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Sample records for affecting peripheral nerves

  1. Peripheral Nerve Disorders

    MedlinePlus

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

  2. Peripheral nerve hyperexcitability syndromes.

    PubMed

    Küçükali, Cem Ismail; Kürtüncü, Murat; Akçay, Halil İbrahim; Tüzün, Erdem; Öge, Ali Emre

    2015-01-01

    Peripheral nerve hyperexcitability (PNH) syndromes can be subclassified as primary and secondary. The main primary PNH syndromes are neuromyotonia, cramp-fasciculation syndrome (CFS), and Morvan's syndrome, which cause widespread symptoms and signs without the association of an evident peripheral nerve disease. Their major symptoms are muscle twitching and stiffness, which differ only in severity between neuromyotonia and CFS. Cramps, pseudomyotonia, hyperhidrosis, and some other autonomic abnormalities, as well as mild positive sensory phenomena, can be seen in several patients. Symptoms reflecting the involvement of the central nervous system occur in Morvan's syndrome. Secondary PNH syndromes are generally seen in patients with focal or diffuse diseases affecting the peripheral nervous system. The PNH-related symptoms and signs are generally found incidentally during clinical or electrodiagnostic examinations. The electrophysiological findings that are very useful in the diagnosis of PNH are myokymic and neuromyotonic discharges in needle electromyography along with some additional indicators of increased nerve fiber excitability. Based on clinicopathological and etiological associations, PNH syndromes can also be classified as immune mediated, genetic, and those caused by other miscellaneous factors. There has been an increasing awareness on the role of voltage-gated potassium channel complex autoimmunity in primary PNH pathogenesis. Then again, a long list of toxic compounds and genetic factors has also been implicated in development of PNH. The management of primary PNH syndromes comprises symptomatic treatment with anticonvulsant drugs, immune modulation if necessary, and treatment of possible associated dysimmune and/or malignant conditions. PMID:25719304

  3. Peripheral nerve stimulation: definition.

    PubMed

    Abejón, David; Pérez-Cajaraville, Juan

    2011-01-01

    Recently, there has been a tremendous evolution in the field of neurostimulation, both from the technological point of view and from development of the new and different indications. In some areas, such as peripheral nerve stimulation, there has been a boom in recent years due to the variations in the surgical technique and the improved results documented by in multiple published papers. All this makes imperative the need to classify and define the different types of stimulation that are used today. The confusion arises when attempting to describe peripheral nerve stimulation and subcutaneous stimulation. Peripheral nerve stimulation, in its pure definition, involves implanting a lead on a nerve, with the aim to produce paresthesia along the entire trajectory of the stimulated nerve.

  4. Ultrasound of Peripheral Nerves

    PubMed Central

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

    2013-01-01

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

  5. Peripheral facial nerve palsy after therapeutic endoscopy.

    PubMed

    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.

  6. Peripheral nerve response to injury.

    PubMed

    Steed, Martin B

    2011-03-01

    Oral and maxillofacial surgeons caring for patients who have sustained a nerve injury to a branch of the peripheral trigeminal nerve must possess a basic understanding of the response of the peripheral nerves to trauma. The series of events that subsequently take place are largely dependent on the injury type and severity. Regeneration of the peripheral nerve is possible in many instances and future manipulation of the regenerative microenvironment will lead to advances in the management of these difficult injuries.

  7. Rehabilitation of peripheral nerve injuries.

    PubMed

    Robinson, Michael D; Shannon, Steven

    2002-02-01

    Traumatic injuries to peripheral nerves pose complex challenges to both military and civilian physicians. Treatment of nerve injuries must consider all aspects of the inherent disability. Pain control is of paramount importance. Little will be accomplished until pain is brought down to tolerable levels. Rehabilitation needs to be instituted as first-line treatment. Focus must be first placed on protection of the affected area from complications stemming from disuse and immobility and then on enhancement of strength, flexibility, sensory discrimination, and dexterity. Early intervention sets the stage for optimal physiologic and functional recovery. PMID:11878078

  8. Peripheral vagus nerve stimulation significantly affects lipid composition and protein secondary structure within dopamine-related brain regions in rats.

    PubMed

    Surowka, Artur Dawid; Krygowska-Wajs, Anna; Ziomber, Agata; Thor, Piotr; Chrobak, Adrian Andrzej; Szczerbowska-Boruchowska, Magdalena

    2015-06-01

    Recent immunohistochemical studies point to the dorsal motor nucleus of the vagus nerve as the point of departure of initial changes which are related to the gradual pathological developments in the dopaminergic system. In the light of current investigations, it is likely that biochemical changes within the peripheral nervous system may influence the physiology of the dopaminergic system, suggesting a putative role for it in the development of neurodegenerative disorders. By using Fourier transform infrared microspectroscopy, coupled with statistical analysis, we examined the effect of chronic, unilateral electrical vagus nerve stimulation on changes in lipid composition and in protein secondary structure within dopamine-related brain structures in rats. It was found that the chronic vagal nerve stimulation strongly affects the chain length of fatty acids within the ventral tegmental area, nucleus accumbens, substantia nigra, striatum, dorsal motor nucleus of vagus and the motor cortex. In particular, the level of lipid unsaturation was found significantly increasing in the ventral tegmental area, substantia nigra and motor cortex as a result of vagal nerve stimulation. When it comes to changes in protein secondary structure, we could see that the mesolimbic, mesocortical and nigrostriatal dopaminergic pathways are particularly affected by vagus nerve stimulation. This is due to the co-occurrence of statistically significant changes in the content of non-ordered structure components, alpha helices, beta sheets, and the total area of Amide I. Macromolecular changes caused by peripheral vagus nerve stimulation may highlight a potential connection between the gastrointestinal system and the central nervous system in rat during the development of neurodegenerative disorders.

  9. Peripheral vagus nerve stimulation significantly affects lipid composition and protein secondary structure within dopamine-related brain regions in rats.

