innervation of peripherally denervated cortical neurons by neurons of adjacent cortical representation areas. They rather suggest that secondary components of the excitatory response to nerve stimulation are lost in cortical areas, which surround the denervated region.

  10. The Outcomes of Late Term Surgical Treatment of Penetrating Peripheral Nerve Injuries.

    Science.gov (United States)

    Gezercan, Yurdal; Menekşe, Güner; Ökten, Ali İhsan; Arslan, Ali; Özsoy, Kerem Mazhar; Ateş, Tuncay; Çikili, Mustafa; Uysal, İsmail; Olmaz, Burak; Güzel, Aslan

    2016-01-01

    The aim of this retrospective study was to evaluate the follow-up results of patients who received late-term surgical treatment for peripheral nerve lesions caused by penetrating injuries. The study included 25 patients who underwent surgery for peripheral nerve injuries in our clinic between 2007 and 2013. The patients were evaluated with respect to age, gender, etiology of the trauma, the affected nerve, clinical examinations, electrophysiological findings, surgical techniques and functional outcomes. The study included 30 nerves of 25 patients (19 male, 6 female; mean age 30.1 years). The mean time between the initial injury and admission to our clinic was 11.5 months (range, 3 to 30 months). Cuts caused by glass were the most common cause of injury (68.5%). The most commonly injured nerves in our patients were the median nerve (43.4%) and ulnar nerve (26.6%). External neurolysis and decompression were performed in eleven patients, epineurotomy and internal neurolysis were performed in eight patients, epineural repair was performed in fourteen patients, fascicular repair was performed in three patients, and interfascicular anastomosis using sural nerve grafting was performed in five patients. Postoperative motor strength and electrophysiological analyses showed significant improvements. Better outcomes were obtained in cases with median nerve injuries rather than other nerve injuries. Additionally, patients undergoing external neurolysis and decompression exhibited better outcomes than those undergoing other surgical approaches. Although surgical treatment is recommended as early as possible for peripheral nerve injuries, late-term surgical treatments may provide positive outcomes.

  11. MR imaging of benign peripheral nerve sheath tumors

    International Nuclear Information System (INIS)

    Soederlund, V.; Goeranson, H.; Bauer, H.C.F.

    1994-01-01

    In a retrospective, nonblind review of MR imaging of 15 benign peripheral nerve neoplasms in 13 patients, the signal pattern of the tumors (including contrast-enhanced images) and stage were assessed. One lesion was subcutaneous, 9 intramuscular, 2 intermuscular and 3 extracompartmental. One lesion was located to the trunk, 5 to the upper extremity and 9 to the lower. The signal on T1-weighted spin-echo images was homogeneous isointense compared to adjacent muscle in 11 lesions and in 2 slightly hyper- and in 2 slightly hypointense. T2-weighted spin-echo images, acquired in all but one examination, showed a hyperintense signal, homogeneous in 8 and centrally inhomogeneous in 6 lesions. Postcontrast T1-weighted images of 11 lesions, showed a strong signal, with an inhomogeneous enhancement in the center of the lesion similar to that obtained in T2-weighted images. In 2 cases there were signal characteristics indicating bleeding in the tumor. In one lesion both the nonenhanced and contrast-enhanced T1-weighted images showed a hypointense signal in the tumor center suggestive of intramuscular myxoma. All lesions were well delineated without reactive edema. In all cases, anatomic tumor location was correctly assessed. Although the findings were not pathognomonic for neurinoma, MR imaging provided valuable information confirming the clinical and cytologic assessments. (orig.)

  12. Ral Overactivation in Malignant Peripheral Nerve Sheath Tumors▿

    Science.gov (United States)

    Bodempudi, Vidya; Yamoutpoor, Farnaz; Pan, Weihong; Dudek, Arkadiusz Z.; Esfandyari, Tuba; Piedra, Mark; Babovick-Vuksanovic, Dusica; Woo, Richard A.; Mautner, Victor F.; Kluwe, Lan; Clapp, D. Wade; De Vries, George H.; Thomas, Stacey L.; Kurtz, Andreas; Parada, Luis F.; Farassati, Faris

    2009-01-01

    Ras leads an important signaling pathway that is deregulated in neurofibromatosis type 1 and malignant peripheral nerve sheath tumor (MPNST). In this study, we show that overactivation of Ras and many of its downstream effectors occurred in only a fraction of MPNST cell lines. RalA, however, was overactivated in all MPNST cells and tumor samples compared to nontransformed Schwann cells. Silencing Ral or inhibiting it with a dominant-negative Ral (Ral S28N) caused a significant reduction in proliferation, invasiveness, and in vivo tumorigenicity of MPNST cells. Silencing Ral also reduced the expression of epithelial mesenchymal transition markers. Expression of the NF1-GTPase-related domain (NF1-GRD) diminished the levels of Ral activation, implicating a role for neurofibromin in regulating RalA activation. NF1-GRD treatment caused a significant decrease in proliferation, invasiveness, and cell cycle progression, but cell death increased. We propose Ral overactivation as a novel cell signaling abnormality in MPNST that leads to important biological outcomes with translational ramifications. PMID:19414599

  13. Ral overactivation in malignant peripheral nerve sheath tumors.

    Science.gov (United States)

    Bodempudi, Vidya; Yamoutpoor, Farnaz; Pan, Weihong; Dudek, Arkadiusz Z; Esfandyari, Tuba; Piedra, Mark; Babovick-Vuksanovic, Dusica; Woo, Richard A; Mautner, Victor F; Kluwe, Lan; Clapp, D Wade; De Vries, George H; Thomas, Stacey L; Kurtz, Andreas; Parada, Luis F; Farassati, Faris

    2009-07-01

    Ras leads an important signaling pathway that is deregulated in neurofibromatosis type 1 and malignant peripheral nerve sheath tumor (MPNST). In this study, we show that overactivation of Ras and many of its downstream effectors occurred in only a fraction of MPNST cell lines. RalA, however, was overactivated in all MPNST cells and tumor samples compared to nontransformed Schwann cells. Silencing Ral or inhibiting it with a dominant-negative Ral (Ral S28N) caused a significant reduction in proliferation, invasiveness, and in vivo tumorigenicity of MPNST cells. Silencing Ral also reduced the expression of epithelial mesenchymal transition markers. Expression of the NF1-GTPase-related domain (NF1-GRD) diminished the levels of Ral activation, implicating a role for neurofibromin in regulating RalA activation. NF1-GRD treatment caused a significant decrease in proliferation, invasiveness, and cell cycle progression, but cell death increased. We propose Ral overactivation as a novel cell signaling abnormality in MPNST that leads to important biological outcomes with translational ramifications.

  14. Malignant peripheral nerve sheath tumours in inherited disease

    Directory of Open Access Journals (Sweden)

    Evans D

    2012-10-01

    Full Text Available Abstract Background Malignant peripheral nerve sheath tumours (MPNST are rare tumours known to occur at high frequency in neurofibromatosis 1 (NF1, but may also occur in other cancer prone syndromes. Methods The North West Regional Genetic Register covers a population of 4.1 million and was interrogated for incidence of MPNST in 12 cancer prone syndromes. Age, incidence and survival curves were generated for NF1. Results Fifty two of 1254 NF1 patients developed MPNST, with MPNST also occurring in 2/181 cases of schwannomatosis and 2/895 NF2 patients. Three cases were also noted in TP53 mutation carriers. However, there were no cases amongst 5727BRCA1/2 carriers and first degree relatives, 2029 members from Lynch syndrome families, nor amongst 447 Familial Adenomatous Polyposis, 202 Gorlin syndrome, nor 87 vHL cases. Conclusion MPNST is associated with schwannomatosis and TP53 mutations and is confirmed at high frequency in NF1. It appears to be only increased in NF2 amongst those that have been irradiated. The lifetime risk of MPNST in NF1 is between 9–13%.

  15. Ultrasound assessment of peripheral nerve pathology in neurofibromatosis type 1 and 2.

    Science.gov (United States)

    Winter, Natalie; Rattay, Tim W; Axer, Hubertus; Schäffer, Eva; Décard, Bernhard F; Gugel, Isabel; Schuhmann, Martin; Grimm, Alexander

    2017-05-01

    The neurofibromatoses (NF) type 1 and 2 are hereditary tumor predisposition syndromes caused by germline mutations in the NF1 and NF2 tumor suppressor genes. In NF1 and 2, peripheral nerve tumors occur regularly. For further characterizing nerve ultrasound was performed in patients with NF1 and 2. Patients with established diagnosis of NF1 (n=27) and NF2 (n=10) were included. Ultrasound of peripheral nerves and cervical roots was performed during routine follow-up visits. Healthy volunteers were studied for comparison. In patients with NF1, median cross-sectional area (CSA) of most nerves was significantly increased compared to controls and to NF2 due to generalized plexiform tumors, which arose out of multiple fascicles in 23 of 27 patients (85%). These were often accompanied by cutaneous or subcutaneous neurofibromas. In NF2, the overall aspect of peripheral nerves consisted of localized schwannomas (80%) and, apart from that, normal nerve segments. Nerve ultrasound is able to visualize different nerve pathologies in NF1 and NF2. It is a precise and inexpensive screening method for peripheral nerve manifestation in neurofibromatosis and should be considered as the first choice screening imaging modality for all peripheral nerves within reach of non-invasive ultrasound techniques. Ultrasound patterns of peripheral nerve pathologies are described for the first time in a large cohort of patients with NF1 and NF2. It is a suitable screening tool and enables targeted MRI analysis. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  16. Tyrosinase expression in malignant melanoma, desmoplastic melanoma, and peripheral nerve tumors

    DEFF Research Database (Denmark)

    Boyle, Jenny L; Haupt, Helen M; Stern, Jere B

    2002-01-01

    . CONCLUSIONS: Our results support the sensitivity of tyrosinase expression and demonstrate the relative specificity of tyrosinase as a marker for melanocytic lesions, including desmoplastic melanoma, although pigmented peripheral nerve tumors may demonstrate focal positive staining. Immunoreactivity...

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

    KAUST Repository

    Morrison, Brett M.

    2015-01-01

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

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

    Science.gov (United States)

    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 (pinflammation 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.

  19. Novel Therapeutic Development of NF1-Associated Malignant Peripheral Nerve Sheath Tumor (MPNST)

    Science.gov (United States)

    2016-08-01

    Biological Analyses of Malignant Peripheral Nerve Sheath Tumors (MPNST)” 2) Journal article : Prieto-Granada CN, Wiesner T, Messina JL, Jungbluth...benign peripheral nerve sheath tumor , and/or focal S100 protein positivity (ង%) in the absence of other markers . The epithelioid MPNST cases displayed...diffusely S100 protein positive, and 2 of the tumors tested with INI1/SMARCB1 (MPNST54, 58) also showed loss of expression of this marker . Prieto

  20. Traumatic injuries of peripheral nerves: a review with emphasis on surgical indication

    Directory of Open Access Journals (Sweden)

    Roberto Sergio Martins

    2013-10-01

    Full Text Available Traumatic peripheral nerve injury is a dramatic condition present in many of the injuries to the upper and lower extremities. An understanding of its physiopathology and selection of a suitable time for surgery are necessary for proper treatment of this challenging disorder. This article reviews the physiopathology of traumatic peripheral nerve injury, considers the most used classification, and discusses the main aspects of surgical timing and treatment of such a condition.

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

    International Nuclear Information System (INIS)

    Wang Weiwei; Liu Hanqiu

    2013-01-01

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

  2. Neuroactive steroids influence peripheral myelination: a promising opportunity for preventing or treating age-dependent dysfunctions of peripheral nerves.

    Science.gov (United States)

    Melcangi, R C; Azcoitia, I; Ballabio, M; Cavarretta, I; Gonzalez, L C; Leonelli, E; Magnaghi, V; Veiga, S; Garcia-Segura, L M

    2003-09-01

    The process of aging deeply influences morphological and functional parameters of peripheral nerves. The observations summarized here indicate that the deterioration of myelin occurring in the peripheral nerves during aging may be explained by the fall of the levels of the major peripheral myelin proteins [e.g., glycoprotein Po (Po) and peripheral myelin protein 22 (PMP22)]. Neuroactive steroids, such as progesterone (PROG), dihydroprogesterone (5alpha-DH PROG), and tetrahydroprogesterone (3alpha,5alpha-TH PROG), are able to stimulate the low expression of these two myelin proteins present in the sciatic nerve of aged male rats. Since Po and PMP22 play an important physiological role in the maintenance of the multilamellar structure of PNS myelin, we have evaluated the effect of PROG and its neuroactive derivatives, 5alpha-DH PROG and 3alpha,5alpha-TH PROG, on the morphological alterations of myelinated fibers in the sciatic nerve of 22-24-month-old male rats. Data obtained clearly indicate that neuroactive steroids are able to reduce aging-associated morphological abnormalities of myelin and aging-associated myelin fiber loss in the sciatic nerve.

  3. Orientated Guidance of Peripheral Nerve Regeneration Using Conduits with a Microtube Array Sheet (MTAS).

    Science.gov (United States)

    Wang, Yueming; Wang, Wenjin; Wo, Yan; Gui, Ting; Zhu, Hao; Mo, Xiumei; Chen, Chien-Chung; Li, Qingfeng; Ding, Wenlong

    2015-04-29

    Material surface topography has been shown to affect the biological behavior of cells in vitro; however, the in vivo effect on peripheral nerve regeneration has not been explored. Here, we studied the potential of a microtube array sheet (MTAS) with a unique longitudinal surface topography to promote peripheral nerve regeneration efficiency, both in vivo and in vitro. Schwann cells, spinal cord motor neurons, and dorsal root ganglion neurons were seeded on the MTAS to study the effect of the construct on the biological properties and behaviors of neural cells. The MTAS guided the oriented migration of Schwann cells without affecting other critical biological properties, such as proliferation and neurotrophin expression. In addition, the MTAS guided the directed extension of neurites from both types of neurons. Next, we tested the capability of the MTAS to facilitate peripheral nerve regeneration by bridging a 10 mm sciatic nerve defect in rats with a nerve conduit equipped with an MTAS lining. The MTAS significantly promoted peripheral nerve regeneration, as suggested by the greater fiber caliber in the midconduit and the greater abundance of fibers in nerve segment distal to the conduit. Moreover, scanning electron microscopy (SEM) analysis suggested the orientated guidance of nerve regeneration by the MTAS, as indicated by the smaller eccentricity of the nerve fibers and the concordant arrangement of the collagen fiber in both the fibers and the matrix in the MTAS group. Our results collectively suggest that the conduits with the MTAS developed in this study have significant potential for facilitating peripheral nerve regeneration by modifying critical biological behaviors and guiding orientated nerve growth.

  4. Complement inhibition accelerates regeneration in a model of peripheral nerve injury

    NARCIS (Netherlands)

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

    2009-01-01

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

  5. Tumours of peripheral nerves in the upper extremity: a 22-year epidemiological study

    DEFF Research Database (Denmark)

    Sandberg, Kristina; Nilsson, Jessica; Søe Nielsen, Niels

    2009-01-01

    Peripheral nerve tumours are uncommon. Our aims were to calculate the incidence and relative frequencies, to define sites of nerve tumours and to judge preoperative symptoms and outcomes of intervention. The results of 53 patients, with 68 tumours and histopathological diagnoses of true neoplasms...

  6. C6 deficiency does not alter intrinsic regeneration speed after peripheral nerve crush injury

    NARCIS (Netherlands)

    Sta, M.; Cappaert, N. L. M.; Ramekers, D.; Ramaglia, V.; Wadman, W. J.; Baas, F.

    2014-01-01

    Peripheral nerve injury leads to Wallerian degeneration, followed by regeneration, in which functionality and morphology of the nerve are restored. We previously described that deficiency for complement component C6, which prevents formation of the membrane attack complex, slows down degeneration

  7. Regulation of semaphorin III/collapsin-1 gene expression during peripheral nerve regeneration

    NARCIS (Netherlands)

    Pasterkamp, R Jeroen; Giger, Roman J; Verhaagen, J

    1998-01-01

    The competence of neurons to regenerate depends on their ability to initiate a program of gene expression supporting growth and on the growth-permissive properties of glial cells in the distal stump of the injured nerve. Most studies on intrinsic molecular mechanisms governing peripheral nerve

  8. Magnetic resonance imaging of peripheral nerve tumours in the upper extremity

    DEFF Research Database (Denmark)

    Nilsson, Jessica; Sandberg, Kristina; Søe Nielsen, Niels

    2009-01-01

    Clinical assessment and various diagnostic tools, particularly magnetic resonance imaging (MRI), of tumours of peripheral nerves are used to get an accurate diagnosis and to plan surgical intervention. Our purpose was to examine the usefulness of MRI in assessing nerve tumours in the upper...

  9. A novel suture method to place and adjust peripheral nerve catheters

    DEFF Research Database (Denmark)

    Rothe, C.; Steen-Hansen, C.; Madsen, M. H.

    2015-01-01

    We have developed a peripheral nerve catheter, attached to a needle, which works like an adjustable suture. We used in-plane ultrasound guidance to place 45 catheters close to the femoral, saphenous, sciatic and distal tibial nerves in cadaver legs. We displaced catheters after their initial...

  10. A Standardized Method for 4D Ultrasound-Guided Peripheral Nerve Blockade and Catheter Placement

    Directory of Open Access Journals (Sweden)

    N. J. Clendenen

    2014-01-01

    Full Text Available We present a standardized method for using four-dimensional ultrasound (4D US guidance for peripheral nerve blocks. 4D US allows for needle tracking in multiple planes simultaneously and accurate measurement of the local anesthetic volume surrounding the nerve following injection. Additionally, the morphology and proximity of local anesthetic spread around the target nerve is clearly seen with the described technique. This method provides additional spatial information in real time compared to standard two-dimensional ultrasound.

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

    OpenAIRE

    Ping Yao; Peng Li; Jun-jian Jiang; Hong-ye Li

    2018-01-01

    Scar hyperplasia at the suture site is an important reason for hindering the repair effect of peripheral nerve injury anastomosis. To address this issue, two repair methods are often used. Biological agents are used to block nerve sutures and the surrounding tissue to achieve physical anti-adhesion effects. Another agent is glucocorticosteroid, which can prevent scar growth by inhibiting inflammation. However, the overall effect of promoting regeneration of the injured nerve is not satisfacto...

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Usman Ghafoor

    2017-10-01

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

  14. Peripheral nerve injury induces adult brain neurogenesis and remodelling.

    Science.gov (United States)

    Rusanescu, Gabriel; Mao, Jianren

    2017-02-01

    Unilateral peripheral nerve chronic constriction injury (CCI) has been widely used as a research model of human neuropathic pain. Recently, CCI has been shown to induce spinal cord adult neurogenesis, which may contribute to the chronic increase in nociceptive sensitivity. Here, we show that CCI also induces rapid and profound asymmetrical anatomical rearrangements in the adult rodent cerebellum and pons. This remodelling occurs throughout the hindbrain, and in addition to regions involved in pain processing, also affects other sensory modalities. We demonstrate that these anatomical changes, partially reversible in the long term, result from adult neurogenesis. Neurogenic markers Mash1, Ngn2, doublecortin and Notch3 are widely expressed in the rodent cerebellum and pons, both under normal and injured conditions. CCI-induced hindbrain structural plasticity is absent in Notch3 knockout mice, a strain with impaired neuronal differentiation, demonstrating its dependence on adult neurogenesis. Grey matter and white matter structural changes in human brain, as a result of pain, injury or learned behaviours have been previously detected using non-invasive neuroimaging techniques. Because neurogenesis-mediated structural plasticity is thought to be restricted to the hippocampus and the subventricular zone, such anatomical rearrangements in other parts of the brain have been thought to result from neuronal plasticity or glial hypertrophy. Our findings suggest the presence of extensive neurogenesis-based structural plasticity in the adult mammalian brain, which may maintain a memory of basal sensory levels, and act as an adaptive mechanism to changes in sensory inputs. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  15. THREE YEARS STUDY OF SCHWANNOMAS OF PERIPHERAL NERVES

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    Subha Dhua

    2017-02-01

    Full Text Available BACKGROUND In this paper authors present three cases of schwannomas including a case of multiple schwannomas without the features of neurofibromatosis (NF. There was no family history of neurofibromatosis. All the patients underwent surgical excision and improved from the symptomatic lesions. Histopathology confirmed these lesions as schwannomas. The authors recommend surgery for symptomatic lesions. Asymptomatic tumours can be monitored. Regular follow up is essential as they may develop fresh lesions at any time. The relevant literature is discussed. • Malignant transformation of the schwannomas is rare and has poor prognosis. It should be considered in the differential diagnosis of schwannomas. • We should distinguish between “ancient schwannoma” and malignant transformation of schwannoma since treatment and prognosis vary. • Imaging is not entirely reliable in differentiating benign from malignant peripheral nerve tumours. MATERIALS AND METHODS All the patients underwent surgical excision and improved from the symptomatic lesions. Histopathology confirmed these lesions as schwannomas. The authors recommend surgery for symptomatic lesions. RESULTS The histopathological studies confirmed the lesion as Flexi Schwannoma and surgery was considered to be the best option. CONCLUSION Schwannomas and meningiomas are usually benign tumours curable by complete removal. They occur either as single sporadic tumors in otherwise healthy individuals in the fourth to sixth decades of life or as multiple tumours at an early age as part of the autosomal dominant genetic disorder neurofibromatosis 2 (NF2. The hallmark feature of NF2 is bilateral vestibular schwannomas. Multiplicity, a lobular growth pattern, and invasiveness are typical features of NF2 schwannomas. The diagnosis of NF2 is difficult in a group of heterogeneous and poorly defined patients who do not have BVSs but present with other features suggestive of NF2, namely (1 multiple

  16. Auricular vagal nerve stimulation in peripheral arterial disease patients.

    Science.gov (United States)

    Hackl, Gerald; Prenner, Andreas; Jud, Philipp; Hafner, Franz; Rief, Peter; Seinost, Gerald; Pilger, Ernst; Brodmann, Marianne

    2017-10-01

    Auricular nerve stimulation has been proven effective in different diseases. We investigated if a conservative therapeutic alternative for claudication in peripheral arterial occlusive disease (PAD) via electroacupuncture of the outer ear can be established. In this prospective, double-blinded trial an ear acupuncture using an electroacupuncture device was carried out in 40 PAD patients in Fontaine stage IIb. Twenty patients were randomized to the verum group using a fully functional electroacupuncture device, the other 20 patients received a sham device (control group). Per patient, eight cycles (1 cycle = 1 week) of electroacupuncture were performed. The primary endpoint was defined as a significantly more frequent doubling of the absolute walking distance after eight cycles in the verum group compared to controls in a standardized treadmill testing. Secondary endpoints were a significant improvement of the total score of the Walking Impairment Questionnaire (WIQ) as well as improvements in health related quality of life using the Short Form 36 Health Survey (SF-36). There were no differences in baseline characteristics between the two groups. The initial walking distance significantly increased in both groups (verum group [means]: 182 [95 % CI 128-236] meters to 345 [95 % CI 227-463] meters [+ 90 %], p < 0.01; control group [means]: 159 [95 % CI 109-210] meters to 268 [95 % CI 182-366] meters [+ 69 %], p = 0.01). Twelve patients (60 %) in the verum group and five patients (25 %) in controls reached the primary endpoint of doubling walking distance (p = 0.05). The total score of WIQ significantly improved in the verum group (+ 22 %, p = 0.01) but not in controls (+ 8 %, p = 0.56). SF-36 showed significantly improvements in six out of eight categories in the verum group and only in one of eight in controls. Electroacupuncture of the outer ear seems to be an easy-to-use therapeutic option in an age of increasingly invasive and mechanically complex treatments for

  17. State-of-the-Art Techniques in Treating Peripheral Nerve Injury.

    Science.gov (United States)

    Kubiak, Carrie A; Kung, Theodore A; Brown, David L; Cederna, Paul S; Kemp, Stephen W P

    2018-03-01

    Peripheral nerve injuries remain a major clinical concern, as they often lead to chronic disability and significant health care expenditures. Despite advancements in microsurgical techniques to enhance nerve repair, biological approaches are needed to augment nerve regeneration and improve functional outcomes after injury. Presented herein is a review of the current literature on state-of-the-art techniques to enhance functional recovery for patients with nerve injury. Four categories are considered: (1) electroceuticals, (2) nerve guidance conduits, (3) fat grafting, and (4) optogenetics. Significant study results are highlighted, focusing on histologic and functional outcome measures. This review documents the current state of the literature. Advancements in neuronal stimulation, tissue engineering, and cell-based therapies demonstrate promise with regard to augmenting nerve regeneration and appropriate rehabilitation. The future of treating peripheral nerve injury will include multimodality use of electroconductive conduits, fat grafting, neuronal stimulation, and optogenetics. Further clinical investigation is needed to confirm the efficacy of these technologies on peripheral nerve recovery in humans, and how best to implement this treatment for a diverse population of nerve-injured patients.

  18. 4.7-T diffusion tensor imaging of acute traumatic peripheral nerve injury.

    Science.gov (United States)

    Boyer, Richard B; Kelm, Nathaniel D; Riley, D Colton; Sexton, Kevin W; Pollins, Alonda C; Shack, R Bruce; Dortch, Richard D; Nanney, Lillian B; Does, Mark D; Thayer, Wesley P

    2015-09-01

    Diagnosis and management of peripheral nerve injury is complicated by the inability to assess microstructural features of injured nerve fibers via clinical examination and electrophysiology. Diffusion tensor imaging (DTI) has been shown to accurately detect nerve injury and regeneration in crush models of peripheral nerve injury, but no prior studies have been conducted on nerve transection, a surgical emergency that can lead to permanent weakness or paralysis. Acute sciatic nerve injuries were performed microsurgically to produce multiple grades of nerve transection in rats that were harvested 1 hour after surgery. High-resolution diffusion tensor images from ex vivo sciatic nerves were obtained using diffusion-weighted spin-echo acquisitions at 4.7 T. Fractional anisotropy was significantly reduced at the injury sites of transected rats compared with sham rats. Additionally, minor eigenvalues and radial diffusivity were profoundly elevated at all injury sites and were negatively correlated to the degree of injury. Diffusion tensor tractography showed discontinuities at all injury sites and significantly reduced continuous tract counts. These findings demonstrate that high-resolution DTI is a promising tool for acute diagnosis and grading of traumatic peripheral nerve injuries.

  19. Ultrasonographic evaluation of the iatrogenic peripheral nerve injuries in upper extremity

    Energy Technology Data Exchange (ETDEWEB)

    Karabay, Nuri [Department of Radiology, Hand and Microsurgery and Orthopaedics and Traumatology (EMOT) Hospital, 1418 Sok. No: 14 Kahramanlar, 35230 Izmir (Turkey)], E-mail: nurikarabay@gmail.com; Toros, Tulgar [Department of Orthopaedics and Traumatology, Hand and Microsurgery and Orthopaedics and Traumatology (EMOT) Hospital, 1418 Sok. No: 14 Kahramanlar, 35230 Izmir (Turkey)], E-mail: tulgartoros@yahoo.com; Ademoglu, Yalcin [Department of Orthopaedics and Traumatology, Hand and Microsurgery and Orthopaedics and Traumatology (EMOT) Hospital, 1418 Sok. No: 14 Kahramanlar, 35230 Izmir (Turkey)], E-mail: yalcinademoglu@yahoo.com; Ada, Sait [Department of Orthopaedics and Traumatology, Hand and Microsurgery and Orthopaedics and Traumatology (EMOT) Hospital, 1418 Sok. No: 14 Kahramanlar, 35230 Izmir (Turkey)], E-mail: sait_ada@yahoo.com

    2010-02-15

    The aim of our study is to assess the efficiency of the ultrasonography (US) in the diagnosis of peripheral nerve injury. This study includes nine patients (six radial, one median and two posterior interosseous (PIO) nerves) with peripheral nerve injury diagnosed by clinical and electrophysiological methods in the last 3 years. Preoperatively, an ultrasonographic examination was performed and correlated with physical exam and surgical findings. Five patients, who were diagnosed as peripheral nerve transection by US, underwent surgery. The ultrasonographic findings were concordant with the intraoperative findings. Axonal swelling alone was found in the remaining three patients, who were treated conservatively because of preserved nerve continuity without display of nerve compression. In one patient, we were unable to visualize the nerve due to obesity and soft tissue edema. High-resolution US provide morphological information about the exact location, intensity and extent of the nerve injuries, facilitating the preoperative diagnosis. Thus, US may be a useful method for planning optimal treatment strategy in especially iatrogenic nerve injuries.

  20. 4.7-T diffusion tensor imaging of acute traumatic peripheral nerve injury

    Science.gov (United States)

    Boyer, Richard B.; Kelm, Nathaniel D.; Riley, D. Colton; Sexton, Kevin W.; Pollins, Alonda C.; Shack, R. Bruce; Dortch, Richard D.; Nanney, Lillian B.; Does, Mark D.; Thayer, Wesley P.

    2015-01-01

    Diagnosis and management of peripheral nerve injury is complicated by the inability to assess microstructural features of injured nerve fibers via clinical examination and electrophysiology. Diffusion tensor imaging (DTI) has been shown to accurately detect nerve injury and regeneration in crush models of peripheral nerve injury, but no prior studies have been conducted on nerve transection, a surgical emergency that can lead to permanent weakness or paralysis. Acute sciatic nerve injuries were performed microsurgically to produce multiple grades of nerve transection in rats that were harvested 1 hour after surgery. High-resolution diffusion tensor images from ex vivo sciatic nerves were obtained using diffusion-weighted spin-echo acquisitions at 4.7 T. Fractional anisotropy was significantly reduced at the injury sites of transected rats compared with sham rats. Additionally, minor eigenvalues and radial diffusivity were profoundly elevated at all injury sites and were negatively correlated to the degree of injury. Diffusion tensor tractography showed discontinuities at all injury sites and significantly reduced continuous tract counts. These findings demonstrate that high-resolution DTI is a promising tool for acute diagnosis and grading of traumatic peripheral nerve injuries. PMID:26323827

  1. High-resolution ultrasound in combat-related peripheral nerve injuries.

    Science.gov (United States)

    Smith, Jonathan K; Miller, Matthew E; Carroll, Craig G; Faillace, Walter J; Nesti, Leon J; Cawley, Christina M; Landau, Mark E

    2016-12-01

    Peripheral nerve injuries (PNI) sustained in combat are typically severe and are frequently associated with marked soft tissue damage, anatomic distortion, and retained metallic fragments. These features complicate clinical and electrodiagnostic assessment and may preclude MRI. We describe 4 cases of military personnel who sustained high-velocity gunshot wounds or blasts with metal fragment injuries in which high resolution peripheral nerve ultrasound (US) proved beneficial. In these cases, the clinical and electrodiagnostic exams provided inadequate localization and severity data of the nerve injuries, and MRI was either precluded or provided no additional information. In each case, US disclosed focal nerve segment abnormalities, including regions of focal enlargement and nerve discontinuity with end-bulb neuroma, which guided surgical planning for nerve repair. The findings on US were subsequently confirmed intra-operatively. High resolution peripheral nerve US is a useful modality in assessment of combat-related PNI. Muscle Nerve, 2016 Muscle Nerve 54: 1139-1144, 2016. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

  2. Parkinson disease affects peripheral sensory nerves in the pharynx.

    Science.gov (United States)

    Mu, Liancai; Sobotka, Stanislaw; Chen, Jingming; Su, Hungxi; Sanders, Ira; Nyirenda, Themba; Adler, Charles H; Shill, Holly A; Caviness, John N; Samanta, Johan E; Sue, Lucia I; Beach, Thomas G

    2013-07-01

    Dysphagia is very common in patients with Parkinson disease (PD) and often leads to aspiration pneumonia, the most common cause of death in PD. Current therapies are largely ineffective for dysphagia. Because pharyngeal sensation normally triggers the swallowing reflex, we examined pharyngeal sensory nerves in PD patients for Lewy pathology.Sensory nerves supplying the pharynx were excised from autopsied pharynges obtained from patients with clinically diagnosed and neuropathologically confirmed PD (n = 10) and healthy age-matched controls (n = 4). We examined the glossopharyngeal nerve (cranial nerve IX), the pharyngeal sensory branch of the vagus nerve (PSB-X), and the internal superior laryngeal nerve (ISLN) innervating the laryngopharynx. Immunohistochemistry for phosphorylated α-synuclein was used to detect Lewy pathology. Axonal α-synuclein aggregates in the pharyngeal sensory nerves were identified in all of the PD subjects but not in the controls. The density of α-synuclein-positive lesions was greater in PD patients with dysphagia versus those without dysphagia. In addition, α-synuclein-immunoreactive nerve fibers in the ISLN were much more abundant than those in cranial nerve IX and PSB-X. These findings suggest that pharyngeal sensory nerves are directly affected by pathologic processes in PD. These abnormalities may decrease pharyngeal sensation, thereby impairing swallowing and airway protective reflexes and contributing to dysphagia and aspiration.

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

    Science.gov (United States)

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

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Ilvana Hasanbegovic

    2013-12-01

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

  5. Organization of peripheral nerves and spinal roots of the Atlantic stingray, Dasyatis sabina.

    Science.gov (United States)

    Coggeshall, R E; Leonard, R B; Applebaum, M L; Willis, W D

    1978-01-01

    1. The sizes and numbers of axons in peripheral nerves and spinal roots were investigated in the stingray, Dasyatis sabina. 2. The axons of the dorsal and ventral roots do not mingle in peripheral nerves of this animal as they do in higher vertebrates. Thus, it was usually possible to split the peripheral nerve into two portions, one containing only dorsal root axons, the other containing only ventral root axons. This feature was useful for the analysis of certain aspects of spinal cord organization. 3. The fact that dorsal and ventral root axons were segregated in peripheral nerves enabled us to demonstrate, without experimental surgery, that the central processes of the dorsal root ganglion cells and the proximal ventral root axons were 10-20% narrower, on the average, than the distal processes of the same dorsal root ganglion cells or the distal parts of the same ventral root axons. 4. The stingray is remarkable in having very few unmyelinated axons in the dorsal roots, ventral roots, or peripheral nerves. This paucity of unmyelinated axons distinguishes the Atlantic stingrays from all other vertebrates whose roots and nerves have been examined for unmyelinated fibers. 5. Similar findings were obtained for one spotted eagle ray (Aetobatus narinari) and two cow-nose rays (Rhinoptera bonasus).

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

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    Lin Wang

    2015-01-01

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

  7. Roles of neural stem cells in the repair of peripheral nerve injury.

    Science.gov (United States)

    Wang, Chong; Lu, Chang-Feng; Peng, Jiang; Hu, Cheng-Dong; Wang, Yu

    2017-12-01

    Currently, researchers are using neural stem cell transplantation to promote regeneration after peripheral nerve injury, as neural stem cells play an important role in peripheral nerve injury repair. This article reviews recent research progress of the role of neural stem cells in the repair of peripheral nerve injury. Neural stem cells can not only differentiate into neurons, astrocytes and oligodendrocytes, but can also differentiate into Schwann-like cells, which promote neurite outgrowth around the injury. Transplanted neural stem cells can differentiate into motor neurons that innervate muscles and promote the recovery of neurological function. To promote the repair of peripheral nerve injury, neural stem cells secrete various neurotrophic factors, including brain-derived neurotrophic factor, fibroblast growth factor, nerve growth factor, insulin-like growth factor and hepatocyte growth factor. In addition, neural stem cells also promote regeneration of the axonal myelin sheath, angiogenesis, and immune regulation. It can be concluded that neural stem cells promote the repair of peripheral nerve injury through a variety of ways.

  8. A 3D-engineered porous conduit for peripheral nerve repair.

    Science.gov (United States)

    Tao, Jie; Hu, Yu; Wang, Shujuan; Zhang, Jiumeng; Liu, Xuan; Gou, Zhiyuan; Cheng, Hao; Liu, Qianqi; Zhang, Qianqian; You, Shenglan; Gou, Maling

    2017-04-12

    End-to-end neurorrhaphy is the most commonly used method for treating peripheral nerve injury. However, only 50% of patients can regain useful function after treating with neurorrhaphy. Here, we constructed a 3D-engineered porous conduit to promote the function recovery of the transected peripheral nerve after neurorrhaphy. The conduit that consisted of a gelatin cryogel was prepared by molding with 3D-printed moulds. Due to its porous structure and excellent mechanical properties, this conduit could be collapsed by the mechanical force and resumed its original shape after absorption of normal saline. This shape-memory property allowed a simply surgery process for installing the conduits. Moreover, the biodegradable conduit could prevent the infiltration of fibroblasts and reduce the risk of scar tissue, which could provide an advantageous environment for nerve regeneration. The efficiency of the conduits in assisting peripheral nerve regeneration after neurorrhaphy was evaluated in a rat sciatic nerve transected model. Results indicated that conduits significantly benefitted the recovery of the transected peripheral nerve after end-to-end neurorrhaphy on the static sciatic index (SSI), electrophysiological results and the re-innervation of the gastrocnemius muscle. This work demonstrates a biodegradable nerve conduit that has potentially clinical application in promoting the neurorrhaphy.

  9. Amniotic mesenchymal stem cells display neurovascular tropism and aid in the recovery of injured peripheral nerves.

    Science.gov (United States)

    Li, YongNan; Guo, Longzhe; Ahn, Hyun Sook; Kim, Moo Hyun; Kim, Sung-Whan

    2014-06-01

    Recently, we reported that human amniotic membrane-derived mesenchymal stem cells (AMMs) possess great angiogenic potential. In this study, we determined whether local injection of AMMs ameliorates peripheral neuropathy. AMMs were transplanted into injured sciatic nerves. AMM injection promoted significant recovery of motor nerve conduction velocity and voltage amplitude compared to human adipose-derived mesenchymal stem cells. AMM implantation also augmented blood perfusion and increased intraneural vascularity. Whole-mount fluorescent imaging analysis demonstrated that AMMs exhibited higher engraftment and endothelial incorporation abilities in the sciatic nerve. In addition, the higher expression of pro-angiogenic factors was detected in AMMs injected into the peripheral nerve. Therefore, these data provide novel therapeutic and mechanistic insights into stem cell biology, and AMM transplantation may represent an alternative therapeutic option for treating peripheral neuropathy. © 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  10. Enhancing Peripheral Nerve Regeneration with a Novel Drug-Delivering Nerve Conduit

    Science.gov (United States)

    2015-10-01

    NGF) and glial cell line-derived neurotrophic factor (GDNF) for at least 30 days to improve rate of nerve regeneration. We have successfully...deliver nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF) for at least 30 days to improve the nerve regeneration. The...regeneration, nerve conduits, autograft, drug delivery device, nerve growth factor, glial cell line-derived neutrophic factor, polytetrafluoroethylene

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

    Directory of Open Access Journals (Sweden)

    Chiung-Chyi Shen

    2013-01-01

    Full Text Available 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.

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

    Science.gov (United States)

    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

  13. Peripheral Nerve Repair with Cultured Schwann Cells: Getting Closer to the Clinics

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    Maria Carolina O. Rodrigues

    2012-01-01

    Full Text Available Peripheral nerve injuries are a frequent and disabling condition, which affects 13 to 23 per 100.000 persons each year. Severe cases, with structural disruption of the nerve, are associated with poor functional recovery. The experimental treatment using nerve grafts to replace damaged or shortened axons is limited by technical difficulties, invasiveness, and mediocre results. Other therapeutic choices include the adjunctive application of cultured Schwann cells and nerve conduits to guide axonal growth. The bone marrow is a rich source of mesenchymal cells, which can be differentiated in vitro into Schwann cells and subsequently engrafted into the damaged nerve. Alternatively, undifferentiated bone marrow mesenchymal cells can be associated with nerve conduits and afterward transplanted. Experimental studies provide evidence of functional, histological, and electromyographical improvement following transplantation of bone-marrow-derived cells in animal models of peripheral nerve injury. This paper focuses on this new therapeutic approach highlighting its direct translational and clinical utility in promoting regeneration of not only acute but perhaps also chronic cases of peripheral nerve damage.

  14. Ischemic preconditioning reduces the severity of ischemia-reperfusion injury of peripheral nerve in rats

    Directory of Open Access Journals (Sweden)

    Kurutas Ergul

    2006-09-01

    Full Text Available Abstract Background and aim Allow for protection of briefly ischemic tissues against the harmful effects of subsequent prolonged ischemia is a phenomennon called as Ischemic Preconditioning (IP. IP has not been studied in ischemia-reperfusion (I/R model of peripheral nerve before. We aimed to study the effects of acute IP on I/R injury of peripheral nerve in rats. Method 70 adult male rats were randomly divided into 5 groups in part 1 experimentation and 3 groups in part 2 experimentation. A rat model of severe nerve ischemia which was produced by tying iliac arteries and all idenfiable anastomotic vessels with a silk suture (6-0 was used to study the effects of I/R and IP on nerve biochemistry. The suture technique used was a slip-knot technique for rapid release at time of reperfusion in the study. Cytoplasmic vacuolar degeneration was also histopathologically evaluated by light microscopic examination in sciatic nerves of rats at 7th day in part 2 study. Results 3 hours of Reperfusion resulted in an increase in nerve malondialdehyde levels when compared with ischemia and non-ischemia groups (p 0.05. There was also a significant decrease in vacoular degeneration of sciatic nerves in IP group than I/R group (p Conclusion IP reduces the severity of I/R injury in peripheral nerve as shown by reduced tissue MDA levels at 3 th hour of reperfusion and axonal vacoulization at 7 th postischemic day.

  15. Brain injury in combination with tacrolimus promotes the regeneration of injured peripheral nerves

    Directory of Open Access Journals (Sweden)

    Xin-ze He

    2017-01-01

    Full Text Available Both brain injury and tacrolimus have been reported to promote the regeneration of injured peripheral nerves. In this study, before transection of rat sciatic nerve, moderate brain contusion was (or was not induced. After sciatic nerve injury, tacrolimus, an immunosuppressant, was (or was not intraperitoneally administered. At 4, 8 and 12 weeks after surgery, Masson's trichrome, hematoxylin-eosin, and toluidine blue staining results revealed that brain injury or tacrolimus alone or their combination alleviated gastrocnemius muscle atrophy and sciatic nerve fiber impairment on the experimental side, simultaneously improved sciatic nerve function, and increased gastrocnemius muscle wet weight on the experimental side. At 8 and 12 weeks after surgery, brain injury induction and/or tacrolimus treatment increased action potential amplitude in the sciatic nerve trunk. Horseradish peroxidase retrograde tracing revealed that the number of horseradish peroxidase-positive neurons in the anterior horn of the spinal cord was greatly increased. Brain injury in combination with tacrolimus exhibited better effects on repair of injured peripheral nerves than brain injury or tacrolimus alone. This result suggests that brain injury in combination with tacrolimus promotes repair of peripheral nerve injury.

  16. Nerve injuries associated with supracondylar fractures of the humerus in children: our experience in a specialist peripheral nerve injury unit.

    Science.gov (United States)

    Kwok, I H Y; Silk, Z M; Quick, T J; Sinisi, M; MacQuillan, A; Fox, M

    2016-06-01

    We aimed to identify the pattern of nerve injury associated with paediatric supracondylar fractures of the humerus. Over a 17 year period, between 1996 and 2012, 166 children were referred to our specialist peripheral nerve injury unit. From examination of the medical records and radiographs were recorded the nature of the fracture, associated vascular and neurological injury, treatment provided and clinical course. Of the 166 patients (111 male, 55 female; mean age at time of injury was seven years (standard deviation 2.2)), 26 (15.7%) had neurological dysfunction in two or more nerves. The injury pattern in the 196 affected nerves showed that the most commonly affected nerve was the ulnar nerve (43.4%), followed by the median (36.7%) and radial (19.9%) nerves. A non-degenerative injury was seen in 27.5%, whilst 67.9% were degenerative in nature. Surgical exploration of the nerves was undertaken in 94 (56.6%) children. The mean follow-up time was 12.8 months and 156 (94%) patients had an excellent or good clinical outcome according to the grading of Birch, Bonney and Parry. Following paediatric supracondylar fractures we recommend prompt referral to a specialist unit in the presence of complete nerve palsy, a positive Tinel's sign, neuropathic pain or vascular compromise, for consideration of nerve exploration. When managed appropriately, nerve recovery and clinical outcomes for this paediatric population are extremely favourable. Cite this article: Bone Joint J 2016;98-B:851-6. ©2016 The British Editorial Society of Bone & Joint Surgery.