    PubMed

    Surowka, Artur Dawid; Krygowska-Wajs, Anna; Ziomber, Agata; Thor, Piotr; Chrobak, Adrian Andrzej; Szczerbowska-Boruchowska, Magdalena

    2015-06-01

    Recent immunohistochemical studies point to the dorsal motor nucleus of the vagus nerve as the point of departure of initial changes which are related to the gradual pathological developments in the dopaminergic system. In the light of current investigations, it is likely that biochemical changes within the peripheral nervous system may influence the physiology of the dopaminergic system, suggesting a putative role for it in the development of neurodegenerative disorders. By using Fourier transform infrared microspectroscopy, coupled with statistical analysis, we examined the effect of chronic, unilateral electrical vagus nerve stimulation on changes in lipid composition and in protein secondary structure within dopamine-related brain structures in rats. It was found that the chronic vagal nerve stimulation strongly affects the chain length of fatty acids within the ventral tegmental area, nucleus accumbens, substantia nigra, striatum, dorsal motor nucleus of vagus and the motor cortex. In particular, the level of lipid unsaturation was found significantly increasing in the ventral tegmental area, substantia nigra and motor cortex as a result of vagal nerve stimulation. When it comes to changes in protein secondary structure, we could see that the mesolimbic, mesocortical and nigrostriatal dopaminergic pathways are particularly affected by vagus nerve stimulation. This is due to the co-occurrence of statistically significant changes in the content of non-ordered structure components, alpha helices, beta sheets, and the total area of Amide I. Macromolecular changes caused by peripheral vagus nerve stimulation may highlight a potential connection between the gastrointestinal system and the central nervous system in rat during the development of neurodegenerative disorders. PMID:25893743

  10. Malignant Peripheral Nerve Sheath Tumor.

    PubMed

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

    2016-10-01

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

  11. Ultrasonographic Evaluation of Peripheral Nerves.

    PubMed

    Ali, Zarina S; Pisapia, Jared M; Ma, Tracy S; Zager, Eric L; Heuer, Gregory G; Khoury, Viviane

    2016-01-01

    There are a variety of imaging modalities for evaluation of peripheral nerves. Of these, ultrasonography (US) is often underused. There are several advantages of this imaging modality, including its cost-effectiveness, time-efficient assessment of long segments of peripheral nerves, ability to perform dynamic maneuvers, lack of contraindications, portability, and noninvasiveness. It can provide diagnostic information that cannot be obtained by electrophysiologic or, in some cases, magnetic resonance imaging studies. Ideally, the neurosurgeon can use US as a diagnostic adjunct in the preoperative assessment of a patient with traumatic, neoplastic, infective, or compressive nerve injury. Perhaps its most unique use is in intraoperative surgical planning. In this article, a brief description of normal US nerve anatomy is presented followed by a description of the US appearance of peripheral nerve disease caused by trauma, tumor, infection, and entrapment.

  12. Peripheral nerve conduits: technology update

    PubMed Central

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

    2014-01-01

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

  13. Sports and peripheral nerve injury.

    PubMed

    Hirasawa, Y; Sakakida, K

    1983-01-01

    Peripheral nerve injury is one of the serious complications of athletic injuries; however, they have rarely been reported. According to the report by Takazawa et al., there were only 28 cases of peripheral nerve injury among 9,550 cases of sports injuries which had been treated in the previous 5 years at the clinic of the Japanese Athletic Association. The authors have encountered 1,167 cases of peripheral nerve injury during the past 18 years. Sixty-six of these cases were related to sports (5.7%). The nerves most frequently involved were: brachial plexus, radial nerve, ulnar, peroneal, and axillary nerves (in their order of frequency). The most common causes of such injuries were mountain climbing, gymnastics, and baseball. More often, peripheral nerve injury seemed to be caused by continuous compression and repeated trauma to the involved nerve. Usually it appeared as an entrapment neuropathy and the symptoms could be improved by conservative treatment. Some of the cases were complicated by fractures and surgical exploration became necessary. Results of treatment produced excellent to good improvement in 87.9% of the cases. With regard to compartment syndrome, the authors stress the importance of early and precise diagnosis and a fasciotomy.

  14. Acellular Nerve Allografts in Peripheral Nerve Regeneration: A Comparative Study

    PubMed Central

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

    2011-01-01

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

  15. [Peripheral Nerve Injuries in Sports].

    PubMed

    Tettenborn, B; Mehnert, S; Reuter, I

    2016-09-01

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

  16. Neurophysiological approach to disorders of peripheral nerve.

    PubMed

    Crone, Clarissa; Krarup, Christian

    2013-01-01

    Disorders of the peripheral nerve system (PNS) are heterogeneous and may involve motor fibers, sensory fibers, small myelinated and unmyelinated fibers and autonomic nerve fibers, with variable anatomical distribution (single nerves, several different nerves, symmetrical affection of all nerves, plexus, or root lesions). Furthermore pathological processes may result in either demyelination, axonal degeneration or both. In order to reach an exact diagnosis of any neuropathy electrophysiological studies are crucial to obtain information about these variables. Conventional electrophysiological methods including nerve conduction studies and electromyography used in the study of patients suspected of having a neuropathy and the significance of the findings are discussed in detail and more novel and experimental methods are mentioned. Diagnostic considerations are based on a flow chart classifying neuropathies into eight categories based on mode of onset, distribution, and electrophysiological findings, and the electrophysiological characteristics in each type of neuropathy are discussed. PMID:23931776

  17. Noninvasive imaging of peripheral nerves.

    PubMed

    Rangavajla, Gautam; Mokarram, Nassir; Masoodzadehgan, Nazanin; Pai, S Balakrishna; Bellamkonda, Ravi V