  17. Silicone Molding and Lifetime Testing of Peripheral Nerve Interfaces for Neuroprostheses

    Energy Technology Data Exchange (ETDEWEB)

    Gupte, Kimaya [Case Western Reserve Univ., Cleveland, OH (United States). Dept. of Biomedical Engineering; Tolosa, Vanessa [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States). Center for Micro- and Nanotechnology

    2016-08-10

    Implantable peripheral nerve cuffs have a large application in neuroprostheses as they can be used to restore sensation to those with upper limb amputations. Modern day prosthetics, while lessening the pain associated with phantom limb syndrome, have limited fine motor control and do not provide sensory feedback to patients. Sensory feedback with prosthetics requires communication between the nervous system and limbs, and is still a challenge to accomplish with amputees. Establishing this communication between the peripheral nerves in the arm and artificial limbs is vital as prosthetics research aims to provide sensory feedback to amputees. Peripheral nerve cuffs restore sensation by electrically stimulating certain parts of the nerve in order to create feeling in the hand. Cuff electrodes have an advantage over standard electrodes as they have high selective stimulation by bringing the electrical interface close to the neural tissue in order to selectively activate targeted regions of a peripheral nerve. In order to further improve the selective stimulation of these nerve cuffs, there is need for finer spatial resolution among electrodes. One method to achieve a higher spatial resolution is to increase the electrode density on the cuff itself. Microfabrication techniques can be used to achieve this higher electrode density. Using L-Edit, a layout editor, microfabricated peripheral nerve cuffs were designed with a higher electrode density than the current model. This increase in electrode density translates to an increase in spatial resolution by at least one order of magnitude. Microfabricated devices also have two separate components that are necessary to understand before implantation: lifetime of the device and assembly to prevent nerve damage. Silicone molding procedures were optimized so that devices do not damage nerves in vivo, and lifetime testing was performed on test microfabricated devices to determine their lifetime in vivo. Future work of this project

  18. Peripheral origins and functional characteristics of vibration-sensitive VIIIth nerve fibers in the frog Rana temporaria

    DEFF Research Database (Denmark)

    Jøgensen, Morten Buhl; Christensen-Dalsgaard, Jakob

    1991-01-01

    1) The peripheral origins of vibration-sensitive VIIIth nerve fibers in European grassfrogs (Rana temporaria) were investigated by recording from individual nerve branchlets within the inner ear. Furthermore, the fibers' responses to both pulsed and continuous, dorsoventral, sinusoidal vibrations...

  19. Optical detection of the brachial plexus for peripheral nerve blocks: an in vivo swine study.

    Science.gov (United States)

    Brynolf, Marcus; Sommer, Micha; Desjardins, Adrien E; van der Voort, Marjolein; Roggeveen, Stefan; Bierhoff, Walter; Hendriks, Benno H W; Rathmell, James P; Kessels, Alfons G H; Söderman, Michael; Holmström, Björn

    2011-01-01

    Accurate identification of nerves is critical to ensure safe and effective delivery of regional anesthesia during peripheral nerve blocks. Nerve stimulation is commonly used, but it is not perfect. Even when nerve stimulation is performed in conjunction with ultrasound guidance, determining when the needle tip is at the nerve target region can be challenging. In this in vivo pilot study, we investigated whether close proximity to the brachial plexus and penetration of the axillary artery can be identified with optical reflectance spectroscopy, using a custom needle stylet with integrated optical fibers. Ultrasound-guided insertions to place the needle tip near the brachial plexus at the axillary level were performed at multiple locations in 2 swine, with the stylet positioned in the cannula of a 20-gauge stimulation needle. During each insertion, optical reflectance spectra were acquired with the needle tip in skeletal muscle, at the surface of muscle fascia, and at the nerve target region; confirmation of the final needle position was provided by nerve stimulation. In addition, an insertion to the lumen of the axillary artery was performed in a third swine. Differences in the spectra were quantified with lipid and hemoglobin parameters that provide contrast for optical absorption by the respective chromophores. The transition of the needle tip from skeletal muscle to the nerve target region was associated with higher lipid parameter values (P ultrasound imaging, and it could potentially allow for reliable identification of the injection site during peripheral nerve blocks.

  20. A multi-walled silk fibroin/silk sericin nerve conduit coated with poly(lactic-co-glycolic acid) sheath for peripheral nerve regeneration.

    Science.gov (United States)

    Rao, Jianwei; Cheng, Yan; Liu, Yanxiao; Ye, Zhou; Zhan, Beilei; Quan, Daping; Xu, Yangbin

    2017-04-01

    The linearly oriented multi-walled silk fibroin/silk sericin (SF/SS) nerve conduits (NCs) can provide physical cues similar to native peripheral nerve fasciculi, but the mechanical properties of which are not excellent enough. In this study, NCs with a novel and bionic design with dual structures were developed. The important features of our NCs is that the internal skeleton (the multi-walled SF/SS conduits) has a bionic structure similar to the architecture of native peripheral nerve fasciculi, which is beneficial for nerve regeneration, and the outer sheath (the hollow poly(lactic-co-glycolic acid) [PLGA] conduits) could provide strong mechanical protection for the internal skeleton. The linearly oriented multi-walled SF/SS conduit was fabricated and inserted in the hollow PLGA sheath lumen and then used for the bridge across the sciatic nerve defect in rats. The outcome of the peripheral nerve repair post implantation was evaluated. The functional and morphological parameters were examined and showed that the novel PLGA-coated SF/SS NCs could promote peripheral nerve regeneration, approaching those elicited by nerve autografts that are the first candidate for repair of peripheral nerve defects. Thus, these updated NCs have potential usefulness to enhance functional recovery after repair of peripheral nerve defect. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Evaluation of peripheral nerve regeneration through biomaterial conduits via micro-CT imaging.

    Science.gov (United States)

    Pixley, Sarah K; Hopkins, Tracy M; Little, Kevin J; Hom, David B

    2016-12-01

    Hollow nerve conduits made of natural or synthetic biomaterials are used clinically to aid regeneration of peripheral nerves damaged by trauma or disease. To support healing, conduit lumen patency must be maintained until recovery occurs. New methods to study conduit structural integrity would provide an important means to optimize conduits in preclinical studies. We explored a novel combined technique to examine structural integrity of two types of nerve conduits after in vivo healing. Micro-CT imaging with iodine contrast was combined with histological analysis to examine two different nerve conduits after in vivo nerve reconstruction in rats. Sciatic nerve gaps in adult Lewis rats were reconstructed with poly(caprolactone) (PCL, 1.6 cm gap, 14-week survival) or silicone (1 cm gap, 6-week survival) conduits (N = 12 total). Conduits with regenerating tissues were imaged by micro-CT with iodine contrast and compared to the histology (hematoxylin and eosin, immunostaining for axons) of regenerated tissues after iodine removal. PCL nerve conduits showed extensive breakage throughout their length, but all showed successful nerve growth through the conduits. The silicone conduits remained intact, although significant constriction was uniquely detected by micro-CT, with 1 of 6 animals showing incomplete tissue regeneration. Micro-CT with iodine contrast offers a unique and valuable means to determine 3D structural integrity of nerve conduits and nerve healing following reconstruction. Furthermore, this paper shows that even if conduit compression and degradation occur, nerve regeneration can still take place.

  2. Peripheral nerve changes assessed by conduction velocity distribution in patients with primary Raynaud's phenomenon and dysautonomia.

    Science.gov (United States)

    Koszewicz, M; Gosk-Bierska, I; Jerzy, G; Bilińska, M; Podemski, R; Budrewicz, S; Adamiec, R

    2011-08-01

    Different mechanisms (neural and intravascular) are thought to be important in the pathogenesis of Raynaud's phenomenon (RP). In a previous study we confirmed autonomic nervous system impairment in patients with primary RP, but the pathogenic role of peripheral nerves remained unclear. The aim of the current study was an electrophysiological analysis of peripheral nerves using both standard conduction velocity and the conduction velocity distribution (CVD) in patients with primary RP in order to investigate the causes of dysautonomia. We examined 34 patients with primary RP and dysautonomia and 31 sex- and age-matched controls. Standard motor and sensory conduction tests in ulnar and peroneal (sural) nerves and a CVD test in the same nerves were performed. Clinically, none of the patients had motor symptoms, while 35.3% of them presented sensory neuropathy. Standard neurographic tests were within the normal limits except for the significant prolongation of mean sensory latency in both examined nerves. CVD revealed significant slowing of motor conduction velocity in all the conduction values, e.g. in the 10th, 50th, and 90th percentiles of velocity. There were no differences in the width of the velocity distribution in the patient group and controls. The results of CVD indicated the presence of generalized subclinical peripheral motor nerve impairment (subclinical polyneuropathy) in patients with primary RP and dysautonomia. Based on the present and previous studies, we conclude that the mechanism of autonomic dysfunction in primary RP is mixed, resulting from both central and peripheral neural abnormalities.

  3. A Rare Malignant Peripheral Nerve Sheath Tumor of the Maxilla Mimicking a Periapical Lesion

    Directory of Open Access Journals (Sweden)

    José Alcides Arruda

    2016-01-01

    Full Text Available Malignant peripheral nerve sheath tumor is a malignant neoplasm that is rarely found in the oral cavity. About 50% of this tumor occurs in patients with neurofibromatosis type I and comprises approximately 10% of all soft tissue sarcomas of head and neck region. Intraosseous malignant peripheral nerve sheath tumor of the maxilla is rare. This article is the first to address malignant peripheral nerve sheath tumor of the maxilla presenting as a periapical radiolucency on nonvital endodontically treated teeth in the English medical literature. Surgical approaches to malignant soft tissue tumor vary based on the extent of the disease, age of the patient, and pathological findings. A rare case of intraosseous malignant peripheral nerve sheath tumor is reported in a 16-year-old woman. The patient presented clinically with a pain involving the upper left incisors region and with defined unilocular periapical radiolucency lesion involved between the upper left incisors. An incisional biopsy was made. Histological and immunohistochemical examination were positive for S-100 protein and glial fibrillary acidic protein showed that the lesion was an intraosseous malignant peripheral nerve sheath tumor of the maxilla. Nine years after the surgery, no regional recurrence was observed.

  4. Omega-3 polyunsaturated fatty acid supplementation for improving peripheral nerve health: protocol for a systematic review.

    Science.gov (United States)

    Zhang, Alexis Ceecee; MacIsaac, Richard J; Roberts, Leslie; Kamel, Jordan; Craig, Jennifer P; Busija, Lucy; Downie, Laura E

    2018-03-25

    Damage to peripheral nerves occurs in a variety of health conditions. Preserving nerve integrity, to prevent progressive nerve damage, remains a clinical challenge. Omega-3 polyunsaturated fatty acids (PUFAs) are implicated in the development and maintenance of healthy nerves and may be beneficial for promoting peripheral nerve health. The aim of this systematic review is to assess the effects of oral omega-3 PUFA supplementation on peripheral nerve integrity, including both subjective and objective measures of peripheral nerve structure and/or function. A systematic review of randomised controlled trials that have evaluated the effects of omega-3 PUFA supplementation on peripheral nerve assessments will be conducted. Comprehensive electronic database searches will be performed in Ovid MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), US National Institutes of Health Clinical Trials Registry and the WHO International Clinical Trials Registry Platform. The title, abstract and keywords of identified articles will be assessed for eligibility by two reviewers. Full-text articles will be obtained for all studies judged as eligible or potentially eligible; these studies will be independently assessed by two reviewers to determine eligibility. Disagreements will be resolved by consensus. Risk of bias assessment will be performed using the Cochrane Collaboration risk of bias tool to appraise the quality of included studies. If clinically meaningful, and there are a sufficient number of eligible studies, a meta-analysis will be conducted and a summary of findings table will be provided. This is a systematic review that will involve the analysis of previously published data, and therefore ethics approval is not required. A manuscript reporting the results of this systematic review will be published in a peer-reviewed journal and may also be presented at relevant scientific conferences. CRD42018086297. © Article author(s) (or their employer

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

    Directory of Open Access Journals (Sweden)

    Berta Kowalska

    2013-03-01

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

  6. Bedside Optic Nerve Sheath Diameter Assessment in the Identification of Increased Intracranial Pressure in Suspected Idiopathic Intracranial Hypertension.

    Science.gov (United States)

    Irazuzta, Jose E; Brown, Martha E; Akhtar, Javed

    2016-01-01

    We determined whether the bedside assessment of the optic nerve sheath diameter could identify elevated intracranial pressure in individuals with suspected idiopathic intracranial hypertension. This was a single-center, prospective, rater-blinded study performed in a freestanding pediatric teaching hospital. Patients aged 12 to 18 years scheduled for an elective lumbar puncture with the suspicion of idiopathic intracranial hypertension were eligible to participate. Optic nerve sheath diameter was measured via ultrasonography before performing a sedated lumbar puncture for measuring cerebrospinal fluid opening pressure. Abnormal measurements were predefined as optic nerve sheath diameter ≥4.5 mm and a cerebrospinal fluid opening pressure greater than 20 cmH2O. Thirteen patients participated in the study, 10 of whom had elevated intracranial pressure. Optic nerve sheath diameter was able to predict or rule out elevated intracranial pressure in all patients. Noninvasive assessment of the optic nerve sheath diameter could help to identify patients with elevated intracranial pressure when idiopathic intracranial hypertension is suspected. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    DEFF Research Database (Denmark)

    Moldovan, Mihai; Sørensen, Jesper; Krarup, Christian

    2006-01-01

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

  8. Multicenter Clinical Trial of Keratin Biomaterial for Peripheral Nerve Regeneration

    Science.gov (United States)

    2012-10-01

    the issues associated w ith the use of autografts, nerve gui dance conduits have been developed to bridge the gap between the trans ected nerve ends...Biomaterial Hydrogel" Western North Carolina Society for Neuroscience : Winston-Salem, NC 11/2011; North Carolina Tissue Engineering and Regenerative...Technology Applications for Combat Casualty Care: St. Pete Beach, FL 8/2010; Society for Neuroscience : San Diego, CA 11/2010; Tissue Engineering and

  9. The clinical, electrophysiologic, and surgical characteristics of peripheral nerve injuries caused by gunshot wounds in adults: a 40-year experience.

    Science.gov (United States)

    Secer, Halil Ibrahim; Daneyemez, Mehmet; Tehli, Ozkan; Gonul, Engin; Izci, Yusuf

    2008-02-01

    There are few large-volume studies on the repair of peripheral nerve lesions caused by gunshot wounds. In this study, the results of peripheral nerve repair are analyzed, and the factors influencing the outcome are investigated. During a 40-year period, 2210 peripheral nerve lesions in 2106 patients who sustained gunshot injury were treated surgically in the Department of Neurosurgery. One thousand thirty-four patients had shrapnel injury, and 1072 patients had missile injury. Twelve peripheral nerves were included in this study, and all of them were repaired by direct suture, using nerve graft, or neurolysis. All patients underwent neurologic and electrophysiologic evaluations in the preoperative period and postoperatively at the end of the follow-up period. The mean time of follow-up was 2.6 years. Final outcome was based on the motor, sensory, and electrophysiologic recoveries, and a patient judgment scale. Using the muscle grading scale, sensory grading scale, EMNG, and patient judgments, the maximal recovery was achieved in the subscapular nerve, but there were only 4 subscapular nerve lesions, which is not sufficient for a statistically significant outcome. Furthermore, the tibial, median, and femoral nerve lesions showed the best recovery rate, whereas the peroneal nerve, ulnar nerve, and brachial plexus lesions had the worst. Type of the peripheral nerve, injury (repair) level, associated injuries, electrophysiologic findings, operation time, intraoperative findings, surgical techniques, and postoperative physical rehabilitation are the prognostic factors for peripheral nerve lesions due to gunshot wounds.

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

    Science.gov (United States)

    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…

  11. Relationship between peripheral nerve decompression and gain of pedal sensibility and balance in patients with peripheral neuropathy.

    Science.gov (United States)

    Ducic, Ivica; Taylor, Nathan S; Dellon, A Lee

    2006-02-01

    This was an initial exploratory study to determine if decompression of the 4 medial ankle tunnels (neurolysis of the tibial, medial and lateral plantar, and calcaneal nerves) could lead to improved foot sensibility, increased proprioception and balance, and decreased falls in a population of patients with impaired lower extremity sensation. Fourteen patients with peripheral neuropathy were included in this study. Seventy-one percent of patients were females. Average age was 67 years. All patients were evaluated preoperatively and postoperatively to assess their lower extremity sensibility, as well as their ability to stand still, maintaining their balance with their eyes open and then closed, which is defined as "sway." Lower extremity sensibility was measured with the Pressure-Specified Sensory Device (PSSD), which evaluates 1- and 2-point discrimination for the pulp of the big toe and medial heel. The MatScan Measurement System measured each patient's sway. Neuropathy was the result of diabetes in 72% of patients, a combination of diabetes and hypothyroidism in 7%, chemotherapy in 7%, and idiopathic in 14%. Eight patients underwent peripheral nerve decompression on 1 lower extremity, whereas 6 patients underwent bilateral lower extremity peripheral nerve decompression. Mean toe and heel sensibility improved 9% and 7%, respectively, in the unilateral group, whereas the bilateral group experienced an improvement in mean toe and heel sensibility of 42% (P = 0.02) and 32%, respectively. Preoperative and postoperative sway comparison in the unilateral group revealed a reduction in sway with eyes open and eyes closed by 5% and 31%, respectively. Comparison of preoperative and postoperative sway in the bilateral group showed a reduction with eyes open and eyes closed by 23% and 145% (P = 0.05), respectively. This initial study suggests that there may be benefit from bilateral lower extremity peripheral nerve decompression in helping improve pedal sensibility and balance

  12. Debates to personal conclusion in peripheral nerve injury and reconstruction: A 30-year experience at Chang Gung Memorial Hospital

    Science.gov (United States)

    Chuang, David Chwei-Chin

    2016-01-01

    Significant progress has been achieved in the science and management of peripheral nerve injuries over the past 40 years. Yet there are many questions and few answers. The author, with 30 years of experience in treating them at the Chang Gung Memorial Hospital, addresses debates on various issues with personal conclusions. These include: (1) Degree of peripheral nerve injury, (2) Timing of nerve repair, (3)Technique of nerve repair, (4) Level of brachial plexus injury,(5) Level of radial nerve injury,(6) Traction avulsion amputation of major limb, (7) Proximal Vs distal nerve transfers in brachial plexus injuries and (8) Post paralysis facial synkinesis. PMID:27833273

  13. Chitosan-film associated with mesenchymal stem cells enhanced regeneration of peripheral nerves: A rat sciatic nerve model.

    Science.gov (United States)

    Moattari, Mehrnaz; Kouchesfehani, Homa Mohseni; Kaka, Gholamreza; Sadraie, Seyed Homayoon; Naghdi, Majid; Mansouri, Korosh

    2018-03-01

    Peripheral nerve injuries comprise significant portion of the nervous system injuries. Although peripheral nerves show some capacity of regeneration after injury, but the extent of regeneration is not remarkable. Regeneration might be through the activity of the mesenchymal stem cells (MSCs) which can release growth factors or extracellular matrix components or by the therapeutic effect of some material with the MSCs. The present study aimed to evaluate the regeneration of transected sciatic nerve by a therapeutic value of mesenchymal stem cells (MSCs) associated with chitosan-film (Cs) in rat. Male Wistar rats (n=42, 180-200g) were randomly divided into intact; control; sham; Cs; MSCs; MSCs + Cs groups. Functional recovery was evaluated at 2, 4, 6 and 8 weeks after surgery using sciatic functional index (SFI), hot water paw immersion test, electrophysiological, histological analyses. The rats in the MSCs+Cs group showed significant decrease in SFI and hot water paw immersion test during the 2nd to 8th weeks after surgery. Electrophysiological findings showed a significant decrease in latency time in the MSCs +Cs group. Amplitude of the nerve impulses also increased. Number of nerve fibers with more than 6 μm diameters increased significantly in MSCs+Cs. The number of nerve fibers with less than 4 μm diameters also increased significantly in MSCs+Cs group. Taken together, mesenchymal stem cells associated with Cs could improve functional and histomorphological properties of the sciatic nerve after injury which may have some clinical outcomes as well. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Peripheral nerve field stimulation for pruritus relief in a patient with notalgia paraesthetica.

    LENUS (Irish Health Repository)

    Ricciardo, Bernadette

    2012-02-01

    This case study is presented to exemplify the application of peripheral nerve field stimulation in the treatment of recalcitrant notalgia paraesthetica. The patient was a 60-year-old woman with severe and disabling notalgia paraesthetica. The itch persisted despite the use of several medications - topical and oral. Following a successful trial of peripheral nerve field stimulation with a temporary electrode, two subcutaneous electrodes were inserted into the affected area with a battery implanted subcutaneously in her right buttock. The patient was reviewed at 5 months post implantation. She reported a greater than 85% improvement in her itch. She also reported a major improvement in her quality of life, with particular improvement in her ability to sleep through the night. This case illustrates the possible utilization of peripheral nerve field stimulation in the treatment of notalgia paraesthetica, which is a common yet poorly understood and treated condition. Replication and controlled studies are required to determine the general applicability of this approach.

  15. Epidemiology of Traumatic Peripheral Nerve Injuries Evaluated with Electrodiagnostic Studies in a Tertiary Care Hospital Clinic.

    Science.gov (United States)

    Miranda, Gerardo E; Torres, Ruben Y

    2016-06-01

    To describe the etiologies and frequency of traumatic peripheral nerve injury (TPNI) seen in the electrodiagnostic laboratory of a tertiary care hospital in Puerto Rico. The charts of patients who underwent an electrodiagnostic study for a TPNI were revised. The main outcome measure was the frequency of each injury by anatomic location, specific nerve or nerves affected, injury mechanism, and injury severity. One hundred forty-six charts were included, and in them were listed a total of 163 nerve injuries; 109 (74.7%) cases were men and 37 (25.3%) were women. The mean age was 33.6 years. The facial nerve, the brachial plexus, and the ulnar nerve were more frequently injured than any other nerve or nerve bundle. The ulnar, sciatic, median, and radial nerves and the lumbosacral plexus were more commonly injured as a result of gunshot wounds than of any other mechanism of injury. The brachial plexus was most frequently injured in motor vehicle accidents and the facial nerve injuries most commonly had an iatrogenic cause. In terms of injury severity, 84.2% were incomplete and 15.8% were complete. TPNIs are common in young individuals and potentially can lead to significant disability. Further studies are needed to assess the socioeconomic impact of these injuries on our population.

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

    Directory of Open Access Journals (Sweden)

    Ping Yao

    2018-01-01

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

  17. [Age-related changes of sensory peripheral nerve system in healthy subjects.

    Science.gov (United States)

    Voitenkov, V B; Ekusheva, E V; Komancev, V N; Skripchenko, N V; Grigoryev, S G; Klimkin, A V; Aksenova, A I

    2017-01-01

    Our aim was to present and evaluate age-related changes of peripheral nerves of limbs on a huge population of healthy subjects of different ages. In 2009-2016 subjects aged from 1months to 90 years were studied by nerve conduction velocity studies (NCV). Data of those confirmed healthy was included in our study. In total there were 372 healthy subjects. NCV for nn. Medianus et Ulnaris was registered, with NCV and amplitude of compound sensory action potential (CSAP) being analyzed. There were significant differences on both these parameters between different age groups. Since the childhood the improvement of conduction (which was reflected in rising of CSAP amplitudes and NCV quickening) was registered; from 40-50 years steady decline of both these parameters were observed in both nerves. Conduction studies of peripheral nerves may be implemented in gerontology for early detection of neurophysiology patterns reflecting physiological aging. Also our results may be implemented for accelerated aging detection.

  18. Peripheral nerve abnormalities in pediatric patients with spinal muscular atrophy.

    Science.gov (United States)

    Yonekawa, Takahiro; Komaki, Hirofumi; Saito, Yuko; Sugai, Kenji; Sasaki, Masayuki

    2013-02-01

    We examined the specific nerve conduction deficits distinguishing spinal muscular atrophy (SMA) subtypes I and II. Five SMA I patients (age, 0.2-1.1 years) and 10 SMA II patients (age, 1.0-2.8 years) were examined. Patients were compared to age-matched controls for motor and sensory conduction velocity (MCV and SCV) changes, compound muscle and sensory nerve action potential amplitudes (CMAP and SNAP), and F-wave occurrence (FO). Slower MCVs were found in three of five SMA I patients; all five exhibited markedly decreased CMAP amplitudes. Tibial nerve CMAP amplitudes significantly reduced in SMA II patients (pnerve of SMA II patients (p=0.031). Loss of motor units may be widespread in the early stage of SMA I, while specific to the legs in young SMA II patients. SMA I showed sensory nerve degeneration, especially of large myelinated fibers. SMA II showed no sensory nerve abnormalities. Copyright © 2012 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  19. Non-invasive electrical and magnetic stimulation of the brain, spinal cord, roots and peripheral nerves

    DEFF Research Database (Denmark)

    Rossini, P M; Burke, D; Chen, R

    2015-01-01

    These guidelines provide an up-date of previous IFCN report on "Non-invasive electrical and magnetic stimulation of the brain, spinal cord and roots: basic principles and procedures for routine clinical application" (Rossini et al., 1994). A new Committee, composed of international experts, some...... theoretical, physiological and practical aspects of non-invasive stimulation of brain, spinal cord, nerve roots and peripheral nerves in the light of more updated knowledge, and include some recent extensions and developments....

  20. Regeneration of peripheral nerve fibres following Haloxon-induced degeneration

    Directory of Open Access Journals (Sweden)

    Maria Veronica de Souza

    1996-12-01

    Full Text Available Delayed neurotoxicity has been associated with organophosphorus poisoning for years. In order to study such condition in sheep, 11 animals were given either one or two high doses of Haloxon. Exposed sheep were observed daily and between 16 and 25 days after administration neurological signs as incoordination and ataxia were detected in six of them. Biopsies of tibial and laryngeal nerves were performed as soon as neurotoxicity was diagnosed, and after death fragments of selected nerves were collected together with CNS tissues for light and electron microscopy and teased fiber studies. Laryngeal, tibial and sciatic nerves showed the most pronouced changes, consisting chiefly of wallerian degeneration that was seen either as a single fiber or as a complete fascicle feature. Exams performed after death clearly showed regenerating fascicles with axonal sprouts growing within a Schwann cell old basal lamina, and some thinly myelinated axonal sprouts.

  1. Necrotizing Lymphocytic Vasculitis Limited to the Peripheral Nerves: Report of Six Cases and Review

    Directory of Open Access Journals (Sweden)

    José Félix Restrepo

    2009-01-01

    Full Text Available Background. The systemic vasculitides are syndromes characterized by inflammation and injury (necrosis or thrombosis of blood vessels, resulting in clinical manifestations according to the affected vascular bed, but not classically in stocking-glove neuropathy. Objective. To describe a form of primary vasculitis affecting strictly peripheral nerves manifesting as stocking-glove neuropathy. Methods. Case series of 110 patients seen in three centers in Bogotá who presented with symptoms and signs of polyneuropathy and/or were identified with vasculitis affecting only the peripheral nerves, and who underwent sural nerve biopsy. Results. Six patients had a vasculitis affecting only the peripheral nerves diagnosed on sural nerve biopsy which demonstrated a mixed infiltrate of monocytes/macrophages and lymphocytes especially in the small epineurial blood vessels. Over time, all had worsening of symptoms, with grip weakness and motor deficits in the hand and feet. Serologies and acute phase reactants were normal in all patients. Treatment response to immunosuppression was satisfactory in 5 patients; 1 patient had progressive neurologic damage. Conclusions. There is a distinct form of primary vasculitis of the peripheral nervous system characterized by distal sensory polyneuropathy with stocking-glove distribution with good prognosis, few and minor relapses and good response to treatment even after delayed diagnosis.

  2. Sensory and Motor Peripheral Nerve Function and Incident Mobility Disability

    DEFF Research Database (Denmark)

    Ward, R. E.; Boudreau, R. M.; Caserotti, P.

    2014-01-01

    ObjectivesTo assess the relationship between sensorimotor nerve function and incident mobility disability over 10years. DesignProspective cohort study with longitudinal analysis. SettingTwo U.S. clinical sites. ParticipantsPopulation-based sample of community-dwelling older adults with no mobilit...... disability at 2000/01 examination (N=1,680; mean age SD 76.52.9, body mass index 27.14.6; 50.2% female, 36.6% black, 10.7% with diabetes mellitus). MeasurementsMotor nerve conduction amplitude (poor...

  3. Mechanical Loading for Peripheral Nerve Stabilization and Regeneration

    Science.gov (United States)

    2013-04-01

    Meissl, G., and Berger, A. The interfascicular nerve-grafting of the median and ulnar nerves. J Bone Joint Surg Am 54, 727, 1972. 13. Strasberg, S.R...seeded with bone marrow stromal cell-derived Schwann cells. Biomaterials 32, 787, 2011. 23. Harvey, A.R., Chen, M., Plant, G.W., and Dyson, S.E. Re...regeneration: a feasibility study. Artif Or- gans 33, 26, 2009. 25. Marchesi, C., Pluderi, M., Colleoni, F., Belicchi, M., Meregalli, M., Farini, A

  4. Intraosseous malignant peripheral nerve sheath tumor in a patient with neurofibromatosis

    International Nuclear Information System (INIS)

    Terry, D.G.; Sauser, D.D.; Gordon, M.D.

    1998-01-01

    Malignant peripheral nerve sheath tumors (MPNSTs) are uncommon sarcomas that almost always arise in soft tissue. They can develop in pre-existing neurofibromas or schwannomas, de novo from peripheral nerves, or following radiation therapy. Primary intraosseous MPNST is rare and has been reported most frequently in the mandible. Of the reported cases involving the long bones, none has been associated with neurofibromatosis type 1 (NF-1). We report a case of MPNST arising in the femur in a patient with NF-1. (orig.)

  5. Early cyclosporin A treatment retards axonal degeneration in an experimental peripheral nerve injection injury model

    Directory of Open Access Journals (Sweden)

    Ibrahim Erkutlu

    2015-01-01

    Full Text Available Injury to peripheral nerves during injections of therapeutic agents such as penicillin G potassium is common in developing countries. It has been shown that cyclosporin A, a powerful immunosuppressive agent, can retard Wallerian degeneration after peripheral nerve crush injury. However, few studies are reported on the effects of cyclosporin A on peripheral nerve drug injection injury. This study aimed to assess the time-dependent efficacy of cyclosporine-A as an immunosuppressant therapy in an experimental rat nerve injection injury model established by penicillin G potassium injection. The rats were randomly divided into three groups based on the length of time after nerve injury induced by penicillin G potassium administration (30 minutes, 8 or 24 hours. The compound muscle action potentials were recorded pre-injury, early post-injury (within 1 hour and 4 weeks after injury and compared statistically. Tissue samples were taken from each animal for histological analysis. Compared to the control group, a significant improvement of the compound muscle action potential amplitude value was observed only when cyclosporine-A was administered within 30 minutes of the injection injury (P < 0.05; at 8 or 24 hours after cyclosporine-A administration, compound muscle action potential amplitude was not changed compared with the control group. Thus, early immunosuppressant drug therapy may be a good alternative neuroprotective therapy option in experimental nerve injection injury induced by penicillin G potassium injection.

  6. Ultrasound and review of evidence for lower extremity peripheral nerve blocks.

    Science.gov (United States)

    Salinas, Francis V

    2010-01-01

    This qualitative systematic review summarizes existing evidence from randomized controlled trials (RCTs) comparing ultrasound (US) to alternative techniques for lower extremity peripheral nerve block. There were 11 RCTs of sufficient quality for inclusion. Jadad scores ranged from 1 to 4 with a median of 3. For femoral nerve blocks, US provided shorter onset and improved quality of sensory and motor block, as well as a decrease in local anesthetic requirements. For sciatic nerve blocks, US resulted in a higher percentage of patients with complete sensory and motor block, as well as decreased local anesthetic requirements. In 2 of the studies for sciatic nerve block, US resulted in a shorter time to successfully complete the procedure. No study was powered to detect a difference in surgical block success. Overall, there was significant heterogeneity in the definitions of successful sensory and motor block. In 2 studies, the optimal peripheral nerve stimulation technique may have not been used, resulting in a potential bias. No RCT reported US as inferior to alternative techniques in any outcome. There is level Ib evidence to make a grade A recommendation that US guidance provides improvements in onset and success of sensory block, a decrease in local anesthetic requirements, and decreased time to perform lower extremity peripheral nerve blocks.

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

    Science.gov (United States)

    2017-07-01

    Peripheral Nerve Repair and Functional Outcomes PRINCIPAL INVESTIGATOR: LTC Leon Nesti MD PhD RECIPIENT: Henry M. Jackson Foundation for the Advancement...of Military Medicine Inc. Bethesda, MD 20817 REPORT DATE: July 2017 TYPE OF REPORT: Annual PREPARED FOR: U.S. Army Medical Research and...REPORT DATE (DD-MM-YYYY) July 2017 2. REPORT TYPE Annual 3. DATES COVERED (From - To) 1/7/2016-30/6/2017 4. TITLE AND SUBTITLE Clinical Evaluation

  8. Early alterations of Hedgehog signaling pathway in vascular endothelial cells after peripheral nerve injury elicit blood-nerve barrier disruption, nerve inflammation, and neuropathic pain development.

    Science.gov (United States)

    Moreau, Nathan; Mauborgne, Annie; Bourgoin, Sylvie; Couraud, Pierre-Olivier; Romero, Ignacio A; Weksler, Babette B; Villanueva, Luis; Pohl, Michel; Boucher, Yves

    2016-04-01

    Changes in the nerve's microenvironment and local inflammation resulting from peripheral nerve injury participate in nerve sensitization and neuropathic pain development. Taking part in these early changes, disruption of the blood-nerve barrier (BNB) allows for infiltration of immunocytes and promotes the neuroinflammation. However, molecular mechanisms engaged in vascular endothelial cells (VEC) dysfunction and BNB alterations remain unclear. In vivo, BNB permeability was assessed following chronic constriction injury (CCI) of the rat sciatic nerve (ScN) and differential expression of markers of VEC functional state, inflammation, and intracellular signaling was followed from 3 hours to 2 months postinjury. Several mechanisms potentially involved in functional alterations of VEC were evaluated in vitro using human VEC (hCMEC/D3), then confronted to in vivo physiopathological conditions. CCI of the ScN led to a rapid disruption of endoneurial vascular barrier that was correlated to a decreased production of endothelial tight-junction proteins and an early and sustained alteration of Hedgehog (Hh) signaling pathway. In vitro, activation of Toll-like receptor 4 in VEC downregulated the components of Hh pathway and altered the endothelial functional state. Inhibition of Hh signaling in the ScN of naive rats mimicked the biochemical and functional alterations observed after CCI and was, on its own, sufficient to evoke local neuroinflammation and sustained mechanical allodynia. Alteration of the Hh signaling pathway in VEC associated with peripheral nerve injury, is involved in BNB disruption and local inflammation, and could thus participate in the early changes leading to the peripheral nerve sensitization and, ultimately, neuropathic pain development.

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

    Directory of Open Access Journals (Sweden)

    Gholam Hossein Farjah

    2013-08-01

    Full Text Available 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. Conclusion:These findings demonstrate that ESM effectively enhances nerve regeneration and promotes functional recovery in injured sciatic nerve of rat.

  10. The role of dexamethasone in peripheral and neuraxial nerve blocks ...

    African Journals Online (AJOL)

    axillary, lumbar plexus, femoral, 3 in 1, sciatic, popliteal, ankle block, caudal, epidural or nerve block. The 'and' function was used to combine these terms with dexamethasone, corticosteroid, or steroid with the definition exploded. The initial search terms with the keywords with the definition exploded were utilised. We.

  11. Ultrastructural changes in peripheral arteries and nerves in diabetic ...

    African Journals Online (AJOL)

    Mohamed E. Salem

    2017-01-30

    Jan 30, 2017 ... biopsies in diabetic neuropathy comparing with biopsies of normal arteries and nerves of traumatic amputation as a control group. ... the metabolism of carbohydrate, protein, fat, water and elec- trolytes, sometimes with grave .... loss of the vessel architecture in some sections. The vasa vasorum changes ...

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

    Science.gov (United States)

    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.

  13. Interfacing peripheral nerve with macro-sieve electrodes following spinal cord injury

    OpenAIRE

    Nathan K Birenbaum; Matthew R MacEwan; Wilson Z Ray

    2017-01-01

    Macro-sieve electrodes were implanted in the sciatic nerve of five adult male Lewis rats following spinal cord injury to assess the ability of the macro-sieve electrode to interface regenerated peripheral nerve fibers post-spinal cord injury. Each spinal cord injury was performed via right lateral hemisection of the cord at the T9?10 site. Five months post-implantation, the ability of the macro-sieve electrode to interface the regenerated nerve was assessed by stimulating through the macro-si...

  14. Possible role of alpha-lipoic acid in the treatment of peripheral nerve injuries

    Directory of Open Access Journals (Sweden)

    Ranieri Maurizio

    2010-08-01

    Full Text Available Abstract Recent findings on the antioxidant effects of pretreatment with α-lipoic acid (α-LA on the crush injury of rat sciatic nerve confirm the possible usefulness of α-LA administration in humans with peripheral nerve injuries. We discussed this issue in relation with our recent results in which the combined employment of α-LA and γ-linolenic acid with a rehabilitation program for six weeks reduced sensory symptoms and neuropathic pain in patients with compressive radiculopathy syndrome from disc-nerve root conflict in comparison with patients submitted to rehabilitation program alone for six weeks.

  15. In vitro electrophoresis and in vivo electrophysiology of peripheral nerve using DC field stimulation

    DEFF Research Database (Denmark)

    Madison, Roger D.; Robinson, Grant A.; Krarup, Christian

    2014-01-01

    BACKGROUND: Given the movement of molecules within tissue that occurs naturally by endogenous electric fields, we examined the possibility of using a low-voltage DC field to move charged substances in rodent peripheral nerve in vitro. NEW METHOD: Labeled sugar- and protein-based markers were...... applied to a rodent peroneal nerve and then a 5-10 V/cm field was used to move the molecules within the extra- and intraneural compartments. Physiological and anatomical nerve properties were also assessed using the same stimulation in vivo. RESULTS: We demonstrate in vitro that charged and labeled...... compounds are capable of moving in a DC field along a nerve, and that the same field applied in vivo changes the excitability of the nerve, but without damage. CONCLUSIONS: The results suggest that low-voltage electrophoresis could be used to move charged molecules, perhaps therapeutically, safely along...

  16. Biomimetic Architectures for Peripheral Nerve Repair: A Review of Biofabrication Strategies.

    Science.gov (United States)

    Wieringa, Paul A; Gonçalves de Pinho, Ana Rita; Micera, Silvestro; van Wezel, Richard J A; Moroni, Lorenzo

    2018-01-19

    Biofabrication techniques have endeavored to improve the regeneration of the peripheral nervous system (PNS), but nothing has surpassed the performance of current clinical practices. However, these current approaches have intrinsic limitations that compromise patient care. The "gold standard" autograft provides the best outcomes but requires suitable donor material, while implantable hollow nerve guide conduits (NGCs) can only repair small nerve defects. This review places emphasis on approaches that create structural cues within a hollow NGC lumen in order to match or exceed the regenerative performance of the autograft. An overview of the PNS and nerve regeneration is provided. This is followed by an assessment of reported devices, divided into three major categories: isotropic hydrogel fillers, acting as unstructured interluminal support for regenerating nerves; fibrous interluminal fillers, presenting neurites with topographical guidance within the lumen; and patterned interluminal scaffolds, providing 3D support for nerve growth via structures that mimic native PNS tissue. Also presented is a critical framework to evaluate the impact of reported outcomes. While a universal and versatile nerve repair strategy remains elusive, outlined here is a roadmap of past, present, and emerging fabrication techniques to inform and motivate new developments in the field of peripheral nerve regeneration. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Prostaglandin E1 Protects the Peripheral Nerve in Diabetics through Preventing Vascular Permeability Changes.

    Science.gov (United States)

    Mo, Feifei; Hu, Guotao; Liu, Wei; He, Li; Wang, Hailan

    2018-02-01

    The aims of this study were to investigate the effects of the vasodilator prostaglandin E1 on microvascular permeability, the expression of vascular endothelial growth factor (VEGF), as well as the structural and functional changes of the peripheral nerve in diabetic rats. Streptozotocin-induced diabetes mellitus were randomly divided into two groups and intraperitoneally received, once daily, an injection of prostaglandin E1 at 1.6 μg/kg in normal saline or the same volume of normal saline (diabetic control), respectively. Six rats were randomly selected as normal controls. Diabetic controls exhibited a significant increase in the tail flick threshold temperature, water content of the sciatic nerve, serum VEGF level, and VEGF level in the sciatic nerve; in addition, a decrease in the sciatic nerve conduction velocity (NCV) was observed, compared with normal rats (Pprostaglandin E1 resulted in similar changes but at a slower rate than in those without treatment. Diabetic control rats also showed histological and ultrastructural abnormalities of the sciatic nerve, whereas prostaglandin E1-treated rats exhibited similar but less severe injury. The serum VEGF level was negatively correlated with the sciatic NCV (r=-0.932, PProstaglandin E1 could protect the peripheral nerve by improving sciatic nerve function, reducing the VEGF level, and decreasing the vascular permeability. This study provides an experimental proof that prostaglandin E1 has potential benefits in improving DPN in early stage. © Georg Thieme Verlag KG Stuttgart · New York.

  18. Local effect of celecoxib on peripheral nerve repair combined with silicone tubulization in rat

    Directory of Open Access Journals (Sweden)

    Mohammadi Rahim

    2013-10-01

    Full Text Available 【Abstract】Objective: To assess local effect of celecoxib on nerve regeneration in a rat sciatic nerve transection model. Methods: Forty-five male healthy white Wistar rats were randomly divided into three experimental groups (n=15 for each: sham-oper ation (SHAM, control (SIL and celecoxib treated (SIL/CLX groups. In SHAM group after anesthesia left sciatic nerve was exposed and after homeostasis muscle was sutured. In SIL group the left sciatic nerve was exposed in the same way and transected proximal to tibioperoneal bifurcation leaving a 10 mm gap. Proximal and distal stumps were each inserted into a silicone tube and filled with 10 µl phosphate buffered solution. In SIL/CLX group defect was bridged using a silicone tube filled with 10 µl celecoxib (0.1 g/L. Results: Functional study and gastrocnemius muscle mass confirmed faster and better recovery of regenerated axons in SIL/CLX than in SIL group(P<0.05. Morphometric indices of regenerated fibers showed number and diameter of the my elinated fibers in SIL/CLX were significantly greater than those in control group. In immunohistochemistry, location of reactions to S-100 in SIL/CLX was clearly more positive than that in SIL group. Conclusion: Response to local treatment of celecoxib demonstrates that it influences and improves functional recovery of peripheral nerve regeneration. Key words: Peripheral nerve; Sciaticnerve; Celecoxib; Nerve regeneration

  19. Congenital muscular dystrophy, cardiomyopathy, and peripheral neuropathy due to merosin deficiency: Peripheral nerve histology of cauda equina

    Directory of Open Access Journals (Sweden)

    Erika Hissong, M.D.

    2016-06-01

    Full Text Available Peripheral neuropathy, white matter abnormalities, and cardiomyopathy are associated findings with merosin-deficient congenital muscular dystrophy. Although characterization of the neuropathy with nerve conduction studies has been well documented, limited research has been able to correlate histopathology with nerve biopsy in humans. Our understanding of the mechanism, described as a demyelinating neuropathy, is mainly derived from mouse model studies. We report a 23-year-old male who succumbed to respiratory failure and ultimately cardiac arrhythmia in the setting of an uncharacterized end stage progressive muscular disease complicated by cardiomyopathy and severe scoliosis. Autopsy revealed extensive muscular atrophy and replacement by fibroadipose tissue throughout the skeletal muscle and myocardium. Immunohistochemical analysis of the muscle biopsy showed a complete loss of merosin. Thus, the cause for both his muscular disease and demyelinating neuropathy was established with the diagnosis of merosin-deficient muscular dystrophy. Nerve biopsy obtained from the cauda equina showed clear evidence of segmental demyelination and remyelination, providing a better understanding of the proximal peripheral nerve histopathological changes in this disease entity.

  20. Rodent model for assessing the long term safety and performance of peripheral nerve recording electrodes

    Science.gov (United States)

    Vasudevan, Srikanth; Patel, Kunal; Welle, Cristin

    2017-02-01

    Objective. In the US alone, there are approximately 185 000 cases of limb amputation annually, which can reduce the quality of life for those individuals. Current prosthesis technology could be improved by access to signals from the nervous system for intuitive prosthesis control. After amputation, residual peripheral nerves continue to convey motor signals and electrical stimulation of these nerves can elicit sensory percepts. However, current technology for extracting information directly from peripheral nerves has limited chronic reliability, and novel approaches must be vetted to ensure safe long-term use. The present study aims to optimize methods to establish a test platform using rodent model to assess the long term safety and performance of electrode interfaces implanted in the peripheral nerves. Approach. Floating Microelectrode Arrays (FMA, Microprobes for Life Sciences) were implanted into the rodent sciatic nerve. Weekly in vivo recordings and impedance measurements were performed in animals to assess performance and physical integrity of electrodes. Motor (walking track analysis) and sensory (Von Frey) function tests were used to assess change in nerve function due to the implant. Following the terminal recording session, the nerve was explanted and the health of axons, myelin and surrounding tissues were assessed using immunohistochemistry (IHC). The explanted electrodes were visualized under high magnification using scanning electrode microscopy (SEM) to observe any physical damage. Main results. Recordings of axonal action potentials demonstrated notable session-to-session variability. Impedance of the electrodes increased upon implantation and displayed relative stability until electrode failure. Initial deficits in motor function recovered by 2 weeks, while sensory deficits persisted through 6 weeks of assessment. The primary cause of failure was identified as lead wire breakage in all of animals. IHC indicated myelinated and unmyelinated axons

  1. A biosynthetic nerve guide conduit based on silk/SWNT/fibronectin nanocomposite for peripheral nerve regeneration.

    Directory of Open Access Journals (Sweden)

    Fatemeh Mottaghitalab

    Full Text Available 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.

  2. end-to-side nerve suture - a technique to repair peripheral nerve injury

    African Journals Online (AJOL)

    Raubenheimer, Head of the Department of Oral Pathology and. Oral Biology, Faculty of Dentistry, MEDUNSA, for the meticulous histology investigations. References. 1. Mennen U. End-lo-side nerve suture in the non-human primate. Hand Surgery 1998; 3(1): 1-6. 2. Mennen U. End-to-side nerve suture in the human patient.

  3. Aging in peripheral nerves: regulation of myelin protein genes by steroid hormones.

    Science.gov (United States)

    Melcangi, R C; Magnaghi, V; Martini, L

    2000-02-01

    The process of aging deeply influences morphological and functional parameters of the peripheral nerves. Interestingly, recent observations performed in our laboratory on the rat sciatic nerves have indicated that the deterioration of myelin occurring in the peripheral nerves during aging may be explained by the fall of the messenger levels of the major peripheral myelin proteins (glycoprotein Po, myelin basic protein and peripheral myelin protein 22). At least in the case of the Po, the low levels of its messengers and of the protein itself found in aged animals are increased by the treatment with a physiological progesterone derivative like dihydroprogesterone. It has also been found that in normal adult male rats the levels of the messengers for Po in the sciatic nerve are increased by progesterone, dihydroprogesterone and tetrahydroprogesterone; surprisingly, the gene expression of peripheral myelin protein 22 is stimulated only by tetrahydroprogesterone. These observations have been confirmed in parallel studies performed on Schwann cell cultures. Since tetrahydroprogesterone does not bind to the progesterone receptor but is a ligand for the GABAA receptor, the hypothesis has been put forward that part of the steroidal effects reported might occur not through the classical progesterone receptor, but rather via an interaction with the GABAA receptor. In other experiments it has been found that the gene expression of Po may be decreased by orchidectomy and restored by treatment with the androgen dihydrotestosterone. Altogether, these observations suggest the future use of physiological and/ or synthetic steroid hormones as a possible therapeutic approach for some pathological situations occurring in peripheral nerves during aging and demyelinating diseases.

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

    Science.gov (United States)

    Moldovan, Mihai; Sørensen, Jesper; Krarup, Christian

    2006-09-01

    Functional outcome after peripheral nerve regeneration is often poor, particularly involving nerve injuries far from their targets. Comparison of sensory and motor axon regeneration before target reinnervation is not possible in the clinical setting, and previous experimental studies addressing the question of differences in growth rates of different nerve fibre populations led to conflicting results. We developed an animal model to compare growth and maturation of the fastest growing sensory and motor fibres within the same mixed nerve after Wallerian degeneration. Regeneration of cat tibial nerve after crush (n = 13) and section (n = 7) was monitored for up to 140 days, using implanted cuff electrodes placed around the sciatic and tibial nerves and wire electrodes at plantar muscles. To distinguish between sensory and motor fibres, recordings were carried out from L6-S2 spinal roots using cuff electrodes. The timing of laminectomy was based on the presence of regenerating fibres along the nerve within the tibial cuff. Stimulation of unlesioned tibial nerves (n = 6) evoked the largest motor response in S1 ventral root and the largest sensory response in L7 dorsal root. Growth rates were compared by mapping the regenerating nerve fibres within the tibial nerve cuff to all ventral or dorsal roots and, regardless of the lesion type, the fastest growth was similar in sensory and motor fibres. Maturation was assessed as recovery of the maximum motor and sensory conduction velocities (CVs) within the tibial nerve cuff. Throughout the observation period the CV was approximately 14% faster in regenerated sensory fibres than in motor fibres in accordance with the difference observed in control nerves. Recovery of amplitude was only partial after section, whereas the root distribution pattern was restored. Our data suggest that the fastest growth and maturation rates that can be achieved during regeneration are similar for motor and sensory myelinated fibres.

  5. Studies of Electrically Stimulated Rat Limb and Peripheral Nerve Regeneration.

    Science.gov (United States)

    1983-08-25

    absoltite necessity for formation of a recognizable limb. In addition, evidence from embryology suggests that externally applied polarizing influences...3], and in others (Borgens et al. * I 1,5 I; Becker, [61) have demonstrated that vertebrate limb regeneration can be .- markedly influenced by the...strikingly histologic evaluation of the nerves. influence the rate of growth and state of dif- ferentiation of adult vertebrate cells. A var- Table I lety

  6. Evaluation of Bcl-2, Bcl-x and Cleaved Caspase-3 in Malignant Peripheral Nerve Sheath Tumors and Neurofibromas

    Directory of Open Access Journals (Sweden)

    KARIN S. CUNHA

    2013-11-01

    Full Text Available AIMS: To study the expression of Bcl-2, Bcl-x, as well the presence of cleaved caspase-3 in neurofibromas and malignant peripheral nerve sheath tumors. The expression of Bcl-2 and Bcl-x and the presence of cleaved caspase 3 were compared to clinicopathological features of malignant peripheral nerve sheath tumors and their impact on survival rates were also investigated. MATERIALS AND METHODS: The evaluation of Bcl-2, Bcl-x and cleaved caspase-3 was performed by immunohistochemistry using tissue microarrays in 28 malignant peripheral nerve sheath tumors and 38 neurofibromas. Immunoquantification was performed by computerized digital image analysis. CONCLUSIONS: Apoptosis is altered in neurofibromas and mainly in malignant peripheral nerve sheath tumors. High levels of cleaved caspase-3 are more common in tumors with more aggressive histological features and it is associated with lower disease free survival of patients with malignant peripheral nerve sheath tumors.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-12-15

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

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

    Science.gov (United States)

    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.

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

    International Nuclear Information System (INIS)

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

    2013-01-01

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

  10. Role and Specificity of LGI4-ADAM22 Interactions in Peripheral Nerve Myelination

    NARCIS (Netherlands)

    L. Kegel (Linde)

    2013-01-01

    textabstractIn the peripheral nervous system, large caliber axons are ensheathed and myelinated by Schwann cells. Myelin is crucial for a faster signal transduction along the nerve. Hence it is not surprising that defects in this myelination process cause serious neurological disease. Despite the

  11. Non-invasive peripheral nerve stimulation via focused ultrasound in vivo

    Science.gov (United States)

    Downs, Matthew E.; Lee, Stephen A.; Yang, Georgiana; Kim, Seaok; Wang, Qi; Konofagou, Elisa E.

    2018-02-01

    Focused ultrasound (FUS) has been employed on a wide range of clinical applications to safely and non-invasively achieve desired effects that have previously required invasive and lengthy procedures with conventional methods. Conventional electrical neuromodulation therapies that are applied to the peripheral nervous system (PNS) are invasive and/or non-specific. Recently, focused ultrasound has demonstrated the ability to modulate the central nervous system and ex vivo peripheral neurons. Here, for the first time, noninvasive stimulation of the sciatic nerve eliciting a physiological response in vivo is demonstrated with FUS. FUS was applied on the sciatic nerve in mice with simultaneous electromyography (EMG) on the tibialis anterior muscle. EMG signals were detected during or directly after ultrasound stimulation along with observable muscle contraction of the hind limb. Transecting the sciatic nerve downstream of FUS stimulation eliminated EMG activity during FUS stimulation. Peak-to-peak EMG response amplitudes and latency were found to be comparable to conventional electrical stimulation methods. Histology along with behavioral and thermal testing did not indicate damage to the nerve or surrounding regions. The findings presented herein demonstrate that FUS can serve as a targeted, safe and non-invasive alternative to conventional peripheral nervous system stimulation to treat peripheral neuropathic diseases in the clinic.

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

    NARCIS (Netherlands)

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

    2012-01-01

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

  13. A novel concept for continuous peripheral nerve blocks. Presentation of a new ultrasound-guided device

    DEFF Research Database (Denmark)

    Rothe, C; Steen-Hansen, C; Madsen, M H

    2015-01-01

    concept and prototype for ultrasound-guided in-plane positioning and readjustment of peripheral nerve catheters (patent pending). The integrated catheter-needle prototype comprises three parts: a curved needle, a catheter with clear echogenic markings attached to the needle tail and a detachable hub...

  14. Recurring intracranial malignant peripheral nerve sheath tumor: case report and systematic review of the literature

    NARCIS (Netherlands)

    van den Munckhof, Pepijn; Germans, Menno R.; Schouten-van Meeteren, Antoinette Y. N.; Oldenburger, Foppe; Troost, Dirk; Vandertop, W. Peter

    2011-01-01

    To report the clinical presentation and management of an intracranial frontoparietal malignant peripheral nerve sheath tumor (MPNST) and its recurrence in a 6-year-old girl, along with a systematic review of the literature. A previously healthy 6-year-old girl presented with severe signs of

  15. Role of spinal microglia in rat models of peripheral nerve injury and inflammation.

    Science.gov (United States)

    Clark, Anna K; Gentry, Clive; Bradbury, Elizabeth J; McMahon, Stephen B; Malcangio, Marzia

    2007-02-01

    Mounting evidence supports the hypothesis that spinal microglia modulate the development and maintenance of some chronic pain states. Here we examined the role of spinal microglia following both peripheral inflammatory insult and peripheral nerve injury. We observed significant ipsilateral dorsal horn microglia activation 2 weeks after injury and bilateral activation 50 days following nerve injury as well as 24 h following intraplantar zymosan but not intraplantar complete Freund's adjuvant (CFA). Ipsilateral but not contralateral microglia activation was associated with hind paw mechanical hyperalgesia. Spinal injection of the glial metabolic inactivator fluorocitrate attenuated ipsilateral hyperalgesia and bilateral spinal microglia activation after peripheral nerve injury. Intrathecal fluorocitrate reversed hyperalgesia after intraplantar zymosan and produced no reversal of CFA-induced hyperalgesia. These data suggest a role for spinal glia in the persistence of mechanical hyperalgesia following peripheral nerve injury. However, activation of spinal microglia contralaterally did not correlate to nociception. Furthermore, it would appear that the time course of microglia activation and their contribution to inflammatory pain is dependent on the inflammatory stimulus administered.

  16. [Clinical effect observation of biodegradable conduit small gap tublization repairing peripheral nerve injury].

    Science.gov (United States)

    Zhang, Pei-xun; Kou, Yu-hui; Han, Na; Dang, Yu; Xue, Feng; Wang, Tian-bing; Xu, Hai-lin; Chen, Jian-hai; Yang, Ming; Lu, Hao; Yin, Xiao-feng; Bai, Lu; Wang, Yan-hua; An, Shuai; Zhang, Dian-ying; Fu, Zhong-guo; Jiang, Bao-guo

    2012-12-18

    To observe the clinical effect of biodegradable conduit small gap tublization to repair peripheral nerve injury. In the study, 30 cases of fresh peripheral nerve injury in the upper extremities were recruited. After formally informed and obtaining the consent, the recruited patients were divided into the degradable chitin conduit tublization group (experimental group: 15 cases) and traditional epineurial neurorrhaphy group (control group: 15 cases). Their nerve functional recovery conditions were clinically observed according to the standard score methods provided by SHEN Ning-jiang and British Medical Research Council. The excellent and good rates of the overall nerve functional recovery were calculated. The electrophysiologic study was carried out after 6 months. Of the total 30 cases, 28 were followed up, and there were 14 cases in the degradable chitin conduit tublization group and traditional epineurial neurorrhaphy group. The operation procedure was very simple, and the mean suture time [(8.0±0.8) min] was 20% shorter than that of the traditional epineurial neurorrhaphy group [(10.0±0.6) min]. All the wounds in the degradable chitin conduit tublization group healed as expected without rejection, hypersensitive reaction or anomalous draining. Electrophysiology examination results after 6 months displayed that the sensory nerves conduction velocity recovery rate was 77.37% of the normal value, and motor nerve conduction velocity recovery rate was 70.09% in the degradable chitin conduit tublization group. The sensory nerves conduction velocity recovery rate was 61.69% of the normal value, and motor nerve conduction velocity recovery rate was 56.15% in the traditional epineurial neurorrhaphy group. The exact propability methods was applied in the comparison of sensory and motor nerve conduction velocity recovery rate, and there was no statistically significant of two groups(sensory nerve conduction velocity recovery rate P=0.678;motor nerve conduction velocity

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

    Science.gov (United States)

    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 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

  18. Toll-Like Receptor 3 Contributes to Wallerian Degeneration after Peripheral Nerve Injury.

    Science.gov (United States)

    Lee, Hyunkyoung; Baek, Jiyeon; Min, Hyunjung; Cho, Ik-Hyun; Yu, Seong-Woo; Lee, Sung Joong

    2016-01-01

    It is well known that Schwann cells play an important role in Wallerian degeneration after peripheral nerve injury. Previously, we reported that toll-like receptor 3 (TLR3) is expressed on Schwann cells, implicating its role in Schwann cell activation during Wallerian degeneration. In this study, we tested this possibility using TLR3 knock-out mice. Sciatic nerve-crush injury was induced in wild-type and TLR3 knock-out mice. Histological sections of the sciatic nerve were analyzed for Wallerian degeneration on days 3 and 7 after injury. The level of macrophage infiltration was measured by real-time RT-PCR, flow cytometry and immunohistochemistry. The macrophage-recruiting chemokine gene expressions in the injured nerve were determined by real-time RT-PCR. In TLR3 knock-out mice, the nerve injury-induced axonal degeneration and subsequent axonal debris clearance were reduced compared to in wild-type mice. In addition, nerve injury-induced macrophage infiltration into injury sites was attenuated in TLR3 knock-out mice and was accompanied by reduced expression of macrophage-recruiting chemokines such as CC-chemokine ligands (CCL)2/MCP-1, CCL4/MIP-1β and CCL5/RANTES. These macrophage-recruiting chemokines were induced in primary Schwann cells upon TLR3 stimulation. Finally, intraneural injection of polyinosinic-polycytidylic acid, a synthetic TLR3 agonist, induced macrophage infiltration into the sciatic nerve in vivo. These data show that TLR3 signaling contributes to Wallerian degeneration after peripheral nerve injury by affecting Schwann cell activation and macrophage recruitment to injured nerves. © 2016 S. Karger AG, Basel.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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. Interfacing peripheral nerve with macro-sieve electrodes following spinal cord injury.

    Science.gov (United States)

    Birenbaum, Nathan K; MacEwan, Matthew R; Ray, Wilson Z

    2017-06-01

    Macro-sieve electrodes were implanted in the sciatic nerve of five adult male Lewis rats following spinal cord injury to assess the ability of the macro-sieve electrode to interface regenerated peripheral nerve fibers post-spinal cord injury. Each spinal cord injury was performed via right lateral hemisection of the cord at the T 9-10 site. Five months post-implantation, the ability of the macro-sieve electrode to interface the regenerated nerve was assessed by stimulating through the macro-sieve electrode and recording both electromyography signals and evoked muscle force from distal musculature. Electromyography measurements were recorded from the tibialis anterior and gastrocnemius muscles, while evoked muscle force measurements were recorded from the tibialis anterior, extensor digitorum longus, and gastrocnemius muscles. The macro-sieve electrode and regenerated sciatic nerve were then explanted for histological evaluation. Successful sciatic nerve regeneration across the macro-sieve electrode interface following spinal cord injury was seen in all five animals. Recorded electromyography signals and muscle force recordings obtained through macro-sieve electrode stimulation confirm the ability of the macro-sieve electrode to successfully recruit distal musculature in this injury model. Taken together, these results demonstrate the macro-sieve electrode as a viable interface for peripheral nerve stimulation in the context of spinal cord injury.

  3. Interfacing peripheral nerve with macro-sieve electrodes following spinal cord injury

    Directory of Open Access Journals (Sweden)

    Nathan K Birenbaum

    2017-01-01

    Full Text Available Macro-sieve electrodes were implanted in the sciatic nerve of five adult male Lewis rats following spinal cord injury to assess the ability of the macro-sieve electrode to interface regenerated peripheral nerve fibers post-spinal cord injury. Each spinal cord injury was performed via right lateral hemisection of the cord at the T9–10 site. Five months post-implantation, the ability of the macro-sieve electrode to interface the regenerated nerve was assessed by stimulating through the macro-sieve electrode and recording both electromyography signals and evoked muscle force from distal musculature. Electromyography measurements were recorded from the tibialis anterior and gastrocnemius muscles, while evoked muscle force measurements were recorded from the tibialis anterior, extensor digitorum longus, and gastrocnemius muscles. The macro-sieve electrode and regenerated sciatic nerve were then explanted for histological evaluation. Successful sciatic nerve regeneration across the macro-sieve electrode interface following spinal cord injury was seen in all five animals. Recorded electromyography signals and muscle force recordings obtained through macro-sieve electrode stimulation confirm the ability of the macro-sieve electrode to successfully recruit distal musculature in this injury model. Taken together, these results demonstrate the macro-sieve electrode as a viable interface for peripheral nerve stimulation in the context of spinal cord injury.

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

    Science.gov (United States)

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

    2016-09-09

    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. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Tumor suppressor menin mediates peripheral nerve injury-induced neuropathic pain through potentiating synaptic plasticity.

    Science.gov (United States)

    Xu, S; Wu, H; Wang, X; Shen, X; Guo, X; Shen, R; Wang, F

    2012-10-25

    Synaptic plasticity is a crucial step in the development of central sensitization in the pathogenesis of neuropathic hyperalgesia. Menin, the product of the multiple endocrine neoplasia type 1 (MEN1) gene, possesses the property of synaptogenesis which plays an essential role in neuronal activity. We tested the contributing role of spinal menin in peripheral nerve injury-induced neuropathic hypersensitivity through modulating neuronal synaptic plasticity. After approval by the Institutional Animal Care and Use Committee, nociceptive responses were detected with von Frey filaments and thermal plate after spared nerve injury in C57BL/6 mice who were treated with either intrathecal antisense oligonucleotide of MEN1 (ASO) or vehicle. Extracellular spontaneous discharge frequency, field excitatory postsynaptic potential (fEPSP), and monosynaptic excitatory postsynaptic currents (EPSCs) were measured electrophysiologically. Intrathecal ASO alleviated nerve injury-induced mechanical and thermal hypersensitivity. Upregulated spinal menin after nerve injury colocalized with NeuN in the superficial laminae; genetic knockdown of spinal menin reduced nerve injury induced in vivo spontaneous activity and instantaneous frequency and in vitro field potentials; ASO decreased the frequency and amplitude of monosynaptic EPSCs, and reduced synaptic strength and total charge. Collectively, these findings highlight the role of upregulated neuronal menin in the spinal cord in potentiating spinal synaptic plasticity in peripheral nerve injury-induced neuropathic hypersensitivity. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Bedowra Zabeen

    Full Text Available To compare rates of microvascular complications in adolescents with type 1 diabetes treated with continuous subcutaneous insulin infusion (CSII versus multiple daily injections (MDI.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.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.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.

  7. Comparative Oncogenomics for Peripheral Nerve Sheath Cancer Gene Discovery

    Science.gov (United States)

    2015-06-01

    and growth factor receptors potentially upstream of some of these signaling cascades (the growth hormone receptor gene Ghr, Il17a, Inhbe) were...Loss of p16 (INK4A) expression is associated with allelic imbalance /loss of heterozygosity of chromosome 9p21 in microdissected malignant peripheral...cell receptor genes) Antigen recognition Ghr (growth hormone receptor) Growth hormone receptor Myc (myelocytomatosis oncogene) Nuclear phosphoprotein

  8. Peripheral nerve block in patients with Ehlers-Danlos syndrome, hypermobility type: a case series.

    Science.gov (United States)

    Neice, Andrew E; Stubblefield, Eryn E; Woodworth, Glenn E; Aziz, Michael F

    2016-09-01

    Ehlers-Danlos syndrome (EDS) is an inherited disease characterized by defects in various collagens or their post translational modification, with an incidence estimated at 1 in 5000. Performance of peripheral nerve block in patients with EDS is controversial, due to easy bruising and hematoma formation after injections as well as reports of reduced block efficacy. The objective of this study was to review the charts of EDS patients who had received peripheral nerve block for any evidence of complications or reduced efficacy. Case series, chart review. Academic medical center. Patients with a confirmed or probable diagnosis of EDS who had received a peripheral nerve block in the last 3 years were identified by searching our institutions electronic medical record system. The patients were classified by their subtype of EDS. Patients with no diagnosed subtype were given a probable subtype based on a chart review of the patient's symptoms. Patient charts were reviewed for any evidence of complications or reduced block efficacy. A total of 21 regional anesthetics, on 16 unique patients were identified, 10 of which had a EDS subtype diagnosis. The majority of these patients had a diagnosis of hypermobility-type EDS. No block complications were noted in any patients. Two block failures requiring repeat block were noted, and four patients reported uncontrolled pain on postoperative day one despite successful placement of a peripheral nerve catheter. Additionally, blocks were performed without incident in patients with classical-type and vascular-type EDS although the number was so small that no conclusions can be drawn about relative safety of regional anesthesia in these groups. This series fails to show an increased risk of complications of peripheral nerve blockade in patients with hypermobility-type EDS. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    M. Foroutan Koudehi

    2014-07-01

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

  10. Monitoring peripheral nerve degeneration in ALS by label-free stimulated Raman scattering imaging

    Science.gov (United States)

    Tian, Feng; Yang, Wenlong; Mordes, Daniel A.; Wang, Jin-Yuan; Salameh, Johnny S.; Mok, Joanie; Chew, Jeannie; Sharma, Aarti; Leno-Duran, Ester; Suzuki-Uematsu, Satomi; Suzuki, Naoki; Han, Steve S.; Lu, Fa-Ke; Ji, Minbiao; Zhang, Rosanna; Liu, Yue; Strominger, Jack; Shneider, Neil A.; Petrucelli, Leonard; Xie, X. Sunney; Eggan, Kevin

    2016-10-01

    The study of amyotrophic lateral sclerosis (ALS) and potential interventions would be facilitated if motor axon degeneration could be more readily visualized. Here we demonstrate that stimulated Raman scattering (SRS) microscopy could be used to sensitively monitor peripheral nerve degeneration in ALS mouse models and ALS autopsy materials. Three-dimensional imaging of pre-symptomatic SOD1 mouse models and data processing by a correlation-based algorithm revealed that significant degeneration of peripheral nerves could be detected coincidentally with the earliest detectable signs of muscle denervation and preceded physiologically measurable motor function decline. We also found that peripheral degeneration was an early event in FUS as well as C9ORF72 repeat expansion models of ALS, and that serial imaging allowed long-term observation of disease progression and drug effects in living animals. Our study demonstrates that SRS imaging is a sensitive and quantitative means of measuring disease progression, greatly facilitating future studies of disease mechanisms and candidate therapeutics.

  11. Tumefactive appearance of peripheral nerve involvement in hematologic malignancies: a new imaging association

    Energy Technology Data Exchange (ETDEWEB)

    Capek, Stepan [Mayo Clinic, Department of Neurosurgery, Rochester, Minnesota (United States); St. Anne' s University Hospital Brno, International Clinical Research Center, Brno (Czech Republic); Hebert-Blouin, Marie-Noelle [McGill University, Department of Neurologic Surgery, Montreal, Quebec (Canada); Puffer, Ross C.; Spinner, Robert J. [Mayo Clinic, Department of Neurosurgery, Rochester, Minnesota (United States); Martinoli, Carlo [Universita degli Studi di Genova, Department of Radiology, Genova (Italy); Frick, Matthew A.; Amrami, Kimberly K. [Mayo Clinic, Department of Radiology, Rochester, MN (United States)

    2015-04-29

    In neurolymphomatosis (NL), the affected nerves are typically described to be enlarged and hyperintense on T2W MR sequences and to avidly enhance on gadolinium-enhanced T1WI. This pattern is highly non-specific. We recently became aware of a ''tumefactive pattern'' of NL, neuroleukemiosis (NLK) and neuroplasmacytoma (NPLC), which we believe is exclusive to hematologic diseases affecting peripheral nerves. We defined a ''tumefactive'' appearance as complex, fusiform, hyperintense on T2WI, circumferential tumor masses encasing the involved peripheral nerves. The nerves appear to be infiltrated by the tumor. Both structures show varying levels of homogenous enhancement. We reviewed our series of 52 cases of NL in search of this pattern; two extra outside cases of NL, three cases of NLK, and one case of NPLC were added to the series. We identified 20 tumefactive lesions in 18 patients (14 NL, three NLK, one NPLC). The brachial plexus (n = 7) was most commonly affected, followed by the sciatic nerve (n = 6) and lumbosacral plexus (n = 3). Four patients had involvement of other nerves. All were proven by biopsy: the diagnosis was high-grade lymphoma (n = 12), low-grade lymphoma (n = 3), acute leukemia (n = 2), and plasmacytoma (n = 1). We present a new imaging pattern of ''tumefactive'' neurolymphomatosis, neuroleukemiosis, or neuroplasmacytoma in a series of 18 cases. We believe this pattern is associated with hematologic diseases directly involving the peripheral nerves. Knowledge of this association can provide a clue to clinicians in establishing the correct diagnosis. Bearing in mind that tumefactive NL, NLK, and NPLC is a newly introduced imaging pattern, we still recommend to biopsy patients with suspicion of a malignancy. (orig.)

  12. Epidemiology of Traumatic Peripheral Nerve Injuries Evaluated by Electrodiagnostic Studies in a Tertiary Care Hospital Clinic.

    Science.gov (United States)

    Torres, Ruben Y; Miranda, Gerardo E

    2015-01-01

    Describe the etiology and frequency of traumatic peripheral nerve injuries (TPNI) in the electrodiagnostic laboratory of a tertiary care hospital. The charts of patients who underwent an electrodiagnostic study for a TPNI were revised. The main outcome measure was the frequency of each injury by anatomic location, involved nerve, mechanism, and severity. 146 charts were included for a total of 163 injured nerves; 109 (74.7%) males and 37 (25.3%) females. The mean age was 33.6 years. The facial nerve and the brachial plexus followed by the ulnar nerve were more frequently involved. The ulnar, sciatic, median, radial nerve, and the lumbosacral plexus were more commonly injured by gunshot wounds, the brachial plexus by motor vehicle accidents, and the facial nerve by iatrogenic causes. The majority of the injuries were incomplete or partial (84.2% were incomplete and 15.8% complete injuries). TPNIs can lead to significant disability, but further investigation is needed to better understand their socio-economic impact.

  13. Local administration of prostaglandin E1 combined with silicone chamber improves peripheral nerve regeneration.

    Science.gov (United States)

    Najafpour, Alireza; Mohammadi, Rahim; Faraji, Darab; Amini, Keyvan

    2013-01-01

    The aim of this study was to assess the effect of locally administered prostaglandin E1 on peripheral nerve regeneration and functional recovery. Sixty male healthy white Wistar rats were divided into four experimental groups (n = 15), randomly: In transected group (TC), left sciatic nerve was transected and stumps were fixed in the adjacent muscle. In treatment group defect was bridged using silicone graft (SIL/PE) filled with 10 μL prostaglandin E1. In silicone graft group (SIL), the graft was filled with phosphate-buffered saline alone. In sham-operated group (SHAM), sciatic nerve was exposed and manipulated. Each group was subdivided into three subgroups of five animals each and regenerated nerve fibers were studied 4, 8 and 12 weeks after surgery. Behavioral testing, sciatic nerve functional study, gastrocnemius muscle mass and morphometric indices confirmed faster recovery of regenerated axons in SIL/PE than SIL group (p prostaglandin E1 improved functional recovery and morphometric indices of sciatic nerve. Local application of prostaglandin E1 improved functional recovery and morphometric indices of sciatic nerve. Copyright © 2013 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

  14. Peripheral Nerve Fibers and Their Neurotransmitters in Osteoarthritis Pathology.

    Science.gov (United States)

    Grässel, Susanne; Muschter, Dominique

    2017-04-28

    The importance of the nociceptive nervous system for maintaining tissue homeostasis has been known for some time, and it has also been suggested that organogenesis and tissue repair are under neuronal control. Changes in peripheral joint innervation are supposed to be partly responsible for degenerative alterations in joint tissues which contribute to development of osteoarthritis. Various resident cell types of the musculoskeletal system express receptors for sensory and sympathetic neurotransmitters, allowing response to peripheral neuronal stimuli. Among them are mesenchymal stem cells, synovial fibroblasts, bone cells and chondrocytes of different origin, which express distinct subtypes of adrenoceptors (AR), receptors for vasoactive intestinal peptide (VIP), substance P (SP) and calcitonin gene-related peptide (CGRP). Some of these cell types synthesize and secrete neuropeptides such as SP, and they are positive for tyrosine-hydroxylase (TH), the rate limiting enzyme for biosynthesis of catecholamines. Sensory and sympathetic neurotransmitters are involved in the pathology of inflammatory diseases such as rheumatoid arthritis (RA) which manifests mainly in the joints. In addition, they seem to play a role in pathogenesis of priori degenerative joint disorders such as osteoarthritis (OA). Altogether it is evident that sensory and sympathetic neurotransmitters have crucial trophic effects which are critical for joint tissue and bone homeostasis. They modulate articular cartilage, subchondral bone and synovial tissue properties in physiological and pathophysiological conditions, in addition to their classical neurological features.

  15. Malignant peripheral nerve sheath tumor of the vulva. A case report.

    Science.gov (United States)

    Maglione, Miguel Angel; Tricarico, Omar Daniel; Calandria, Lucía

    2002-09-01

    Malignant peripheral nerve sheath tumors (MPNSTs) are rare tumors in the head and neck, and their location in the genitalia, especially the vulva, is very rare. An 81-year-old woman with a solid, round vulvar tumor, 2 cm in diameter, underwent a radical hemivulvectomy after recurrence of MPNST with no evidence of neural involvement or stigmata of neurofibromatosis. The tumor cells were positive for S-100 protein and negative for cytokeratin, actin smooth muscle, HMB45 and alpha-1-antitrypsin. The biopsy diagnosis was MPNST with clear surgical margins. The patient was followed for nine months after surgery, without evidence of disease. MPNSTs constitute a small fraction of peripheral nerve tumors. Their site of origin, immunohistochemical staining pattern and ultrastructural morphology are thought to indicate a schwannian origin; however, the histogenesis of the tumor remains controversial. A definite relationship to a peripheral nerve may or may not be present. Diagnosis of MPNST is based on the pathologic appearance, immunohistochemistry and clinical features, such as predominant cell type (spindle cell), nerve involvement or differentiation, and association with neurofibromatosis disease. There have been few documented cases of MPNST arising in the vulva.

  16. Desmoplastic melanoma may mimic a cutaneous peripheral nerve sheath tumor: Report of 3 challenging cases.

    Science.gov (United States)

    Machado, Isidro; Llombart, Beatriz; Cruz, Julia; Traves, Víctor; Requena, Celia; Nagore, Eduardo; Parafioriti, Antonina; Monteagudo, Carlos; Llombart-Bosch, Antonio

    2017-04-12

    Desmoplastic melanoma (DM) and cutaneous malignant peripheral nerve sheath tumors (MPNST) reveal histological and immunohistochemical similarities, including S100 positivity and negative staining for conventional melanocytic markers. We present 3 cases of cutaneous S100-positive spindle cell tumors in elderly patients, in which first findings led to initial misdiagnoses as cutaneous MPNST and benign peripheral sheath nerve tumor (neurofibroma). The identification of adjacent atypical melanocytic hyperplasia in the overlying skin along with tumor cell proliferation, also in the superficial dermis, the neurotropic component and the absence of any relationship between the tumor and a major nerve, pre-existing neural benign tumor or the existence of stigmata suggestive of neurofibromatosis raised consideration of a DM. Careful attention should be paid to the presence of a firm dermal nodule and atypical scar lesions especially in sun-exposed areas (mainly head and neck region) in elderly patients associated with S100-positive spindle cell proliferation, solar elastosis and adjacent atypical melanocytic proliferation. In such cases, the possibility of a DM should be excluded with caution, especially if the tumor reveals a paucicellular morphology resembling various non-melanocytic neoplasms including malignant or benign peripheral sheath nerve tumors. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Peripheral nerve injuries: an international survey of current treatments and future perspectives.

    Science.gov (United States)

    Scholz, Thomas; Krichevsky, Alisa; Sumarto, Andrew; Jaffurs, Daniel; Wirth, Garrett A; Paydar, Keyianoosh; Evans, Gregory R D

    2009-07-01

    Peripheral nerve injuries are a serious health concern and leave many patients with lifelong disabilities. There is little information about incidences, current practice, outcomes, and type of research that may help delineate new strategies. A questionnaire was designed to determine characteristics of peripheral nerve injuries and the need for alternative strategies and sent to 889 plastic, hand, trauma, and orthopedic surgeons in 49 countries; 324 completed surveys were collected and analyzed (total response rate of 36.45%). The majority of institutions treat more than 3000 patients annually. Trauma was the leading cause of injury with the majority located on the upper extremity. In most cases, a primary repair was achieved, but 2.52% were unrepairable. The overall outcome was linked to their Sunderland classification (SCL). A grade 1 nerve injury (SCL-1) reached a maximum outcome after 7.15 months. SCL-2, -3, -4, and -5 needed 10.69, 14.08, 17.66, and 19.03 months, respectively. Tissue engineering was considered the most important research field, resulting in a visual analogue scale of 8.6. Despite marked advances in the treatment of peripheral nerve injuries, clinical outcomes still appear unsatisfactory. The importance of research in the field of tissue engineering should be emphasized as a pathway toward improving these outcomes.

  18. Peripheral nerve injury induces a transitory microglial reaction in the rat infralimbic cortex.

    Science.gov (United States)

    Chu Sin Chung, Paul; Panigada, Tania; Cardis, Romain; Decosterd, Isabelle; Gosselin, Romain-Daniel

    2017-08-10

    Undeniable evidence shows that microglia in the spinal cord undergo marked reactions following peripheral injuries. However, only rare studies have investigated the possible short and long term microglial reaction in brain regions following peripheral nerve injury and its interspecies specificities. In the present study we examined microglia in subdivisions of the prefrontal cortex in mice and rats, 7days and 42days after spared nerve injury (SNI) of the sciatic nerve. We show that a bilateral increase of microglial density takes place in the infralimbic cortex in rats 7days post-injury (sham vs. SNI, n=5: ipsilateral 35.4% increase of the median, p=0.0317; contralateral 24.9% increase of the median, p=0.0079), without any detectable change in the other investigated regions, namely the anterior cingulate, prelimbic and agranular insular cortices. In mice, no observable difference could be found in any region at both time points, neither using Iba-1 immunostaining nor with CX3CR1-eGFP animals. Our results indicate that a transitory, species-specific and highly regionalized microglial reaction takes place in the prefrontal cortex following peripheral nerve injury. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Shi-lei Guo

    2015-01-01

    Full Text Available 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.

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

    International Nuclear Information System (INIS)

    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 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 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

  1. Future considerations for pharmacologic adjuvants in single-injection peripheral nerve blocks for patients with diabetes mellitus.

    Science.gov (United States)

    Williams, Brian A; Murinson, Beth B; Grable, Benjamin R; Orebaugh, Steven L

    2009-01-01

    As the epidemics of obesity and diabetes expand, there are more patients with these disorders requiring elective surgery. For surgery on the extremities, peripheral nerve blocks have become a highly favorable anesthetic option when compared with general anesthesia. Peripheral blocks reduce respiratory and cardiac stresses, while potentially mitigating untreated peripheral pain that can foster physiologic conditions that increase risks for general health complications. However, local anesthetics are generally accepted to be a rare but possible cause of nerve damage, and there are no evidence-based recommendations for dosing local anesthetic nerve blocks in patients with diabetes. This is important because anesthesiologists do not want to potentially accelerate peripheral nerve dysfunction in diabetic patients at risk. This translational vignette (i) examines laboratory models of diabetes, (ii) summarizes the pharmacology of perineural adjuvants (epinephrine, clonidine, buprenorphine, midazolam, tramadol, and dexamethasone), and (iii) identifies areas that warrant further research to determine viability of monotherapy or combination therapy for peripheral nerve analgesia in diabetic patients. Conceivably, future translational research regarding peripheral nerve blocks in diabetic patients may logically include study of nontoxic injectable analgesic adjuvants, in combination, to provide desired analgesia, while possibly avoiding peripheral nerve toxicity that diabetic animal models have exhibited when exposed to traditional local anesthetics.

  2. 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.

    Science.gov (United States)

    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

  3. Design and synthesis of elastin-like polypeptides for an ideal nerve conduit in peripheral nerve regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Hsueh, Yu-Sheng [Institute of Biomedical Engineering, College of Engineering, National Taiwan University, Taipei 100, Taiwan (China); Institute of Biomedical Engineering, College of Medicine, National Taiwan University, Taipei 100, Taiwan (China); Savitha, S. [Institute of Biomedical Engineering, College of Engineering, National Taiwan University, Taipei 100, Taiwan (China); Department of Biotechnology, Sree Sastha Institute of Engineering and Technology, Chennai (India); Institute of Biomedical Engineering, College of Medicine, National Taiwan University, Taipei 100, Taiwan (China); Sadhasivam, S. [Division of Biomedical Engineering and Nanomedicine Research, National Health Research Institutes, Miaoli 350, Taiwan (China); Lin, Feng-Huei, E-mail: double@ntu.edu.tw [Institute of Biomedical Engineering, College of Engineering, National Taiwan University, Taipei 100, Taiwan (China); Division of Biomedical Engineering and Nanomedicine Research, National Health Research Institutes, Miaoli 350, Taiwan (China); Institute of Biomedical Engineering, College of Medicine, National Taiwan University, Taipei 100, Taiwan (China); Shieh, Ming-Jium [Institute of Biomedical Engineering, College of Engineering, National Taiwan University, Taipei 100, Taiwan (China); College of Medicine, National Taiwan University Hospital, Taipei 100, Taiwan (China); Institute of Biomedical Engineering, College of Medicine, National Taiwan University, Taipei 100, Taiwan (China)

    2014-05-01

    The study involves design and synthesis of three different elastin like polypeptide (ELP) gene monomers namely ELP1, ELP2 and ELP3 that encode for ELP proteins. The formed ELPs were assessed as an ideal nerve conduit for peripheral nerve regeneration. ELP1 was constructed with a small elongated pentapeptide carrying VPGVG sequence to mimic the natural polypeptide ELP. The ELP2 was designed by the incorporation of 4-penta peptide chains to improve the biocompatibility and mechanical strength. Thus, the third position in unique VPGVG was replaced with alanine to VPAVG and in a similar way modified to VPGKG, VPGEG and VPGIG with the substitution of lysine, glutamic acid and isoleucine. In ELP3, fibronectin C5 domain endowed with REDV sequence was introduced to improve the cell attachment. The ELP1, ELP2 and ELP3 proteins expressed by Escherichia coli were purified by inverse transition cycling (ITC). The purified ELPs were confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting. The Schwann cell (SC) morphology and cell adhesion were assessed by fabrication of ELP membrane cross-linked with glutaraledhyde. The Schwann cell proliferation was measured by WST-1 assay. Immunofluorostaining of Schwann cells was accomplished with SC specific phenotypic marker, S100. - Highlights: • Design and synthesis of three gene monomers of elastin like polypeptides (ELP1, 2 and 3) were reported. • Molecular weight of ITC purified ELP1, ELP2 and ELP3 was in the range of 37–38 kDa. • Schwann cell adhesion was found to be prominent in ELP3 and could be used as nerve conduit for peripheral nerve regeneration.

  4. Design and synthesis of elastin-like polypeptides for an ideal nerve conduit in peripheral nerve regeneration

    International Nuclear Information System (INIS)

    Hsueh, Yu-Sheng; Savitha, S.; Sadhasivam, S.; Lin, Feng-Huei; Shieh, Ming-Jium

    2014-01-01

    The study involves design and synthesis of three different elastin like polypeptide (ELP) gene monomers namely ELP1, ELP2 and ELP3 that encode for ELP proteins. The formed ELPs were assessed as an ideal nerve conduit for peripheral nerve regeneration. ELP1 was constructed with a small elongated pentapeptide carrying VPGVG sequence to mimic the natural polypeptide ELP. The ELP2 was designed by the incorporation of 4-penta peptide chains to improve the biocompatibility and mechanical strength. Thus, the third position in unique VPGVG was replaced with alanine to VPAVG and in a similar way modified to VPGKG, VPGEG and VPGIG with the substitution of lysine, glutamic acid and isoleucine. In ELP3, fibronectin C5 domain endowed with REDV sequence was introduced to improve the cell attachment. The ELP1, ELP2 and ELP3 proteins expressed by Escherichia coli were purified by inverse transition cycling (ITC). The purified ELPs were confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting. The Schwann cell (SC) morphology and cell adhesion were assessed by fabrication of ELP membrane cross-linked with glutaraledhyde. The Schwann cell proliferation was measured by WST-1 assay. Immunofluorostaining of Schwann cells was accomplished with SC specific phenotypic marker, S100. - Highlights: • Design and synthesis of three gene monomers of elastin like polypeptides (ELP1, 2 and 3) were reported. • Molecular weight of ITC purified ELP1, ELP2 and ELP3 was in the range of 37–38 kDa. • Schwann cell adhesion was found to be prominent in ELP3 and could be used as nerve conduit for peripheral nerve regeneration

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

    Science.gov (United States)

    2017-10-01

    6. AUTHOR(S) 5d.  PROJECT  NUMBER   Rocky Tuan, Peter Alexander 5e.  TASK  NUMBER   E-­Mail:    rst13@pitt.edu   5f.   WORK  UNIT  NUMBER 7...than 3 cm, mainly because of their lack of appropriate nerve-enhancing biological activities. In our current work , we have identified and isolated...seeded conduits exhibit a remarkable ability to allow for S100 schwann cell migration into the growing nerve with complete continuity after only 6 weeks

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

    Science.gov (United States)

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

    2017-05-01

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

  7. Peripheral nervous system manifestations in a Sandhoff disease mouse model: nerve conduction, myelin structure, lipid analysis

    Directory of Open Access Journals (Sweden)

    Strichartz Gary R

    2007-07-01

    Full Text Available Abstract Background Sandhoff disease is an inherited lysosomal storage disease caused by a mutation in the gene for the β-subunit (Hexb gene of β-hexosaminidase A (αβ and B (ββ. The β-subunit together with the GM2 activator protein catabolize ganglioside GM2. This enzyme deficiency results in GM2 accumulation primarily in the central nervous system. To investigate how abnormal GM2 catabolism affects the peripheral nervous system in a mouse model of Sandhoff disease (Hexb-/-, we examined the electrophysiology of dissected sciatic nerves, structure of central and peripheral myelin, and lipid composition of the peripheral nervous system. Results We detected no significant difference in signal impulse conduction velocity or any consistent change in the frequency-dependent conduction slowing and failure between freshly dissected sciatic nerves from the Hexb+/- and Hexb-/- mice. The low-angle x-ray diffraction patterns from freshly dissected sciatic and optic nerves of Hexb+/- and Hexb-/- mice showed normal myelin periods; however, Hexb-/- mice displayed a ~10% decrease in the relative amount of compact optic nerve myelin, which is consistent with the previously established reduction in myelin-enriched lipids (cerebrosides and sulfatides in brains of Hexb-/- mice. Finally, analysis of lipid composition revealed that GM2 content was present in the sciatic nerve of the Hexb-/- mice (undetectable in Hexb+/-. Conclusion Our findings demonstrate the absence of significant functional, structural, or compositional abnormalities in the peripheral nervous system of the murine model for Sandhoff disease, but do show the potential value of integrating multiple techniques to evaluate myelin structure and function in nervous system disorders.