    2014-01-01

    Recent developments in the field of peripheral nerve imaging extend the capabilities of imaging modalities to assist in the diagnosis and treatment of patients with peripheral nerve maladies. Methods such as magnetic resonance imaging (MRI) and its derivative diffusion tensor imaging (DTI), ultrasound (US) and positron emission tomography (PET) are capable of assessing nerve structure and function following injury and relating the state of the nerve to electrophysiological and histological analysis. Of the imaging methods surveyed here, each offered unique and interesting advantages related to the field. MRI offered the opportunity to visualize immune activity on the injured nerve throughout the course of the regeneration process, and DTI offered numerical characterization of the injury and the ability to develop statistical bases for diagnosing injury. US extends imaging to the treatment phase by enabling more precise analgesic applications following surgery, and PET represents a novel method of assessing nerve injury through analysis of relative metabolism rates in injured and healthy tissue. Exciting new possibilities to enhance and extend the abilities of imaging methods are also discussed, including innovative contrast agents, some of which enable multimodal imaging approaches and present opportunities for treatment application. PMID:25766202

  18. Pleiotrophin and peripheral nerve injury.

    PubMed

    Jin, Li; Jianghai, Chen; Juan, Liu; Hao, Kang

    2009-10-01

    The proto-oncogene pleiotrophin, discovered in 1989, was considered as a multifunctional growth factor, which played an important role in tumor occurrence, development, and central nervous system. The latest research showed that pleiotrophin signal pathway probably participated in neural repair after peripheral nerve injury, especially in the following critical points, such as the protection of spinal cord neuron, the promotion of the speed of neuron axon regeneration, the guidance of neuron axon regeneration, skeleton muscle reinnervation, and so on. It potentially plays a key role in the guidance of neural axon regeneration in peripheral nervous system and muscle reinnervation. With the deepening of related researches, pleiotrophin gene would become a controllable target for improving the repairing effect of peripheral nerve injury and reconstruction of the neuromuscular junction.

  19. Peripheral nerve disease in pregnancy.

    PubMed

    Klein, Autumn

    2013-06-01

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

  20. Detection of peripheral nerve pathology

    PubMed Central

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

    2013-01-01

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

  1. Label-free photoacoustic microscopy of peripheral nerves

    PubMed Central

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

    2014-01-01

    Abstract. Peripheral neuropathy is a common neurological problem that affects millions of people worldwide. Diagnosis and treatment of this condition are often hindered by the difficulties in making objective, noninvasive measurements of nerve fibers. Photoacoustic microscopy (PAM) has the ability to obtain high resolution, specific images of peripheral nerves without exogenous contrast. We demonstrated the first proof-of-concept imaging of peripheral nerves using PAM. As validated by both standard histology and photoacoustic spectroscopy, the origin of photoacoustic signals is myelin, the primary source of lipids in the nerves. An extracted sciatic nerve sandwiched between two layers of chicken tissue was imaged by PAM to mimic the in vivo case. Ordered fibrous structures inside the nerve, caused by the bundles of myelin-coated axons, could be observed clearly. With further technical improvements, PAM can potentially be applied to monitor and diagnose peripheral neuropathies. PMID:24395587

  2. Peripheral nerve blocks for distal extremity surgery.

    PubMed

    Offierski, Chris

    2013-10-01

    Peripheral nerve block is well suited for distal extremity surgery. Blocking the nerves at the distal extremity is easily done. It does not require ultrasound or stimulators to identify the nerve. Blocking nerves in the distal extremity is safe with low risk of toxicity. The effect of the nerve block is limited to the distribution of the nerve. The distal nerves in the lower extremity are sensory branches of the sciatic nerve. This provides a sensory block only. This has the advantage of allowing the patient to actively contract tendons in the foot and ambulate more quickly after surgery. PMID:24093651

  3. Raman microspectroscopy for visualization of peripheral nerves

    NASA Astrophysics Data System (ADS)

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

    2013-02-01

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

  4. Technology for Peripheral Nerve Stimulation.

    PubMed

    Parker, John L; Cameron, Tracy

    2015-01-01

    Peripheral nerve stimulation (PNS) has been in use for over 50 years to treat patients suffering from chronic pain who have failed conservative treatments. Despite this long history, the devices being used have changed very little. In fact, current PNS technology was developed specifically for spinal cord stimulation. The use of technology developed for other applications in PNS has led to an unnecessary number of device complications and the limited adoption of this promising therapy. The following chapter provides an overview of PNS technology throughout the years, outlining both the benefits and limitations. We will briefly explore the electrophysiology of PNS stimulation, with an emphasis on technology and indication-specific devices. Finally, design and technical requirements of an ideal PNS device will be discussed.

  5. Cryoanalgesia for painful peripheral nerve lesions.

    PubMed

    Wang, J K

    1985-06-01

    Twelve patients with chronically painful peripheral nerve lesions were treated with cryoanalgesia. The pain was relieved in 6 patients for 1-12 months. Although the pain eventually recurred, the patients resumed normal activities during remission. It is necessary to improve the techniques of nerve localization and to determine the proper mode of nerve freezing. PMID:2995903

  6. Altered peripheral nerve function resulting from haemodialysis.

    PubMed

    Stanley, E; Brown, J C; Pryor, J S

    1977-01-01

    The amplitudes of muscle and nerve action potentials evoked median nerve stimulation were recorded just before and immediately after haemodialysis. These revealed a growht of action potential amplitude during dialysis. It is suggested that some component of the defective peripheral nerve function that inevitably accompanies uraemia is temporarily improved during dialysis. PMID:845605

  7. Tissue engineered constructs for peripheral nerve surgery

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2015-12-01

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

  9. Malignant Peripheral Nerve Sheath Tumors.

    PubMed

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

    2016-01-01

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

  10. Designing ideal conduits for peripheral nerve repair

    PubMed Central

    de Ruiter, Godard C. W.; Malessy, Martijn J. A.; Yaszemski, Michael J.; Windebank, Anthony J.; Spinner, Robert J.

    2010-01-01

    Nerve tubes, guides, or conduits are a promising alternative for autologous nerve graft repair. The first biodegradable empty single lumen or hollow nerve tubes are currently available for clinical use and are being used mostly in the repair of small-diameter nerves with nerve defects of < 3 cm. These nerve tubes are made of different biomaterials using various fabrication techniques. As a result these tubes also differ in physical properties. In addition, several modifications to the common hollow nerve tube (for example, the addition of Schwann cells, growth factors, and internal frameworks) are being investigated that may increase the gap that can be bridged. This combination of chemical, physical, and biological factors has made the design of a nerve conduit into a complex process that demands close collaboration of bioengineers, neuroscientists, and peripheral nerve surgeons. In this article the authors discuss the different steps that are involved in the process of the design of an ideal nerve conduit for peripheral nerve repair. PMID:19435445

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

    PubMed

    Kowalska, Berta; Sudoł-Szopińska, Iwona

    2012-06-01

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

  12. Peripheral nerve injuries in the athlete.

    PubMed

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

    1997-12-01

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

  13. Intraoperative ultrasound-assisted peripheral nerve surgery.

    PubMed

    Haldeman, Clayton L; Baggott, Christopher D; Hanna, Amgad S

    2015-09-01

    Historically, peripheral nerve surgery has relied on landmarks and fairly extensive dissection for localization of both normal and pathological anatomy. High-resolution ultrasonography is a radiation-free imaging modality that can be used to directly visualize peripheral nerves and their associated pathologies prior to making an incision. It therefore helps in localization of normal and pathological anatomy, which can minimize the need for extensive exposures. The authors found intraoperative ultrasound (US) to be most useful in the management of peripheral nerve tumors and neuromas of nerve branches that are particularly small or have a deep location. This study presents the use of intraoperative US in 5 cases in an effort to illustrate some of the applications of this useful surgical adjunct.

  14. Peripheral nerve imaging: Not only cross-sectional area.

    PubMed

    Tagliafico, Alberto Stefano

    2016-08-28

    Peripheral nerve imaging is recognized as a complement to clinical and neurophysiological assessment in the evaluation of peripheral nerves with the ability to impact patient management, even for small and difficult nerves. The European Society of Musculoskeletal Radiology, suggest to use ultrasound (US) for nerve evaluation due to the fact that, in sever anatomical area, magnetic resonance imaging is not able to give additional informations. US could be considered the first-choice approach for the assessment of peripheral nerves. The relative drawback of peripheral nerve US is the long learning curve and the deep anatomic competence to evaluate even small nerves. In the recent years, the role of US in peripheral nerve evaluation has been widened. In the past, nerve US was mainly used to assess nerve-cross sectional area, but now more advanced measurements and considerations are desirable and can boost the role of peripheral nerve US. Nerve echotexture evaluation was defined in 2010: The ratio between the hypoechoic and hyperechoic areas of peripheral nerves on US was called "nerve density". For evaluation of patients who have peripheral neuropathies, the role of peripheral nerve is US wider than simple cross-sectional area evaluation. Quantitative measurements describing the internal fascicular echotexture of peripheral nerves introduce the concept of considering US as a possible quantitative imaging biomarker technique. The potential of nerve US has started to be uncovered. It seems clear that only cross-sectional area measurement is no more sufficient for a comprehensive US evaluation of peripheral nerves.

  15. Peripheral nerve imaging: Not only cross-sectional area

    PubMed Central

    Tagliafico, Alberto Stefano

    2016-01-01

    Peripheral nerve imaging is recognized as a complement to clinical and neurophysiological assessment in the evaluation of peripheral nerves with the ability to impact patient management, even for small and difficult nerves. The European Society of Musculoskeletal Radiology, suggest to use ultrasound (US) for nerve evaluation due to the fact that, in sever anatomical area, magnetic resonance imaging is not able to give additional informations. US could be considered the first-choice approach for the assessment of peripheral nerves. The relative drawback of peripheral nerve US is the long learning curve and the deep anatomic competence to evaluate even small nerves. In the recent years, the role of US in peripheral nerve evaluation has been widened. In the past, nerve US was mainly used to assess nerve-cross sectional area, but now more advanced measurements and considerations are desirable and can boost the role of peripheral nerve US. Nerve echotexture evaluation was defined in 2010: The ratio between the hypoechoic and hyperechoic areas of peripheral nerves on US was called “nerve density”. For evaluation of patients who have peripheral neuropathies, the role of peripheral nerve is US wider than simple cross-sectional area evaluation. Quantitative measurements describing the internal fascicular echotexture of peripheral nerves introduce the concept of considering US as a possible quantitative imaging biomarker technique. The potential of nerve US has started to be uncovered. It seems clear that only cross-sectional area measurement is no more sufficient for a comprehensive US evaluation of peripheral nerves.

  16. Peripheral nerve imaging: Not only cross-sectional area.

    PubMed

    Tagliafico, Alberto Stefano

    2016-08-28

    Peripheral nerve imaging is recognized as a complement to clinical and neurophysiological assessment in the evaluation of peripheral nerves with the ability to impact patient management, even for small and difficult nerves. The European Society of Musculoskeletal Radiology, suggest to use ultrasound (US) for nerve evaluation due to the fact that, in sever anatomical area, magnetic resonance imaging is not able to give additional informations. US could be considered the first-choice approach for the assessment of peripheral nerves. The relative drawback of peripheral nerve US is the long learning curve and the deep anatomic competence to evaluate even small nerves. In the recent years, the role of US in peripheral nerve evaluation has been widened. In the past, nerve US was mainly used to assess nerve-cross sectional area, but now more advanced measurements and considerations are desirable and can boost the role of peripheral nerve US. Nerve echotexture evaluation was defined in 2010: The ratio between the hypoechoic and hyperechoic areas of peripheral nerves on US was called "nerve density". For evaluation of patients who have peripheral neuropathies, the role of peripheral nerve is US wider than simple cross-sectional area evaluation. Quantitative measurements describing the internal fascicular echotexture of peripheral nerves introduce the concept of considering US as a possible quantitative imaging biomarker technique. The potential of nerve US has started to be uncovered. It seems clear that only cross-sectional area measurement is no more sufficient for a comprehensive US evaluation of peripheral nerves. PMID:27648165