  8. A novel concept for continuous peripheral nerve blocks. Presentation of a new ultrasound-guided device.

    Science.gov (United States)

    Rothe, C; Steen-Hansen, C; Madsen, M H; Lange, K H W

    2015-02-01

    Existing techniques for placing and maintaining the position of peripheral nerve catheters are associated with variable success rates and frequent secondary failures. These factors may affect the clinical efficacy and usefulness of peripheral nerve catheters. We developed a new concept and prototype for ultrasound-guided in-plane positioning and readjustment of peripheral nerve catheters (patent pending). The integrated catheter-needle prototype comprises three parts: a curved needle, a catheter with clear echogenic markings attached to the needle tail and a detachable hub allowing injection of local anesthetic while advancing the needle in the tissue. The system works like a suture and is introduced through the skin, passes in close relation to the nerve and exits through the skin. This allows in-plane ultrasound guidance throughout the procedure both during initial positioning as well as during later in-plane readjustment of the catheter. We tested the system in the popliteal region of two fresh cadavers in a preliminary proof of concept study. Both initial placement and secondary readjustment were precise, judged by the catheter orifices placed close to the sciatic nerve in the popliteal fossa. Circumferential spread of 3-ml isotonic saline around the sciatic nerve was observed on ultrasound images in both conditions. Preliminary proof of concept of this novel method demonstrates that precise in-plane ultrasound-guided initial placement and secondary in-plane readjustment is possible in fresh cadavers. Future studies should address the clinical efficacy and usefulness of this novel concept. © 2014 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  9. Sequential variation in brain functional magnetic resonance imaging after peripheral nerve injury: A rat study.

    Science.gov (United States)

    Onishi, Okihiro; Ikoma, Kazuya; Oda, Ryo; Yamazaki, Tetsuro; Fujiwara, Hiroyoshi; Yamada, Shunji; Tanaka, Masaki; Kubo, Toshikazu

    2018-03-07

    Although treatment protocols are available, patients experience both acute neuropathic pain and chronic neuropathic pain, hyperalgesia, and allodynia after peripheral nerve injury. The purpose of this study was to identify the brain regions activated after peripheral nerve injury using functional magnetic resonance imaging (fMRI) sequentially and assess the relevance of the imaging results using histological findings. To model peripheral nerve injury in male Sprague-Dawley rats, the right sciatic nerve was crushed using an aneurysm clip, under general anesthesia. We used a 7.04T MRI system. T 2 * weighted image, coronal slice, repetition time, 7 ms; echo time, 3.3 ms; field of view, 30 mm × 30 mm; pixel matrix, 64 × 64 by zero-filling; slice thickness, 2 mm; numbers of slices, 9; numbers of average, 2; and flip angle, 8°. fMR images were acquired during electrical stimulation to the rat's foot sole; after 90 min, c-Fos immunohistochemical staining of the brain was performed in rats with induced peripheral nerve injury for 3, 6, and 9 weeks. Data were pre-processed by realignment in the Statistical Parametric Mapping 8 software. A General Linear Model first level analysis was used to obtain T-values. One week after the injury, significant changes were detected in the cingulate cortex, insular cortex, amygdala, and basal ganglia; at 6 weeks, the brain regions with significant changes in signal density were contracted; at 9 weeks, the amygdala and hippocampus showed activation. Histological findings of the rat brain supported the fMRI findings. We detected sequential activation in the rat brain using fMRI after sciatic nerve injury. Many brain regions were activated during the acute stage of peripheral nerve injury. Conversely, during the chronic stage, activation of the amygdala and hippocampus may be related to chronic-stage hyperalgesia, allodynia, and chronic neuropathic pain. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. A review of nerve conduction studies in cases of suspected compression neuropathies of the upper limb.

    LENUS (Irish Health Repository)

    Neligan, A

    2010-01-01

    Entrapment neuropathies, particularly those affecting upper limbs, are common reasons for referral for nerve conduction studies (NCS). However, concordance between clinical findings and NCS findings, especially in patients being considered for intervention including decompressive surgery, has not been assessed.

  11. Evaluation of Na+/K+ pump function following repetitive activity in mouse peripheral nerve

    DEFF Research Database (Denmark)

    Moldovan, Mihai; Krarup, Christian

    2006-01-01

    After conduction of prolonged trains of impulses the increased Na+/K+ pump activity leads to hyperpolarization. The aim of this study was to develop a mouse model to investigate the Na+/K+ pump function in peripheral nerve by measuring the decrease in excitability during activity...... change after repetitive stimulation of the mouse tibial nerve is an indicator of the Na+/K+ pump function in vivo. Evaluation of activity-dependent hyperpolarization may be an important indicator of axonal ability to cope with Na+ load....

  12. Peripheral nerve injuries in weight training: sites, pathophysiology, diagnosis, and treatment.

    Science.gov (United States)

    Lodhia, Keith R; Brahma, Barunashish; McGillicuddy, John E

    2005-07-01

    Direct trauma, compression caused by muscle hypertrophy or other soft tissue changes, or excessive stretching of a peripheral nerve in the upper extremity may lead to uncommon-but potentially serious-complications. Clinicians are seeing more of these injuries as weight training, power lifting, bodybuilding, cross-training, and general physical conditioning with weights become more popular. Symptoms of pain, weakness, paresthesia, or palsy; physical exam findings; electromyography; and nerve conduction studies are used to make the diagnosis. Most conditions respond well to conservative measures, such as rest from the offending exercise and correction of poor technique, but surgery may be required for complete clinical resolution in severe cases.

  13. Entropion in children with isolated peripheral facial nerve paresis.

    Science.gov (United States)

    Alsuhaibani, A H; Bosley, T M; Goldberg, R A; Al-Faky, Y H

    2012-08-01

    Adults with facial nerve paresis (FNP) generally develop ectropion, but a recent report of children with syndromatic FNPs implies that entropion may be more common in this setting than ectropion. This study evaluates eyelid position and other periorbital changes in children with isolated, non-syndromatic FNP. Charts were reviewed of 10 sequential children who presented to a major national eye referral centre with isolated FNP of variable aetiology. Severity of FNP was assessed according to the House-Brackmann scale. All 10 patients (4 males and 6 females; mean age at presentation, 4 years) had unilateral, isolated FNP. Mild lower-eyelid entropion was present in four patients, and severe lower-eyelid entropion required surgical correction in three patients. All patients had lower eyelid retraction (mean 2.3 mm) and lagophthalmos (mean 2.9 mm). None had enophthalmos, lower eyelid ectropion, or brow ptosis. Unlike adults, children with isolated FNP seem prone to develop entropion rather than ectropion. Entropion reported previously in five syndromic children with FNP seems more likely related to patients' age than to their congenital syndromes.

  14. Peripheral nervous system maturation in preterm infants: longitudinal motor and sensory nerve conduction studies.

    Science.gov (United States)

    Lori, S; Bertini, Giovanna; Bastianelli, M; Gabbanini, S; Gualandi, D; Molesti, E; Dani, C

    2018-04-10

    To study the evolution of sensory-motor nerves in the upper and lower limbs in neurologically healthy preterm infants and to use sensory-motor studies to compare the rate of maturation in preterm infants at term age and full-term healthy neonates. The study comprised 26 neurologically normal preterm infants born at 23-33 weeks of gestational age, who underwent sensory nerve conduction and motor nerve conduction studies from plantar medial and median nerves and from tibial and ulnar nerves, respectively. We repeated the same neurophysiological studies in 19 of the preterm infants every 2 weeks until postnatal term age. The data from the preterm infants at term was matched with a group of ten full-term babies a few days after birth. The motor nerve conduction velocity of the tibial and ulnar nerves showed progressive increases in values in relation to gestational age, but there was a decrease of values in distal latencies and F wave latencies. Similarly, there was a gradual increase of sensory nerve conduction velocity values of the medial plantar and median nerves and decreases in latencies in relation to gestational age. At term age, the preterm infants showed significantly lower values of conduction velocities and distal latencies than the full-term neonates. These results were probably because the preterm infants had significantly lower weights, total length and, in particular, distal segments of the limbs at term age. The sensory-motor conduction parameters were clearly related to gestational age, but extrauterine life did not affect the maturation of the peripheral nervous system in the very preterm babies who were neurologically healthy.

  15. Role of IL-10 in Resolution of Inflammation and Functional Recovery after Peripheral Nerve Injury.

    Science.gov (United States)

    Siqueira Mietto, Bruno; Kroner, Antje; Girolami, Elizabeth I; Santos-Nogueira, Eva; Zhang, Ji; David, Samuel

    2015-12-16

    A rapid proinflammatory response after peripheral nerve injury is required for clearance of tissue debris (Wallerian degeneration) and effective regeneration. Unlike the CNS, this response is rapidly terminated in peripheral nerves starting between 2 and 3 weeks after crush injury. We examined the expression and role of the anti-inflammatory cytokine IL-10 in the resolution of inflammation and regeneration after sciatic nerve crush injury in mice. IL-10 mRNA increased over the first 7 d after injury, whereas at the protein level, immunofluorescence labeling showed IL-10(+) cells increased almost 3-fold in the first 3 weeks, with macrophages being the major cell type expressing IL-10. The role of IL-10 in nerve injury was assessed using IL-10-null mice. Increased numbers of macrophages were found in the distal segment of IL-10-null mice at early (3 d) and late (14 and 21 d) time points, suggesting that IL-10 may play a role in controlling the early influx and the later efflux of macrophages out of the nerve. A chemokine/cytokine PCR array of the nerve 24 h after crush showed a 2- to 4-fold increase in the expression of 10 proinflammatory mediators in IL-10(-/-) mice. In addition, myelin phagocytosis in vitro by LPS stimulated bone-marrow-derived macrophages from IL-10-null mice failed to downregulate expression of proinflammatory chemokines/cytokines, suggesting that IL-10 is required for the myelin-phagocytosis-induced shift of macrophages from proinflammatory to anti-inflammatory/pro-repair phenotype. The failure to switch off inflammation in IL-10-null mice was accompanied by impaired axon regeneration and poor recovery of motor and sensory function. An appropriately regulated inflammatory response after peripheral nerve injury is essential for axon regeneration and recovery. The aim of this study was to investigate the expression and role of the anti-inflammatory cytokine IL-10 in terminating inflammation after sciatic nerve crush injury and promoting

  16. Adverse outcomes associated with nerve stimulator-guided and ultrasound-guided peripheral nerve blocks by supervised trainees: update of a single-site database.

    Science.gov (United States)

    Orebaugh, Steven L; Kentor, Michael L; Williams, Brian A

    2012-01-01

    We previously published a retrospective review of complications related to peripheral nerve blocks performed by supervised trainees, from our quality assurance and billing data, guided by either ultrasound, with nerve stimulator confirmation, or landmark-based nerve stimulator techniques. This report updates our results, for the period from May 2008 through December 2011, representing ongoing transition to near-complete combined ultrasound/nerve stimulator guidance in a block-oriented, outpatient orthopedic anesthesia practice. We queried our deidentified departmental quality improvement electronic database for adverse outcomes associated with peripheral nerve blocks. Billing records were also deidentified and used to provide the denominator of total number of blocks using each technique of neurolocation. The types of blocks considered in this analysis were interscalene, axillary, femoral, sciatic, and popliteal-sciatic blocks. Nerve block complications based on each type of guidance were then compared for the entire recent 30-month time period, as well as for the 6-year period of this report. There were 9062 blocks performed by ultrasound/nerve stimulator, and 5436 by nerve stimulator alone over the entire 72-month period. Nerve injuries lasting longer than 1 year were rare, but similar in frequency with both nerve guidance techniques. The incidence of local anesthetic systemic toxicity was found to be higher with landmark-nerve stimulator technique than with use of ultrasound-guided nerve blocks (6/5436 vs 0/9069, P = 0.0061). We report a large series of combined ultrasound/nerve stimulator nerve blocks by supervised trainees without major local anesthetic systemic toxicity. While lacking the compelling evidence of randomized controlled trials, this observational database nonetheless allows increased confidence in the safety of using combined ultrasound/nerve stimulator in the setting of anesthesiologists-in-training.

  17. Some questions of the treatment of injuries of extremities peripheral nerves

    Directory of Open Access Journals (Sweden)

    Виктор Александрович Вишневский

    2015-11-01

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

  18. Model-based Bayesian signal extraction algorithm for peripheral nerves

    Science.gov (United States)

    Eggers, Thomas E.; Dweiri, Yazan M.; McCallum, Grant A.; Durand, Dominique M.

    2017-10-01

    Objective. Multi-channel cuff electrodes have recently been investigated for extracting fascicular-level motor commands from mixed neural recordings. Such signals could provide volitional, intuitive control over a robotic prosthesis for amputee patients. Recent work has demonstrated success in extracting these signals in acute and chronic preparations using spatial filtering techniques. These extracted signals, however, had low signal-to-noise ratios and thus limited their utility to binary classification. In this work a new algorithm is proposed which combines previous source localization approaches to create a model based method which operates in real time. Approach. To validate this algorithm, a saline benchtop setup was created to allow the precise placement of artificial sources within a cuff and interference sources outside the cuff. The artificial source was taken from five seconds of chronic neural activity to replicate realistic recordings. The proposed algorithm, hybrid Bayesian signal extraction (HBSE), is then compared to previous algorithms, beamforming and a Bayesian spatial filtering method, on this test data. An example chronic neural recording is also analyzed with all three algorithms. Main results. The proposed algorithm improved the signal to noise and signal to interference ratio of extracted test signals two to three fold, as well as increased the correlation coefficient between the original and recovered signals by 10–20%. These improvements translated to the chronic recording example and increased the calculated bit rate between the recovered signals and the recorded motor activity. Significance. HBSE significantly outperforms previous algorithms in extracting realistic neural signals, even in the presence of external noise sources. These results demonstrate the feasibility of extracting dynamic motor signals from a multi-fascicled intact nerve trunk, which in turn could extract motor command signals from an amputee for the end goal of

  19. Rapid Turnover of Cortical NCAM1 Regulates Synaptic Reorganization after Peripheral Nerve Injury

    Directory of Open Access Journals (Sweden)

    Hyoung-Gon Ko

    2018-01-01

    Full Text Available Peripheral nerve injury can induce pathological conditions that lead to persistent sensitized nociception. Although there is evidence that plastic changes in the cortex contribute to this process, the underlying molecular mechanisms are unclear. Here, we find that activation of the anterior cingulate cortex (ACC induced by peripheral nerve injury increases the turnover of specific synaptic proteins in a persistent manner. We demonstrate that neural cell adhesion molecule 1 (NCAM1 is one of the molecules involved and show that it mediates spine reorganization and contributes to the behavioral sensitization. We show striking parallels in the underlying mechanism with the maintenance of NMDA-receptor- and protein-synthesis-dependent long-term potentiation (LTP in the ACC. Our results, therefore, demonstrate a synaptic mechanism for cortical reorganization and suggest potential avenues for neuropathic pain treatment.

  20. Tyrosinase expression in malignant melanoma, desmoplastic melanoma, and peripheral nerve tumors

    DEFF Research Database (Denmark)

    Boyle, Jenny L; Haupt, Helen M; Stern, Jere B

    2002-01-01

    CONTEXT: Pathologists may encounter problems in the differential diagnosis of malignant melanoma, spindle and epithelioid neoplasms of peripheral nerves, and fibrohistiocytic tumors. Tyrosinase has been demonstrated to be a sensitive marker for melanoma. OBJECTIVE: To determine the specificity...... of tyrosinase expression in the differential diagnosis of melanoma, desmoplastic melanoma, and peripheral nerve sheath tumors. DESIGN: Immunoreactivity for tyrosinase, HMB-45 (anti-gp100 protein), S100 protein, CD34, and vimentin was studied in 70 tumors, including 15 melanomas (5 desmoplastic, 4 amelanotic, 6...... at 121 degrees C. RESULTS: All melanomas demonstrated positive immunostaining for tyrosinase, HMB-45, and S100 protein. Immunoreactivity for HMB-45 was generally stronger than that for tyrosinase in amelanotic lesions and significantly stronger in 1 of the desmoplastic lesions. The 4 pigmented...

  1. Rapid Turnover of Cortical NCAM1 Regulates Synaptic Reorganization after Peripheral Nerve Injury.

    Science.gov (United States)

    Ko, Hyoung-Gon; Choi, Jun-Hyeok; Park, Dong Ik; Kang, SukJae Joshua; Lim, Chae-Seok; Sim, Su-Eon; Shim, Jaehoon; Kim, Ji-Il; Kim, Siyong; Choi, Tae-Hyeok; Ye, Sanghyun; Lee, Jaehyun; Park, Pojeong; Kim, Somi; Do, Jeehaeh; Park, Jihye; Islam, Md Ariful; Kim, Hyun Jeong; Turck, Christoph W; Collingridge, Graham L; Zhuo, Min; Kaang, Bong-Kiun

    2018-01-16

    Peripheral nerve injury can induce pathological conditions that lead to persistent sensitized nociception. Although there is evidence that plastic changes in the cortex contribute to this process, the underlying molecular mechanisms are unclear. Here, we find that activation of the anterior cingulate cortex (ACC) induced by peripheral nerve injury increases the turnover of specific synaptic proteins in a persistent manner. We demonstrate that neural cell adhesion molecule 1 (NCAM1) is one of the molecules involved and show that it mediates spine reorganization and contributes to the behavioral sensitization. We show striking parallels in the underlying mechanism with the maintenance of NMDA-receptor- and protein-synthesis-dependent long-term potentiation (LTP) in the ACC. Our results, therefore, demonstrate a synaptic mechanism for cortical reorganization and suggest potential avenues for neuropathic pain treatment. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    2016-10-01

    Demonstration of nerve repair in vivo using cell-laden MPC-NC prepared in a point-of- care single- step procedure (9/30/18, 0%)  The major... osteogenesis may be constructed by the 3D printing method of projection stereolithography (PSL) to produce functional osteochondral constructs using...temporospatially specific differentiation cues for chondrogenesis and osteogenesis may be constructed by the 3D printing method of projection

  3. Enhancing Peripheral Nerve Regeneration with a Novel Drug Delivering Nerve Conduit

    Science.gov (United States)

    2014-10-01

    stump. Silicone sealant and a PDMS plug are used to seal and fix the two tubes. First generation device: Due to its relatively short half life...tubes of the PLGA nerve conduit. A polyether sulfone (PES) filter membrane, a polydimethyl siloxane (PDMS) plug and silicone sealant (RTV silicone , Dow...filled with the desired drug and sealed using the PDMS plug end with silicone sealant . The device was dried for 1 hour and then mounted individually

  4. Time-dependent differential expression of long non-coding RNAs following peripheral nerve injury.

    Science.gov (United States)

    Pan, Bin; Zhou, Heng-Xing; Liu, Yi; Yan, Jia-Yin; Wang, Yao; Yao, Xue; Deng, Yan-Qiu; Chen, Shu-Yi; Lu, Lu; Wei, Zhi-Jian; Kong, Xiao-Hong; Feng, Shi-Qing

    2017-06-01

    Long non-coding RNAs (lncRNAs) are widely accepted as key players in various biological processes. However, the roles of lncRNA in peripheral nerve regeneration remain completely unknown. Thus, in this study, we performed microarray analysis to measure lncRNA expression in the distal segment of the sciatic nerve at 0, 3, 7 and 14 days following injury. We identified 5,354 lncRNAs that were differentially expressed: 3,788 lncRNAs were differentially expressed between days 0 and 3; 3,314 lncRNAs were differentially expressed between days 0 and 7; and 2,400 lncRNAs were differentially expressed between days 0 and 14. The results of RT-qPCR of two dysregulated lncRNAs were consistent with those of microarray analysis. Bioinformatics approaches, including lncRNA classification, gene ontology (GO) analysis and target prediction, were utilized to investigate the functions of these dysregulated lncRNAs in peripheral nerve damage. Importantly, we predicted that several lncRNA-mRNA pairs may participate in biological processes related to peripheral nerve injury. RT-qPCR was performed for the preliminary verification of three lncRNA‑mRNA pairs. The overexpression of NONMMUG014387 promoted the proliferation of mouse Schwann cells. Thus, the findings of our study may enhance our knowledge of the role of lncRNAs in nerve injury.

  5. [Malignant peripheral nerve sheath tumor with perineural differentiation (malignant perineurinoma) of the cervix uteri].

    Science.gov (United States)

    Dolzhikov, A A; Mukhina, T S

    2014-01-01

    The paper describes a case of a malignant peripheral nerve sheath tumor with perineural differentiation and at the rare site of the cervix uteri in a 57-year-old patient. The diagnosis was established on the basis of extensive immunohistochemical examination, by excluding the similar neoplasms and detecting an immunophenotype characteristic of perineural differentiation. There are data available in the literature on the morphological and immunophenotypical characteristics of this tumor.

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

    Science.gov (United States)

    2017-07-01

    AWARD NUMBER: W81XWH-16-0-DM167033 TITLE: Establishment of Peripheral Nerve Injury Data Repository to Monitor and Support Population Health...Injury Data Repository to Monitor and Support Population Health Decisions 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-16-0-DM167033 5c. PROGRAM...patient enrollment. Collected data will be utilized to 1) describe the outcomes of various PNI and 2) suggest outcomes that support population health

  7. Behavioral models of pain states evoked by physical injury to the peripheral nerve

    OpenAIRE

    Sorkin, Linda S.; Yaksh, Tony L.

    2009-01-01

    Physical injury or compression of the root, dorsal root ganglion, or peripheral sensory axon leads to well-defined changes in biology and function. Behaviorally, humans report ongoing painful dysesthesias and aberrations in function, such that an otherwise innocuous stimulus will yield a pain report. These behavioral reports are believed to reflect the underlying changes in nerve function after injury, wherein increased spontaneous activity arises from the neuroma and dorsal root ganglion and...

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

    DEFF Research Database (Denmark)

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

    2009-01-01

    of the present study was to evaluate the long-term clinical efficacy of PNS in a group of patients with peripheral neuropathic pain treated with PNS since the 1980s. METHODS: Of an original series of 11 patients, 5 patients could be invited for clinical examination, detailed assessment of clinical pain and QST...

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Weimin Liu

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

  11. Technical Note: Treatment of Sacroiliac Joint Pain with Peripheral Nerve Stimulation.

    Science.gov (United States)

    Guentchev, Marin; Preuss, Christian; Rink, Rainer; Peter, Levente; Wocker, Ernst-Ludwig; Tuettenberg, Jochen

    2015-07-01

    Sacroiliac joint (SIJ) pain affects older adults with a prevalence of up to 20% among patients with chronic low back pain. While pain medication, joint blocks and denervation procedures achieve pain relief in most patients, some cases fail to improve. Our goal was to determine the effectiveness of SIJ peripheral nerve stimulation in patients with severe conservative therapy-refractory SIJ pain. Here we present 12 patients with severe conservative therapy-refractory pain receiving an SIJ peripheral nerve stimulation. Patient satisfaction, pain, and quality of life were evaluated by means of the International Patient Satisfaction Index (IPSI), visual analog scale (VAS), and Oswestry Disability Index 2.0 (ODI) using standard questionnaires. For stimulation we placed an eight-pole peripheral nerve electrode parallel to the SIJ. Two weeks postoperatively, our patients reported an average ODI reduction from 57% to 32% and VAS from 9 to 2.1. IPSI was 1.1. After six months, the therapy was rated as effective in seven out of eight patients reporting at that period. The average ODI was low at 34% (p = 0.0006), while the VAS index rose to 3.8 (p VAS 1.7 (p < 0.0001), and IPSI 1.3. We conclude that SIJ stimulation is a promising therapeutic strategy in the treatment of intractable SIJ pain. Further studies are required to determine the precise target group and long-term effect of this novel treatment method. © 2014 International Neuromodulation Society.

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

    Science.gov (United States)

    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.

  13. Myelination of the Postnatal Mouse Cochlear Nerve at the Peripheral-Central Nervous System Transitional Zone

    Directory of Open Access Journals (Sweden)

    Jue eWang

    2013-12-01

    Full Text Available In the nerve roots of vertebrates, the peripheral nervous system (PNS and central nervous system (CNS interface at the PNS-CNS transitional zone (PCTZ, which consists of cell boundaries with various myelin components. We have recently shown that the mouse cochlear nerve presents an exceptionally long segment of the CNS tissue extending into the PNS using light microscopy. However, it is unclear how oligodendrocytes and Schwann cells contribute to the formation of myelin components of the PCTZ. It is undetermined how myelination is initiated along the cochlear nerve, and when it adopts a mature pattern. In this study, immunofluorescence using antibodies specific to oligodendrocyte marker myelin oligodendrocyte glycoprotein (MOG and Schwann cell marker myelin protein zero (MPZ were used to detail the expression of myelin components along the postnatal mouse cochlear nerve. We found that the expression of MPZ was initially observed in the soma of bipolar spiral ganglion neurons at postnatal day 0 (P0 and progressed to the central and peripheral processes after P8-P10. Myelination of the CNS tissue was initiated in close proximity to the PCTZ from P7-P8 and then extended centrally. Myelination of the PCTZ reached a mature style at P14, when the interface of the expression of MOG and MPZ was clearly identified along the cochlear nerve. This knowledge of PCTZ formation of the cochlear nerve will be essential to future myelination research, and it will also gain clinical interest because of its relevance to the degeneration and regeneration of the auditory pathway in hearing impairment.

  14. Selective Fiber Degeneration in the Peripheral Nerve of a Patient With Severe Complex Regional Pain Syndrome

    Directory of Open Access Journals (Sweden)

    Adrien Yvon

    2018-04-01

    Full Text Available Aims: Complex regional pain syndrome (CRPS is characterized by chronic debilitating pain disproportional to the inciting event and accompanied by motor, sensory, and autonomic disturbances. The pathophysiology of CRPS remains elusive. An exceptional case of severe CRPS leading to forearm amputation provided the opportunity to examine nerve histopathological features of the peripheral nerves.Methods: A 35-year-old female developed CRPS secondary to low voltage electrical injury. The CRPS was refractory to medical therapy and led to functional loss of the forelimb, repeated cutaneous wound infections leading to hospitalization. Specifically, the patient had exhausted a targeted conservative pain management programme prior to forearm amputation. Radial, median, and ulnar nerve specimens were obtained from the amputated limb and analyzed by light and transmission electron microscopy (TEM.Results: All samples showed features of selective myelinated nerve fiber degeneration (47–58% of fibers on electron microscopy. Degenerating myelinated fibers were significantly larger than healthy fibers (p < 0.05, and corresponded to the larger Aα fibers (motor/proprioception whilst smaller Aδ (pain/temperature fibers were spared. Groups of small unmyelinated C fibers (Remak bundles also showed evidence of degeneration in all samples.Conclusions: We are the first to show large fiber degeneration in CRPS using TEM. Degeneration of Aα fibers may lead to an imbalance in nerve signaling, inappropriately triggering the smaller healthy Aδ fibers, which transmit pain and temperature. These findings suggest peripheral nerve degeneration may play a key role in CRPS. Improved knowledge of pathogenesis will help develop more targeted treatments.

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

    Science.gov (United States)

    2017-10-01

    studies, which will be used to develop testing in a large, clinically relevant animal model, as a basis for future clinical trial. Our long-term goal...provide sufficient information to move to MPC-NC technology to testing in a large, clinically relevant animal model, which will be designed after... test of the MPC-NC constructs in small animal models (rat/rabbit) of sciatic nerve repair §   Task 5: Proof-of-concept functional test of the MPC-NC

  16. Schwann cell mitochondria as key regulators in the development and maintenance of peripheral nerve axons.

    Science.gov (United States)

    Ino, Daisuke; Iino, Masamitsu

    2017-03-01

    Formation of myelin sheaths by Schwann cells (SCs) enables rapid and efficient transmission of action potentials in peripheral axons, and disruption of myelination results in disorders that involve decreased sensory and motor functions. Given that construction of SC myelin requires high levels of lipid and protein synthesis, mitochondria, which are pivotal in cellular metabolism, may be potential regulators of the formation and maintenance of SC myelin. Supporting this notion, abnormal mitochondria are found in SCs of neuropathic peripheral nerves in both human patients and the relevant animal models. However, evidence for the importance of SC mitochondria in myelination has been limited, until recently. Several studies have recently used genetic approaches that allow SC-specific ablation of mitochondrial metabolic activity in living animals to show the critical roles of SC mitochondria in the development and maintenance of peripheral nerve axons. Here, we review current knowledge about the involvement of SC mitochondria in the formation and dysfunction of myelinated axons in the peripheral nervous system.

  17. Peripheral nerve pathology at fixed stage in spinal muscular atrophy with respiratory distress type 1.

    Science.gov (United States)

    Ikeda, Azusa; Yamashita, Sumimasa; Tsuyusaki, Yu; Tanaka, Mio; Tanaka, Yukichi; Hashiguchi, Akihiro; Takashima, Hiroshi; Goto, Tomohide

    2018-02-01

    Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is characterized by severe respiratory failure due to diaphragmatic paralysis and distal muscular weakness in early infancy. After an initial decline in respiratory state and motor function until 1-2years of age, residual capabilities reach a plateau. We report the peripheral neuropathological findings of a patient with SMARD1 at 1year and 1month of age, when his muscle strength and respiratory symptoms had deteriorated and then stabilized for several months. Peripheral nerve biopsy revealed severely progressed axonal degeneration. This finding suggests the rapid progression of peripheral axonal neuropathy in SMARD1 that leads to its characteristic clinical course of respiratory failure and paralysis in the early infantile period. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Lingli eZhang

    2015-05-01

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

  19. Identification and validation of suitable housekeeping genes for normalizing quantitative real-time PCR assays in injured peripheral nerves.

    Science.gov (United States)

    Gambarotta, Giovanna; Ronchi, Giulia; Friard, Olivier; Galletta, Pantaleo; Perroteau, Isabelle; Geuna, Stefano

    2014-01-01

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

  20. Reduction of neural adhesions by biodegradable autocrosslinked hyaluronic acid gel after injury of peripheral nerves: An experimental study

    NARCIS (Netherlands)

    X. Smit (Xander); J.W. van Neck (Han); A. Afoke; S.E.R. Hovius (Steven)

    2004-01-01

    textabstractObject. Adhesion formation is a serious problem in peripheral nerve surgery, frequently causing dysfunction and pain. The authors aimed to develop an objective biomechanical method of quantifying nerve adhesions and to use this technique for the evaluation of the efficacy of an

  1. Diabetic peripheral neuropathy assessment through texture based analysis of corneal nerve images

    Science.gov (United States)

    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.

  2. Modelled temperature-dependent excitability behaviour of a generalised human peripheral sensory nerve fibre.

    Science.gov (United States)

    Smit, Jacoba E; Hanekom, Tania; Hanekom, Johan J

    2009-08-01

    The objective of this study was to determine if a recently developed human Ranvier node model, which is based on a modified version of the Hodgkin-Huxley model, could predict the excitability behaviour in human peripheral sensory nerve fibres with diameters ranging from 5.0 to 15.0 microm. The Ranvier node model was extended to include a persistent sodium current and was incorporated into a generalised single cable nerve fibre model. Parameter temperature dependence was included. All calculations were performed in Matlab. Sensory nerve fibre excitability behaviour characteristics predicted by the new nerve fibre model at different temperatures and fibre diameters compared well with measured data. Absolute refractory periods deviated from measured data, while relative refractory periods were similar to measured data. Conduction velocities showed both fibre diameter and temperature dependence and were underestimated in fibres thinner than 12.5 microm. Calculated strength-duration time constants ranged from 128.5 to 183.0 micros at 37 degrees C over the studied nerve fibre diameter range, with chronaxie times about 30% shorter than strength-duration time constants. Chronaxie times exhibited temperature dependence, with values overestimated by a factor 5 at temperatures lower than body temperature. Possible explanations include the deviated absolute refractory period trend and inclusion of a nodal strangulation relationship.

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

    DEFF Research Database (Denmark)

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

    1989-01-01

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

  4. Storage and allogeneic transplantation of peripheral nerve using a green tea polyphenol solution in a canine model

    Directory of Open Access Journals (Sweden)

    Noguchi Takashi

    2010-11-01

    Full Text Available Abstract Background In our previous study, allogeneic-transplanted peripheral nerve segments preserved for one month in a polyphenol solution at 4°C could regenerate nerves in rodents demonstrated the same extent of nerve regeneration as isogeneic fresh nerve grafts. The present study investigated whether the same results could be obtained in a canine model. Methods A sciatic nerve was harvested from a male beagle dog, divided into fascicules of Sry and β-actin to investigate whether cells of donor origin remained in the allogeneic nerve segments. FK506 concentration was measured in blood samples taken before the animals were killed. Results The total myelinated axon numbers and amplitudes of the muscle action potentials correlated significantly with the blood FK506 concentration. Few axons were observed in the allogeneic-transplanted nerve segments in the PA0.025 group. PCR showed clear Sry-specific bands in specimens from the PA0.1 and PA0.05 groups but not from the PA0.025 group. Conclusions Successful nerve regeneration was observed in the polyphenol-treated nerve allografts when transplanted in association with a therapeutic dose of FK506. The data indicate that polyphenols can protect nerve tissue from ischemic damage for one month; however, the effects of immune suppression seem insufficient to permit allogeneic transplantation of peripheral nerves in a canine model.

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

    Science.gov (United States)

    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; pnerve. 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 autologous nerve transplant.

  6. A mm-Sized Wireless Implantable Device for Electrical Stimulation of Peripheral Nerves.

    Science.gov (United States)

    Charthad, Jayant; Chang, Ting Chia; Liu, Zhaokai; Sawaby, Ahmed; Weber, Marcus J; Baker, Sam; Gore, Felicity; Felt, Stephen A; Arbabian, Amin

    2018-04-01

    A wireless electrical stimulation implant for peripheral nerves, achieving >10× improvement over state of the art in the depth/volume figure of merit, is presented. The fully integrated implant measures just 2 mm × 3 mm × 6.5 mm (39 mm 3 , 78 mg), and operates at a large depth of 10.5 cm in a tissue phantom. The implant is powered using ultrasound and includes a miniaturized piezoelectric receiver (piezo), an IC designed in 180 nm HV BCD process, an off-chip energy storage capacitor, and platinum stimulation electrodes. The package also includes an optional blue light-emitting diode for potential applications in optogenetic stimulation in the future. A system-level design strategy for complete operation of the implant during the charging transient of the storage capacitor, as well as a unique downlink command/data transfer protocol, is presented. The implant enables externally programmable current-controlled stimulation of peripheral nerves, with a wide range of stimulation parameters, both for electrical (22 to 5000 μA amplitude, ∼14 to 470 μs pulse-width, 0 to 60 Hz repetition rate) and optical (up to 23 mW/mm 2 optical intensity) stimulation. Additionally, the implant achieves 15 V compliance voltage for chronic applications. Full integration of the implant components, end-to-end in vitro system characterizations, and results for the electrical stimulation of a sciatic nerve, demonstrate the feasibility and efficacy of the proposed stimulator for peripheral nerves.

  7. Assessment of vascularization and myelination following peripheral nerve repair using angiographic and polarization sensitive optical coherence tomography (Conference Presentation)

    Science.gov (United States)

    Nam, Ahhyun S.; Chico-Calero, Isabel; Easow, Jeena M.; Villiger, Martin; Welt, Jonathan; Winograd, Jonathan M.; Randolph, Mark A.; Redmond, Robert W.; Vakoc, Benjamin J.

    2017-02-01

    A severe traumatic injury to a peripheral nerve often requires surgical graft repair. However, functional recovery after these surgical repairs is often unsatisfactory. To improve interventional procedures, it is important to understand the regeneration of the nerve grafts. The rodent sciatic nerve is commonly used to investigate these parameters. However, the ability to longitudinally assess the reinnervation of injured nerves are limited, and to our knowledge, no methods currently exist to investigate the timing of the revascularization in functional recovery. In this work, we describe the development and use of angiographic and polarization-sensitive (PS) optical coherence tomography (OCT) to visualize the vascularization, demyelination and remyelination of peripheral nerve healing after crush and transection injuries, and across a variety of graft repair methods. A microscope was customized to provide 3.6 cm fields of view along the nerve axis with a capability to track the nerve height to maintain the nerve within the focal plane. Motion artifact rejection was implemented in the angiography algorithm to reduce degradation by bulk respiratory motion in the hindlimb site. Vectorial birefringence imaging methods were developed to significantly enhance the accuracy of myelination measurements and to discriminate birefringent contributions from the myelin and epineurium. These results demonstrate that the OCT platform has the potential to reveal new insights in preclinical studies and may ultimately provide a means for clinical intra-surgical assessment of peripheral nerve function.

  8. Digital versus film stereo-photography for assessment of the optic nerve head in glaucoma and glaucoma suspect patients.

    Science.gov (United States)

    Hasanreisoglu, Murat; Priel, Ethan; Naveh, Lili; Lusky, Moshe; Weinberger, Dov; Benjamini, Yoav; Gaton, Dan D

    2013-03-01

    One of the leading methods for optic nerve head assessment in glaucoma remains stereoscopic photography. This study compared conventional film and digital stereoscopy in the quantitative and qualitative assessment of the optic nerve head in glaucoma and glaucoma suspect patients. Fifty patients with glaucoma or suspected glaucoma underwent stereoscopic photography of the optic nerve head with a 35-mm color slide film and a digital camera. Photographs/images were presented in random order to 3 glaucoma specialists for independent analysis using a standardized assessment form. Findings for the following parameters were compared among assessors and between techniques: cup/disc (C/D) ratio, state of the optic rim, presence of peripapillary atrophy and appearance of the retinal nerve fiber layer, blood vessels, and lamina cribrosa. The film-based and image-based diagnoses (glaucoma yes/no) were compared as well. Despite high level of agreement across graders using the same method for the horizontal and vertical C/D ratio, (intraclass correlations 0.80 to 0.83), the agreement across graders was much lower for the other parameters using the same method. Similarly the agreement between the findings of the same grader using either method was high for horizontal and vertical C/D ratio, but low for the other parameters. The latter differences were reflected in the disagreement regarding the final diagnosis: The diagnoses differed by technique for each grader in 18% to 46% of eyes, resulting in 38.5% of eyes diagnosed with glaucoma by film photography that "lost" their diagnosis on the digital images, whereas 18.7% of eyes diagnosed as nonglaucomatous by film photography were considered to have glaucoma on the digital images. Although there is consistency between 35-mm film stereoscopy and digital stereoscopy in determining the cup/disc (C/D) ratio, in all other parameters large differences exist, leading to differences in diagnosis. Differences in capturing images between

  9. In vitro assessment of TAT — Ciliary Neurotrophic Factor therapeutic potential for peripheral nerve regeneration

    International Nuclear Information System (INIS)

    Barbon, Silvia; Stocco, Elena; Negro, Alessandro; Dalzoppo, Daniele; Borgio, Luca; Rajendran, Senthilkumar; Grandi, Francesca; Porzionato, Andrea; Macchi, Veronica; De Caro, Raffaele

    2016-01-01

    In regenerative neurobiology, Ciliary Neurotrophic Factor (CNTF) is raising high interest as a multifunctional neurocytokine, playing a key role in the regeneration of injured peripheral nerves. Despite its promising trophic and regulatory activity, its clinical application is limited by the onset of severe side effects, due to the lack of efficient intracellular trafficking after administration. In this study, recombinant CNTF linked to the transactivator transduction domain (TAT) was investigated in vitro and found to be an optimized fusion protein which preserves neurotrophic activity, besides enhancing cellular uptake for therapeutic advantage. Moreover, a compelling protein delivery method was defined, in the future perspective of improving nerve regeneration strategies. Following determination of TAT-CNTF molecular weight and concentration, its specific effect on neural SH-SY5Y and PC12 cultures was assessed. Cell proliferation assay demonstrated that the fusion protein triggers PC12 cell growth within 6 h of stimulation. At the same time, the activation of signal transduction pathway and enhancement of cellular trafficking were found to be accomplished in both neural cell lines after specific treatment with TAT-CNTF. Finally, the recombinant growth factor was successfully loaded on oxidized polyvinyl alcohol (PVA) scaffolds, and more efficiently released when polymer oxidation rate increased. Taken together, our results highlight that the TAT domain addiction to the protein sequence preserves CNTF specific neurotrophic activity in vitro, besides improving cellular uptake. Moreover, oxidized PVA could represent an ideal biomaterial for the development of nerve conduits loaded with the fusion protein to be delivered to the site of nerve injury. - Highlights: • TAT-CNTF is an optimized fusion protein that preserves neurotrophic activity. • In neural cell lines, TAT-CNTF triggers the activation of signal transduction. • Fast cellular uptake of TAT-CNTF was

  10. PERIPHERAL FACIAL PALSY IN CHILDHOOD - LYME BORRELIOSIS TO BE SUSPECTED UNLESS PROVEN OTHERWISE

    NARCIS (Netherlands)

    CHRISTEN, HJ; BARTLAU, N; HANEFELD, F; EIFFERT, H; THOMSSEN, R

    1990-01-01

    27 consecutive cases with acute peripheral facial palsy were studied for Lyme borreliosis. In 16 out of 27 children Lyme borreliosis could be diagnosed by detection of specific IgM antibodies in CSF. CSF findings allow a clear distinction according to etiology. All children with facial palsy due to

  11. In vitro and in vivo optimization of infrared laser treatment for injured peripheral nerves.

    Science.gov (United States)

    Anders, Juanita J; Moges, Helina; Wu, Xingjia; Erbele, Isaac D; Alberico, Stephanie L; Saidu, Edward K; Smith, Jason T; Pryor, Brian A

    2014-01-01

    Repair of peripheral nerve injuries remains a major challenge in restorative medicine. Effective therapies that can be used in conjunction with surgical nerve repair to improve nerve regeneration and functional recovery are being actively investigated. It has been demonstrated by a number of peer reviewed publications that photobiomodulation (PBM) supports nerve regeneration, reinnervation of the denervated muscle, and functional recovery after peripheral nerve injury. However, a key issue in the use of PBM as a treatment for peripheral nerve injury is the lack of parameter optimization for any given wavelength. The objective of this study was to demonstrate that for a selected wavelength effective in vitro dosing parameters could be translated to effective in vivo parameters. Comparison of infra-red (810 and 980 nm wavelengths) laser treatment parameters for injured peripheral nerves was done beginning with a series of in vitro experiments using primary human fibroblasts and primary rat cortical neurons. The primary rat cortical neurons were used for further optimization of energy density for 980 nm wavelength light using measurement of total neurite length as the bioassay. For these experiments, the parameters included a 1 W output power, power density of 10 mW/cm(2) , and energy densities of 0.01, 0.1, 0.5, 2, 10, 50, 200, 1,000, and 5,000 mJ/cm(2) . For translation of the in vitro data for use in vivo it was necessary to determine the transcutaneous penetration of 980 nm wavelength light to the level of the peroneal nerve. Two anesthetized, male White New Zealand rabbits were used for these experiments. The output power of the laser was set at 1.0 or 4.0 W. Power density measurements were taken at the surface of the skin, sub-dermally, and at the level of the nerve. Laser parameters used in the in vivo studies were calculated based on data from the in vitro studies and the light penetration measurements. For the in vivo experiments, a total of 22

  12. Cerebrolysin improves sciatic nerve dysfunction in a mouse model of diabetic peripheral neuropathy

    Directory of Open Access Journals (Sweden)

    Han-yu Dong

    2016-01-01

    Full Text Available 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.

  13. Malignant peripheral nerve sheath tumor arising from the greater omentum: Case report

    Directory of Open Access Journals (Sweden)

    Tokunaga Masakazu

    2011-03-01

    Full Text Available Abstract Malignant peripheral nerve sheath tumors (MPNSTs are rare soft tissue tumors that arise from a peripheral nerve or exhibit nerve sheath differentiation. Most of these tumors arise on the trunk, extremities, or head and neck regions; they are very rarely located in the abdominal cavity. The patient was a 71-year-old man who was referred to our hospital for a mass and pain in the right lower abdomen. Abdominal computed tomography revealed a large (9 × 9 cm, well-circumscribed, lobulated, heterogeneously enhanced mass in the pelvis. Exploratory laparotomy revealed a large mass in the greater omentum, and the tumor was completely excised. Histopathological analysis revealed that the tumor was composed of spindle cells with high mitotic activity. On staining the tumor, positive results were obtained for S-100 but negative results were obtained for c-kit, cluster of differentiation (CD34, α-smooth muscle actin, and desmin. These findings strongly supported a diagnosis of MPNST primarily arising from the greater omentum. To the best of our knowledge, this is the first reported case of an MPNST arising from the greater omentum. In this report, we have described the case of a patient with an MPNST arising from the greater omentum and have discussed the clinical characteristics and management of MPNSTs.

  14. Behavioral models of pain states evoked by physical injury to the peripheral nerve.

    Science.gov (United States)

    Sorkin, Linda S; Yaksh, Tony L

    2009-10-01

    Physical injury or compression of the root, dorsal root ganglion, or peripheral sensory axon leads to well-defined changes in biology and function. Behaviorally, humans report ongoing painful dysesthesias and aberrations in function, such that an otherwise innocuous stimulus will yield a pain report. These behavioral reports are believed to reflect the underlying changes in nerve function after injury, wherein increased spontaneous activity arises from the neuroma and dorsal root ganglion and spinal changes increase the response of spinal projection neurons. These pain states are distinct from those associated with tissue injury and pose particular problems in management. To provide for developing an understanding of the underlying mechanisms of these pain states and to promote development of therapeutic agents, preclinical models involving section, compression, and constriction of the peripheral nerve or compression of the dorsal root ganglion have been developed. These models give rise to behaviors, which parallel those observed in the human after nerve injury. The present review considers these models and their application.