  17. Peripheral nerve imaging: Not only cross-sectional area

    PubMed Central

    Tagliafico, Alberto Stefano

    2016-01-01

    Peripheral nerve imaging is recognized as a complement to clinical and neurophysiological assessment in the evaluation of peripheral nerves with the ability to impact patient management, even for small and difficult nerves. The European Society of Musculoskeletal Radiology, suggest to use ultrasound (US) for nerve evaluation due to the fact that, in sever anatomical area, magnetic resonance imaging is not able to give additional informations. US could be considered the first-choice approach for the assessment of peripheral nerves. The relative drawback of peripheral nerve US is the long learning curve and the deep anatomic competence to evaluate even small nerves. In the recent years, the role of US in peripheral nerve evaluation has been widened. In the past, nerve US was mainly used to assess nerve-cross sectional area, but now more advanced measurements and considerations are desirable and can boost the role of peripheral nerve US. Nerve echotexture evaluation was defined in 2010: The ratio between the hypoechoic and hyperechoic areas of peripheral nerves on US was called “nerve density”. For evaluation of patients who have peripheral neuropathies, the role of peripheral nerve is US wider than simple cross-sectional area evaluation. Quantitative measurements describing the internal fascicular echotexture of peripheral nerves introduce the concept of considering US as a possible quantitative imaging biomarker technique. The potential of nerve US has started to be uncovered. It seems clear that only cross-sectional area measurement is no more sufficient for a comprehensive US evaluation of peripheral nerves. PMID:27648165

  18. Effects of Laser Irradiation on Peripheral Nerve

    NASA Astrophysics Data System (ADS)

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

    2009-06-01

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

  19. Decellularisation and histological characterisation of porcine peripheral nerves.

    PubMed

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

    2016-09-01

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

  20. Peripheral nerve regeneration and neurotrophic factors

    PubMed Central

    TERENGHI, GIORGIO

    1999-01-01

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

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

    SciTech Connect

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

    1980-04-01

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

  2. Peripheral nerve morphogenesis induced by scaffold micropatterning

    PubMed Central

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

    2014-01-01

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

  3. Peripheral nerve lipoma: Case report of an intraneural lipoma of the median nerve and literature review

    PubMed Central

    Teles, Alisson Roberto; Finger, Guilherme; Schuster, Marcelo N.; Gobbato, Pedro Luis

    2016-01-01

    Adipose lesions rarely affect the peripheral nerves. This can occur in two different ways: Direct compression by an extraneural lipoma, or by a lipoma originated from the adipose cells located inside the nerve. Since its first description, many terms have been used in the literature to mention intraneural lipomatous lesions. In this article, the authors report a case of a 62-year-old female who presented with an intraneural median nerve lipoma and review the literature concerning the classification of adipose lesions of the nerve, radiological diagnosis and treatment. PMID:27695575

  4. Peripheral nerve lipoma: Case report of an intraneural lipoma of the median nerve and literature review

    PubMed Central

    Teles, Alisson Roberto; Finger, Guilherme; Schuster, Marcelo N.; Gobbato, Pedro Luis

    2016-01-01

    Adipose lesions rarely affect the peripheral nerves. This can occur in two different ways: Direct compression by an extraneural lipoma, or by a lipoma originated from the adipose cells located inside the nerve. Since its first description, many terms have been used in the literature to mention intraneural lipomatous lesions. In this article, the authors report a case of a 62-year-old female who presented with an intraneural median nerve lipoma and review the literature concerning the classification of adipose lesions of the nerve, radiological diagnosis and treatment.

  5. Regenerative scaffold electrodes for peripheral nerve interfacing.

    PubMed

    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. PMID:23033438

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

    PubMed Central

    Sudoł-Szopińska, Iwona

    2012-01-01

    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. PMID:26674017

  7. α2δ-1 Gene Deletion Affects Somatosensory Neuron Function and Delays Mechanical Hypersensitivity in Response to Peripheral Nerve Damage

    PubMed Central

    Patel, Ryan; Bauer, Claudia S.; Nieto-Rostro, Manuela; Margas, Wojciech; Ferron, Laurent; Chaggar, Kanchan; Crews, Kasumi; Ramirez, Juan D.; Bennett, David L. H.; Schwartz, Arnold; Dickenson, Anthony H.

    2013-01-01

    The α2δ-1 subunit of voltage-gated calcium channels is upregulated after sensory nerve injury and is also the therapeutic target of gabapentinoid drugs. It is therefore likely to play a key role in the development of neuropathic pain. In this study, we have examined mice in which α2δ-1 gene expression is disrupted, to determine whether α2δ-1 is involved in various modalities of nociception, and for the development of behavioral hypersensitivity after partial sciatic nerve ligation (PSNL). We find that naive α2δ-1−/− mice show a marked behavioral deficit in mechanical and cold sensitivity, but no change in thermal nociception threshold. The lower mechanical sensitivity is mirrored by a reduced in vivo electrophysiological response of dorsal horn wide dynamic range neurons. The CaV2.2 level is reduced in brain and spinal cord synaptosomes from α2δ-1−/− mice, and α2δ-1−/− DRG neurons exhibit lower calcium channel current density. Furthermore, a significantly smaller number of DRG neurons respond to the TRPM8 agonist menthol. After PSNL, α2δ-1−/− mice show delayed mechanical hypersensitivity, which only develops at 11 d after surgery, whereas in wild-type littermates it is maximal at the earliest time point measured (3 d). There is no compensatory upregulation of α2δ-2 or α2δ-3 after PSNL in α2δ-1−/− mice, and other transcripts, including neuropeptide Y and activating transcription factor-3, are upregulated normally. Furthermore, the ability of pregabalin to alleviate mechanical hypersensitivity is lost in PSNL α2δ-1−/− mice. Thus, α2δ-1 is essential for rapid development of mechanical hypersensitivity in a nerve injury model of neuropathic pain. PMID:24133248

  8. Malignant peripheral nerve sheet tumour of cervix.

    PubMed

    Akhavan, Ali; Moghimi, Mansour; Karimi-Zarchi, Mojgan; Navabii, Hossein

    2012-05-30

    Sarcomas account for less than 1% of malignancies of the uterine cervix. Among them, rhabdomyosarcomas are the ones most frequently reported. Malignant peripheral nerve sheet tumour (MPNST) is very rare. In this paper we present a 53-year-old woman with MPNST of the uterine cervix.

  9. Non-Invasive Imaging of Peripheral Nerves

    PubMed Central

    Rangavajla, Gautam; Mokarram, Nassir; Masoodzadehgan, Nazanin; Pai, S. Balakrishna; Bellamkonda, Ravi V.

    2015-01-01

    Recent developments in the field of peripheral nerve imaging extend the capabilities of imaging modalities to assist in the diagnosis and treatment of patients with peripheral nerve maladies. Methods such as MRI and its derivative DTI, ultrasound, and PET are capable of assessing nerve structure and function following injury and relating the state of the nerve to electrophysiological and histological analysis. Of the imaging methods surveyed here, each offered unique and interesting advantages related to the field. MRI offered the opportunity to visualize immune activity on the injured nerve throughout the course of the regeneration process, and DTI offered numerical characterization of the injury and the ability to develop statistical bases for diagnosing injury. Ultrasound extends imaging to the treatment phase by enabling more precise analgesic applications following surgery, and PET represents a novel method of assessing nerve injury through analysis of relative metabolism rates in injured and healthy tissue. Exciting new possibilities to enhance and extend the abilities of imaging methods are also discussed here, including innovative contrast agents, some of which enable multimodal imaging approaches and present opportunities for treatment application. PMID:25766202

  10. The multicellular complexity of peripheral nerve regeneration.

    PubMed

    Cattin, Anne-Laure; Lloyd, Alison C

    2016-08-01

    Peripheral nerves show a remarkable ability to regenerate following a transection injury. Downstream of the cut, the axons degenerate and so to regenerate the nerve, the severed axons need to regrow back to their targets and regain function. This requires the axons to navigate through two different environments. (1) The bridge of new tissue that forms between the two nerve stumps and (2) the distal stump of the nerve that remains associated with the target tissues. This involves distinct, complex multicellular responses that guide and sustain axonal regrowth. These processes have important implications for our understanding of the regeneration of an adult tissue and have parallels to aspects of tumour formation and spread. PMID:27128880

  11. Lithium enhances remyelination of peripheral nerves

    PubMed Central

    Makoukji, Joelle; Belle, Martin; Meffre, Delphine; Stassart, Ruth; Grenier, Julien; Shackleford, Ghjuvan'Ghjacumu; Fledrich, Robert; Fonte, Cosima; Branchu, Julien; Goulard, Marie; de Waele, Catherine; Charbonnier, Frédéric; Sereda, Michael W.; Baulieu, Etienne-Emile; Schumacher, Michael; Bernard, Sophie; Massaad, Charbel

    2012-01-01

    Glycogen synthase kinase 3β (GSK3β) inhibitors, especially the mood stabilizer lithium chloride, are also used as neuroprotective or anti-inflammatory agents. We studied the influence of LiCl on the remyelination of peripheral nerves. We showed that the treatment of adult mice with LiCl after facial nerve crush injury stimulated the expression of myelin genes, restored the myelin structure, and accelerated the recovery of whisker movements. LiCl treatment also promoted remyelination of the sciatic nerve after crush. We also demonstrated that peripheral myelin gene MPZ and PMP22 promoter activities, transcripts, and protein levels are stimulated by GSK3β inhibitors (LiCl and SB216763) in Schwann cells as well as in sciatic and facial nerves. LiCl exerts its action in Schwann cells by increasing the amount of β-catenin and provoking its nuclear localization. We showed by ChIP experiments that LiCl treatment drives β-catenin to bind to T-cell factor/lymphoid-enhancer factor response elements identified in myelin genes. Taken together, our findings open perspectives in the treatment of nerve demyelination by administering GSK3β inhibitors such as lithium. PMID:22355115

  12. Tendon Transfers for Combined Peripheral Nerve Injuries.

    PubMed

    Makarewich, Christopher A; Hutchinson, Douglas T

    2016-08-01

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

  13. High-resolution MR neurography of diffuse peripheral nerve lesions.

    PubMed

    Thawait, S K; Chaudhry, V; Thawait, G K; Wang, K C; Belzberg, A; Carrino, J A; Chhabra, A

    2011-09-01

    High-resolution MR imaging of peripheral nerves is becoming more common and practical with the increasing availability of 3T magnets. There are multiple reports of MR imaging of peripheral nerves in compression and entrapment neuropathies. However, there is a relative paucity of literature on MRN appearance of diffuse peripheral nerve lesions. We attempted to highlight the salient imaging features of myriad diffuse peripheral nerve disorders and imaging techniques for MRN. Using clinical and pathologically proved relevant examples, we present the MRN appearance of various types of diffuse peripheral nerve lesions, such as traumatic, inflammatory, infectious, hereditary, radiation-induced, neoplastic, and tumor variants. PMID:20966057

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

    PubMed

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

    2016-09-01

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

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

    PubMed

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

    2016-09-01

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

  16. Management of peripheral facial nerve palsy

    PubMed Central

    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 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. PMID:18368417

  17. Management of peripheral facial nerve palsy.

    PubMed

    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.