  15. A meta-analysis of peripheral blood nerve growth factor levels in patients with schizophrenia.

    Science.gov (United States)

    Qin, X-Y; Wu, H-T; Cao, C; Loh, Y P; Cheng, Y

    2017-09-01

    Neurotrophins particularly brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are crucial modulators in the neurodevelopment and maintenance of central and peripheral nervous systems. Neurotrophin hypothesis of schizophrenia (SCZ) postulated that the changes in the brains of SCZ patients are the result of disturbances of developing processes involving neurotrophic factors. This hypothesis was mainly supported by the abnormal regulation of BDNF in SCZ, especially the decreased peripheral blood BDNF levels in SCZ patients validated by several meta-analyses. However, the regulation of NGF in SCZ remains unclear because of the inconsistent findings from the clinical studies. Therefore, we undertook, to the best of our knowledge, the first systematic review with a meta-analysis to quantitatively summarize the peripheral blood NGF data in SCZ patients compared with healthy control (HC) subjects. A systematic search of Pubmed, PsycINFO and Web of Science identified 13 articles encompassing a sample of 1693 individuals for the meta-analysis. Random-effects meta-analysis showed that patients with SCZ had significantly decreased peripheral blood levels of NGF when compared with the HC subjects (Hedges's g=-0.633, 95% confidence interval (CI)=-0.948 to -0.318, Panalysis, whereas disease severity might be a confounding factor for the meta-analysis. These results demonstrated that patients with SCZ are accompanied by the decreased peripheral blood NGF levels, strengthening the clinical evidence of an abnormal neurotrophin profile in the patients with SCZ.

  16. Multimodal therapeutic assessment of peripheral nerve stimulation in neuropathic pain: five case reports with a 20-year follow-up

    DEFF Research Database (Denmark)

    Kupers, Ron; Laere, Koen Van; Calenbergh, Frank Van

    2011-01-01

    Neuropathic pain following peripheral nerve lesion is highly resistant to conventional pain treatments but may respond well to direct electrical peripheral nerve stimulation (PNS). In the 1980s, we treated a series of 11 peripheral neuropathic pain patients with PNS. A first outcome assessment......, conducted after a 52-month follow-up, revealed that the majority of the patients were significantly improved. Here, we present the results of a second and more comprehensive follow-up, conducted after more than 20years of PNS usage. Of the six patients still using PNS, five participated in a multimodality...

  17. Effects of Xueshuantong combined with antioxidant drugs on nerve conduction function and oxidative stress in patients with diabetic peripheral neuropathy

    Directory of Open Access Journals (Sweden)

    Yuan-Zhen Chu

    2017-07-01

    Full Text Available Objective: To study the effect of Xueshuantong combined with antioxidant drugs on nerve conduction function and oxidative stress in patients with diabetic peripheral neuropathy. Methods: 138 cases of patients with diabetic peripheral neuropathy who were treated in endocrinology department of our hospital between June 2014 and October 2016 were enrolled and randomly divided into two groups. The combination group received Xueshuantong combined with antioxidant drug therapy, and the control group received antioxidant drug therapy. Before and after treatment, the nerve conduction velocity as well as serum content of oxidative stress indexes and nerve cytokines was measured. Results: 4 weeks and 8 weeks after treatment, common peroneal nerve and median nerve MNCV and SNCV as well as serum SOD, GSH-Px, HO-1, CAT, CNTF, BDNF and SDF-1α levels of both groups were significantly higher than those before treatment while serum MDA, AOPP and 8-OHdG levels were significantly lower than those before treatment, and common peroneal nerve and median nerve MNCV and SNCV as well as serum SOD, GSH-Px, HO-1, CAT, CNTF, BDNF and SDF-1α levels of combination group were significantly higher than those of control group while serum MDA, AOPP and 8-OHdG levels were significantly lower than those of control group. Conclusion: Xueshuantong combined with antioxidant drugs can improve the nerve conduction function, inhibit oxidative stress response and improve neurotrophy status in patients with diabetic peripheral neuropathy.

  18. Human umbilical cord mesenchymal stem cells promote peripheral nerve repair via paracrine mechanisms

    Directory of Open Access Journals (Sweden)

    Zhi-yuan Guo

    2015-01-01

    Full Text Available Human umbilical cord-derived mesenchymal stem cells (hUCMSCs represent a promising young-state stem cell source for cell-based therapy. hUCMSC transplantation into the transected sciatic nerve promotes axonal regeneration and functional recovery. To further clarify the paracrine effects of hUCMSCs on nerve regeneration, we performed human cytokine antibody array analysis, which revealed that hUCMSCs express 14 important neurotrophic factors. Enzyme-linked immunosorbent assay and immunohistochemistry showed that brain-derived neurotrophic factor, glial-derived neurotrophic factor, hepatocyte growth factor, neurotrophin-3, basic fibroblast growth factor, type I collagen, fibronectin and laminin were highly expressed. Treatment with hUCMSC-conditioned medium enhanced Schwann cell viability and proliferation, increased nerve growth factor and brain-derived neurotrophic factor expression in Schwann cells, and enhanced neurite growth from dorsal root ganglion explants. These findings suggest that paracrine action may be a key mechanism underlying the effects of hUCMSCs in peripheral nerve repair.

  19. Treadmill Training Enhances Axon Regeneration In Injured Mouse Peripheral Nerves Without Increased Loss of Topographic Specificity

    Science.gov (United States)

    English, Arthur W.; Cucoranu, Delia; Mulligan, Amanda; Sabatier, Manning

    2009-01-01

    We investigated the extent of misdirection of regenerating axons when that regeneration was enhanced using treadmill training. Retrograde fluorescent tracers were applied to the cut proximal stumps of the tibial and common fibular nerves two or four weeks after transection and surgical repair of the mouse sciatic nerve. The spatial locations of retrogradely labeled motoneurons were studied in untreated control mice and in mice receiving two weeks of treadmill training, either according to a continuous protocol (10 m/min, one hour/day, five day/week) or an interval protocol (20 m/min for two minutes, followed by a five minute rest, repeated 4 times, five days/week). More retrogradely labeled motoneurons were found in both treadmill trained groups. The magnitude of this increase was as great as or greater than that found after using other enhancement strategies. In both treadmill trained groups, the proportions of motoneurons labeled from tracer applied to the common fibular nerve that were found in spinal cord locations reserved for tibial motoneurons in intact mice was no greater than in untreated control mice and significantly less than found after electrical stimulation or chondroitinase treatment. Treadmill training in the first two weeks following peripheral nerve injury produces a marked enhancement of motor axon regeneration without increasing the propensity of those axons to choose pathways leading to functionally inappropriate targets. PMID:19731339

  20. Willin, an upstream component of the hippo signaling pathway, orchestrates mammalian peripheral nerve fibroblasts.

    Directory of Open Access Journals (Sweden)

    Susana Moleirinho

    Full Text Available Willin/FRMD6 was first identified in the rat sciatic nerve, which is composed of neurons, Schwann cells, and fibroblasts. Willin is an upstream component of the Hippo signaling pathway, which results in the inactivation of the transcriptional co-activator YAP through Ser127 phosphorylation. This in turn suppresses the expression of genes involved in cell growth, proliferation and cancer development ensuring the control of organ size, cell contact inhibition and apoptosis. Here we show that in the mammalian sciatic nerve, Willin is predominantly expressed in fibroblasts and that Willin expression activates the Hippo signaling cascade and induces YAP translocation from the nucleus to the cytoplasm. In addition within these cells, although it inhibits cellular proliferation, Willin expression induces a quicker directional migration towards scratch closure and an increased expression of factors linked to nerve regeneration. These results show that Willin modulates sciatic nerve fibroblast activity indicating that Willin may have a potential role in the regeneration of the peripheral nervous system.

  1. The incidence of peripheral nerve injury in trauma patients in Iran.

    Science.gov (United States)

    Saadat, Soheil; Eslami, Vahid; Rahimi-Movaghar, Vafa

    2011-11-01

    In patients aged 1-34 years, injury is the leading cause of mortality, disability and health care costs. Two to 3% of Level I trauma patients have peripheral nerve injury (PNI). Data were collected from the Iran National Trauma Registry database, compiled according to the International Classification of Diseases, 9th revision (ICD9) codes, from August 1999 to February 2004. The information included demography, mechanism, levels and regions of PNI, associated injuries, Abbreviated Injury Scale, duration of hospital stay, and costs. Of 16,753 patients, 219 (1.3%) had PNI; 182 (83.1%) were male. The mean age of the patients with PNI was lower than of those without nerve injury (28.6±14.45 vs. 33±21.08 years; pinjuries (5.6% vs. 0.4%, pnerve was the most commonly injured nerve. The most common area of ulnar nerve injury was at the forearm (15.3%). Sharp laceration and road traffic crash have the highest rates of PNI, which are more common in young males. Open wounds from the elbow to the hand should raise suspicion of PNI in triage. Although injuries leading to PNI are rare, their outcomes and disabilities require further research.

  2. Cyclooxygenase-1 in the spinal cord is altered after peripheral nerve injury.

    Science.gov (United States)

    Zhu, Xiaoying; Eisenach, James C

    2003-11-01

    The mechanisms underlying neuropathic pain are incompletely understood and its treatment is often unsatisfactory. Spinal cyclooxygenase-2 (COX-2) expression is upregulated after peripheral inflammation, associated with spinal prostaglandin production leading to central sensitization, but the role of COX isoenzymes in sensitization after nerve injury is less well characterized. The current study was undertaken to determine whether COX-1 was altered in this model. Male rats underwent partial sciatic nerve transsection (PSNT) or L5-L6 spinal nerve ligation (SNL). Four weeks after PSNT and 4 h, 4 days, or 2 weeks after SNL, COX-1 immunohistochemistry was performed on the L2-S2 spinal cord. COX-1 immunoreactivity (COX-1-IR) was unaffected 4 h after SNL. In contrast, 4 days after SNL, the number of COX-1-IR cells increased in the ipsilateral spinal cord. COX-1-IR increased in cells with glial morphology in the superficial laminae, but decreased in the rest of the ipsilateral spinal cord 4 weeks after PSNT and 2 weeks after SNL. These changes in immunostaining were greatest at the L5 level. These data suggest that COX-1 expression in the spinal cord is not static, but changes in a time- and laminar-dependent manner after nerve injury. These anatomic data are consistent with observations by others that spinally administered specific COX-1 inhibitors may be useful to prevent and treat neuropathic pain.

  3. Astrocytes promote peripheral nerve injury-induced reactive synaptogenesis in the neonatal CNS.

    Science.gov (United States)

    Lo, Fu-Sun; Zhao, Shuxin; Erzurumlu, Reha S

    2011-12-01

    Neonatal damage to the trigeminal nerve leads to "reactive synaptogenesis" in the brain stem sensory trigeminal nuclei. In vitro models of brain injury-induced synaptogenesis have implicated an important role for astrocytes. In this study we tested the role of astrocyte function in reactive synaptogenesis in the trigeminal principal nucleus (PrV) of neonatal rats following unilateral transection of the infraorbital (IO) branch of the trigeminal nerve. We used electrophysiological multiple input index analysis (MII) to estimate the number of central trigeminal afferent fibers that converge onto single barrelette neurons. In the developing PrV, about 30% of afferent connections are eliminated within 2 postnatal weeks. After neonatal IO nerve damage, multiple trigeminal inputs (2.7 times that of the normal inputs) converge on single barrelette cells within 3-5 days; they remain stable up to the second postnatal week. Astrocyte proliferation and upregulation of astrocyte-specific proteins (GFAP and ALDH1L1) accompany reactive synaptogenesis in the IO nerve projection zone of the PrV. Pharmacological blockade of astrocyte function, purinergic receptors, and thrombospondins significantly reduced or eliminated reactive synaptogenesis without changing the MII in the intact PrV. GFAP immunohistochemistry further supported these electrophysiological results. We conclude that immature astrocytes, purinergic receptors, and thrombospondins play an important role in reactive synaptogenesis in the peripherally deafferented neonatal PrV.

  4. Utility of Assessing Nerve Morphology in Central Cornea Versus Whorl Area for Diagnosing Diabetic Peripheral Neuropathy.

    Science.gov (United States)

    Pritchard, Nicola; Dehghani, Cirous; Edwards, Katie; Burgin, Edward; Cheang, Nick; Kim, Hannah; Mikhaiel, Merna; Stanton, Gemma; Russell, Anthony W; Malik, Rayaz A; Efron, Nathan

    2015-07-01

    To compare small nerve fiber damage in the central cornea and whorl area in participants with diabetic peripheral neuropathy (DPN) and to examine the accuracy of evaluating these 2 anatomical sites for the diagnosis of DPN. A cohort of 187 participants (107 with type 1 diabetes and 80 controls) was enrolled. The neuropathy disability score (NDS) was used for the identification of DPN. The corneal nerve fiber length at the central cornea (CNFLcenter) and whorl (CNFLwhorl) was quantified using corneal confocal microscopy and a fully automated morphometric technique and compared according to the DPN status. Receiver operating characteristic analyses were used to compare the accuracy of the 2 corneal locations for the diagnosis of DPN. CNFLcenter and CNFLwhorl were able to differentiate all 3 groups (diabetic participants with and without DPN and controls) (P cornea. Quantification of CNFL from the corneal center is as accurate as CNFL quantification of the whorl area for the diagnosis of DPN.

  5. Peripheral Nerve Stimulation of Brachial Plexus Nerve Roots and Supra-Scapular Nerve for Chronic Refractory Neuropathic Pain of the Upper Limb.

    Science.gov (United States)

    Bouche, Bénédicte; Manfiotto, Marie; Rigoard, Philippe; Lemarie, Jean; Dix-Neuf, Véronique; Lanteri-Minet, Michel; Fontaine, Denys

    2017-10-01

    We report the outcome of a consecutive series of 26 patients suffering from chronic medically-refractory neuropathic pain of the upper limb (including 16 patients with complex regional pain syndrome), topographically limited, treated by brachial plexus (BP) nerve roots or supra-scapular nerve (SSN) peripheral nerve stimulation (PNS). The technique consisted in ultrasound-guided percutaneous implantation of a cylindrical lead (Pisces-Quad, Medtronic) close to the SSN or the cervical nerve roots within the BP, depending on the pain topography. All the patients underwent a positive trial stimulation before lead connection to a subcutaneous stimulator. Chronic bipolar stimulation mean parameters were: frequency 55.5 Hertz, voltage 1.17 Volts. The voltage was set below the threshold inducing muscle contractions or paresthesias. Two patients were lost immediately after surgery. At last follow-up (mean 27.5 months), the 20 patients still using the stimulation experienced a mean pain relief of 67.1%. Seventeen patients were improved ≥50%, including 12 improved ≥70%. In 11 patients with a follow-up >2 years, the mean pain relief was 68%. At last follow-up, respectively, six out of the nine (67%) patients treated by SSN stimulation and 10 out of 17 patients (59%) treated by BP stimulation were improved ≥50%. At last follow-up, 12 out of 20 patients still using the stimulation were very satisfied, six were satisfied, and two were poorly satisfied. Complications were: stimulation intolerance due to shock-like sensations (three cases), superficial infection (1), lead fractures (2), and migration (1). In this pilot study, SSN or BP roots PNS provided a relatively safe, durable and effective option to control upper limb neuropathic pain. © 2017 International Neuromodulation Society.

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

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    Madiai Francesca

    2006-01-01

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

  7. Thermoregulation in peripheral nerve injury-induced cold-intolerant rats.

    Science.gov (United States)

    Duraku, L S; Smits, E S; Niehof, S P; Hovius, S E R; Walbeehm, E T; Selles, R W

    2012-06-01

    Cold intolerance is defined as pain after exposure to non-painful cold. It is suggested that cold intolerance may be related to dysfunctional thermoregulation in upper extremity nerve injury patients. The purpose of this study was to examine if the re-warming of a rat hind paw is altered in different peripheral nerve injury models and if these patterns are related to severity of cold intolerance. In the spared nerve injury (SNI) and complete sciatic lesion (CSL) model, the re-warming patterns after cold stress exposure were investigated preoperatively and at 3, 6 and 9 weeks postoperatively with a device to induce cooling of the hind paws. Thermocouples were attached on the dorsal side of the hind paw to monitor re-warming patterns. The Von Frey test and cold plate test indicated a significantly lower paw-withdrawal threshold and latency in the SNI compared to the Sham model. The CSL group, however, had only significantly lower paw-withdrawal latency on the cold plate test compared to the Sham group. While we found no significantly different re-warming patterns in the SNI and CSL group compared to Sham group, we did find a tendency in temperature increase in the CSL group 3 weeks postoperatively. Overall, our findings indicate that re-warming patterns are not altered after peripheral nerve injury in these rat models despite the fact that these animals did develop cold intolerance. This suggests that disturbed thermoregulation may not be the prime mechanism for cold intolerance and that, other, most likely, neurological mechanisms may play a more important role. There is no direct correlation between cold intolerance and re-warming patterns in different peripheral nerve injury rat models. This is an important finding for future developing treatments for this common problem, since treatment focussing on vaso-regulation may not help diminish symptoms of cold-intolerant patients. Copyright © 2011 British Association of Plastic, Reconstructive and Aesthetic Surgeons

  8. Chronic cough and an atypical pattern of peripheral pulmonary opacities: A case report secondary to suspected drug onset.

    Science.gov (United States)

    Alas, Ronnie; Williams, Mark Tony; Yamin, Ghiam; Rofoogaran, Mohsen

    2018-01-01

    Chronic eosinophilic pneumonia (CEP) is an idiopathic interstitial lung disease with nonspecific symptoms that involves a complex inflammatory cascade. A 36-year-old prisoner with a history of psoriasis presented with progressive worsening dyspnea, chest pain, and cough. His symptoms started 2-months after starting adalimumab, a tumor necrosis factor (TNF)-inhibitor, for psoriasis treatment. Initial workup revealed 27% eosinophils on complete blood count, elevated IgE levels on bronchoalveolar lavage, and bilateral peripheral lung opacities on imaging. The patient's symptoms and eosinophilia improved markedly after starting corticosteroids. Based on these findings, the patient was diagnosed with CEP. To our knowledge, this is the first case of asthma and CEP in a patient taking adalimumab. We suspect adalimumab unmasked the Th2 cell pathway response that was otherwise suppressed by psoriasis, a primarily Th1 cell pathway disease. The patient's pulmonary changes can be attributed to an eosinophilic asthma phenotype with adalimumab putatively indirectly causing CEP.

  9. Malignant peripheral nerve sheath tumor arisen from plexiform Neurofibromatosis type 1

    International Nuclear Information System (INIS)

    Kirova, G.; Penkov, M.; Hadjidekov, G.; Parvanova, V.

    2005-01-01

    Neurofibromatosis type 1 is multisystemic neurocutaneous disorder involving both neuroectodermal and mesenchymal texture and the most common familial cancer predisposing syndrome in humans. Tumors occurring in patients with NF1 are primarily peripheral neurofibromas. They can continue to develop throughout life and the rate of appearance may vary greatly from year to year. At the same time any new and rapid change noted at clinical examination - increase volume, pain or neurological deficit, requires biopsy because of potential malignant transformation of the neurofibroma into neurofibrosarcoma. The definitive treatment depends on the respectable character of the tumor. In this case the authors document two cases of malignant peripheral nerve sheath tumor occurring in the association with NF type l

  10. Vascular endothelial growth factor promotes anatomical and functional recovery of injured peripheral nerves in the avascular cornea.

    Science.gov (United States)

    Pan, Zan; Fukuoka, Shima; Karagianni, Natalia; Guaiquil, Victor H; Rosenblatt, Mark I

    2013-07-01

    Peripheral nerve injury is a major neurological disorder that can cause severe motor and sensory dysfunction. Neurogenic effects of vascular endothelial growth factor (VEGF) have been found in the central nervous system, and we examined whether VEGF could promote anatomical and functional recovery of peripheral nerves after injury using an avascular corneal nerve injury model. We found that VEGF enhanced neurite elongation in isolated trigeminal ganglion neurons in a dose-dependent manner. This effect was suppressed by neutralizing antibodies for VEGF receptor (VEGFR) 1 and 2 or neuropilin receptor 1 or by VEGFR2 inhibitors (SU 1498 and Ki 8751). In vivo, mice receiving sustained VEGF via implanted pellets showed increased corneal nerve regeneration after superficial injury compared with those receiving vehicle. VEGF injected subconjunctivally at the time of injury accelerated reinnervation, the recovery of mechanosensation, and epithelial wound healing. Endogenous VEGF expression was up-regulated in the corneal epithelium and stroma after wounding. Thus, VEGF can mediate peripheral neuron growth but requires the activation of multiple VEGF receptor types. In addition, VEGF can accelerate the return of sensory and trophic functions of damaged peripheral nerves. Wounding induces the expression of VEFG, which may modulate physiological nerve repair.

  11. Dynamic Quantification of Host Schwann Cell Migration into Peripheral Nerve Allografts

    Science.gov (United States)

    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

  12. Should we add clonidine to local anesthetic for peripheral nerve blockade? A qualitative systematic review of the literature.

    Science.gov (United States)

    McCartney, Colin J L; Duggan, Edel; Apatu, Emma

    2007-01-01

    Although clonidine has been shown to prolong analgesia in central neuraxial blocks, its use in peripheral nerve blocks remains controversial. We performed a systematic review of the current literature to determine the benefit of adding clonidine to peripheral nerve blocks. A systematic, qualitative review of double-blind randomized controlled trials on the benefit of clonidine as an adjunct to peripheral nerve block was performed. Studies were identified by searching PubMed (www.ncbi.nlm.nih.gov/entrez) and EMBASE (www.embase.com) databases (July 1991 to October 2006) for terms related to clonidine as an adjunct to peripheral nerve blocks. Studies were classified as supportive if the use of clonidine demonstrated reduced pain and total analgesic consumption, or prolonged block duration versus negative if no difference was found. Twenty-seven studies were identified that met the inclusion criteria. Five studies included a systemic control group. The total number of patients reviewed was 1,385. The dose of clonidine varied from 30 to 300 mug. Overall 15 studies supported the use of clonidine as an adjunct to peripheral nerve blocks with 12 studies failing to show a benefit. Based on qualitative analysis, clonidine appeared to prolong analgesia when added to intermediate-acting local anesthetics for axillary and peribulbar blocks. Clonidine improves duration of analgesia and anesthesia when used as an adjunct to intermediate-acting local anesthetics for some peripheral nerve blocks. Side-effects appear to be limited at doses up to 150 mug. Evidence is lacking for the use of clonidine as an adjunct to local anesthetics for continuous catheter techniques. Further research is required to examine the peripheral analgesic mechanism of clonidine.

  13. Enhancing nerve regeneration in the peripheral nervous system using polymeric scaffolds, stem cell engineering and nanoparticle delivery system

    Science.gov (United States)

    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.

  14. Ultrasound assessment on selected peripheral nerve pathologies. Part I: Entrapment neuropathies of the upper limb – excluding carpal tunnel syndrome

    Directory of Open Access Journals (Sweden)

    Berta Kowalska

    2012-09-01

    Full Text Available Ultrasound (US is one of the methods for imaging entrapment neuropathies, post-trau‑ matic changes to nerves, nerve tumors and postoperative complications to nerves. This type of examination is becoming more and more popular, not only for economic reasons, but also due to its value in making accurate diagnosis. It provides a very precise assess‑ ment of peripheral nerve trunk pathology – both in terms of morphology and localization. During examination there are several options available to the specialist: the making of a dynamic assessment, observation of pain radiation through the application of precise palpation and the comparison of resultant images with the contra lateral limb. Entrap‑ ment neuropathies of the upper limb are discussed in this study, with the omission of median nerve neuropathy at the level of the carpal canal, as extensive literature on this subject exists. The following pathologies are presented: pronator teres muscle syndrome, anterior interosseus nerve neuropathy, ulnar nerve groove syndrome and cubital tun‑ nel syndrome, Guyon’s canal syndrome, radial nerve neuropathy, posterior interosseous nerve neuropathy, Wartenberg’s disease, suprascapular nerve neuropathy and thoracic outlet syndrome. Peripheral nerve examination technique has been presented in previous articles presenting information about peripheral nerve anatomy [Journal of Ultrasonog‑ raphy 2012; 12 (49: 120–163 – Normal and sonographic anatomy of selected peripheral nerves. Part I: Sonohistology and general principles of examination, following the exam‑ ple of the median nerve; Part II: Peripheral nerves of the upper limb; Part III: Peripheral nerves of the lower limb]. In this article potential compression sites of particular nerves are discussed, taking into account pathomechanisms of damage, including predisposing anatomical variants (accessory muscles. The parameters of ultrasound assessment have been established – echogenicity and

  15. The development of military medical care for peripheral nerve injuries during World War I.

    Science.gov (United States)

    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.

  16. Breast metastases from a malignant peripheral nerve sheath tumor of the kidney: An unusual presentation

    Directory of Open Access Journals (Sweden)

    Shalini Koppisetty

    2016-01-01

    Full Text Available 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.

  17. Superficial or cutaneous malignant peripheral nerve sheath tumor--clinical experience at Taipei Veterans General Hospital.

    Science.gov (United States)

    Feng, Chin-Jung; Ma, Hsu; Liao, Wen-Chieh

    2015-05-01

    Primary malignant peripheral nerve sheath tumors (MPNSTs) with a cutaneous or subcutaneous origin represent a small subset of MPNSTs thought to be derived from cutaneous neurofibromas or small peripheral nerves. Few cases of superficial MPNSTs originating from the skin have been reported in the literature. From October 1999 to February 2014, 13 patients were diagnosed with superficial or cutaneous MPNSTs and received treatment at Taipei Veterans General Hospital. Clinical data were collected via retrospective chart review. A retrospective study was performed to compare superficial and deep-seated lesions in terms of local recurrence, distal metastasis, and survival analysis. The relevant literature is also briefly reviewed. The most frequent initial symptoms were local swelling and pain. Ten tumors were found in the extremities, and 3 tumors were located on the trunk. All patients underwent surgery with curative intent. Four patients developed local recurrence, and 3 developed distant metastasis. Three of 13 patients died after a follow-up period of 11 to 180 months (mean, 53.4). Compared to deep-seated MPNSTs, superficial MPNSTs had a lower histopathological grading and better survival rate. Superficial MPNSTs are a rare variant of MPNST. The relatively frequent lack of associated neurofibromatosis and superficial location within the dermis and subcutis may result in this entity being overlooked. According to our clinical experience, superficial MPNSTs might have better prognosis, but similar recurrence and metastasis rates compared with deep-seated lesions. Hence, awareness of this entity should prompt its consideration in the differential diagnosis of cutaneous sarcomas.

  18. Bayesian spatial filters for source signal extraction: a study in the peripheral nerve.

    Science.gov (United States)

    Tang, Y; Wodlinger, B; Durand, D M

    2014-03-01

    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 ±3.45 dB) amongst the group of methodologies compared with average correlation between the extracted source signal and the original source signal R = 0.93. The results support the efficacy of the BSFE algorithm for extracting source signals from the peripheral nerve.

  19. Exercise training improves hypertension-induced autonomic dysfunction without influencing properties of peripheral cardiac vagus nerve.

    Science.gov (United States)

    Neto, Octávio Barbosa; de Sordi, Carla Cristina; da Mota, Gustavo Ribeiro; Marocolo, Moacir; Chriguer, Rosângela Soares; da Silva, Valdo José Dias

    2017-12-01

    We examined the vagal transfer function of autonomic heart rate (HR) control in anesthetized sedentary and exercise-trained Spontaneously Hypertensive Rats (SHR). To this end, male SHR and Wystar-Kyoto (WKY) rats with 48-50weeks of age-old were divided into 4 groups: sedentary (SHR S , n=12) and trained (SHR T , n=14) hypertensive rats, sedentary (WKY S , n=13) and trained (WKY T , n=13) normotensive rats. The trained groups were submitted to swimming protocol for 9weeks. Blood pressure (BP), HR, HR variability (HRV), BP variability (BPV), baroreflex sensitivity and cardiac tonus were recorded in baseline conditions. Following, electric stimulation of peripheral vagus nerve was performed in anesthetized conditions. Resting bradycardia was observed in SHR T and WKY T when compared to their respective sedentary groups (pbaroreflex-mediated tachycardia values when compared to their respective sedentary counterparts (pBaroreflex bradycardic response in SHR T was higher than in SHR S (ptraining decreased BP in SHR and improved cardiovascular autonomic balance to the heart without changes in transduction properties of peripheral cardiac vagus nerve. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Gpr126/Adgrg6 Has Schwann Cell Autonomous and Nonautonomous Functions in Peripheral Nerve Injury and Repair.

    Science.gov (United States)

    Mogha, Amit; Harty, Breanne L; Carlin, Dan; Joseph, Jessica; Sanchez, Nicholas E; Suter, Ueli; Piao, Xianhua; Cavalli, Valeria; Monk, Kelly R

    2016-12-07

    Schwann cells (SCs) are essential for proper peripheral nerve development and repair, although the mechanisms regulating these processes are incompletely understood. We previously showed that the adhesion G protein-coupled receptor Gpr126/Adgrg6 is essential for SC development and myelination. Interestingly, the expression of Gpr126 is maintained in adult SCs, suggestive of a function in the mature nerve. We therefore investigated the role of Gpr126 in nerve repair by studying an inducible SC-specific Gpr126 knock-out mouse model. Here, we show that remyelination is severely delayed after nerve-crush injury. Moreover, we also observe noncell-autonomous defects in macrophage recruitment and axon regeneration in injured nerves following loss of Gpr126 in SCs. This work demonstrates that Gpr126 has critical SC-autonomous and SC-nonautonomous functions in remyelination and peripheral nerve repair. Lack of robust remyelination represents one of the major barriers to recovery of neurological functions in disease or following injury in many disorders of the nervous system. Here we show that the adhesion class G protein-coupled receptor (GPCR) Gpr126/Adgrg6 is required for remyelination, macrophage recruitment, and axon regeneration following nerve injury. At least 30% of all approved drugs target GPCRs; thus, Gpr126 represents an attractive potential target to stimulate repair in myelin disease or following nerve injury. Copyright © 2016 the authors 0270-6474/16/3612351-17$15.00/0.

  1. The Association between Serum Cytokines and Damage to Large and Small Nerve Fibers in Diabetic Peripheral Neuropathy.

    Science.gov (United States)

    Magrinelli, Francesca; Briani, Chiara; Romano, Marcello; Ruggero, Susanna; Toffanin, Elisabetta; Triolo, Giuseppa; Peter, George Chummar; Praitano, Marialuigia; Lauriola, Matteo Francesco; Zanette, Giampietro; Tamburin, Stefano

    2015-01-01

    Diabetic peripheral neuropathy (DPN) is a frequent complication of type 2 diabetes mellitus (DM) and may involve small and large peripheral nerve fibers. Recent evidence suggests a role of cytokines in DPN. The paper is aimed at exploring whether the serum concentration of cytokines is associated with small and large nerve fiber function and with neuropathic pain (NP). We recruited a group of 32 type 2 DM patients who underwent serum cytokines (TNF-α, IL-2, IL-4, IL-6, and IL-10) dosage as well as electrodiagnostic and quantitative sensory testing (QST) assessment to explore damage to large and small nerve fibers. Raised serum levels of IL-6 and IL-10 correlated with markers of large nerve fiber sensory and motor axonal damage. Raised IL-10 serum level was associated with signs of motor nerve demyelination. No differences were found in pain characteristics and electrodiagnostic and QST markers of small nerve fiber function in relation to cytokines serum levels. IL-6 and IL-10 serum levels were associated with large nerve fiber damage but not to small fibers function or NP. IL-6 and IL-10 cytokines might play a role in the pathogenesis of nerve fiber damage or represent a compensatory or neuroprotective mechanism.

  2. The Association between Serum Cytokines and Damage to Large and Small Nerve Fibers in Diabetic Peripheral Neuropathy

    Directory of Open Access Journals (Sweden)

    Francesca Magrinelli

    2015-01-01

    Full Text Available Diabetic peripheral neuropathy (DPN is a frequent complication of type 2 diabetes mellitus (DM and may involve small and large peripheral nerve fibers. Recent evidence suggests a role of cytokines in DPN. The paper is aimed at exploring whether the serum concentration of cytokines is associated with small and large nerve fiber function and with neuropathic pain (NP. We recruited a group of 32 type 2 DM patients who underwent serum cytokines (TNF-α, IL-2, IL-4, IL-6, and IL-10 dosage as well as electrodiagnostic and quantitative sensory testing (QST assessment to explore damage to large and small nerve fibers. Raised serum levels of IL-6 and IL-10 correlated with markers of large nerve fiber sensory and motor axonal damage. Raised IL-10 serum level was associated with signs of motor nerve demyelination. No differences were found in pain characteristics and electrodiagnostic and QST markers of small nerve fiber function in relation to cytokines serum levels. IL-6 and IL-10 serum levels were associated with large nerve fiber damage but not to small fibers function or NP. IL-6 and IL-10 cytokines might play a role in the pathogenesis of nerve fiber damage or represent a compensatory or neuroprotective mechanism.

  3. A unified approach to model peripheral nerves across different animal species

    Directory of Open Access Journals (Sweden)

    Elisabetta Giannessi

    2017-11-01

    Full Text Available Peripheral nerves are extremely complex biological structures. The knowledge of their response to stretch is crucial to better understand physiological and pathological states (e.g., due to overstretch. Since their mechanical response is deterministically related to the nature of the external stimuli, theoretical and computational tools were used to investigate their behaviour. In this work, a Yeoh-like polynomial strain energy function was used to reproduce the response of in vitro porcine nerve. Moreover, this approach was applied to different nervous structures coming from different animal species (rabbit, lobster, Aplysia and tested for different amount of stretch (up to extreme ones. Starting from this theoretical background, in silico models of both porcine nerves and cerebro-abdominal connective of Aplysia were built to reproduce experimental data (R2 > 0.9. Finally, bi-dimensional in silico models were provided to reduce computational time of more than 90% with respect to the performances of fully three-dimensional models.

  4. Electrical impedance myography for discriminating traumatic peripheral nerve injury in the upper extremity.

    Science.gov (United States)

    Li, Zhao; Tian, Dong; Chen, Lingfen; Wang, Xiaoqing; Jiang, Lijuan; Yu, Yude

    2017-02-01

    To evaluate the potential of electrical impedance myography (EIM), which is sensitive to the changes in muscle structure and physiology, in discriminating traumatic peripheral nerve injury (TPNI) in the upper extremity. To identify factors that primarily influence muscle atrophy secondary to nerve injury. Thirty-nine patients with TPNI underwent EIM measurement and standard electromyography tests for multiple muscles in the upper extremity. The side-to-side differences in EIM parameters were calculated for each subject and compared with the compound motor action potential (CMAP) amplitude, which is a measure of injury severity, and the time since injury. The reactance and phase values of the affected muscles were consistently lower than those of healthy muscles, with an average side-to-side difference of approximately -50% (pinjury, had a greater effect on the side-to-side difference of phase values. EIM discriminates TPNI by revealing asymmetries in reactance and phase values. The severity of injury had a larger influence than the time since injury on muscle atrophy secondary to nerve injury. These results demonstrate the putative use of EIM in discriminating TPNI and deserves further study. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  5. Assessing Autophagy in Sciatic Nerves of a Rat Model that Develops Inflammatory Autoimmune Peripheral Neuropathies

    Directory of Open Access Journals (Sweden)

    Susana Brun

    2017-09-01

    Full Text Available The rat sciatic nerve has attracted widespread attention as an excellent model system for studying autophagy alterations in peripheral neuropathies. In our laboratory, we have developed an original rat model, which we used currently in routine novel drug screening and to evaluate treatment strategies for chronic inflammatory demyelinating polyneuropathy (CIDP and other closely related diseases. Lewis rats injected with the S-palmitoylated P0(180-199 peptide develop a chronic, sometimes relapsing-remitting type of disease. Our model fulfills electrophysiological criteria of demyelination with axonal degeneration, confirmed by immunohistopathology and several typical features of CIDP. We have set up a series of techniques that led us to examine the failures of autophagy pathways in the sciatic nerve of these model rats and to follow the possible improvement of these defects after treatment. Based on these newly introduced methods, a novel area of investigation is now open and will allow us to more thoroughly examine important features of certain autophagy pathways occurring in sciatic nerves.

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

    Directory of Open Access Journals (Sweden)

    Popovich Phillip G

    2011-08-01

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

  7. Evaluation and use of regenerative multi electrode interfaces in peripheral nerves

    Science.gov (United States)

    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

  8. Injection Pressure as a Marker of Intraneural Injection in Procedures of Peripheral Nerves Blockade

    Directory of Open Access Journals (Sweden)

    Ilvana Vučković

    2006-11-01

    Full Text Available The blockade of peripheral nerves carries a certain risk of unwanted complications, which can follow after unintentional intraneural injection of a local anesthetic. Up till today, the research of measuring injection pressure has been based on animal models, even though the histological structure of periphery nerve is different for animal and human population, so the application pressure which presages intraneural injection in human population is still unknown. As material in performing this study there have been used 12 Wistar rats and 12 delivered stillborns. After bilateral access to the median nerve, we applied 3 ml of 2% lidocaine with epinephrine, with the help of automatic syringe charger. The needle was at first placed perineural on one side, and then intraneural on the other side of both examination groups. During every application the pressure values were monitored using the manometer, and then they were analyzed by special software program BioBench. All perineural injections resulted with the pressure < or = 27.92 kPa, while the majority of intraneural injections were combined with the injectionpressure > or = 69.8 kPa. The difference between intraneural and perineural injection pressures for the two different examination groups (rats and delivered stillborns was not statistically significant (P>0.05. As prevention from intraneural injections today are in use two methods: the method of causing paresthesia or the method of using the peripheral nerve stimulator. However the nerve injury can still occur, independent from the technique used. If our results are used in clinical practice on human population, than the high injection pressure could be the markerof intraneural lodging of a needle.

  9. Photobiostimulation reverses allodynia and peripheral nerve damage in streptozotocin-induced type 1 diabetes.

    Science.gov (United States)

    Rocha, Igor Rafael Correia; Ciena, Adriano Polican; Rosa, Alyne Santana; Martins, Daniel Oliveira; Chacur, Marucia

    2017-04-01

    For better evaluation of the efficacy of low-level laser therapy in treating painful diabetic neuropathy and in protecting nerve fiber damage, we conducted a study with type 1 diabetic rats induced by streptozotocin. It is well known that diabetic peripheral neuropathy is the leading cause of pain in those individuals who suffer from diabetes. Despite the efficacy of insulin in controlling glucose level in blood, there is no effective treatment to prevent or reverse neuropathic damage for total pain relief.Male Wistar rats were divided into saline, vehicle, and treatment groups. A single intraperitoneal (i.p.) injection of streptozotocin (STZ) (85 mg/kg) was administered for the induction of diabetes. The von Frey filaments were used to assess nociceptive thresholds (allodynia). Behavioral measurements were accessed 14, 28, 48, and 56 days after STZ administration. Rats were irradiated with GaAs Laser (Gallium Arsenide, Laserpulse, Ibramed Brazil) emitting a wavelength of 904 nm, an output power of 45 mWpk, beam spot size at target 0.13 cm 2 , a frequency of 9500 Hz, a pulse time 60 ns, and an energy density of 6,23 J/cm 2 .The application of four sessions of low-level laser therapy was sufficient to reverse allodynia and protect peripheral nerve damage in diabetic rats.The results of this study indicate that low-level laser therapy is feasible to treat painful diabetic condition in rats using this protocol. Although its efficacy in reversing painful stimuli and protecting nerve fibers from damage was demonstrated, this treatment protocol must be further evaluated in biochemical levels to confirm its biological effects.

  10. BMI, HOMA-IR, and Fasting Blood Glucose Are Significant Predictors of Peripheral Nerve Dysfunction in Adult Overweight and Obese Nondiabetic Nepalese Individuals: A Study from Central Nepal.

    Science.gov (United States)

    Thapa, Lekhjung; Rana, P V S

    2016-01-01

    Objective. Nondiabetic obese individuals have subclinical involvement of peripheral nerves. We report the factors predicting peripheral nerve function in overweight and obese nondiabetic Nepalese individuals. Methodology. In this cross-sectional study, we included 50 adult overweight and obese nondiabetic volunteers without features of peripheral neuropathy and 50 healthy volunteers to determine the normative nerve conduction data. In cases of abnormal function, the study population was classified on the basis of the number of nerves involved, namely, "HOMA-IR) was the significant predictor (P = 0.019, 96% CI = 1.420-49.322) of sensory nerve dysfunction. Body mass index (BMI) was the significant predictor (P = 0.034, 95% CI = 1.018-1.577) in case of ≥2 mixed nerves' involvement. Conclusion. FBG, HOMA-IR, and BMI were significant predictors of peripheral nerve dysfunction in overweight and obese Nepalese individuals.

  11. Association Between Baseline Iris Thickness and Prophylactic Laser Peripheral Iridotomy Outcomes in Primary Angle Closure Suspects

    Science.gov (United States)

    Lee, Roland Y.; Kasuga, Toshimitsu; Cui, Qi N.; Porco, Travis C.; Huang, Guofu; He, Mingguang; Lin, Shan C.

    2014-01-01

    Objective To evaluate the association between baseline measurements of iris thickness at three positions and change in anterior segment biometric parameters after prophylactic laser peripheral iridotomy (LPI). Design Prospective clinical cohort study. Participants Fifty-two eyes of 52 nonglaucomatous subjects with anatomically narrow angles. Methods Anterior segment optical coherence tomography images captured before and after LPI were analyzed using customized software, the Zhongshan Angle Assessment Program. Differences in preoperative and postoperative measurements for anterior segment biometric parameters were compared by paired Student’s t-tests. Multivariate linear regression models, adjusted for age, sex, ethnicity, and preoperative pupil diameter, were used to examine the association between the baseline measurements of iris thickness at three positions and the change in anterior segment biometric parameters after LPI. Main Outcome Measures Baseline iris thickness measured at 750μm (IT750) and 2000μm (IT2000) from the scleral spur and maximal iris thickness (ITM). Changes in iris curvature (ICURV) and trabecular–iris space area at 500μm (TISA500) and 750μm (TISA750) from the scleral spur after LPI. Results ICURV significantly decreased, while TISA500 and TISA750 significantly increased following LPI (all Piris thickness are associated with greater decrease in ICURV and increases in TISA500 and TISA750 after LPI. This suggests that eyes with thinner irides undergoing LPI were more likely to exhibit greater magnitude of change in terms of flattening of the iris convexity (i.e., ICURV) and widening of the anterior chamber angle (i.e., TISA500 and TISA750). PMID:24534754

  12. In vitro assessment of TAT - Ciliary Neurotrophic Factor therapeutic potential for peripheral nerve regeneration.

    Science.gov (United States)

    Barbon, Silvia; Stocco, Elena; Negro, Alessandro; Dalzoppo, Daniele; Borgio, Luca; Rajendran, Senthilkumar; Grandi, Francesca; Porzionato, Andrea; Macchi, Veronica; De Caro, Raffaele; Parnigotto, Pier Paolo; Grandi, Claudio

    2016-10-15

    In regenerative neurobiology, Ciliary Neurotrophic Factor (CNTF) is raising high interest as a multifunctional neurocytokine, playing a key role in the regeneration of injured peripheral nerves. Despite its promising trophic and regulatory activity, its clinical application is limited by the onset of severe side effects, due to the lack of efficient intracellular trafficking after administration. In this study, recombinant CNTF linked to the transactivator transduction domain (TAT) was investigated in vitro and found to be an optimized fusion protein which preserves neurotrophic activity, besides enhancing cellular uptake for therapeutic advantage. Moreover, a compelling protein delivery method was defined, in the future perspective of improving nerve regeneration strategies. Following determination of TAT-CNTF molecular weight and concentration, its specific effect on neural SH-SY5Y and PC12 cultures was assessed. Cell proliferation assay demonstrated that the fusion protein triggers PC12 cell growth within 6h of stimulation. At the same time, the activation of signal transduction pathway and enhancement of cellular trafficking were found to be accomplished in both neural cell lines after specific treatment with TAT-CNTF. Finally, the recombinant growth factor was successfully loaded on oxidized polyvinyl alcohol (PVA) scaffolds, and more efficiently released when polymer oxidation rate increased. Taken together, our results highlight that the TAT domain addiction to the protein sequence preserves CNTF specific neurotrophic activity in vitro, besides improving cellular uptake. Moreover, oxidized PVA could represent an ideal biomaterial for the development of nerve conduits loaded with the fusion protein to be delivered to the site of nerve injury. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. The Association between Serum Cytokines and Damage to Large and Small Nerve Fibers in Diabetic Peripheral Neuropathy

    OpenAIRE

    Magrinelli, Francesca; Briani, Chiara; Romano, Marcello; Ruggero, Susanna; Toffanin, Elisabetta; Triolo, Giuseppa; Peter, George Chummar; Praitano, Marialuigia; Lauriola, Matteo Francesco; Zanette, Giampietro; Tamburin, Stefano

    2015-01-01

    Diabetic peripheral neuropathy (DPN) is a frequent complication of type 2 diabetes mellitus (DM) and may involve small and large peripheral nerve fibers. Recent evidence suggests a role of cytokines in DPN. The paper is aimed at exploring whether the serum concentration of cytokines is associated with small and large nerve fiber function and with neuropathic pain (NP). We recruited a group of 32 type 2 DM patients who underwent serum cytokines (TNF-α, IL-2, IL-4, IL-6, and IL-10) dosage as we...