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

    PubMed Central

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

    2015-01-01

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

  19. Microsurgical treatment of peripheral nerve injuries.

    PubMed

    Dolene, V

    1977-01-01

    In the period from 1972 to 1976, 536 patients with injuries of the peripheral nerves were treated at the Neurosurgical University Clinic Lyublyana. The treatment was performed according to the principles of microsurgery. Preoperative and postoperative supervision included EMG, electroneurography and nerve conduction speed. Subdivision: N. facialis 6, plexus brachialis 78, n. radialis 58, n. medianus 189, n. ulnaris 212, n. ischiadicus 17, n. femoralis 3, n. tibialis 12, n. fibularis 37. On the plexus brachialis 50 funiculolyses and 28 raphies were carried out. Immobilisation for 10 days. The length of the transplants showed no negative influence. After-observation was necessary for three and more years, especially in case of plexus injuries. Complete restoration was only found in children. Sensitivity in 80% more than Seddon III, 17% III and 3% less than III. Motor function in 60% IV, 20% III, 12% II and 8% less than II.

  20. Axonal transport disruption in peripheral nerve disease

    PubMed Central

    Lloyd, Thomas E.

    2015-01-01

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

  1. Autologous fibrin glue in peripheral nerve regeneration in vivo.

    PubMed

    Choi, Byung-Ho; Han, Sang-Gyun; Kim, Sung-Hoon; Zhu, Shi-Jiang; Huh, Jin-Young; Jung, Jae-Hyung; Lee, Seoung-Ho; Kim, Byung-Yong

    2005-01-01

    The activity of several growth factors on peripheral nerve regeneration is reported. Autologous fibrin glue contains a large number of platelets, which release significant quantities of growth factors. In order to understand the role of autologous fibrin glue in peripheral nerve regeneration, a 15-mm rabbit peroneal nerve defect was repaired using a vein graft filled with autologous fibrin glue. Axonal regeneration was examined using histological and electrophysiological methods. The extent of axonal regeneration was superior when treated with autologous fibrin glue. Our data suggest that fibrin nets formed by fibrinogen, in combination with growth factors present in autologous fibrin glue, might effectively promote peripheral nerve regeneration in nerve defects.

  2. Interactions among biotic and abiotic factors affect the reliability of tungsten microneedles puncturing in vitro and in vivo peripheral nerves: A hybrid computational approach.

    PubMed

    Sergi, Pier Nicola; Jensen, Winnie; Yoshida, Ken

    2016-02-01

    Tungsten is an elective material to produce slender and stiff microneedles able to enter soft tissues and minimize puncture wounds. In particular, tungsten microneedles are used to puncture peripheral nerves and insert neural interfaces, bridging the gap between the nervous system and robotic devices (e.g., hand prostheses). Unfortunately, microneedles fail during the puncture process and this failure is not dependent on stiffness or fracture toughness of the constituent material. In addition, the microneedles' performances decrease during in vivo trials with respect to the in vitro ones. This further effect is independent on internal biotic effects, while it seems to be related to external biotic causes. Since the exact synergy of phenomena decreasing the in vivo reliability is still not known, this work explored the connection between in vitro and in vivo behavior of tungsten microneedles through the study of interactions between biotic and abiotic factors. A hybrid computational approach, simultaneously using theoretical relationships and in silico models of nerves, was implemented to model the change of reliability varying the microneedle diameter, and to predict in vivo performances by using in vitro reliability and local differences between in vivo and in vitro mechanical response of nerves.

  3. Introduction: peripheral nerve surgery--biology, entrapment, and injuries.

    PubMed

    Friedman, Allan H; Elias, W Jeffrey; Midha, Rajiv

    2009-02-01

    Surgery aimed at repairing damaged peripheral nerves has a long history. Refuting the time-honored nihilism of Hippocrates and Galen that an injured nerve cannot regain function, a few adventurous medieval surgeons attempted to repair severed nerves. However, the ability of a peripheral nerve repair to restore function was not generally accepted until 1800. Neurosurgeons, beginning with Harvey Cushing, have had an interest in repairing damaged peripheral nerves. Significant progress in the treatment of peripheral nerve injuries resulted from experience with the numerous injuries that occurred during World Wars I and II. Surgeons steadily defined the anatomy of peripheral nerves and developed techniques for decompressing and repairing peripheral nerves. Kline and Dejonge developed an intraoperative electrophysiological technique for detecting axons regenerating across a damaged segment of nerve. In the second 2 decades of the 20th century, distal nerve transfers were rediscovered whereby the proximal end of a less essential nerve is used to reinnervate the distal end of a nerve, providing a more vital function. PMID:19435439

  4. Advances in the neurological and neurosurgical management of peripheral nerve trauma.

    PubMed

    Simon, Neil G; Spinner, Robert J; Kline, David G; Kliot, Michel

    2016-02-01

    Peripheral nerve trauma frequently affects younger people and may result in significant and long-lasting functional disability. Currently, diagnosis and monitoring of peripheral nerve injury relies on clinical and electrodiagnostic information, supplemented by intraoperative electrophysiological studies. However, in a significant proportion of nerve injuries, the likelihood of spontaneous regeneration resulting in good functional outcome remains uncertain and unnecessary delays to treatment may be faced while monitoring for recovery. Advances in non-invasive imaging techniques to diagnose and monitor nerve injury and regeneration are being developed, and have the potential to streamline the decision-making process. In addition, advances in operative and non-operative treatment strategies may provide more effective ways to maximise functional outcomes following severe peripheral nerve trauma. This review discusses these advances in light of the current state of the art of management of peripheral nerve trauma.