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

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    James B Graham

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

  15. The efficacy of a scaffold-free Bio 3D conduit developed from human fibroblasts on peripheral nerve regeneration in a rat sciatic nerve model.

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    Hirofumi Yurie

    Full Text Available Although autologous nerve grafting is the gold standard treatment of peripheral nerve injuries, several alternative methods have been developed, including nerve conduits that use supportive cells. However, the seeding efficacy and viability of supportive cells injected in nerve grafts remain unclear. Here, we focused on a novel completely biological, tissue-engineered, scaffold-free conduit.We developed six scaffold-free conduits from human normal dermal fibroblasts using a Bio 3D Printer. Twelve adult male rats with immune deficiency underwent mid-thigh-level transection of the right sciatic nerve. The resulting 5-mm nerve gap was bridged using 8-mm Bio 3D conduits (Bio 3D group, n = 6 and silicone tube (silicone group, n = 6. Several assessments were conducted to examine nerve regeneration eight weeks post-surgery.Kinematic analysis revealed that the toe angle to the metatarsal bone at the final segment of the swing phase was significantly higher in the Bio 3D group than the silicone group (-35.78 ± 10.68 versus -62.48 ± 6.15, respectively; p < 0.01. Electrophysiological studies revealed significantly higher compound muscle action potential in the Bio 3D group than the silicone group (53.60 ± 26.36% versus 2.93 ± 1.84%; p < 0.01. Histological and morphological studies revealed neural cell expression in all regions of the regenerated nerves and the presence of many well-myelinated axons in the Bio 3D group. The wet muscle weight of the tibialis anterior muscle was significantly higher in the Bio 3D group than the silicone group (0.544 ± 0.063 versus 0.396 ± 0.031, respectively; p < 0.01.We confirmed that scaffold-free Bio 3D conduits composed entirely of fibroblast cells promote nerve regeneration in a rat sciatic nerve model.

  16. Vitamin B complex treatment improves motor nerve regeneration and recovery of muscle function in a rodent model of peripheral nerve injury

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    Nedeljković Predrag

    2017-01-01

    Full Text Available It is well known that the peripheral nervous system has a good potential for regeneration. The aim of this study was to explore the effects of vitamin B therapy (with a complex of vitamins B1, B2, B3, B5, B6, and B12 on motor nerve recovery after femoral nerve injury. Our study was conducted on an experimental animal model of femoral nerve injury in rats. All animals used in the experiment were subjected to the same set of analyses. A behavior test was used for the assessment of motor function recovery. Body weight was measured and electromyography was performed in order to assess recovery of quadriceps muscle. Samples of muscles and nerves were used for counting nuclei and determining nuclear density. The results of this study showed enhanced functional recovery, including improved walking, a decreased level of muscle atrophy and better electromyography recovery after administration of vitamin B complex. Further, after 14 days of treatment with the vitamin B complex nuclear nerve and muscle density was significantly lowered. In conclusion, using a model of femoral nerve injury we demonstrated that the application of vitamin B complex improved recovery of motor nerve in rats. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. 175033

  17. A transgenic rat expressing green fluorescent protein (GFP) in peripheral nerves provides a new hindlimb model for the study of nerve injury and regeneration.

    Science.gov (United States)

    Moore, Amy M; Borschel, Gregory H; Santosa, Katherine A; Flagg, Eric R; Tong, Alice Y; Kasukurthi, Rahul; Newton, Piyaraj; Yan, Ying; Hunter, Daniel A; Johnson, Philip J; Mackinnon, Susan E

    2012-02-15

    In order to evaluate nerve regeneration in clinically relevant hindlimb surgical paradigms not feasible in fluorescent mice models, we developed a rat that expresses green fluorescent protein (GFP) in neural tissue. Transgenic Sprague-Dawley rat lines were created using pronuclear injection of a transgene expressing GFP under the control of the thy1 gene. Nerves were imaged under fluorescence microscopy and muscles were imaged with confocal microscopy to determine GFP expression following sciatic nerve crush, transection and direct suturing, and transection followed by repair with a nerve isograft from nonexpressing littermates. In each surgical paradigm, fluorescence microscopy demonstrated the loss and reappearance of fluorescence with regeneration of axons following injury. Nerve regeneration was confirmed with imaging of Wallerian degeneration followed by reinnervation of extensor digitorum longus (EDL) muscle motor endplates using confocal microscopy. The generation of a novel transgenic rat model expressing GFP in neural tissue allows in vivo imaging of nerve regeneration and visualization of motor endplate reinnervation. This rat provides a new model for studying peripheral nerve injury and regeneration over surgically relevant distances. Copyright © 2011 Elsevier B.V. All rights reserved.

  18. Design and fabrication of a nanofibrous polycaprolactone tubular nerve guide for peripheral nerve tissue engineering using a two-pole electrospinning system

    International Nuclear Information System (INIS)

    Panahi-Joo, Y; Abd-Emami, B; Bonakdar, S; Karkhaneh, A; Nourinia, A; Negahdari, B; Renaud, P

    2016-01-01

    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. (paper)

  19. Electron microscopic study of the myelinated nerve fibres and the perineurial cell basement membrane in the diabetic human peripheral nerves

    International Nuclear Information System (INIS)

    ElBarrany, Wagih G.; Hamdy, Raid M.; AlHayani, Abdulmonem A.; Jalalah, Sawsan M.

    2009-01-01

    To study the quantitative and ultrastructural changes in myelinated nerve fibers and the basement membranes of the perineurial cells in diabetic nerves. The study was performed at the Department of Anatomy, Faculty of Medicine, King Abdul-Aziz University, Jeddah, Saudi Arabia from 2003 to 2005. Human sural nerves were obtained from 15 lower limbs and 5 diabetic nerve biopsies. The total mean and density of myelinated nerve fibers per fascicle were calculated, with density of microtubules and mitochondria in the axoplasm. The number of the perineurial cell basement membrane layers was counted, and thickness of the basement membrane was measured. Among the 15 diabetic and 5 normal human sural nerves, the average diameters, number and surface area of myelinated nerve fibers and axonal microtubules density were found to be less in diabetic nerves. Mitochondrial density was higher in diabetic axons. Thickness of the perineurial cell basement membrane had a greater mean, but the number of perineurial cell layers was less than that of the diabetic group. The inner cellular layer of the perineurium of the diabetic nerves contained large vacuoles containing electron-dense degenerated myelin. A few specimens showed degenerated myelinated nerve fibers, while others showed recovering ones. Retracted axoplasms were encountered with albumin extravasation. Diabetes caused an increase in perineurial permeability. The diabetic sural nerve showed marked decrease in the myelinated nerve fibres, increase degenerated mitochondria, and decreased microtubules. (author)

  20. Enhanced peripheral nerve regeneration by the combination of a polycaprolactone tubular prosthesis and a scaffold of collagen with supramolecular organization.

    Science.gov (United States)

    Maturana, Luiz G; Pierucci, Amauri; Simões, Gustavo F; Vidigal, Mateus; Duek, Eliana A R; Vidal, Benedicto C; Oliveira, Alexandre L R

    2013-07-01

    The purpose of this study was to investigate the influence of implanting collagen with a supramolecular organization on peripheral nerve regeneration, using the sciatic nerve tubulization technique. For this purpose, adult female Sprague Dawley rats were divided into five groups: (1) TP - sciatic nerve repaired with empty polyethylene tubular prothesis (n = 10), (2) TPCL - nerve repair with empty polycaprolactone (PCL) tubing (n = 8), (3) TPCLF - repair with PCL tubing filled with an implant of collagen with a supramolecular organization (n = 10), (4) AG - animals that received a peripheral nerve autograft (n = 8), and (5) Normal nerves (n = 8). The results were assessed by quantification of the regenerated fibers, nerve morphometry, and transmission electron microscopy, 60 days after surgery. Immunohistochemistry and polarization microscopy were also used to analyze the regenerated nerve structure and cellular elements. The results showed that the AG group presented a larger number of regenerated axons. However, the TPCL and TPCLF groups presented more compact regenerated fibers with a morphometric profile closer to normal, both at the tube midpoint and 2 mm distal to the prosthesis. These findings were reinforced by polarization microscopy, which indicated a better collagen/axons suprastructural organization in the TPCLF derived samples. In addition, the immunohistochemical results obtained using the antibody anti-p75NTR as a Schwann cell reactivity marker demonstrated that the Schwann cells were more reactive during the regenerative process in the TPCLF group as compared to the TPCL group and the normal sciatic nerve. Altogether, the results of this study indicated that the implant of collagen with a supramolecular organization positively influenced and stimulated the regeneration process through the nerve gap, resulting in the formation of a better morphologically arranged tissue.

  1. Liposomal bupivacaine peripheral nerve block for the management of postoperative pain.

    Science.gov (United States)

    Hamilton, Thomas W; Athanassoglou, Vassilis; Trivella, Marialena; Strickland, Louise H; Mellon, Stephen; Murray, David; Pandit, Hemant G

    2016-08-25

    Postoperative pain remains a significant issue with poor perioperative pain management associated with an increased risk of morbidity and mortality. Liposomal bupivacaine is an analgesic consisting of bupivacaine hydrochloride encapsulated within multiple, non-concentric lipid bi-layers offering a novel method of sustained release. To assess the analgesic efficacy and adverse effects of liposomal bupivacaine infiltration peripheral nerve block for the management of postoperative pain. We identified randomised trials of liposomal bupivacaine peripheral nerve block for the management of postoperative pain. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2016, Issue 1), Ovid MEDLINE (1946 to January Week 1 2016), Ovid MEDLINE In-Process (14 January 2016), EMBASE (1974 to 13 January 2016), ISI Web of Science (1945 to 14 January 2016), and reference lists of retrieved articles. We sought unpublished studies from Internet sources, and searched clinical trials databases for ongoing trials. The date of the most recent search was 15 January 2016. Randomised, double-blind, placebo- or active-controlled clinical trials of a single dose of liposomal bupivacaine administered as a peripheral nerve block in adults aged 18 years or over undergoing elective surgery at any surgical site. We included trials if they had at least two comparison groups for liposomal bupivacaine peripheral nerve block compared with placebo or other types of analgesia. Two review authors independently considered trials for inclusion in the review, assessed risk of bias, and extracted data. We performed analyses using standard statistical techniques as described in the Cochrane Handbook for Systematic Reviews of Interventions, using Review Manager 5. We planned to perform a meta-analysis, however there were insufficient data to ensure a clinically meaningful answer; as such we have produced a 'Summary of findings' table in a narrative format, and where possible we assessed the

  2. Peripheral nerve stimulation (PNS) in the trapezius muscle region alleviate chronic neuropathic pain after lower brachial plexus root avulsion lesion: A case report

    DEFF Research Database (Denmark)

    Sørensen, Jens Christian Hedemann; Meier, Kaare; Perinpam, Larshan

    Peripheral nerve stimulation (PNS) in the trapezius muscle region alleviate chronic neuropathic pain after lower brachial plexus root avulsion lesion: A case report......Peripheral nerve stimulation (PNS) in the trapezius muscle region alleviate chronic neuropathic pain after lower brachial plexus root avulsion lesion: A case report...

  3. Brain-derived neurotrophic factor from bone marrow-derived cells promotes post-injury repair of peripheral nerve.

    Directory of Open Access Journals (Sweden)

    Yoshinori Takemura

    Full Text Available Brain-derived neurotrophic factor (BDNF stimulates peripheral nerve regeneration. However, the origin of BNDF and its precise effect on nerve repair have not been clarified. In this study, we examined the role of BDNF from bone marrow-derived cells (BMDCs in post-injury nerve repair. Control and heterozygote BDNF knockout mice (BDNF+/- received a left sciatic nerve crush using a cerebral blood clip. Especially, for the evaluation of BDNF from BMDCs, studies with bone marrow transplantation (BMT were performed before the injury. We evaluated nerve function using a rotarod test, sciatic function index (SFI, and motor nerve conduction velocity (MNCV simultaneously with histological nerve analyses by immunohistochemistry before and after the nerve injury until 8 weeks. BDNF production was examined by immunohistochemistry and mRNA analyses. After the nerve crush, the controls showed severe nerve dysfunction evaluated at 1 week. However, nerve function was gradually restored and reached normal levels by 8 weeks. By immunohistochemistry, BDNF expression was very faint before injury, but was dramatically increased after injury at 1 week in the distal segment from the crush site. BDNF expression was mainly co-localized with CD45 in BMDCs, which was further confirmed by the appearance of GFP-positive cells in the BMT study. Variant analysis of BDNF mRNA also confirmed this finding. BDNF+/- mice showed a loss of function with delayed histological recovery and BDNF+/+→BDNF+/- BMT mice showed complete recovery both functionally and histologically. These results suggested that the attenuated recovery of the BDNF+/- mice was rescued by the transplantation of BMCs and that BDNF from BMDCs has an essential role in nerve repair.

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

    Directory of Open Access Journals (Sweden)

    Marcela Fernandes

    2018-01-01

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

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

    Science.gov (United States)

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

    2016-03-23

    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.

  6. Study of the Peripheral Nerve Fibers Myelin Structure Changes during Activation of Schwann Cell Acetylcholine Receptors.

    Science.gov (United States)

    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.

  7. Peripheral nerve function during hyperglycemic clamping in insulin-dependent diabetic patients

    DEFF Research Database (Denmark)

    Sindrup, S H; Ejlertsen, B; Gjessing, H

    1989-01-01

    The influence of hyperglycemia on peripheral nerve function was studied in 9 patients with long-term insulin-dependent diabetes. Blood glucose concentration was raised 13.5 +/- 0.5 mmol/l (mean +/- SEM) within 15 min and kept approximately 15 mmol/l over basal level for 120 min by intravenous...... decreased from 3.1 ms to 2.8 ms (P less than 0.005) immediately after induction of hyperglycemia. During hyperglycemia it increased from 2.8 ms to 3.1 ms (P less than 0.001). We conclude that acute induction of hyperglycemia in long-term diabetics seems to increase sensory conduction and decrease distal...

  8. Clinical course of a malignant peripheral nerve sheath tumor in a Siberian tiger (Panthera tigris altaica).

    Science.gov (United States)

    Steinmetz, Hanspeter W; Rütten, Maja; Ruess-Melzer, Katja; Ohlerth, Stefanie; Lischer, Christoph; Oevermann, Anna; Bode-Lesniewska, Beata; Hatt, Jean-Michel

    2010-11-01

    A 14-year-old male Siberian tiger (Panthera tigris altaica) was admitted with an ulcerating mass on the right thoracic wall. Radiographic and computed tomographic evaluation indicated 2 isolated cutaneous masses without any signs of metastasis. Histology of a Tru-Cut biopsy revealed an anaplastic sarcoma with giant cells. Both tumors were resected with appropriate normal tissue margins. The size of the defect did not allow primary closure of the wound; therefore, a mesh expansion technique was attempted. Three months later, the tiger had to be euthanized due to extensive metastasis to the lungs. Histomorphological features and immunohistochemical results confirmed the diagnosis of malignant peripheral nerve sheath tumor. In contrast to domestic animal experience, the tumor had spread extensively to the lungs without local reccurrence in a short period of time. Correct diagnosis requires various immunohistochemical evaluations of the tumor tissue.

  9. Long-Term Reduction of Sacroiliac Joint Pain With Peripheral Nerve Stimulation.

    Science.gov (United States)

    Guentchev, Marin; Preuss, Christian; Rink, Rainer; Peter, Levente; Sailer, Martin H M; Tuettenberg, Jochen

    2017-10-01

    We recently demonstrated that 86% of the patients treated with peripheral nerve stimulation (PNS) for therapy-refractory sacroiliac joint (SIJ) pain were satisfied with the result after 1 year of treatment. To investigate the long-term (up to 4 years) response rate of this novel treatment. Sixteen consecutive patients with therapy-refractory SIJ pain were treated with PNS and followed for 4 years in 3 patients, 3 years in 6 patients, and 2 years in 1 patient. Quality of life, pain, and patient satisfaction were assessed using the Oswestry Disability Index 2.0, Visual Analog Scale (VAS), and International Patient Satisfaction Index. Patients reported a pain reduction from 8.8 to 1.6 (VAS) at 1 year ( P VAS of 2.0 ( P < .005). At 4 years, 2 of 3 patients were satisfied with the treatment results. We have shown for the first time that PNS is a successful long-term therapy for SIJ pain.

  10. Primary Cutaneous Carcinosarcoma: The first reported case with peripheral nerve sheath differentiation

    Directory of Open Access Journals (Sweden)

    Pelin Yıldız

    2014-06-01

    Full Text Available Primary cutaneous carcinosarcomas (CS are extremely rare biphasic tumors mainly located on sun-exposed areas. Two hypotheses–multiclonal (convergence and monoclonal (divergence- have been suggested for the evolution of the tumor. According to multiclonal hypothesis two or more stem cells of epithelial and mesenchymal origin give rise to these tumors, while a single totipotential cell differentiatiate into epithelial and mesenchymal components, either synchronously or metachronously according to monoclonal hypothesis. Cutaneous CSs are subdivided into two distinct groups as epidermal and adnexal CSs, due to their epithelial content. We present an interesting cutaneous adnexal CS, showing peripheral nerve sheath differentiation and having the spiradenocarcinoma component derived from spiradenoma. As far as we know, it is the first case of the literature with this features.

  11. Manual Tactile Test Predicts Sensorimotor Control Capability of Hands for Patients With Peripheral Nerve Injury.

    Science.gov (United States)

    Hsu, Hsiu-Yun; Shieh, Shyh-Jou; Kuan, Ta-Shen; Yang, Hsiu-Ching; Su, Fong-Chin; Chiu, Haw-Yen; Kuo, Li-Chieh

    2016-06-01

    To comprehend the merits of a Manual Tactile Test (MTT) in assessing hand sensorimotor functions by exploring the relations among 3 subtests along with the precision pinch performances for patients with peripheral nerve injuries (PNIs); and to understand the accuracy of the MTT by constructing the sensitivity and specificity of the test for patients with PNI. Case-control study. Hospital and local community. Patients with PNI (n=28) were recruited along with age-, sex-, and handedness-matched healthy controls (n=28) (N=56). Not applicable. The Semmes-Weinstein monofilament, moving and static 2-point discrimination, roughness differentiation, stereognosis and barognosis subtests of the MTT, and precision pinch performance were used to examine the sensory and sensorimotor status of the hand. The worst results in all sensibility tests were found for the patients with PNI (PRehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  12. Lithium Enhances Axonal Regeneration in Peripheral Nerve by Inhibiting Glycogen Synthase Kinase 3β Activation

    Directory of Open Access Journals (Sweden)

    Huanxing Su

    2014-01-01

    Full Text Available 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.

  13. Peripheral nerve field stimulation for otalgia: A novel therapy for refractory deep ear pain

    Directory of Open Access Journals (Sweden)

    Mayur Sharma, MD

    2014-12-01

    Full Text Available Refractory otalgia or deep ear pain is a complex clinical problem that poses significant challenges to the physicians. Here we report a case of a 39 year old female who presented to us with deep right ear pain which started following cholesteatoma excision 11 years ago. Since onset of right ear pain, she had multiple ear surgeries including microvascular decompression and excision of right temporal bone before presentation. Following neuropsychological assessment and excluding underlying depression/anxiety, she underwent peripheral nerve field stimulation (PFNS trial. She had a successful PFNS trial and underwent permanent implantation of PFNS and pulse generator. She had >50% reduction in her pain intensity on VAS and pain medications. She required explantation due to superficial infection; however she was satisfied with her therapy and looking forward for reimplantation. We report the first case of successful management of refractory deep ear pain using PFNS with a review of pertinent literature.

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

    Science.gov (United States)

    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. Primary peripheral nerve sheath tumors of the thyroid gland: A case report and literature review.

    Science.gov (United States)

    Chen, Guang; Liu, Zengguang; Su, Chang; Guan, Qiang; Wan, Fang; Dong, Bingfei; Bao, Liang; Zhang, Wenxin; Wang, Yinping; Wang, Guimin

    2016-02-01

    Primary peripheral nerve sheath tumors (PNSTs) of the thyroid gland are rare, with fewer than 30 cases reported in the medical literature to date. Primary PNSTs of the thyroid gland are classified into malignant and benign PNSTs. The benign PNSTs may be further subclassified into neurofibromas and Schwannomas. This is the case report of a 51-year-old male patient presenting with multiple primary PNSTs involving the left lobe of the thyroid gland. The patient underwent total excision of the thyroid gland and the pathological results indicated a Schwannoma with Antoni type A and B cells. The literature was reviewed briefly and, to the best of our knowledge, this is the first case report of multiple primary PNSTs of the thyroid gland.

  16. Malignant Peripheral Nerve Sheath Tumor of Prostate: A Rare Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Kun-Lin Hsieh

    2016-01-01

    Full Text Available A mid-aged male presented with progressive lower urinary tract symptoms (LUTS for years. Huge prostate with low serum prostate-specific antigen (PSA level was detected. The specimen from transurethral resection revealed surprising pathology finding as malignant peripheral nerve sheath tumor (MPNST. Considering its huge size (more than 300 gm and location, we prescribed neoadjuvant chemotherapy firstly. The tumor became regressive and then radical surgical resection was achieved. Adjuvant multimodality treatment including concurrent chemoradiotherapy (CCRT and target therapy was given. However, he expired about one year later. MPNST originating from prostate is very rare and seldom reported before. We here present this extremely rare disease and share our treatment experience.

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

    Science.gov (United States)

    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

  18. Macrophage-derived microvesicles promote proliferation and migration of Schwann cell on peripheral nerve repair

    Energy Technology Data Exchange (ETDEWEB)

    Zhan, Chuan, E-mail: zhchuansy@163.com; Ma, Cheng-bin; Yuan, Hong-mou; Cao, Bao-yuan; Zhu, Jia-jun

    2015-12-04

    Background: Macrophages have been implicated in peripheral nerve regeneration. However, whether macrophages-derived microvesicles (MVs) are involved in this process remains unknown. In the present study, the effects of macrophages-derived MVs on proliferation and migration of Schwann cells (SCs) were evaluated in both in vitro and in vivo. Methods: Human monocytic leukaemia cell line (THP-1) was successfully driven to M1 and M2 phenotypes by delivery of either IFN-γ or IL-4, respectively. SCs incubated with M1 or M2 macrophages-derived MVs, the cell migration and proliferation were assessed, and expression levels of nerve growth factor (NGF) and Laminin were measured. A rat model of sciatic nerve was established and the effects of macrophages-derived MVs on nerve regeneration were investigated. Results: M2-derived MVs elevated migration, proliferation, NFG and Laminin protein levels of SCs compared with M1-or M0-derived MVs. The relative expression levels of miR-223 were also increased in M2 macrophages and M2-derived MVs. Transfected M2 macrophages with miR-223 inhibitor then co-incubated with SCs, an inhibition of cell migration and proliferation and a down-regulated levels of NFG and Laminin protein expression were observed. In vivo, M2-derived MVs significantly increased the infiltration and axon number of SCs. Conclusion: M2-derived MVs promoted proliferation and migration of SCs in vitro and in vivo, which provided a therapeutic strategy for nerve regeneration. - Highlights: • M2 macrophages-derived MVs elevated migration and proliferation of SCs. • M2 macrophages-derived MVs up-regulated NFG and Laminin expression of SCs. • MiR-223 expression was increased in M2 macrophages-derived MVs. • MiR-223 inhibitor reduced migration and proliferation of SCs co-incubated with MVs. • MiR-223 inhibitor down-regulated NFG and Laminin levels of SCs co-incubated with MVs.

  19. Immune mapping of the peripheral part of the visual analyzer and optic nerve

    Directory of Open Access Journals (Sweden)

    V. G. Likhvantseva

    2014-01-01

    Full Text Available Aim. To perform immune mapping of the peripheral part of visual analyzer and optic nerve in order to identify potential antigenic targets of autoimmune attack. Methods. Eyes enucleated for terminal painful glaucoma (n = 30 were studied. Immunohistochemistry (IHC was performed on paraffin-embedded sections of isolated retina and optic nerve using a broad panel of antibodies, i.e., monoclonal murine anti-MBP (myelin basic protein antibodies, polyclonal rabbit anti-alpha fodrin antibodies, monoclonal murine anti-NSE2 (neuron-specific enolase antibodies, monoclonal murine anti-GFAP (glial fibrillary acidic protein, and polyclonal rabbit anti-S100 antibodies. IHC reaction was visualized using Mouse and Rabbit Specific HRP / AEC Detection IHC Kit. IHC reaction without primary antibodies included was a negative control. IHC reaction was considered as follows: negative — no specific cellular staining or less than 10 % of cells are stained; mild — 10‑30 % of cells are stained (+; moderate — 30‑75 % of cells are stained (++; marked — more than 75 % of cells are stained (+++; overexpression — 100 % of cells intensively express markers. Additionally, staining intensity was considered as mild (+1, moderate (+2, strong (+3 and intense (+4.Results. Immune mapping with a broad panel of monoclonal antibodies identified ocular structures which were stained with IHC markers. Retina was stained with almost all markers of neural differentiation (i.e., antibodies against NSE, GFAP, S100, and α-fodrin excepting anti-MBP autoantibodies. IHC reaction intensity in retinal layers and structures varied and depended on markers. Moderate (2+ staining with antibodies against MBP, NSE, GFAP, and S100 and marked (3+ staining with antibodies against alpha-fodrin was detected in the cytoplasm of optic nerve glia.Conclusion. Complete labelling of retina structures was performed. As a result, IHC profiles of retinal neurons, optic nerve axons

  20. Correlation of serum homocysteine metabolism and oxidative stress level with peripheral nerve damage in patients with Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Wei-Xia Gu

    2016-11-01

    Full Text Available Objective: To analyze the correlation of serum homocysteine metabolism and oxidative stress level with peripheral nerve damage in patients with Parkinson's disease. Methods: A total of 58 patients with Parkinson's disease and 67 normal human beings were included in the study, levels of plasma homocysteine (Hcy as well as superoxide dismutase (SOD, GSH, malondialdehyde (MDA and other oxidative stress indexes were detected, and common peroneal nerve motor conduction velocity (MCV, latent period (LP and amplitude (Amp were determined. Results: Serum Hcy level of observation group was higher than that of control group while folic acid and vitamin B6 levels were lower than those of control group; serum oxidative indexes LHP, H2O2, AOPP and MDA levels were higher than those of control group while antioxidant indexes SOD T, SOD Mn, SOD Cu-Zn, GSH-PX, T-AOC and CAT levels were lower than those of control group; common peroneal nerve MCV and Amp values were lower than those of control group while LP value was higher than that of control group. Peripheral nerve damage parameter values in patients with Parkinson's disease were directly correlated with serum levels of Hcy metabolism indexes and oxidative stress indexes. Conclusions: Peripheral nerve damage in patients with Parkinson's disease is associated with hyperhomocysteinemia and oxidative stress disorder, and intervention in serum levels of Hcy and oxidative stress indexes is expected to become a new way for treatment of Parkinson's disease.

  1. Anesthetic Block of Pain-related Cortical Activity in Patients with Peripheral Nerve Injury Measured by Magnetoencephalography

    NARCIS (Netherlands)

    Theuvenet, P.J.; de Munck, J.C.; Peters, M.J.L.; van Ree, J.M.; da Silva, F.L.; Chen, A.C.

    2011-01-01

    Background: This study examined whether chronic neuropathic pain, modulated by a local anesthetic block, is associated with cortical magnetic field changes. Methods: In a group of 20 patients with pain caused by unilateral traumatic peripheral nerve injury, a local block with lidocaine 1% was

  2. Peripheral site ligand-oxime conjugates: A novel concept towards reactivation of nerve agent-inhibited human acetylcholinesterase

    NARCIS (Netherlands)

    Koning, M.C. de; Joosen, M.J.A.; Noort, D.; Zuylen, A. van; Tromp, M.C.

    2011-01-01

    A conceptually novel approach to the design of reactivators of nerve agent-inhibited acetylcholinesterase (AChE) is presented. The concept comprises the linkage of a peripheral site ligand via a spacer to a reactivating moiety with the eventual goal to develop non-ionic reactivators with sufficient

  3. Evaluation of several techniques to modify denatured muscle tissue to obtain a scaffold for peripheral nerve regeneration

    NARCIS (Netherlands)

    Meek, MF; den Dunnen, WFA; Schakenraad, JM; Robinson, PH

    The aim of this study was to (1) evaluate the effect of several preparation techniques of denatured muscle tissue to obtain an open three-dimensional structure, and (2) test if this scaffold is suitable for peripheral nerve regeneration. Four samples (A-D) of muscle tissue specimens were evaluated

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

    NARCIS (Netherlands)

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

    2014-01-01

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

  5. Expression patterns of cell cycle components in sporadic and neurofibromatosis type 1-related malignant peripheral nerve sheath tumors

    NARCIS (Netherlands)

    Agesen, Trude Holmeide; Florenes, Viva Ann; Molenaar, Willemina M.; Lind, Guro E.; Berner, Jeane-Marie; Plaat, Boudewijn E.C.; Komdeur, Rudy; Myklebost, Ola; van den Berg, Eva; Lothe, Ragnhild A.

    The molecular biology underlying the development of highly malignant peripheral nerve sheath tumors (MPNSTs) remains mostly unknown. In the present study, the expression pattern of 10 selected cell cycle components is investigated in a series of 15 MPNSTs from patients with (n = 9) or without (n =

  6. Peripheral somatic nerve function in relation to glucose tolerance in an elderly caucasian population : The Hoorn study

    NARCIS (Netherlands)

    De Neeling, J. N D; Beks, P. J.; Bertelsmann, F. W.; Heine, R. J.; Bouter, L. M.

    1996-01-01

    Only sparse and contradictory data are available on peripheral somatic nerve function in relation to the total range of glucose tolerance. A random sample (n = 708) of people, stratified by age, sex, and glucose tolerance, from a Caucasian population aged 50 to 74 years was invited to undergo an

  7. Cognitive capacity: no association with recovery of sensibility by Semmes Weinstein test score after peripheral nerve injury of the forearm

    NARCIS (Netherlands)

    Boender, Z. J.; Ultee, J.; Hovius, S. E. R.

    2010-01-01

    In the recovery process of sensibility after repair of a peripheral nerve injury of the forearm, not only age but also surgical repair techniques are of importance. If regenerating axons are misdirected, reorganisation or other adaptic processes are needed at the level of the somatosensory brain

  8. Egr2-dependent microRNA-138 is dispensable for peripheral nerve myelination.

    Science.gov (United States)

    Lin, Hsin-Pin; Oksuz, Idil; Svaren, John; Awatramani, Rajeshwar

    2018-02-28

    Recent studies have elucidated the crucial role for microRNAs in peripheral nerve myelination by ablating components of the microRNA synthesis machinery. Few studies have focused on the role of individual microRNAs. To fill this gap, we focused this study on miR-138, which was shown to be drastically reduced in Dicer1 and Dgcr8 knockout mice with hypomyelinating phenotypes and to potentially target the negative regulators of Schwann cell differentiation. Here, we show that of two miR-138 encoding loci, mir-138-1 is the predominant locus transcribed in Schwann cells. mir-138-1 is transcriptionally upregulated during myelination and downregulated upon nerve injury. EGR2 is required for mir-138-1 transcription during development, and both SOX10 and EGR2 bind to an active enhancer near the mir-138-1 locus. Based on expression analyses, we hypothesized that miR-138 facilitates the transition between undifferentiated Schwann cells and myelinating Schwann cells. However, in conditional knockouts, we could not detect significant changes in Schwann cell proliferation, cell cycle exit, or myelination. Overall, our results demonstrate that miR-138 is an Egr2-dependent microRNA but is dispensable for Schwann cell myelination.

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

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    Nan Gu

    2016-07-01

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

  10. Trophic Effects of Dental Pulp Stem Cells on Schwann Cells in Peripheral Nerve Regeneration.

    Science.gov (United States)

    Yamamoto, Tsubasa; Osako, Yohei; Ito, Masataka; Murakami, Masashi; Hayashi, Yuki; Horibe, Hiroshi; Iohara, Koichiro; Takeuchi, Norio; Okui, Nobuyuki; Hirata, Hitoshi; Nakayama, Hidenori; Kurita, Kenichi; Nakashima, Misako

    2016-01-01

    Recently, mesenchymal stem cells have demonstrated a potential for neurotrophy and neurodifferentiation. We have recently isolated mobilized dental pulp stem cells (MDPSCs) using granulocyte-colony stimulating factor (G-CSF) gradient, which has high neurotrophic/angiogenic potential. The aim of this study is to investigate the effects of MDPSC transplantation on peripheral nerve regeneration. Effects of MDPSC transplantation were examined in a rat sciatic nerve defect model and compared with autografts and control conduits containing collagen scaffold. Effects of conditioned medium of MDPSCs were also evaluated in vitro. Transplantation of MDPSCs in the defect demonstrated regeneration of myelinated fibers, whose axons were significantly higher in density compared with those in autografts and control conduits only. Enhanced revascularization was also observed in the MDPSC transplants. The MDPSCs did not directly differentiate into Schwann cell phenotype; localization of these cells near Schwann cells induced several neurotrophic factors. Immunofluorescence labeling demonstrated reduced apoptosis and increased proliferation in resident Schwann cells in the MDPSC transplant compared with control conduits. These trophic effects of MDPSCs on proliferation, migration, and antiapoptosis in Schwann cells were further elucidated in vitro. The results demonstrate that MDPSCs promote axon regeneration through trophic functions, acting on Schwann cells, and promoting angiogenesis.

  11. Salidroside promotes peripheral nerve regeneration based on tissue engineering strategy using Schwann cells and PLGA: in vitro and in vivo

    Science.gov (United States)

    Liu, Hui; Lv, Peizhen; Zhu, Yongjia; Wu, Huayu; Zhang, Kun; Xu, Fuben; Zheng, Li; Zhao, Jinmin

    2017-01-01

    Salidriside (SDS), a phenylpropanoid glycoside derived from Rhodiola rosea L, has been shown to be neuroprotective in many studies, which may be promising in nerve recovery. In this study, the neuroprotective effects of SDS on engineered nerve constructed by Schwann cells (SCs) and Poly (lactic-co-glycolic acid) (PLGA) were studied in vitro. We further investigated the effect of combinational therapy of SDS and PLGA/SCs based tissue engineering on peripheral nerve regeneration based on the rat model of nerve injury by sciatic transection. The results showed that SDS dramatically enhanced the proliferation and function of SCs. The underlying mechanism may be that SDS affects SCs growth through the modulation of neurotrophic factors (BDNF, GDNF and CNTF). 12 weeks after implantation with a 12 mm gap of sciatic nerve injury, SDS-PLGA/SCs achieved satisfying outcomes of nerve regeneration, as evidenced by morphological and functional improvements upon therapy by SDS, PLGA/SCs or direct suture group assessed by sciatic function index, nerve conduction assay, HE staining and immunohistochemical analysis. Our results demonstrated the significant role of introducing SDS into neural tissue engineering to promote nerve regeneration.

  12. Effect of local administration of platelet-derived growth factor B on functional recovery of peripheral nerve regeneration: A sciatic nerve transection model.

    Science.gov (United States)

    Golzadeh, Atefeh; Mohammadi, Rahim

    2016-01-01

    Effects of platelet-derived growth factor B (PDGF-B) on peripheral nerve regeneration was studied using a rat sciatic nerve transection model. 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. 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 recovery and may have clinical implications for the surgical management of patients after facial nerve transection.

  13. Peripheral Nerve Dysfunction in Middle-Aged Subjects Born with Thalidomide Embryopathy.

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    Alessia Nicotra

    Full Text Available Phocomelia is an extremely rare congenital malformation that emerged as one extreme of a range of defects resulting from in utero exposure to thalidomide. Individuals with thalidomide embryopathy (TE have reported developing symptoms suggestive of peripheral nervous system dysfunction in the mal-developed limbs in later life.Case control study comparing TE subjects with upper limb anomalies and neuropathic symptoms with healthy controls using standard neurophysiological testing. Other causes of a peripheral neuropathy were excluded prior to assessment.Clinical examination of 17 subjects with TE (aged 50.4±1.3 [mean±standard deviation] years, 10 females and 17 controls (37.9±9.0 years; 8 females demonstrated features of upper limb compressive neuropathy in three-quarters of subjects. Additionally there were examination findings suggestive of mild sensory neuropathy in the lower limbs (n = 1, L5 radiculopathic sensory impairment (n = 1 and cervical myelopathy (n = 1. In TE there were electrophysiological changes consistent with a median large fibre neuropathic abnormality (mean compound muscle action potential difference -6.3 mV ([-9.3, -3.3], p = 0.0002 ([95% CI], p-value and reduced sympathetic skin response amplitudes (-0.8 mV ([-1.5, -0.2], p = 0.0089 in the affected upper limbs. In the lower limbs there was evidence of sural nerve dysfunction (sensory nerve action potential -5.8 μV ([-10.7, -0.8], p = 0.0232 and impaired warm perception thresholds (+3.0°C ([0.6, 5.4], p = 0.0169.We found a range of clinical features relevant to individuals with TE beyond upper limb compressive neuropathies supporting the need for a detailed neurological examination to exclude other treatable pathologies. The electrophysiological evidence of large and small fibre axonal nerve dysfunction in symptomatic and asymptomatic limbs may be a result of the original insult and merits further investigation.

  14. Peripheral nerve injury induces trans-synaptic modification of channels, receptors and signal pathways in rat dorsal spinal cord.

    Science.gov (United States)

    Yang, Liang; Zhang, Fang-Xiong; Huang, Fen; Lu, Yin-Jing; Li, Guo-Dong; Bao, Lan; Xiao, Hua-Sheng; Zhang, Xu

    2004-02-01

    Peripheral tissue injury-induced central sensitization may result from the altered biochemical properties of spinal dorsal horn. However, peripheral nerve injury-induced modification of genes in the dorsal horn remains largely unknown. Here we identified strong changes of 14 channels, 25 receptors and 42 signal transduction related molecules in Sprague-Dawley rat dorsal spinal cord 14 days after peripheral axotomy by cDNA microarray. Twenty-nine genes were further confirmed by semiquantitative RT-PCR, Northern blotting, in situ hybridization and immunohistochemistry. These regulated genes included Ca2+ channel alpha1E and alpha2/delta1 subunits, alpha subunits for Na+ channel 1 and 6, Na+ channel beta subunit, AMAP receptor GluR3 and 4, GABAA receptor alpha5 subunit, nicotinic acetylcholine receptor alpha5 and beta2 subunits, PKC alpha, betaI and delta isozymes, JNK1-3, ERK2-3, p38 MAPK and BatK and Lyn tyrosine-protein kinases, indicating that several signal transduction pathways were activated in dorsal spinal cord by peripheral nerve injury. These results demonstrate that peripheral nerve injury causes phenotypic changes in spinal dorsal horn. Increases in Ca2+ channel alpha2/delta1 subunit, GABAA receptor alpha5 subunit, Na+ channels and nicotinic acetylcholine receptors in both dorsal spinal cord and dorsal root ganglia indicate their potential roles in neuropathic pain control.

  15. Peripheral nerve blocks in patients with Ehlers-Danlos syndrome, hypermobility type: a report of 2 cases.

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    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. Published by Elsevier Inc.

  16. Sensorimotor Peripheral Nerve Function and the Longitudinal Relationship with Endurance Walking in the Health, Aging and Body Composition Study

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    Lange-Maia, Brittney S.; Newman, Anne B.; Cauley, Jane A.; Boudreau, Robert M.; Jakicic, John M.; Caserotti, Paolo; Glynn, Nancy W.; Harris, Tamara B.; Kritchevsky, Stephen B.; Schwartz, Ann V.; Satterfield, Suzanne; Simonsick, Eleanor M.; Vinik, Aaron I.; Zivkovic, Sasa; Strotmeyer, Elsa S.

    2015-01-01

    Objectives To determine whether lower extremity sensorimotor peripheral nerve deficits are associated with reduced walking endurance in older adults. Design Prospective cohort study with six years of follow-up. Setting Two U.S. clinical sites in (Pittsburgh, PA and Memphis, TN). Participants Community-dwelling older adults enrolled in Health, Aging and Body Composition study from the 2000/01 annual clinical examination (n=2393; age 76.5 ± 2.9 years; 48.2% male; 38.2% black) and subset with longitudinal data (n=1,178). Interventions Not applicable Main Outcome Measures Participants underwent peripheral nerve function examination in 2000/01, including peroneal motor nerve conduction amplitude and velocity, vibration perception threshold, and monofilament testing. Symptoms of lower-extremity peripheral neuropathy included numbness or tingling and sudden stabbing, burning, pain, or aches in the feet or legs. The long distance corridor walk (LDCW; 400m) was administered in 2000/01 and every two years afterwards for 6 years to assess endurance walking performance over time. Results In separate fully adjusted linear mixed models poor vibration threshold (>130 microns), 10-g and 1.4-g monofilament insensitivity were each associated with slower LDCW completion time (16.0, 14.1, and 6.7, seconds slower, respectively, P<.05 for each). Poor motor amplitude (<1mV), poor vibration perception threshold, and 10-g monofilament insensitivity were related to greater slowing/year (4.7, 4.3, and 4.3 additional seconds/year, respectively, P<.05), though poor motor amplitude was not associated with initial completion time. Conclusions Poorer sensorimotor peripheral nerve function is related to slower endurance walking and greater slowing longitudinally. Interventions to reduce the burden of sensorimotor peripheral nerve function impairments should be considered in order to help older adults to maintain walking endurance—a critical component for remaining independent in the community

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

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    Brook Gary A

    2003-05-01

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

  18. Involvement of TRPM2 in peripheral nerve injury-induced infiltration of peripheral immune cells into the spinal cord in mouse neuropathic pain model.

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    Kouichi Isami

    Full Text Available Recent evidence suggests that transient receptor potential melastatin 2 (TRPM2 expressed in immune cells plays an important role in immune and inflammatory responses. We recently reported that TRPM2 expressed in macrophages and spinal microglia contributes to the pathogenesis of inflammatory and neuropathic pain aggravating peripheral and central pronociceptive inflammatory responses in mice. To further elucidate the contribution of TRPM2 expressed by peripheral immune cells to neuropathic pain, we examined the development of peripheral nerve injury-induced neuropathic pain and the infiltration of immune cells (particularly macrophages into the injured nerve and spinal cord by using bone marrow (BM chimeric mice by crossing wildtype (WT and TRPM2-knockout (TRPM2-KO mice. Four types of BM chimeric mice were prepared, in which irradiated WT or TRPM2-KO recipient mice were transplanted with either WT-or TRPM2-KO donor mouse-derived green fluorescence protein-positive (GFP(+ BM cells (TRPM2(BM+/Rec+, TRPM2(BM-/Rec+, TRPM2(BM+/Rec-, and TRPM2(BM-/Rec- mice. Mechanical allodynia induced by partial sciatic nerve ligation observed in TRPM2(BM+/Rec+ mice was attenuated in TRPM2(BM-/Rec+, TRPM2(BM+/Rec-, and TRPM2(BM-/Rec- mice. The numbers of GFP(+ BM-derived cells and Iba1/GFP double-positive macrophages in the injured sciatic nerve did not differ among chimeric mice 14 days after the nerve injury. In the spinal cord, the number of GFP(+ BM-derived cells, particularly GFP/Iba1 double-positive macrophages, was significantly decreased in the three TRPM2-KO chimeric mouse groups compared with TRPM2(BM+/Rec+ mice. However, the numbers of GFP(-/Iba1(+ resident microglia did not differ among chimeric mice. These results suggest that TRPM2 plays an important role in the infiltration of peripheral immune cells, particularly macrophages, into the spinal cord, rather than the infiltration of peripheral immune cells into the injured nerves and activation of spinal

  19. Cognitive capacity: no association with recovery of sensibility by Semmes Weinstein test score after peripheral nerve injury of the forearm.

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    Boender, Z J; Ultee, J; Hovius, S E R

    2010-02-01

    In the recovery process of sensibility after repair of a peripheral nerve injury of the forearm, not only age but also surgical repair techniques are of importance. If regenerating axons are misdirected, reorganisation or other adaptic processes are needed at the level of the somatosensory brain cortex. These processes are thought to be dependent on the patient's cognitive capacity. We conducted a prospective multicentre study to assess the association between cognitive capacity and recovery of sensibility after peripheral nerve damage of the forearm. Patients with a traumatic peripheral nerve lesion of the forearm and consecutive surgical repair were included. After 12 months, the patients were assessed with respect to recovery of sensibility (Semmes-Weinstein monofilaments) and cognitive capacity, with four tests assessing different aspects of cognitive functioning. Twenty-eight patients (25 male, three female; median age: 28.5 years; range: 15-79 years) with median and/or ulnar nerve injury of the forearm were included in the study. Younger age showed a positive association with sensory recovery (beta =-0.845, 95% CI: -1.456 to -0.233; p=0.01). No association was found between the cognitive-capacity tests used and sensory recovery. The present prospective study did not reveal any association between recovery of sensibility measured by Semmes-Weinstein test score and cognitive capacity. Further studies should be performed to confirm these results. 2008 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  20. [Surgical treatment outcomes ın peripheral nerve lesions due to gunshot injuries: assessment of 28 cases].

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    Topuz, Ali Kıvanç; Eroğlu, Ahmet; Atabey, Cem; Cetinkal, Ahmet

    2013-05-01

    In this retrospective study, we present the results and outcomes in our clinic of 28 patients over 8 years who received surgical treatment for peripheral nerve lesions due to gunshot injury. The patients came to our clinic between January 2002 and February 2010. All came within 1-6 months after the initial gunshot injury and underwent surgery due to the diagnosis of peripheral nerve lesion. Preoperative and postoperative electromyographic analysis (EMG) and motor strength rating were performed on all patients. All patients were called for postoperative follow-up at 1, 6 and 12 months after surgery. The mean time after initial injury before being seen at our clinic was 3.6 months (1 day - 6 months). The most commonly injured nerve was the sciatic nerve, in 14 cases (50%). Of the patients, 23 came due to a bullet injury (9 were civilian injury with a gun, 14 were military injury with a rifle) and 5 came due to shrapnel injury. Since in all cases integrity of the nervous tissue was fully intact, nerve grafting was not required during surgery. Relatively improved EMG findings, and recovery in motor functions were detected in cases who had undergone postoperative external epineurolysis plus decompression. We recommend surgical treatment within the first six months in neural lesions, depending on gunshot injury, on the condition that surgical technique rules are obeyed (except infection, skin defect, vascular injury, and the presence of bone fracture).

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

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

    2016-12-01

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

  2. Incidence, Risk Factors, and Trends of Motor Peripheral Nerve Injury After Colorectal Surgery: Analysis of the National Surgical Quality Improvement Program Database.

    Science.gov (United States)

    Al-Temimi, Mohammed H; Chandrasekaran, Bindupriya; Phelan, Michael J; Pigazzi, Alessio; Mills, Steven D; Stamos, Michael J; Carmichael, Joseph C

    2017-03-01

    Motor peripheral nerve injury is a rare but serious event after colorectal surgery, and a nationwide study of this complication is lacking. The purpose of this study was to report the incidence, trends, and risk factors of motor peripheral nerve injury during colorectal surgery. The National Surgical Quality Improvement Program database was surveyed for motor peripheral nerve injury complicating colorectal procedures. Risk factors for this complication were identified using logistic regression analysis. The study used a national database. Patients undergoing colorectal resection between 2005 and 2013 were included. The incidence, trends, and risk factors for motor peripheral nerve injury complicating colorectal procedures were measured. We identified 186,936 colorectal cases, of which 50,470 (27%) were performed laparoscopically. Motor peripheral nerve injury occurred in 122 patients (0.065%). Injury rates declined over the study period, from 0.025% in 2006 to nerve injury were younger (mean ± SD; 54.02 ± 15.41 y vs 61.56 ± 15.95 y; p Nerve injury was also associated with longer operative times (277.16 ± 169.79 min vs 176.69 ± 104.80 min; p nerve injury (OR = 1.04 (95% CI, 1.03-1.04)), whereas increasing age was associated with a protective effect (OR = 0.80 (95% CI, 0.71-0.90)). This study was limited by its retrospective nature. Motor peripheral nerve injury during colorectal procedures is uncommon (0.065%), and its rate declined significantly over the study period. Prolonged operative time is the strongest predictor of motor peripheral nerve injury during colorectal procedures. Instituting and documenting measures to prevent nerve injury is imperative; however, special attention to this complication is necessary when surgeons contemplate long colorectal procedures.

  3. The role of p38alpha in Schwann cells in regulating peripheral nerve myelination and repair.

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    Roberts, Sheridan L; Dun, Xin-Peng; Dee, Gemma; Gray, Bethany; Mindos, Thomas; Parkinson, David B

    2017-04-01

    Myelination in the peripheral nervous system (PNS) is controlled by both positive and negative regulators within Schwann cells to ensure timely onset and correct myelin thickness for saltatory conduction by neurons. Transcription factors such as Sox10, octamer-binding transcription factor 6 (Oct6) and Krox20 form a positive regulatory network, whereas negative regulators such as cJun and Sox2 oppose myelination in Schwann cells. The role of the p38 MAPK pathway has been studied in PNS myelination, but its precise function remains unclear, with both positive and negative effects of p38 activity reported upon both myelination and processes of nerve repair. To clarify the role of p38 MAPK in the PNS, we have analysed mice with a Schwann cell-specific ablation of the major p38 isoform, p38alpha. In line with previous findings of an inhibitory role for p38 MAPK, we observe acceleration of post-natal myelination in p38alpha null nerves, a delay in myelin down-regulation following injury, together with a small increase in levels of re-myelination following injury. Finally we explored roles for p38alpha in controlling axonal regeneration and functional repair following PNS injury and observe that loss of p38alpha function in Schwann cells does not appear to affect these processes as previously reported. These studies therefore provide further proof for a role of p38 MAPK signalling in the control of myelination by Schwann cells in the PNS, but do not show an apparent role for signalling by this MAP kinase in Schwann cells controlling other elements of Wallerian degeneration and functional repair following injury. Cover Image for this issue: doi: 10.1111/jnc.13793. © 2016 International Society for Neurochemistry.

  4. Impulse conduction increases mitochondrial transport in adult mammalian peripheral nerves in vivo.

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    Marija Sajic

    2013-12-01

    Full Text Available Matching energy supply and demand is critical in the bioenergetic homeostasis of all cells. This is a special problem in neurons where high levels of energy expenditure may occur at sites remote from the cell body, given the remarkable length of axons and enormous variability of impulse activity over time. Positioning mitochondria at areas with high energy requirements is an essential solution to this problem, but it is not known how this is related to impulse conduction in vivo. Therefore, to study mitochondrial trafficking along resting and electrically active adult axons in vivo, confocal imaging of saphenous nerves in anaesthetised mice was combined with electrical and pharmacological stimulation of myelinated and unmyelinated axons, respectively. We show that low frequency activity induced by electrical stimulation significantly increases anterograde and retrograde mitochondrial traffic in comparison with silent axons. Higher frequency conduction within a physiological range (50 Hz dramatically further increased anterograde, but not retrograde, mitochondrial traffic, by rapidly increasing the number of mobile mitochondria and gradually increasing their velocity. Similarly, topical application of capsaicin to skin innervated by the saphenous nerve increased mitochondrial traffic in both myelinated and unmyelinated axons. In addition, stationary mitochondria in axons conducting at higher frequency become shorter, thus supplying additional mitochondria to the trafficking population, presumably through enhanced fission. Mitochondria recruited to the mobile population do not accumulate near Nodes of Ranvier, but continue to travel anterogradely. This pattern of mitochondrial redistribution suggests that the peripheral terminals of sensory axons represent sites of particularly high metabolic demand during physiological high frequency conduction. As the majority of mitochondrial biogenesis occurs at the cell body, increased anterograde

  5. Lower extremity nerve function, calf skeletal muscle characteristics, and functional performance in peripheral arterial disease.

    Science.gov (United States)

    Garg, Parveen K; Liu, Kiang; Ferrucci, Luigi; Guralnik, Jack M; Criqui, Michael H; Tian, Lu; Sufit, Robert; Nishida, Takashi; Tao, Huimin; Liao, Yihua; McDermott, Mary M

    2011-10-01

    To determine whether poor lower extremity nerve function is associated with less-favorable calf muscle characteristics and greater functional impairment in people with and without peripheral arterial disease (PAD). Cross-sectional. Three Chicago-area medical centers. Four hundred thirteen participants with PAD (ankle-brachial index (ABI) Calf muscle cross-sectional area and percentage fat were measured using computed tomography at 66.7% of the distance between the distal and proximal tibia. Six-minute walk performance was measured. Adjusting for age, sex, race, ABI, leg symptoms, smoking, physical activity, comorbidities, and other covariates, lower peroneal nerve conduction velocity (NCV) was associated with lower calf muscle area (first quartile 4,770.3 mm(2) , fourth quartile 5,571 mm(2) , P calf muscle area (first quartile 5,166.0 mm(2) , fourth quartile 6,003.8 mm(2) , P = .01) and poorer 6-minute walk distance (first quartile 866.4 feet, fourth quartile 1,082.5 feet, P = .01) in participants with diabetes mellitus and PAD as well. In participants without PAD, lower peroneal NCV was not associated with lower calf muscle area but was associated with poorer 6-minute walk distance only in participants without diabetes mellitus (first quartile 1,317.0 feet, fourth quartile 1,570.4 feet, P-trend calf muscle area and greater functional impairment in individuals with PAD. Future study is needed to determine whether improving peroneal NCV prevents loss of calf muscle and functional decline in people with PAD. © 2011, Copyright the Authors Journal compilation © 2011, The American Geriatrics Society.

  6. Ultra-high field upper extremity peripheral nerve and non-contrast enhanced vascular imaging.

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    Shailesh B Raval

    proper digital palmar arteries and superficial palmar arch could also be clearly visualized using TOF nCE 7T MRI.Ultra-high resolution neurovascular imaging in upper extremities is possible at 7T without use of renal toxic intravenous contrast. 7T MRI can provide superior peripheral nerve [based on fiber anisotropy and diffusion coefficient parameters derived from diffusion tensor/spectrum imaging] and vascular [nCE MRA and vessel segmentation] imaging.

  7. Epithelioid malignant peripheral nerve sheath tumor: a case report and review of literature

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    CHEN Juan-zhi

    2013-11-01

    Full Text Available Background Epithelioid malignant peripheral nerve sheath tumor (EMPNST is a rare malignant soft tissue tumor, and is more common in adult male. EMPNST originates from nerve, mainly located in the limbs, head and neck, and spine. It is an aggressive tumor with high tendency for local recurrence, and about half of the cases appear distant metastasis. This paper aims to investigate the clinicopathological features of cervial EMPNST. Methods and Results A 48- year-old male mainly presented weakness of limbs, expecially left lower extremty with ankle swelling. MRI showed space-occupying lesion in segment C3-5, considering recurrence of intraspinal tumor 2 years after operation. Tumorresection, repairing of spinal dura mater and laminectomy were made from inion to C7 level. It was foundduring the surgery that most part of the tumor was located in front of C3-5 spinal nerve, left intraspinal and outside of dura mater. Because part of the tumor grew through the opening of titanium plate, the tumor could not be totally removed. According to postoperative histomorphological observation, tumor cells arranged in sheets or nests, and were separated by fibrous tissue. Most tumor cells were epithelioid, while small part of tumor cells were fusiform. Frequent mitotic activity was found, and part of the region appeared focal necrosis. Immunohistochemical staining showed that tumor cells were positive for pan cytokeratin (PCK, epithelial membrane antigen (EMA, vimentin (Vim, synaptophysin (Syn, chromogranin A (CgA, and S-100 protein (S?100; and were negative for actin, desmin (Des, progestrone receptor (PR, glial fibrillary acidic protein (GFAP, CD34, CD31 and HMB45; Ki-67 labeling index was above 25% . Reticular fiber staining showed that the epithelioid cell nests were surrounded by reticular fibers. Fluorescence in situ hybridization (FISH detection showed negative for SS18 gene translocation. Combining with the history, the final pathological diagnosis was

  8. The vestibular nerve of the chinchilla. III. Peripheral innervation patterns in the utricular macula

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    Fernandez, C.; Goldberg, J. M.; Baird, R. A.

    1990-01-01

    1. Nerve fibers supplying the utricular macula of the chinchilla were labeled by extracellular injection of horseradish peroxidase into the vestibular nerve. The peripheral terminations of individual fibers were reconstructed and related to the regions of the end organ they innervated and to the sizes of their parent axons. 2. The macula is divided into medial and lateral parts by the striola, a narrow zone that runs for almost the entire length of the sensory epithelium. The striola can be distinguished from the extrastriolar regions to either side of it by the wider spacing of its hair cells. Calyx endings in the striola have especially thick walls, and, unlike similar endings in the extrastriola, many of them innervate more than one hair cell. The striola occupies 10% of the sensory epithelium; the lateral extrastriola, 50%; and the medial extrastriola, 40%. 3. The utricular nerve penetrates the bony labyrinth anterior to the end organ. Axons reaching the anterior part of the sensory epithelium run directly through the connective tissue stroma. Those supplying more posterior regions first enter a fiber layer located at the bottom of the stroma. Approximately one-third of the axons bifurcate below the epithelium, usually within 5-20 microns of the basement membrane. Bifurcations are more common in fibers destined for the extrastriola than for the striola. 4. Both calyx and bouton endings were labeled. Calyces can be simple or complex. Simple calyces innervate individual hair cells, whereas complex calyces supply 2-4 adjacent hair cells. Complex endings are more heavily concentrated in the striola than in the extrastriola. Simple calyces and boutons are found in all parts of the epithelium. Calyces emerge from the parent axon or one of its thick branches. Boutons, whether en passant or terminal, are located on thin collaterals. 5. Fibers can be classified into calyx, bouton, or dimorphic categories. The first type only has calyx endings; the second, only bouton

  9. Peripheral nerve and ureteralo tolerance to intraoperative radiation therapy; Clinical and dose-response analysis

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    Shaw, E.G.; Gunderson, L.L.; Martin, J.K.; Baers, R.W.; Nagorney, D.M.; Podratz, K.C. (Mayo Clinic, Rochester, MN (USA))

    1990-07-01

    Between April 1981 and July 1984, 51 received intraoperative radiation therapy (IORT) as a component of therapy for the management of primary of recurrent pelvic malignancies which were initially unresectable for cure. For these patients, curative surgical alternatives did not exist, or would have involved extensive procedures such as pelvic exenteration, distal sacrectomy, hemipelvectomy, or hemicorporectemy. The primary disease was colorectal in 38 patients. Treatment consisted of external beam radiation (range 3000 to 6890 cGy, median 5040 cGy), surgical debulking when feasible, and an intraoperative electron beam boost to the gross of microscopic residual desease (dose range 1000 to 2500 cGy, median 1750 cGy) utilizing 9-18 MeV electrons. The most common IORT associated toxicities were peripheral neurophaty and ureteral obstruction. None were life-threatening or fatal in severity. Of the 50 patients evaluable for neurotoxicity analysis, 16 (32%) developed peripheral neurophaty consisting of pain in 16 patients, numbness and tingling in 11, and weakness in 8. The pain, numbness and tingling resolved in about 40% of patients, while weakness resolved in only 1 of 8. Sixteen ureters were initially unobstructed by tumor at the time of IORT. Of these, 10 (63%) subsequently showed evidence of obstruction and hydronephrosis. The development of neurotoxicity was more common at IORT doses of 1500 cGy or more versus 1000 cGy. Ureteral obstruction with hydronephrosis occurred more frequently at IORT doses of 1250 cGy or more compared to 1000 cGy. There was no relationship between the likelihood of developing complications and the total external beam dose. The observed dependence of human nerve toxicity primarily on the IORT dose is consistent with data generated form animal experiments. (author). 21 refs.; 4 tabs.

  10. Treating intractable phantom limb pain with ambulatory continuous peripheral nerve blocks: a pilot study.

    Science.gov (United States)

    Ilfeld, Brian M; Moeller-Bertram, Tobias; Hanling, Steven R; Tokarz, Kyle; Mariano, Edward R; Loland, Vanessa J; Madison, Sarah J; Ferguson, Eliza J; Morgan, Anya C; Wallace, Mark S

    2013-06-01

    There is currently no reliable treatment for phantom limb pain (PLP). Chronic PLP and associated cortical abnormalities may be maintained from abnormal peripheral input, raising the possibility that a continuous peripheral nerve block (CPNB) of extended duration may permanently reorganize cortical pain mapping, thus providing lasting relief. Three men with below-the-knee (2) or -elbow (1) amputations and intractable PLP received femoral/sciatic or infraclavicular perineural catheter(s), respectively. Subjects were randomized in a double-masked fashion to receive perineural ropivacaine (0.5%) or normal saline for over 6 days as outpatients using portable electronic infusion pumps. Four months later, subjects returned for repeated perineural catheter insertion and received an ambulatory infusion with the alternate solution ("crossover"). Subjects were followed for up to 1 year. By chance, all three subjects received saline during their initial infusion and reported little change in their PLP. One subject did not receive crossover treatment, but the remaining two subjects reported complete resolution of their PLP during and immediately following treatment with ropivacaine. One subject experienced no PLP recurrence through the 52-week follow-up period and the other reported mild PLP occurring once each week of just a small fraction of his original pain (pretreatment: continuous PLP rated 10/10; posttreatment: no PLP at baseline with average of one PLP episode each week rated 2/10) for 12 weeks (lost to follow-up thereafter). A prolonged ambulatory CPNB may be a reliable treatment for intractable PLP. The results of this pilot study suggest that a large, randomized clinical trial is warranted. Wiley Periodicals, Inc.

  11. ATF3 upregulation in glia during Wallerian degeneration: differential expression in peripheral nerves and CNS white matter

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    Coffin Robert S

    2004-03-01

    regulating changes in gene expression necessary for preparing the distal segments of injured peripheral nerves for axonal regeneration. The absence of the ATF3 and c-Jun from CNS glia during Wallerian degeneration may limit their ability to support regeneration.

  12. Comparison of peripheral nerve damages according to glucose control timing in experimental diabetes.

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    Jin, H Y; Kang, S M; Liu, W J; Song, C H; Lee, K A; Baek, H S; Park, T S

    2012-09-01

    In addition to tight glucose control, early intensive therapy has been reported to be more important for the prevention of diabetic micro- and macro-vascular complications. What is not known exactly is the quantitative difference according to timing delay in glucose control and whether early period control is really better than late control in terms of diabetic peripheral neuropathy. In this study, we investigated the effect of timing differences in glucose control on the peripheral nerves in an experimental diabetic model. 5 groups (6-8 rats in each group) were comprised of normal glucose rats (designated control), rats with hyperglycemia (designated DM), rats with glucose control for the entire 28-week study period (designated DM + INS [W0-28]), rats with glucose control for the early 14-week period followed by hyperglycemia for the late 14-week period (designated DM + INS [W0-14]), and rats with hyperglycemia for the early 14-week period followed by glucose control in the late 14-week period (designated DM + INS [W15-28]). We found that the current perception threshold (CPT) was lower in the DM + INS (W0-28) and DM + INS (W15-28) groups than in the DM + INS (W0-14) or DM groups (Pnerve was significantly greater in the DM + INS (W0-28) and DM + INS (W15-28) groups (63.5±2.32 and 60.1±2.14 um, respectively) than in the DM + INS (W0-14) or DM groups (55.5±2.81 or 51.5±2.64 um, respectively) (Pnerve fiber (IENF) density was significantly higher in the DM + INS (W0-28) and DM + INS (W15-28) groups (6.9±0.46 and 6.8±0.11, respectively) than in the DM + INS (W0-14) or DM groups (59.5±0.32 and 5.3±0.39/mm, respectively) (Pnerve damage and that glycemic control during the later period may be more important than early period management. The importance of continuous glucose control, including the later period of diabetes, should therefore be emphasized in diabetic peripheral neuropathy. © J. A. Barth Verlag in

  13. Peripheral nerve injury increases glutamate-evoked calcium mobilization in adult spinal cord neurons

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    Doolen Suzanne

    2012-07-01

    Full Text Available Abstract Background Central sensitization in the spinal cord requires glutamate receptor activation and intracellular Ca2+ mobilization. We used Fura-2 AM bulk loading of mouse slices together with wide-field Ca2+ imaging to measure glutamate-evoked increases in extracellular Ca2+ to test the hypotheses that: 1. Exogenous application of glutamate causes Ca2+ mobilization in a preponderance of dorsal horn neurons within spinal cord slices taken from adult mice; 2. Glutamate-evoked Ca2+ mobilization is associated with spontaneous and/or evoked action potentials; 3. Glutamate acts at glutamate receptor subtypes to evoked Ca2+ transients; and 4. The magnitude of glutamate-evoked Ca2+ responses increases in the setting of peripheral neuropathic pain. Results Bath-applied glutamate robustly increased [Ca2+]i in 14.4 ± 2.6 cells per dorsal horn within a 440 x 330 um field-of-view, with an average time-to-peak of 27 s and decay of 112 s. Repeated application produced sequential responses of similar magnitude, indicating the absence of sensitization, desensitization or tachyphylaxis. Ca2+ transients were glutamate concentration-dependent with a Kd = 0.64 mM. Ca2+ responses predominantly occurred on neurons since: 1 Over 95% of glutamate-responsive cells did not label with the astrocyte marker, SR-101; 2 62% of fura-2 AM loaded cells exhibited spontaneous action potentials; 3 75% of cells that responded to locally-applied glutamate with a rise in [Ca2+]i also showed a significant increase in AP frequency upon a subsequent glutamate exposure; 4 In experiments using simultaneous on-cell recordings and Ca2+ imaging, glutamate elicited a Ca2+ response and an increase in AP frequency. AMPA/kainate (CNQX- and AMPA (GYKI 52466-selective receptor antagonists significantly attenuated glutamate-evoked increases in [Ca2+]i, while NMDA (AP-5, kainate (UBP-301 and class I mGluRs (AIDA did not. Compared to sham controls, peripheral nerve injury

  14. Peripheral nerve injury increases glutamate-evoked calcium mobilization in adult spinal cord neurons.

    Science.gov (United States)

    Doolen, Suzanne; Blake, Camille B; Smith, Bret N; Taylor, Bradley K

    2012-07-28

    Central sensitization in the spinal cord requires glutamate receptor activation and intracellular Ca2+ mobilization. We used Fura-2 AM bulk loading of mouse slices together with wide-field Ca2+ imaging to measure glutamate-evoked increases in extracellular Ca2+ to test the hypotheses that: 1. Exogenous application of glutamate causes Ca2+ mobilization in a preponderance of dorsal horn neurons within spinal cord slices taken from adult mice; 2. Glutamate-evoked Ca2+ mobilization is associated with spontaneous and/or evoked action potentials; 3. Glutamate acts at glutamate receptor subtypes to evoked Ca2+ transients; and 4. The magnitude of glutamate-evoked Ca2+ responses increases in the setting of peripheral neuropathic pain. Bath-applied glutamate robustly increased [Ca2+]i in 14.4 ± 2.6 cells per dorsal horn within a 440 x 330 um field-of-view, with an average time-to-peak of 27 s and decay of 112 s. Repeated application produced sequential responses of similar magnitude, indicating the absence of sensitization, desensitization or tachyphylaxis. Ca2+ transients were glutamate concentration-dependent with a Kd = 0.64 mM. Ca2+ responses predominantly occurred on neurons since: 1) Over 95% of glutamate-responsive cells did not label with the astrocyte marker, SR-101; 2) 62% of fura-2 AM loaded cells exhibited spontaneous action potentials; 3) 75% of cells that responded to locally-applied glutamate with a rise in [Ca2+]i also showed a significant increase in AP frequency upon a subsequent glutamate exposure; 4) In experiments using simultaneous on-cell recordings and Ca2+ imaging, glutamate elicited a Ca2+ response and an increase in AP frequency. AMPA/kainate (CNQX)- and AMPA (GYKI 52466)-selective receptor antagonists significantly attenuated glutamate-evoked increases in [Ca2+]i, while NMDA (AP-5), kainate (UBP-301) and class I mGluRs (AIDA) did not. Compared to sham controls, peripheral nerve injury significantly decreased mechanical paw

  15. Fibrin glue repair leads to enhanced axonal elongation during early peripheral nerve regeneration in an in vivo mouse model

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    Georgios Koulaxouzidis

    2015-01-01

    Full Text Available Microsurgical suturing is the gold standard of nerve coaptation. Although literature on the usefulness of fibrin glue as an alternative is becoming increasingly available, it remains contradictory. Furthermore, no data exist on how both repair methods might influence the morphological aspects (arborization; branching of early peripheral nerve regeneration. We used the sciatic nerve transplantation model in thy-1 yellow fluorescent protein mice (YFP; n = 10. Pieces of nerve (1cm were grafted from YFP-negative mice (n = 10 into those expressing YFP. We performed microsuture coaptations on one side and used fibrin glue for repair on the contralateral side. Seven days after grafting, the regeneration distance, the percentage of regenerating and arborizing axons, the number of branches per axon, the coaptation failure rate, the gap size at the repair site and the time needed for surgical repair were all investigated. Fibrin glue repair resulted in regenerating axons travelling further into the distal nerve. It also increased the percentage of arborizing axons. No coaptation failure was detected. Gap sizes were comparable in both groups. Fibrin glue significantly reduced surgical repair time. The increase in regeneration distance, even after the short period of time, is in line with the results of others that showed faster axonal regeneration after fibrin glue repair. The increase in arborizing axons could be another explanation for better functional and electrophysiological results after fibrin glue repair. Fibrin glue nerve coaptation seems to be a promising alternative to microsuture repair.

  16. Differences and similarities in development of corneal nerve damage and peripheral neuropathy and in diet-induced obesity and type 2 diabetic rats.

    Science.gov (United States)

    Davidson, Eric P; Coppey, Lawrence J; Kardon, Randy H; Yorek, Mark A

    2014-03-03

    Peripheral neuropathy has been shown to exist in prediabetic and diabetic patients and animal models. However, the development of peripheral neuropathy in prediabetes and posthyperglycemia is likely different. The purpose of this study was to examine the progression of peripheral neuropathy in diet-induced obese rats and high-fat-fed rats treated with a low dose of streptozotocin, a model for type 2 diabetes, using standard endpoints as well as corneal sensitivity and innervation. Diet-induced obese rats and high-fat/low-dose streptozotocin diabetic rats were used to examine standard peripheral neuropathy endpoints and innervation of the cornea and corneal epithelium using corneal and standard confocal microscopy, respectively, and corneal sensitivity using a Cochet-Bonnet esthesiometer at three different time points. Obese rats and to a greater extent diabetic rats were insulin resistant. Obese and diabetic rats had developed sensory nerve deficits, but only diabetic rats had motor nerve dysfunction as determined by measuring nerve conduction velocity, thermal nociception, and intraepidermal nerve fiber density. In the cornea there was a decrease in corneal nerve fiber length, innervation of the corneal epithelium, and corneal sensitivity in both diet-induced obese and diabetic rats. These studies demonstrate that changes in corneal nerve innervation and sensitivity occur in both obese and type 2 diabetic rat models that are consistent with development of peripheral neuropathy. Examination of corneal nerve changes may be valuable endpoints for exploring potential treatments for peripheral neuropathy in both prediabetes with insulin resistance and diabetes.

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

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    Ruirui Lu

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

  18. A Case of Malignant Peripheral Nerve Sheath Tumor with Rhabdomyoblastic Differentiation: Malignant Triton Tumor

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    Kenichiro Mae

    2013-12-01

    Full Text Available Malignant peripheral nerve sheath tumors (MPNST constitute a rare variety of soft tissue sarcomas thought to originate from Schwann cells or pluripotent cells of the neural crest. Malignant triton tumor (MTT, a very rare, highly aggressive soft tissue tumor, is a subgroup of MPNST and is comprised of malignant Schwann cells coexisting with malignant rhabdomyoblasts. We herein report the case of a 24-year-old man who presented a subcutaneous mass in his right thigh. The mass was removed surgically in its entirety and radiation therapy was applied locally to prevent tumor regrowth. Nonetheless, the patient died 10 months after surgery from metastases to the lung and brain. He presented neither cafe-au-lait spots nor cutaneous neurofibromas. The histopathology showed a transition from a neurofibroma to an MTT, making this the second report of an MTT arising from a neurofibroma without neurofibromatosis type 1, an autosomal dominant disorder with which 50-70% of tumors reported in previous studies were associated. A histopathological examination using immunostaining with desmin confirmed this diagnosis. MTT has a poorer prognosis than MPNST and should therefore be regarded as a distinct clinical entity.

  19. A case of desmoplastic melanoma that was difficult to distinguish from malignant peripheral nerve sheath tumor

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    Kenji Yorita

    2018-03-01

    Full Text Available The clinical and pathological diagnosis of desmoplastic melanoma is difficult, because almost 50% of desmoplastic melanoma cases involve non-pigmented lesions and the tumor cells can resemble fibroblasts or Schwannian cells based on their frequent amelanotic features. Moreover, desmoplastic melanoma typically has low positive rates for melanoma markers, with the exception of the S-100 protein. We report the case of an 81-year-old Japanese man with an 8-mm desmoplastic melanoma. He initially noticed a painless and non-pigmented skin lesion that did not grow noticeably for 6 months. It was unlikely that he had von Recklinghausen disease, and the mass was initially considered a dermatofibroma. Excisional biopsy revealed an intradermal mass, with the superficial portion mimicking neurofibroma and the deeper portion exhibiting nodular growth of sarcomatoid spindle cells. The tumor region lacked intradermal proliferation of atypical melanocytic cells, intracytoplasmic melanin, and expression of melanoma markers (except S-100 protein and Sox10. Although a malignant peripheral nerve sheath tumor derived from neurofibroma was possible, the slow growth with diffuse and strong immunoreactivity to the S-100 protein and Sox10 favored a diagnosis of desmoplastic melanoma. Pathologists should recognize that desmoplastic melanoma may not involve in situ lesions or the immunohistochemical expression of standard melanoma markers.

  20. The Thermal Sensitivity Test in Evaluating Outcome after Peripheral Nerve Injury.

    Science.gov (United States)

    Ceynowa, Marcin; Mazurek, Tomasz; Pankowski, Rafał; Rocławski, Marek; Treder, Mariusz

    2015-01-01

    The purpose of this study was to evaluate the ability to discriminate temperatures in patients following peripheral nerve injury. Knowing that temperature sensibility is mediated by different receptors, the scores were compared to other functional hand scores in order to determine whether the ability to discriminate temperatures is restored to a different extent compared with other commonly evaluated hand function modalities. The test was performed using the NTE-2 device (Physitemp Instruments Inc., 154 Huron Avenue, Clifton, New Jersey, USA). Out of 57 patients, 27 had normal thermal discrimination scores, and 9 could not tell the temperatures apart in the differences set on the measuring device. Overall, patients with better thermal discrimination had also better hand function as evaluated with different methods. However, some patients who did regain the ability to differentiate temperatures correctly did not have any measurable return of hand function in other tests. Thermal discrimination scores correlated similarly with different functional scores, except for vibration sensibility, which did not show any significant correlation. The development and severity of cold intolerance seem to be unrelated to temperature sense.

  1. The Thermal Sensitivity Test in Evaluating Outcome after Peripheral Nerve Injury

    Directory of Open Access Journals (Sweden)

    Marcin Ceynowa

    2015-01-01

    Full Text Available The purpose of this study was to evaluate the ability to discriminate temperatures in patients following peripheral nerve injury. Knowing that temperature sensibility is mediated by different receptors, the scores were compared to other functional hand scores in order to determine whether the ability to discriminate temperatures is restored to a different extent compared with other commonly evaluated hand function modalities. The test was performed using the NTE-2 device (Physitemp Instruments Inc., 154 Huron Avenue, Clifton, New Jersey, USA. Out of 57 patients, 27 had normal thermal discrimination scores, and 9 could not tell the temperatures apart in the differences set on the measuring device. Overall, patients with better thermal discrimination had also better hand function as evaluated with different methods. However, some patients who did regain the ability to differentiate temperatures correctly did not have any measurable return of hand function in other tests. Thermal discrimination scores correlated similarly with different functional scores, except for vibration sensibility, which did not show any significant correlation. The development and severity of cold intolerance seem to be unrelated to temperature sense.

  2. Ras signaling influences permissiveness of malignant peripheral nerve sheath tumor cells to oncolytic herpes.

    Science.gov (United States)

    Farassati, Faris; Pan, Weihong; Yamoutpour, Farnaz; Henke, Susann; Piedra, Mark; Frahm, Silke; Al-Tawil, Said; Mangrum, Wells I; Parada, Luis F; Rabkin, Samuel D; Martuza, Robert L; Kurtz, Andreas

    2008-12-01

    Lack of expression of neurofibromin in neurofibromatosis 1 and its lethal derivative, malignant peripheral nerve sheath tumors (MPNSTs), is thought to result in the overactivation of the Ras signaling pathway. Our previous studies have shown that cells with overactivation in the Ras pathway are more permissive to infection with herpes simplex virus 1 and its mutant version R3616. In this study, we show that among five different mouse MPNST cell lines, only the ones with elevated levels of Ras signaling are highly permissive to infection with oncolytic herpes G207. Specific inhibitors of the Ras, ERK, and JNK pathways all reduced the synthesis of viral proteins in MPNST cells. The cell lines that contained lower levels of Ras and decreased activation of downstream signaling components underwent an enhancement in apoptosis upon exposure to G207. Additionally, mouse SW10 Schwann cells were able to become infected by parental herpes but were found to be resistant to G207. The immortalization of these cell lines with the expression of SV40 large T antigen increased the levels of Ras activation and permissiveness to oncolytic herpes. A Ras/Raf kinase inhibitor reduced the synthesis of both herpes simplex virus-1 and G207 proteins in SW10 cells. The results of this study, therefore, introduce Ras signaling as a divergent turning point for the response of MPNST cells to an assault by oncolytic herpes.

  3. Neuraxial and peripheral nerve blocks in patients taking anticoagulant or thromboprophylactic drugs: challenges and solutions

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    Li J

    2015-08-01

    Full Text Available Jinlei Li, Thomas Halaszynski Department of Anesthesiology, Yale University, Yale New Haven Hospital, New Haven, CT, USA Abstract: Incidence of hemorrhagic complications from neuraxial blockade is unknown, but classically cited as 1 in 150,000 epidurals and 1 in 220,000 spinals. However, recent literature and epidemiologic data suggest that for certain patient populations the frequency is higher (1 in 3,000. Due to safety concerns of bleeding risk, guidelines and recommendations have been designed to reduce patient morbidity/mortality during regional anesthesia. Data from evidence-based reviews, clinical series and case reports, collaborative experience of experts, and pharmacology used in developing consensus statements are unable to address all patient comorbidities and are not able to guarantee specific outcomes. No laboratory model identifies patients at risk, and rarity of neuraxial hematoma defies prospective randomized study so “patient-specific” factors and “surgery-related” issues should be considered to improve patient-oriented outcomes. Details of advanced age, older females, trauma patients, spinal cord and vertebral column abnormalities, organ function compromise, presence of underlying coagulopathy, traumatic or difficult needle placement, as well as indwelling catheter(s during anticoagulation pose risks for significant bleeding. Therefore, balancing between thromboembolism, bleeding risk, and introduction of more potent antithrombotic medications in combination with regional anesthesia has resulted in a need for more than “consensus statements” to safely manage regional interventions during anticoagulant/thromboprophylactic therapy. Keywords: antithrombotics, novel oral anticoagulant, regional, neurologic dysfunction, hematoma, peripheral nerve blockade

  4. Efficacy of Tape Feedback Therapy on Synkinesis Following Severe Peripheral Facial Nerve Palsy.

    Science.gov (United States)

    Kasahara, Takashi; Ikeda, Saori; Sugimoto, Ayaka; Sugawara, Shinji; Koyama, Yuji; Toyokura, Minoru; Masakado, Yoshihisa

    2017-09-20

    Mirror feedback rehabilitation is effective in preventing the development of oro-ocular synkinesis following severe facial palsy. However, we do not have effective maneuvers to prevent the deterioration of oculo-oral synkinesis. We developed a new method of biofeedback rehabilitation using tape for the prevention of oculo-oral synkinesis. The aim of the present study was to investigate the efficacy of taping feedback rehabilitation. Twelve consecutive patients with peripheral facial nerve palsy who developed synkinesis were divided into 2 groups. Six patients were treated with the new training method, and the remaining 6 patients were treated with conventional therapy as controls. In the experiment group, tape was placed around the mouth, and the patient was instructed to close the eyes so that no movements of the mouth would be perceived from sensations of the taped skin. After 4 weeks of training, facial movements were recorded and movie images were graded for mouth synkinesis using the revised Sunnybrook facial grading system by examiners blinded to patient grouping. Mouth corner contraction during eye closure was significantly weaker in the experimental group than in the control group. Our new feedback method could help prevent the deterioration of oculo-oral synkinesis.

  5. Appropriate modulation of autophagy sensitizes malignant peripheral nerve sheath tumor cells to treatment with imatinib mesylate.

    Science.gov (United States)

    Okano, Munehiro; Sakata, Naoki; Ueda, Satoshi; Takemura, Tsukasa

    2014-04-01

    Malignant peripheral nerve sheath tumor (MPNST), very rare in childhood, is a highly aggressive soft-tissue tumor. We experienced a case of a 7-year-old boy with MPNST who was treated with imatinib mesylate (imatinib) after the identification of platelet-derived growth factor receptor expression in his tumor. We were unable to observe clinical benefits of imatinib in this patient. Therefore, cellular reactions of imatinib were investigated in vitro using 3 MPNST cell lines. Imatinib induced cytotoxicity in vitro with variable IC50 values (11.7 to >30 μM). Induction of apoptosis was not a pivotal mechanism in the inhibitory effects. We found that the treatment of MPNST cell lines with imatinib induced autophagy. Suppression of the initiation of autophagy by 3-methyladenine or small interfering RNA (siRNA) against beclin-1 attenuated the imatinib-mediated cytotoxicity. In contrast, blocking the formation of autophagosomes or the development of autolysosomes using siRNA against microtubule-associated protein light chain 3B, bafilomycin A1, chloroquine, or an MEK1/2 inhibitor (U0126) enhanced the imatinib-induced cytotoxicity in MPNST cells. Our data showed that the imatinib-mediated autophagy can function as a cytotoxic mechanism and that appropriate modulation of autophagy may sensitize MPNST cells to imatinib, which in turn may be a novel therapeutic strategy for MPNST.

  6. Does Peripheral Neuropathy Associate with Cranial Nerves Neuropathy in Type 2 diabetes Patients?

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    Walaa Fadhil Jalal

    2017-02-01

    Full Text Available Diabetic peripheral neuropathy (DPN is the most common complication of type 2 diabetes mellitus. Cranial neuropathies is usually presenting as mononeuropathies coexist with DPN either presented clinically or in subclinical form. The aim of this study is to detect cranial neuropathy in diabetic patients. Eighty three patients with type 2 diabetes mellitus (T2DM with an age range of 30-69 years were included in the study. The study also involved normal healthy persons whose age and gender are harmonized with that of our patients that were deliberated as control group (60 persons. Diabetic patients with DPN had significant difference in age, highly significant difference in the duration of the disease and highly significance difference in BMI had poor glycemic control reflected by high FBS and HbA1c, while lipid profile picture showed insignificant difference when compared with diabetic patients without DPN. Nerve conduction study (sensory and motor showed a significant difference regarding latency, amplitude, and conduction velocity between diabetic patients with DPN and those without DPN. The results of blink reflex showed highly significant difference between diabetic patients and controls.

  7. Effects of pesticides on the peripheral and central nervous system in tobacco farmers in Malaysia: studies on peripheral nerve conduction, brain-evoked potentials and computerized posturography.

    Science.gov (United States)

    Kimura, Kaoru; Yokoyama, Kazuhito; Sato, Hajime; Nordin, Rusli Bin; Naing, Lin; Kimura, Satoshi; Okabe, Shingo; Maeno, Takashi; Kobayashi, Yasuki; Kitamura, Fumihiko; Araki, Shunichi

    2005-04-01

    We examined the effects of pesticides on the central and peripheral nervous system in the setting of a tobacco farm at a developing country. Maximal motor and sensory nerve conduction velocities (MCV and SCV, respectively) in the median, sural and tibial nerves, postural sway, and brain-evoked potentials (auditory event-related and visual-evoked potentials) were measured in 80 male tobacco farmers and age- and sex-matched 40 controls in Kelantan, Malaysia. Median SCV (finger-wrist) in farmers using Delsen (mancozeb, dithiocarbamate fungicide), who showed significant decrease of serum cholinesterase activities, were significantly lower compared with the controls. Sural SCV in farmers using Fastac (alpha-cypermethrin, pyrethroid insecticide) and median MCV (elbow-wrist) in farmers using Tamex (butralin, dinitroaniline herbicide) were significantly slowed compared with their respective controls. In Delsen (mancozeb, dithiocarbamate) users, the power of postural sway of 0-1 Hz was significantly larger than that in the controls both in the anterior-posterior direction with eyes open and in the right-left direction with eyes closed. The former type of sway was also significantly increased in Tamaron (methamidophos, organophosphorus insecticide) users. In conclusion, nerve conduction velocities and postural sway seem to be sensitive indicators of the effects of pesticides on the central and peripheral nervous system.

  8. Chronic recording of hand prosthesis control signals via a regenerative peripheral nerve interface in a rhesus macaque

    Science.gov (United States)

    Irwin, Z. T.; Schroeder, K. E.; Vu, P. P.; Tat, D. M.; Bullard, A. J.; Woo, S. L.; Sando, I. C.; Urbanchek, M. G.; Cederna, P. S.; Chestek, C. A.

    2016-08-01

    Objective. Loss of even part of the upper limb is a devastating injury. In order to fully restore natural function when lacking sufficient residual musculature, it is necessary to record directly from peripheral nerves. However, current approaches must make trade-offs between signal quality and longevity which limit their clinical potential. To address this issue, we have developed the regenerative peripheral nerve interface (RPNI) and tested its use in non-human primates. Approach. The RPNI consists of a small, autologous partial muscle graft reinnervated by a transected peripheral nerve branch. After reinnervation, the graft acts as a bioamplifier for descending motor commands in the nerve, enabling long-term recording of high signal-to-noise ratio (SNR), functionally-specific electromyographic (EMG) signals. We implanted nine RPNIs on separate branches of the median and radial nerves in two rhesus macaques who were trained to perform cued finger movements. Main results. No adverse events were noted in either monkey, and we recorded normal EMG with high SNR (>8) from the RPNIs for up to 20 months post-implantation. Using RPNI signals recorded during the behavioral task, we were able to classify each monkey’s finger movements as flexion, extension, or rest with >96% accuracy. RPNI signals also enabled functional prosthetic control, allowing the monkeys to perform the same behavioral task equally well with either physical finger movements or RPNI-based movement classifications. Significance. The RPNI signal strength, stability, and longevity demonstrated here represents a promising method for controlling advanced prosthetic limbs and fully restoring natural movement.

  9. Malignant peripheral nerve sheath tumor associated with neurofibromatosis type 1, with metastasis to the heart: a case report

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    Araki Nobuhito

    2010-01-01

    Full Text Available Abstract A rare case is presented of a 61-year-old man with a malignant peripheral nerve sheath tumor associated with neurofibromatosis type 1, with metastasis to the heart. The primary tumor originated in the right thigh in 1982. Since then, the patient has had repeated local recurrences in spite of repeated surgical treatment and adjuvant chemotherapy. He has developed previous metastases of the lung and heart. The patient died of cardiac involvement.

  10. Tesamorelin Therapy to Enhance Axonal Regeneration, Minimize Muscle Atrophy and Improve Functional Outcomes Following Peripheral Nerve Injury and Repair

    Science.gov (United States)

    2017-10-01

    with REDCap and our biostatistician. We have received IRB approval from JHU IRB and IRB waivers from our primary recruitment sites (Union Memorial ...will be eligible for enrolment. Subject recruitment will take place primarily at Johns Hopkins Hospital, Union Memorial Hospital (Curtis National Hand...peripheral nerve regeneration, Phase 2 clinical trial, motor recovery, sensory recovery. 3. ACCOMPLISHMENTS:  What were the major goals of the project? Below

  11. A High Density Electrophysiological Data Analysis System for a Peripheral Nerve Interface Communicating with Individual Neurons in the Brain

    Science.gov (United States)

    2016-11-14

    microdevices. Cable to TDT Headplug fixed with dental cement Subcutaneous wires Regenerative microchannel electrode implant Figure 7...s) and should not contrued as an official Department of the Army position, policy or decision, unless so designated by other documentation. 9...nerve interface (μPNI) placed on the peripheral nervous system and custom- designed µCuff/µECoG interfaces on the central nervous system. A neuron

  12. Characterisation of malignant peripheral nerve sheath tumours in neurofibromatosis-1 using heterogeneity analysis of {sup 18}F-FDG PET

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    Cook, Gary J.R.; Siddique, Muhammad; Goh, Vicky; Warbey, Victoria S. [King' s College London, Cancer Imaging Department, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); Lovat, Eitan [King' s College London, Guy' s, Kings and St Thomas' Medical School, London (United Kingdom); Ferner, Rosalie [Guys and St Thomas' NHS Foundation Trust, National Neurofibromatosis Service, Department of Neurology, London (United Kingdom)

    2017-10-15

    Measurement of heterogeneity in {sup 18}F-fluorodeoxyglucose ({sup 18}F-FDG) positron emission tomography (PET) images is reported to improve tumour phenotyping and response assessment in a number of cancers. We aimed to determine whether measurements of {sup 18}F-FDG heterogeneity could improve differentiation of benign symptomatic neurofibromas from malignant peripheral nerve sheath tumours (MPNSTs). {sup 18}F-FDG PET data from a cohort of 54 patients (24 female, 30 male, mean age 35.1 years) with neurofibromatosis-1 (NF1), and clinically suspected malignant transformation of neurofibromas into MPNSTs, were included. Scans were performed to a standard clinical protocol at 1.5 and 4 h post-injection. Six first-order [including three standardised uptake value (SUV) parameters], four second-order (derived from grey-level co-occurrence matrices) and four high-order (derived from neighbourhood grey-tone difference matrices) statistical features were calculated from tumour volumes of interest. Each patient had histological verification or at least 5 years clinical follow-up as the reference standard with regards to the characterisation of tumours as benign (n = 30) or malignant (n = 24). There was a significant difference between benign and malignant tumours for all six first-order parameters (at 1.5 and 4 h; p < 0.0001), for second-order entropy (only at 4 h) and for all high-order features (at 1.5 h and 4 h, except contrast at 4 h; p < 0.0001-0.047). Similarly, the area under the receiver operating characteristic curves was high (0.669-0.997, p < 0.05) for the same features as well as 1.5-h second-order entropy. No first-, second- or high-order feature performed better than maximum SUV (SUVmax) at differentiating benign from malignant tumours. {sup 18}F-FDG uptake in MPNSTs is higher than benign symptomatic neurofibromas, as defined by SUV parameters, and more heterogeneous, as defined by first- and high-order heterogeneity parameters. However, heterogeneity analysis

  13. Vascular mechanism of axonal degeneration in peripheral nerves in hemiplegic sides after cerebral hemorrhage: An experimental study

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    Bayram Ednan

    2008-04-01

    Full Text Available Abstract Background Though retrograde neuronal death and vascular insufficiency have been well established in plegics following intracerebral hemorrhage, the effects of plegia on arterial nervorums of peripheral nerves have not been reported. In this study, the histopathological effects of the intracerebral hemorrhage on the dorsal root ganglions and sciatic nerves via affecting the arterial nervorums were investigated. Methods This study was conducted on 13 male hybrid rabbits. Three animals were taken as control group and did not undergo surgery. The remaining 10 subjects were anesthetized and were injected with 0.50 ml of autologous blood into their right sensory-motor region. All rabbits were followed-up for two months and then sacrificed. Endothelial cell numbers and volume values were estimated a three dimensionally created standardized arterial nervorums model of lumbar 3. Neuron numbers of dorsal root ganglions, and axon numbers in the lumbar 3 nerve root and volume values of arterial nervorums were examined histopathologically. The results were analyzed by using a Mann-Whitney-U test. Results Left hemiplegia developed in 8 animals. On the hemiplegic side, degenerative vascular changes and volume reduction in the arterial nervorums of the sciatic nerves, neuronal injury in the dorsal root ganglions, and axonal injury in the lumbar 3 were detected. Statistical analyses showed a significant correlation between the normal or nonplegic sides and plegic sides in terms of the neurodegeneration in the dorsal root ganglions (p Conclusion Intracerebral hemorrhage resulted in neurodegeneration in the dorsal root ganglion and axonolysis in the sciatic nerves, endothelial injury, and volume reduction of the arterial nervorums in the sciatic nerves. The interruption of the neural network connection in the walls of the arterial nervorums in the sciatic nerves may be responsible for circulation disorders of the arterial nervorums, and arterial

  14. Fabrication and characterization of electrospun laminin-functionalized silk fibroin/poly(ethylene oxide) nanofibrous scaffolds for peripheral nerve regeneration.

    Science.gov (United States)

    Rajabi, Mina; Firouzi, Masoumeh; Hassannejad, Zahra; Haririan, Ismaeil; Zahedi, Payam

    2017-08-14

    The peripheral nerve regeneration is still one of the major clinical problems, which has received a great deal of attention. In this study, the electrospun silk fibroin (SF)/poly(ethylene oxide) (PEO) nanofibrous scaffolds were fabricated and functionalized their surfaces with laminin (LN) without chemical linkers for potential use in the peripheral nerve tissue engineering. The morphology, surface chemistry, thermal behavior and wettability of the scaffolds were examined to evaluate their performance by means of scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC) and water contact angle (WCA) measurements, respectively. The proliferation and viability of Schwann cells onto the surfaces of SF/PEO nanofibrous scaffolds were investigated using SEM and thiazolyl blue (MTT) assay. The results showed an improvement of SF conformation and surface hydrophilicity of SF/PEO nanofibers after methanol and O 2 plasma treatments. The immunostaining observation indicated a continuous coating of LN on the scaffolds. Improving the surface hydrophilicity and LN functionalization significantly increased the cell proliferation and this was more prominent after 5 days of culture time. In conclusion, the obtained results revealed that the electrospun LN-functionalized SF/PEO nanofibrous scaffold could be a promising candidate for peripheral nerve tissue regeneration. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2017. © 2017 Wiley Periodicals, Inc.

  15. Efficacy and safety of novel collagen conduits filled with collagen filaments to treat patients with peripheral nerve injury: A multicenter, controlled, open-label clinical trial.

    Science.gov (United States)

    Saeki, Masaomi; Tanaka, Kenji; Imatani, Junya; Okamoto, Hideki; Watanabe, Kentaro; Nakamura, Toshiyasu; Gotani, Hiroyuki; Ohi, Hiroyuki; Nakamura, Ryogo; Hirata, Hitoshi

    2018-03-13

    The safety and efficacy of using artificial collagen nerve conduits filled with collagen filaments to treat nerve defects has not been fully studied in humans. We conducted a multicenter, controlled, open-label study to compare the safety and efficacy of artificial nerve conduit grafts with those of autologous nerve grafts. We included patients with a sensory nerve defect of ≤30 mm, at the level of the wrist or a more distal location, with the first-line surgical methods selected according to a patient's preference. We compared sensory recovery using static two-point discrimination and adverse events between the artificial collagen nerve conduit and autologous nerve grafting. The artificial nerve conduit group included 49 patients, with a mean age of 42 years and nerve defect of 12.6 mm. The autologous nerve graft group included 7 patients, with historical data of an additional 31 patients, with a mean age of 36 years and nerve defect of 18.7 mm. The rate of recovery of sensory function at 12 months was 75% (36/49) for the artificial nerve conduit group and 73.7% (28/38) in the autologous nerve group. No serious adverse events directly associated with use of the artificial nerve conduit were identified. The treatment of nerve defects ≤30 mm using artificial collagen nerve conduits was not inferior to treatment using autologous nerve grafts. Based on our data, the new artificial collagen nerve conduit can provide an alternative to autologous nerve for the treatment of peripheral nerve defects. Copyright © 2018. Published by Elsevier Ltd.

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

    Science.gov (United States)

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

    2014-05-01

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

  17. Peripheral nerve reconstruction with epsilon-caprolactone conduits seeded with vasoactive intestinal peptide gene-transfected mesenchymal stem cells in a rat model

    Science.gov (United States)

    Hernández-Cortés, P.; Toledo-Romero, M. A.; Delgado, M.; Sánchez-González, C. E.; Martin, F.; Galindo-Moreno, P.; O'Valle, F.

    2014-08-01

    Objective. Attempts have been made to improve nerve conduits in peripheral nerve reconstruction. We investigated the potential therapeutic effect of a vasoactive intestinal peptide (VIP), a neuropeptide with neuroprotective, trophic and developmental regulatory actions, in peripheral nerve regeneration in a severe model of nerve injury that was repaired with nerve conduits. Approach. The sciatic nerve of each male Wistar rat was transected unilaterally at 10 mm and then repaired with Dl-lactic-ɛ-caprolactone conduits. The rats were treated locally with saline, with the VIP, with adipose-derived mesenchymal stem cells (ASCs) or with ASCs that were transduced with the VIP-expressing lentivirus. The rats with the transected nerve, with no repairs, were used as untreated controls. At 12 weeks post-surgery, we assessed their limb function by measuring the ankle stance angle and the percentage of their muscle mass reduction, and we evaluated the histopathology, immunohistochemistry and morphometry of the myelinated fibers. Main results. The rats that received a single injection of VIP-expressing ASCs showed a significant functional recovery in the ankle stance angle (p = 0.049) and a higher number of myelinated fibers in the middle and distal segments of the operated nerve versus the other groups (p = 0.046). Significance. These results suggest that utilization of a cellular substrate, plus a VIP source, is a promising method for enhancing nerve regeneration using Dl-lactic-ɛ-caprolactone conduits and that this method represents a potential useful clinical approach to repairing peripheral nerve damage.

  18. Neurophysiological assessment of auditory, peripheral nerve, somatosensory, and visual system function after developmental exposure to gasoline, E15, and E85 vapors.

    Data.gov (United States)

    U.S. Environmental Protection Agency — Visual, auditory, somatosensory, and peripheral nerve evoked responses. This dataset is associated with the following publication: Herr , D., D. Freeborn , L. Degn ,...

  19. [Perception of gustatory sensation after treatment of the third branch trigeminal nerve and lingual nerve by peripheral alcohol injection].

    Science.gov (United States)

    Marcinkowski, Michał; Lewandowski, Leszek

    2006-01-01

    Objective testing was an aim of the examination whether excluding the sensory zone of the tongue is causing the slope of the gustatory sensitivity after alcoholic blocks. Material is embracing 15 ill neuralgia treated in a maxillary-facial surgical clinic in Poznań because of neuralgia, in the age on average 60 years, which one should block the sensory leadership of the mandibular nerve with alcohol at and additionally lingual branch. There were 6 women and 9 men amongst treated patients. Objective electrogustomertic examinations demonstrated worsening the gustatory sensitivity with the Pruszewicz's method at 86.7% of ill, on the alcoholised side of the lingual nerve, however at stayed impressions of the gustatory sensitivity were located in upper limits of the norm. Worsening gustatory impressions isn't forming with injuring of the of chorda tympani fibres but it is an effect of bearing feeling surface in the area of the innervation through the lingual nerve after of it alcoholization.

  20. Lentiviral-mediated transfer of CNTF to schwann cells within reconstructed peripheral nerve grafts enhances adult retinal ganglion cell survival and axonal regeneration

    NARCIS (Netherlands)

    Hu, Ying; Leaver, Simone G; Plant, Giles W; Hendriks, William T J; Niclou, Simone P; Verhaagen, J.; Harvey, Alan R; Cui, Qi

    We recently described a method for reconstituting peripheral nerve (PN) sheaths using adult Schwann cells (SCs). Reconstructed PN tissue grafted onto the cut optic nerve supports the regeneration of injured adult rat retinal ganglion cell (RGC) axons. To determine whether genetic manipulation of

  1. Soluble CD163 levels are elevated in cerebrospinal fluid and serum in people with Type 2 diabetes mellitus and are associated with impaired peripheral nerve function

    DEFF Research Database (Denmark)

    Kallestrup, M; Møller, Holger Jon; Tankisi, H

    2015-01-01

    nerve function. Higher levels of soluble CD163 in people with diabetic polyneuropathy suggest that inflammation plays a role in the development of neural impairment. The relationship between cerebrospinal fluid soluble CD163 level and peripheral nerve conduction indicates that soluble CD163 may...

  2. 17β-Estradiol Promotes Schwann Cell Proliferation and Differentiation, Accelerating Early Remyelination in a Mouse Peripheral Nerve Injury Model

    Directory of Open Access Journals (Sweden)

    Yan Chen

    2016-01-01

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

  3. Zonisamide Enhances Neurite Elongation of Primary Motor Neurons and Facilitates Peripheral Nerve Regeneration In Vitro and in a Mouse Model.

    Directory of Open Access Journals (Sweden)

    Hideki Yagi

    Full Text Available No clinically applicable drug is currently available to enhance neurite elongation after nerve injury. To identify a clinically applicable drug, we screened pre-approved drugs for neurite elongation in the motor neuron-like NSC34 cells. We found that zonisamide, an anti-epileptic and anti-Parkinson's disease drug, promoted neurite elongation in cultured primary motor neurons and NSC34 cells in a concentration-dependent manner. The neurite-scratch assay revealed that zonisamide enhanced neurite regeneration. Zonisamide was also protective against oxidative stress-induced cell death of primary motor neurons. Zonisamide induced mRNA expression of nerve growth factors (BDNF, NGF, and neurotrophin-4/5, and their receptors (tropomyosin receptor kinase A and B. In a mouse model of sciatic nerve autograft, intragastric administration of zonisamide for 1 week increased the size of axons distal to the transected site 3.9-fold. Zonisamide also improved the sciatic function index, a marker for motor function of hindlimbs after sciatic nerve autograft, from 6 weeks after surgery. At 8 weeks after surgery, zonisamide was protective against denervation-induced muscle degeneration in tibialis anterior, and increased gene expression of Chrne, Colq, and Rapsn, which are specifically expressed at the neuromuscular junction. We propose that zonisamide is a potential therapeutic agent for peripheral nerve injuries as well as for neuropathies due to other etiologies.

  4. Effects of Valproic Acid on Axonal Regeneration and Recovery of Motor Function after Peripheral Nerve Injury in the Rat

    Directory of Open Access Journals (Sweden)

    Ting Rao

    2014-03-01

    Full Text Available Background:   Valproic acid (VPA is used to be an effective anti-epileptic drug and mood stabilizer. It has recently been demonstrated that VPA could promote neurite outgrowth, activate the extracellular signal regulated kinase pathway, and increases bcl-2 and growth cone-associated protein 43 levels in spinal cord. In the present research we demonstrate the effect of VPA on peripheral nerve regeneration and recovery of motor function following sciatic nerve transaction in rats. Methods:   The rats in VPA group and control group were administered with valproic acid (300mg/kg and sodium chloride respectively after operation. Each animal was observed sciatic nerve index (SFI at 2-week intervals and studied electrophysiology at 4-week intervals for 12 weeks. Histological and morphometrical analyses were performed 12 weeks after operation. Using the digital image-analysis system, thickness of the myelin sheath was measured, and total numbers of regenerated axons were counted. Results:   There was a significant difference in SFI, electrophysiological index (motor-nerve conduct velocity, and morphometrical results (regenerated axon number and thickness of myelin sheath in nerve regeneration between the VPA group and controls (   P

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

    Science.gov (United States)

    Wrobel, Melissa Renee

    Clinically available treatments are insufficient to achieve full functional recovery in large (> 3cm) peripheral nerve injuries (PNI). The objectives in this thesis were 1) to study often overlooked elements of intrinsic PNI repair including release of inhibitory CSPGs and post-injury responses of inflammatory macrophages and dedifferentiated Schwann cells; 2) to create biomaterial scaf-folds featuring topographical and adhesive cues to enhance neurite outgrowth; and 3) to test the ability of those cues to direct macrophages and Schwann cells towards a pro-regenerative phe-notype. It is hypothesized that recapitulating the positive and negative cues of the PNI microenvi-ronment can better improve regeneration. The effect of a characteristic CSPG, Chondroitin Sul-fate A (CSA), was tested on neurite dynamics of dissociated chick embryo dorsal root ganglion (DRG) neurons using time lapse video microscopy. DRG growth was recorded on different ad-hesive substrates, including a novel, porcine-derived spinal cord matrix (SCM). The SCM signifi-cantly increased neurite extension, reduced neurite stalling, and mitigated CSA inhibition. Flow cytometry was used to measure changes in cell-substrate binding receptor expression in the neurons. Results showed a significant increase in Syndecan-3 receptor expression in neurons treated with CSA, suggesting a possible priming of the cells for regrowth. The CSA was success-fully immobilized within electrospun hyaluronic acid (HA) nanofibers using a methacrylation re-action. Blended electrospinning was used to create scaffolds featuring the CSA and SCM cues. Results showed significantly increased neurite outgrowth on scaffolds with the SCM and low levels of CSA. Higher incorporation of CSA maintained its inhibitory properties. Next the CSA, SCM, and HA fiber cues were tested for their effects on macrophage and Schwann cell pheno-type. It was hypothesized that one or more of the cues would accelerate the macrophages return to rest

  6. Comparative outcomes of peripheral nerve blocks versus general anesthesia for hip fractures in geriatric Chinese patients

    Science.gov (United States)

    Liu, Jun Le; Wang, Xiao Lin; Gong, Mao Wei; Mai, Hai Xing; Pei, Shu Jun; Yuan, Wei Xiu; Zhang, Hong

    2014-01-01

    Background Geriatric patients undergoing hemiarthroplasty for hip fractures have unacceptably high rates of postoperative complications and mortality. Whether anesthesia type can affect the outcomes has still been inconclusive. Objectives We compared general anesthesia (GA) and peripheral nerve blocks (PNBs) on postoperative complications and mortality in elderly patients with femoral neck fractures (FNF) undergoing hemiarthroplasty. Materials and methods This retrospective study involved data collection from an electronic database. Two hundred and seventeen patients underwent hemiarthroplasty for FNF between January 2008 and December 2012 at the Chinese People’s Liberation Army General Hospital. Data on mortality within in-hospital, 30-day, and 1-year, complications, comorbidities, blood loss and transfusion, operative time, postoperative hospital length of stay, intensive care unit admission, and hospital charge were collected and analyzed. Univariate and multivariate Cox regression analyses of all variables were used for 30-day and 1-year mortality. Results Seventy-two patients receiving GA and 145 receiving PNBs were eventually submitted and analyzed. Mortality was 6.9%, 14.7%, and 23.5% at in-hospital, 30-day, and 1-year, respectively postoperatively, while mortality and cardiovascular complications did not differ between the two anesthetic techniques. Preoperative comorbidities and intraoperative parameters were not statistically different except that patients receiving GA were more likely to have dementia (χ2=10.45, P=0.001). The most common complications were acute cardiovascular events, electrolyte disturbances, and delirium. Postoperative acute respiratory events and hypoxemia both were also common, but no differences were found between groups (χ2=0.68, P=0.410; χ2=3.42, P=0.065, respectively). Key factors negatively influencing mortality included: age, male gender, American Society of Anesthesiologists status, dementia, perioperative cardiovascular

  7. Ultrastructural dimensions of myelinated peripheral nerve fibres in the cat and their relation to conduction velocity.

    Science.gov (United States)

    Arbuthnott, E R; Boyd, I A; Kalu, K U

    1980-11-01

    equation may be improved by deducting 3 m/sec in the case of small fibres. This conclusion is compatible with experimental observations of the relation between l and D (Hursh, 1939; Lubinska, 1960; Coppin, 1973) and between l and Theta (Coppin & Jack, 1972).8. From the theoretical analyses of Rushton (1951) and others Theta should be proportional to the external dimensions of the fibre rather than to axon size. It is shown that the thinning of the myelin sheath ought to affect Theta substantially. Thus some other factors must compensate for the thinning of the sheath.9. Small fibres are significantly more non-circular than large fibres. From the quantitative data of Arbuthnott et al. (1980) it is concluded that non-circularity may contribute to the fact that Theta proportional, variant s rather than Theta proportional, variant S, but cannot wholly account for it. Other possibilities considered are that axoplasmic resistivity or specific nodal conductance may differ for large and small fibres.10. It is suggested that myelinated peripheral nerve fibres may fall into two distinct classes with different properties, one comprising groups I and alpha and the other groups II, III and gamma. The conclusion predicted from theory may apply to each of these classes separately so that Theta = 2.0 S for the large-fibre class and Theta = 1.6 S for the small-fibre class.

  8. Human dental pulp stem cells expressing STRO-1, c-kit and CD34 markers in peripheral nerve regeneration.

    Science.gov (United States)

    Carnevale, Gianluca; Pisciotta, Alessandra; Riccio, Massimo; Bertoni, Laura; De Biasi, Sara; Gibellini, Lara; Zordani, Alessio; Cavallini, Gian Maria; La Sala, Giovanni Battista; Bruzzesi, Giacomo; Ferrari, Adriano; Cossarizza, Andrea; de Pol, Anto

    2018-02-01

    Peripheral nerve injuries are a commonly encountered clinical problem and often result in long-term functional defects. The application of stem cells able to differentiate in Schwann cell-like cells in vitro and in vivo, could represent an attractive therapeutic approach for the treatment of nerve injuries. Further, stem cells sources sharing the same embryological origin as Schwann cells might be considered a suitable tool. The aim of this study was to demonstrate the ability of a neuroectodermal subpopulation of human STRO-1 + /c-Kit + /CD34 + DPSCs, expressing P75 NTR , nestin and SOX-10, to differentiate into Schwann cell-like cells in vitro and to promote axonal regeneration in vivo, which led to functional recovery as measured by sustained gait improvement, in animal rat model of peripheral nerve injury. Transplanted human dental pulp stem cells (hDPSCs) engrafted into sciatic nerve defect, as revealed by the positive staining against human nuclei, showed the expression of typical Schwann cells markers, S100b and, noteworthy, a significant number of myelinated axons was detected. Moreover, hDPSCs promoted axonal regeneration from proximal to distal stumps 1 month after transplantation. This study demonstrates that STRO-1 + /c-Kit + /CD34 + hDPSCs, associated with neural crest derivation, represent a promising source of stem cells for the treatment of demyelinating disorders and might provide a valid alternative tool for future clinical applications to achieve functional recovery after injury or peripheral neuropathies besides minimizing ethical issues. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  9. Nerve conduction

    Science.gov (United States)

    ... the central nervous system (CNS) and peripheral nervous system (PNS). The CNS contains the brain and the spinal cord and the PNS consists of thousands of nerves that connect the spinal cord to muscles and sensory receptors. A peripheral nerve is composed of nerve ...

  10. Delaying the onset of treadmill exercise following peripheral nerve injury has different effects on axon regeneration and motoneuron synaptic plasticity.

    Science.gov (United States)

    Brandt, Jaclyn; Evans, Jonathan T; Mildenhall, Taylor; Mulligan, Amanda; Konieczny, Aimee; Rose, Samuel J; English, Arthur W

    2015-04-01

    Transection of a peripheral nerve results in withdrawal of synapses from motoneurons. Some of the withdrawn synapses are restored spontaneously, but those containing the vesicular glutamate transporter 1 (VGLUT1), and arising mainly from primary afferent neurons, are withdrawn permanently. If animals are exercised immediately after nerve injury, regeneration of the damaged axons is enhanced and no withdrawal of synapses from injured motoneurons can be detected. We investigated whether delaying the onset of exercise until after synapse withdrawal had occurred would yield similar results. In Lewis rats, the right sciatic nerve was cut and repaired. Reinnervation of the soleus muscle was monitored until a direct muscle (M) response was observed to stimulation of the tibial nerve. At that time, rats began 2 wk of daily treadmill exercise using an interval training protocol. Both M responses and electrically-evoked H reflexes were monitored weekly for an additional seven wk. Contacts made by structures containing VGLUT1 or glutamic acid decarboxylase (GAD67) with motoneurons were studied from confocal images of retrogradely labeled cells. Timing of full muscle reinnervation was similar in both delayed and immediately exercised rats. H reflex amplitude in delayed exercised rats was only half that found in immediately exercised animals. Unlike immediately exercised animals, motoneuron contacts containing VGLUT1 in delayed exercised rats were reduced significantly, relative to intact rats. The therapeutic window for application of exercise as a treatment to promote restoration of synaptic inputs onto motoneurons following peripheral nerve injury is different from that for promoting axon regeneration in the periphery. Copyright © 2015 the American Physiological Society.

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

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    Ghanouni Pejman

    2012-06-01

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

  12. Peripheral nerve P2 basic protein and the Guillain-Barre syndrome : In vitro demonstration of P2-specific antibody-secreting cells

    NARCIS (Netherlands)

    Luijten, J.A.F.M.; Jong, W.A.C. de; Demel, R.A.; Heijnen, C.J.; Ballieux, R.E.

    1984-01-01

    An immune response to the peripheral nerve basic protein P2 may be operative in the pathogenesis of the Guillain-Barré syndrome (GBS). A method is described for the purification of P2 of human origin. Purified P2 was used to investigate whether lymphocytes derived from peripheral blood of GBS

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

    Directory of Open Access Journals (Sweden)

    Costigan Michael

    2008-12-01

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

  14. Peripheral nerve ultrasound in cerebellar ataxia neuropathy vestibular areflexia syndrome (CANVAS).

    Science.gov (United States)

    Pelosi, Luciana; Leadbetter, Ruth; Mulroy, Eoin; Chancellor, Andrew M; Mossman, Stuart; Roxburgh, Richard

    2017-07-01

    We report preliminary findings of nerve ultrasound in patients with cerebellar ataxia neuropathy vestibular areflexia syndrome (CANVAS) who have sensory impairment due to dorsal root ganglionopathy. The ultrasound cross-sectional area (CSA) of median and ulnar nerves of 7 CANVAS patients was compared with 7 age- and gender-matched controls and with the mean CSA of our reference population. The nerve CSA of CANVAS patients was significantly smaller than that of controls at all sites (P CANVAS patients fell outside the normal control range and was >2 standard deviations below the reference mean. The small nerves in CANVAS probably reflect nerve thinning from axonal loss secondary to ganglion cell loss. Our data show a role for ultrasound in the diagnosis of CANVAS ganglionopathy. This may also be applicable to ganglionopathy from other causes. Muscle Nerve 56: 160-162, 2017. © 2016 Wiley Periodicals, Inc.

  15. Peripheral Motor and Sensory Nerve Conduction following Transplantation of Undifferentiated Autologous Adipose Tissue-Derived Stem Cells in a Biodegradable U.S. Food and Drug Administration-Approved Nerve Conduit.

    Science.gov (United States)

    Klein, Silvan M; Vykoukal, Jody; Li, De-Pei; Pan, Hui-Lin; Zeitler, Katharina; Alt, Eckhard; Geis, Sebastian; Felthaus, Oliver; Prantl, Lukas

    2016-07-01

    Conduits preseeded with either Schwann cells or stem cells differentiated into Schwann cells demonstrated promising results for the outcome of nerve regeneration in nerve defects. The concept of this trial combines nerve repair by means of a commercially available nerve guidance conduit and preseeding with autologous, undifferentiated, adipose tissue-derived stem cells. Adipose tissue-derived stem cells were harvested from rats and subsequently seeded onto a U.S. Food and Drug Administration-approved type I collagen conduit. Sciatic nerve gaps 10 mm in length were created, and nerve repair was performed by the transplantation of either conduits preseeded with autologous adipose tissue-derived stem cells or acellular (control group) conduits. After 6 months, the motor and sensory nerve conduction velocity were assessed. Nerves were removed and examined by hematoxylin and eosin, van Gieson, and immunohistochemistry (S100 protein) staining for the quality of axonal regeneration. Nerve gaps treated with adipose tissue-derived stem cells showed superior nerve regeneration, reflected by higher motor and sensory nerve conduction velocity values. The motor and sensory nerve conduction velocity were significantly greater in nerves treated with conduits preseeded with adipose tissue-derived stem cells than in nerves treated with conduits alone (p adipose tissue-derived stem cell group. In this group, axon arrangement inside the conduits was more organized. Transplantation of adipose tissue-derived stem cells significantly improves motor and sensory nerve conduction velocity in peripheral nerve gaps. Preseeded conduits showed a more organized axon arrangement inside the conduit in comparison with nerve conduits alone. The approach used here could readily be translated into a clinical therapy. Therapeutic, V.

  16. Use of 5% lidocaine medicated plaster to treat localized neuropathic pain secondary to traumatic injury of peripheral nerves

    Directory of Open Access Journals (Sweden)

    Correa-Illanes G

    2012-07-01

    Full Text Available Gerardo Correa-Illanes,1 Ricardo Roa,2 José Luis Piñeros,2 Wilfredo Calderón31Rehabilitation Department, 2Burns and Plastic Surgery Department, Hospital del Trabajador, 3Plastic Surgery Department, Hospital del Salvador, Santiago, ChileObjective: The efficacy of 5% lidocaine medicated plaster (LMP has previously been demonstrated in post-traumatic localized neuropathic pain. This study evaluated the use of LMP in localized neuropathic pain secondary to traumatic peripheral nerve injury.Patients and methods: This prospective observational study enrolled patients with traumatic injuries to peripheral nerves that were accompanied by localized neuropathic pain of more than 3 months duration. Demographic variables, pain intensity (measured using the numeric rating scale; NRS, answers to the Douleur Neuropathique 4 (DN4 questionnaire, and the size of the painful area were recorded.Results: Nineteen patients were included, aged (mean ± standard deviation 41.4 ± 15.7 years. Nerve injuries affected the upper (eight patients or lower (11 patients limbs. The mean duration of pain before starting treatment with LMP was 22.6 ± 43.5 months (median 8 months. Mean baseline values included: NRS 6.7 ± 1.6, painful area 17.8 ± 10.4 cm2 (median 18 cm2, and DN4 score 6.7 ± 1.4. The mean duration of treatment with LMP was 19.5 ± 10.0 weeks (median 17.4 weeks. Mean values after treatment were: NRS 2.8 ± 1.5 (≥3 point reduction in 79% of patients, ≥50% reduction in 57.9% of patients and painful area 2.1 ± 2.3 cm2 (median 1 cm2, ≥50% reduction in 94.7% of patients. Functional improvement after treatment was observed in 14/19 patients (73.7%.Conclusion: LMP effectively treated traumatic injuries of peripheral nerves which presented with chronic localized neuropathic pain, reducing both pain intensity and the size of the painful area.Keywords: chronic post-surgical pain, chronic post-traumatic pain, 5% lidocaine medicated plaster, neuropathic pain

  17. Acute- and late-phase matrix metalloproteinase (MMP)-9 activity is comparable in female and male rats after peripheral nerve injury.

    Science.gov (United States)

    Remacle, Albert G; Hullugundi, Swathi K; Dolkas, Jennifer; Angert, Mila; Chernov, Andrei V; Strongin, Alex Y; Shubayev, Veronica I

    2018-03-20

    In the peripheral nerve, pro-inflammatory matrix metalloproteinase (MMP)-9 performs essential functions in the acute response to injury. Whether MMP-9 activity contributes to late-phase injury or whether MMP-9 expression or activity after nerve injury is sexually dimorphic remains unknown. Patterns of MMP-9 expression, activity and excretion were assessed in a model of painful peripheral neuropathy, sciatic nerve chronic constriction injury (CCI), in female and male rats. Real-time Taqman RT-PCR for MMP-9 and its endogenous inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1) of nerve samples over a 2-month time course of CCI was followed by gelatin zymography of crude nerve extracts and purified MMP-9 from the extracts using gelatin Sepharose-beads. MMP excretion was determined using protease activity assay of urine in female and male rats with CCI. The initial upsurge in nerve MMP-9 expression at day 1 post-CCI was superseded more than 100-fold at day 28 post-CCI. The high level of MMP-9 expression in late-phase nerve injury was accompanied by the reduction in TIMP-1 level. The absence of MMP-9 in the normal nerve and the presence of multiple MMP-9 species (the proenzyme, mature enzyme, homodimers, and heterodimers) was observed at day 1 and day 28 post-CCI. The MMP-9 proenzyme and mature enzyme species dominated in the early- and late-phase nerve injury, consistent with the high and low level of TIMP-1 expression, respectively. The elevated nerve MMP-9 levels corresponded to the elevated urinary MMP excretion post-CCI. All of these findings were comparable in female and male rodents. The present study offers the first evidence for the excessive, uninhibited proteolytic MMP-9 activity during late-phase painful peripheral neuropathy and suggests that the pattern of MMP-9 expression, activity, and excretion after peripheral nerve injury is universal in both sexes.

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

    Directory of Open Access Journals (Sweden)

    Tseng Chi-Yu

    2011-06-01

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

  19. X-ray irradiation has positive effects for the recovery of peripheral nerve injury maybe through the vascular smooth muscle contraction signaling pathway.

    Science.gov (United States)

    Jiang, Bo; Zhang, Yong; She, Chang; Zhao, Jiaju; Zhou, Kailong; Zuo, Zhicheng; Zhou, Xiaozhong; Wang, Peiji; Dong, Qirong

    2017-09-01

    It is well known that moderate to high doses of ionizing radiation have a toxic effect on the organism. However, there are few experimental studies on the mechanisms of LDR ionizing radiation on nerve regeneration after peripheral nerve injury. We established the rats' peripheral nerve injury model via repaired Peripheral nerve injury nerve, vascular endothelial growth factor a and Growth associated protein-43 were detected from different treatment groups. We performed transcriptome sequencing focusing on investigating the differentially expressed genes and gene functions between the control group and 1Gy group. Sequencing was done by using high-throughput RNA-sequencing (RNA-seq) technologies. The results showed the 1Gy group to be the most effective promoting repair. RNA-sequencing identified 619 differently expressed genes between control and treated groups. A Gene Ontology analysis of the differentially expressed genes revealed enrichment in the functional pathways. Among them, candidate genes associated with nerve repair were identified. Pathways involved in cell-substrate adhesion, vascular smooth muscle contraction and cell adhesion molecule signaling may be involved in recovery from peripheral nerve injury. Copyright © 2017. Published by Elsevier B.V.

  20. ErbB2 receptor over-expression improves post-traumatic peripheral nerve regeneration in adult mice.

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    Ronchi, Giulia; Gambarotta, Giovanna; Di Scipio, Federica; Salamone, Paolina; Sprio, Andrea E; Cavallo, Federica; Perroteau, Isabelle; Berta, Giovanni N; Geuna, Stefano

    2013-01-01

    In a transgenic mice (BALB-neuT) over-expressing ErbB2 receptor, we investigated the adult mouse median nerve in physiological and pathological conditions. Results showed that, in physiological conditions, the grip function controlled by the median nerve in BALB-neuT mice was similar to wild-type (BALB/c). Stereological assessment of ErbB2-overexpressing intact nerves revealed no difference in number and size of myelinated fibers compared to wild-type mice. By contrast, after a nerve crush injury, the motor recovery was significantly faster in BALB-neuT compared to BALB/c mice. Moreover, stereological assessment revealed a significant higher number of regenerated myelinated fibers with a thinner axon and fiber diameter and myelin thickness in BALB-neuT mice. At day-2 post-injury, the level of the mRNAs coding for all the ErbB receptors and for the transmembrane (type III) Neuregulin 1 (NRG1) isoforms significantly decreased in both BALB/c and BALB-neuT mice, as shown by quantitative real time PCR. On the other hand, the level of the mRNAs coding for soluble NRG1 isoforms (type I/II, alpha and beta) increased at the same post-traumatic time point though, intriguingly, this response was significantly higher in BALB-neuT mice with respect to BALB/c mice. Altogether, these results suggest that constitutive ErbB2 receptor over-expression does not influence the physiological development of peripheral nerves, while it improves nerve regeneration following traumatic injury, possibly through the up-regulation of soluble NRG1 isoforms.

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

    Science.gov (United States)

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

    2018-03-01

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

  2. Changes in ocular biometry and anterior chamber parameters after pharmacologic mydriasis and peripheral iridotomy in primary angle closure suspects

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    Mohammad Reza Razeghinejad

    2016-07-01

    Conclusions: This study showed no change in the ocular biometric and anterior chamber parameters including iridocorneal angle after PI and/or pharmacologic mydriasis except for increments in anterior chamber volume. This factor has the potential to be used as a numerical proxy for iris position in evaluating and monitoring patients with primary angle closure suspects after PI.

  3. The Safety of EXPAREL ® (Bupivacaine Liposome Injectable Suspension Administered by Peripheral Nerve Block in Rabbits and Dogs

    Directory of Open Access Journals (Sweden)

    Brigitte M. Richard

    2012-01-01

    Full Text Available A sustained-release DepoFoam injection formulation of bupivacaine (EXPAREL, 15 mg/mL is currently being investigated for postsurgical analgesia via peripheral nerve block (PNB. Single-dose toxicology studies of EXPAREL (9, 18, and 30 mg/kg, bupivacaine solution (Bsol, 9 mg/kg, and saline injected around the brachial plexus nerve bundle were performed in rabbits and dogs. The endpoints included clinical pathology, pharmacokinetics, and histopathology evaluation on Day 3 and Day 15 (2/sex/group/period. EXPAREL resulted in a nearly 4-fold lower Cmax versus Bsol at the same dose. EXPAREL was well tolerated at doses up to 30 mg/kg. The only EXPAREL-related effect seen was minimal to mild granulomatous inflammation of adipose tissue around nerve roots (8 of 24 rabbits and 7 of 24 dogs in the brachial plexus sites. The results indicate that EXPAREL was well tolerated in these models and did not produce nerve damage after PNB in rabbits and dogs.

  4. The treatment of peripheral nerve injuries using irradiated allografts and temporary host immunosuppression (in a rat model)

    International Nuclear Information System (INIS)

    Easterling, K.J.; Trumble, T.E.

    1990-01-01

    Irradiation of allografts prior to transplantation and host immunosuppression with cyclosporin-A were studied separately and in combination as means of lessening the rejection of transplanted peripheral nerve tissue. Lewis and Brown Norway rats were used in the animal model, as they differ at both major and minor histocompatibility loci. Sciatic nerve grafts (2.5 cm) were used and the animals were followed for 16 weeks after nerve grafting. The outcome was studied by functional measurements (sensory testing, gait analysis, joint flexion contracture, and muscle weight), as well as by measurements of biochemical and histologic parameters (hydroxyproline concentration and axon counts, respectively). Sensory testing was not reliable because of crossover innervation by the saphenous nerve. Evaluation by standard gait-testing techniques was found to be unsatisfactory. However, the allografted animals receiving cyclosporin-A had significantly smaller flexion contractures, compared to the allografted animals without immunosuppression (17 degrees +/- 12 degrees vs. 44 degrees +/- 13 degrees and 51 degrees +/- 13 degrees, p less than 0.005). Allografted animals receiving short-term cyclosporin-A had contractures that were not significantly different from those seen in isografted control animals (17 degrees +/- 12 degrees vs. 22 degrees +/- 15 degrees, NS). Muscle hydroxyproline concentration analysis revealed a lower hydroxyproline concentration among the allografted groups that received irradiated allografts, compared to groups receiving nonirradiated allogeneic grafts. The studies of muscle hydroxyproline concentration and muscle weight both showed substantial reinnervation, even in allografted animals without pretreatment of the grafts or immunosuppression of the recipient animal

  5. The treatment of peripheral nerve injuries using irradiated allografts and temporary host immunosuppression (in a rat model)

    Energy Technology Data Exchange (ETDEWEB)

    Easterling, K.J.; Trumble, T.E. (Yale Univ. School of Medicine, New Haven, CT (USA))

    1990-10-01

    Irradiation of allografts prior to transplantation and host immunosuppression with cyclosporin-A were studied separately and in combination as means of lessening the rejection of transplanted peripheral nerve tissue. Lewis and Brown Norway rats were used in the animal model, as they differ at both major and minor histocompatibility loci. Sciatic nerve grafts (2.5 cm) were used and the animals were followed for 16 weeks after nerve grafting. The outcome was studied by functional measurements (sensory testing, gait analysis, joint flexion contracture, and muscle weight), as well as by measurements of biochemical and histologic parameters (hydroxyproline concentration and axon counts, respectively). Sensory testing was not reliable because of crossover innervation by the saphenous nerve. Evaluation by standard gait-testing techniques was found to be unsatisfactory. However, the allografted animals receiving cyclosporin-A had significantly smaller flexion contractures, compared to the allografted animals without immunosuppression (17 degrees +/- 12 degrees vs. 44 degrees +/- 13 degrees and 51 degrees +/- 13 degrees, p less than 0.005). Allografted animals receiving short-term cyclosporin-A had contractures that were not significantly different from those seen in isografted control animals (17 degrees +/- 12 degrees vs. 22 degrees +/- 15 degrees, NS). Muscle hydroxyproline concentration analysis revealed a lower hydroxyproline concentration among the allografted groups that received irradiated allografts, compared to groups receiving nonirradiated allogeneic grafts. The studies of muscle hydroxyproline concentration and muscle weight both showed substantial reinnervation, even in allografted animals without pretreatment of the grafts or immunosuppression of the recipient animal.

  6. Dual-Component Gelatinous Peptide/Reactive Oligomer Formulations as Conduit Material and Luminal Filler for Peripheral Nerve Regeneration.

    Science.gov (United States)

    Kohn-Polster, Caroline; Bhatnagar, Divya; Woloszyn, Derek J; Richtmyer, Matthew; Starke, Annett; Springwald, Alexandra H; Franz, Sandra; Schulz-Siegmund, Michaela; Kaplan, Hilton M; Kohn, Joachim; Hacker, Michael C

    2017-05-21

    Toward the next generation of nerve guidance conduits (NGCs), novel biomaterials and functionalization concepts are required to address clinical demands in peripheral nerve regeneration (PNR). As a biological polymer with bioactive motifs, gelatinous peptides are promising building blocks. In combination with an anhydride-containing oligomer, a dual-component hydrogel system (cGEL) was established. First, hollow cGEL tubes were fabricated by a continuous dosing and templating process. Conduits were characterized concerning their mechanical strength, in vitro and in vivo degradation and biocompatibility. Second, cGEL was reformulated as injectable shear thinning filler for established NGCs, here tyrosine-derived polycarbonate-based braided conduits. Thereby, the formulation contained the small molecule LM11A-31. The biofunctionalized cGEL filler was assessed regarding building block integration, mechanical properties, in vitro cytotoxicity, and growth permissive effects on human adipose tissue-derived stem cells. A positive in vitro evaluation motivated further application of the filler material in a sciatic nerve defect. Compared to the empty conduit and pristine cGEL, the functionalization performed superior, though the autologous nerve graft remains the gold standard. In conclusion, LM11A-31 functionalized cGEL filler with extracellular matrix (ECM)-like characteristics and specific biochemical cues holds great potential to support PNR.

  7. Tonsil-Derived Mesenchymal Stem Cells Differentiate into a Schwann Cell Phenotype and Promote Peripheral Nerve Regeneration.

    Science.gov (United States)

    Jung, Namhee; Park, Saeyoung; Choi, Yoonyoung; Park, Joo-Won; Hong, Young Bin; Park, Hyun Ho Choi; Yu, Yeonsil; Kwak, Geon; Kim, Han Su; Ryu, Kyung-Ha; Kim, Jae Kwang; Jo, Inho; Choi, Byung-Ok; Jung, Sung-Chul

    2016-11-09

    Schwann cells (SCs), which produce neurotropic factors and adhesive molecules, have been reported previously to contribute to structural support and guidance during axonal regeneration; therefore, they are potentially a crucial target in the restoration of injured nervous tissues. Autologous SC transplantation has been performed and has shown promising clinical results for treating nerve injuries and donor site morbidity, and insufficient production of the cells have been considered as a major issue. Here, we performed differentiation of tonsil-derived mesenchymal stem cells (T-MSCs) into SC-like cells (T-MSC-SCs), to evaluate T-MSC-SCs as an alternative to SCs. Using SC markers such as CAD19 , GFAP , MBP , NGFR , S100B , and KROX20 during quantitative real-time PCR we detected the upregulation of NGFR , S100B , and KROX20 and the downregulation of CAD19 and MBP at the fully differentiated stage. Furthermore, we found myelination of axons when differentiated SCs were cocultured with mouse dorsal root ganglion neurons. The application of T-MSC-SCs to a mouse model of sciatic nerve injury produced marked improvements in gait and promoted regeneration of damaged nerves. Thus, the transplantation of human T-MSCs might be suitable for assisting in peripheral nerve regeneration.

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

    Science.gov (United States)

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

    2017-09-27

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

  9. Hypertension-induced peripheral neuropathy and the combined effects of hypertension and diabetes on nerve structure and function in rats.

    Science.gov (United States)

    Gregory, Joshua A; Jolivalt, Corinne G; Goor, Jared; Mizisin, Andrew P; Calcutt, Nigel A

    2012-10-01

    Diabetic neuropathy includes damage to neurons, Schwann cells and blood vessels. Rodent models of diabetes do not adequately replicate all pathological features of diabetic neuropathy, particularly Schwann cell damage. We, therefore, tested the hypothesis that combining hypertension, a risk factor for neuropathy in diabetic patients, with insulin-deficient diabetes produces a more pertinent model of peripheral neuropathy. Behav