  5. Regulation of Peripheral Nerve Stimulation Technology.

    PubMed

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

    2015-01-01

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

  6. Peripheral nerve blocks for ambulatory surgery.

    PubMed

    Salinas, Francis V; Joseph, Raymond S

    2014-06-01

    Peripheral nerve blocks (PNBs) provide significant improvement in postoperative analgesia and quality of recovery for ambulatory surgery. Use of continuous PNB techniques extend these benefits beyond the limited duration of single-injection PNBs. The use of ultrasound guidance has significantly improved the overall success, efficiency, and has contributed to the increased use of PNBs in the ambulatory setting. More recently, the use of ultrasound guidance has been demonstrated to decrease the risk of local anesthetic systemic toxicity. This article provides a broad overview of the indications and clinically useful aspects of the most commonly used upper and lower extremity PNBs in the ambulatory setting. Emphasis is placed on approaches that can be used for single-injection PNBs and continuous PNB techniques.

  7. Physiological and pharmacologic aspects of peripheral nerve blocks

    PubMed Central

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

    2015-01-01

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

  8. Strategy and timing of peripheral nerve surgery.

    PubMed

    Brunelli, G; Brunelli, F

    1990-01-01

    The authors review the latest theories of peripheral nerve regeneration and repair. They present their research on nerve regeneration including the alterations in the mother cell body, and in the distal part of the axon, and the time required to reach the best production of amino acids for cytoskeleton reconstruction. Other research of particular interest which is presented regards the chemotactic arrangement of motor and sensory axons inside a vein. This research has shown that the axons are able to find their way to the appropriate (sensory or motor) distal endoneural tubes. Adoption phenomena are also presented. The discussion of surgery includes the type (suture, glueing, grafts, tubulization) and the time of surgical repair. Timing and repair strategies are related to the site of the lesion (which can require that a greater or smaller amount of cytoskeleton be reconstructed), the type of the injury, the state of surrounding tissues, the age of the patients, injuries to muscles, tendons, bones, vessels and skin. A scheme of strategy is proposed. PMID:2187163

  9. The challenges and beauty of peripheral nerve regrowth.

    PubMed

    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.

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

    PubMed Central

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

    2015-01-01

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

  11. Collagenosis in wallerian degeneration depends on peripheral nerve type.

    PubMed

    Eather, T F; Pollock, M

    1988-06-01

    In the mature rat we determined the extent of peripheral nerve collagenosis in response to Wallerian degeneration and examined whether or not nonfibroblastic elements such as Schwann cells were important. Collagen was estimated as the hydroxy-proline content of normal and axotomized nerve fascicles after single or double crush lesions of both myelinated and unmyelinated nerves. Crushed unmyelinated nerve produced two to four times more collagen relative to control nerve than did the sciatic nerve. The nature of the interaction between two successive crushes was different in the two nerves. These results suggest that the degree of collagen fibrillogenesis occurring in Wallerian degeneration is dependent on peripheral nerve type and that the presence of myelin is not necessary for collagen fibrillogenesis.

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

    PubMed

    Allodi, Ilary; Udina, Esther; Navarro, Xavier

    2012-07-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

    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.

  16. A biomaterials approach to peripheral nerve regeneration: bridging the peripheral nerve gap and enhancing functional recovery

    PubMed Central

    Daly, W.; Yao, L.; Zeugolis, D.; Windebank, A.; Pandit, A.

    2012-01-01

    Microsurgical techniques for the treatment of large peripheral nerve injuries (such as the gold standard autograft) and its main clinically approved alternative—hollow nerve guidance conduits (NGCs)—have a number of limitations that need to be addressed. NGCs, in particular, are limited to treating a relatively short nerve gap (4 cm in length) and are often associated with poor functional recovery. Recent advances in biomaterials and tissue engineering approaches are seeking to overcome the limitations associated with these treatment methods. This review critically discusses the advances in biomaterial-based NGCs, their limitations and where future improvements may be required. Recent developments include the incorporation of topographical guidance features and/or intraluminal structures, which attempt to guide Schwann cell (SC) migration and axonal regrowth towards their distal targets. The use of such strategies requires consideration of the size and distribution of these topographical features, as well as a suitable surface for cell–material interactions. Likewise, cellular and molecular-based therapies are being considered for the creation of a more conductive nerve microenvironment. For example, hurdles associated with the short half-lives and low stability of molecular therapies are being surmounted through the use of controlled delivery systems. Similarly, cells (SCs, stem cells and genetically modified cells) are being delivered with biomaterial matrices in attempts to control their dispersion and to facilitate their incorporation within the host regeneration process. Despite recent advances in peripheral nerve repair, there are a number of key factors that need to be considered in order for these new technologies to reach the clinic. PMID:22090283

  17. PERIPHERAL NERVE REGENERATION: CELL THERAPY AND NEUROTROPHIC FACTORS

    PubMed Central

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

    2015-01-01

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

  18. A Novel Internal Fixator Device for Peripheral Nerve Regeneration

    PubMed Central

    Chuang, Ting-Hsien; Wilson, Robin E.; Love, James M.; Fisher, John P.

    2013-01-01

    Recovery from peripheral nerve damage, especially for a transected nerve, is rarely complete, resulting in impaired motor function, sensory loss, and chronic pain with inappropriate autonomic responses that seriously impair quality of life. In consequence, strategies for enhancing peripheral nerve repair are of high clinical importance. Tension is a key determinant of neuronal growth and function. In vitro and in vivo experiments have shown that moderate levels of imposed tension (strain) can encourage axonal outgrowth; however, few strategies of peripheral nerve repair emphasize the mechanical environment of the injured nerve. Toward the development of more effective nerve regeneration strategies, we demonstrate the design, fabrication, and implementation of a novel, modular nerve-lengthening device, which allows the imposition of moderate tensile loads in parallel with existing scaffold-based tissue engineering strategies for nerve repair. This concept would enable nerve regeneration in two superposed regimes of nerve extension—traditional extension through axonal outgrowth into a scaffold and extension in intact regions of the proximal nerve, such as that occurring during growth or limb-lengthening. Self-sizing silicone nerve cuffs were fabricated to grip nerve stumps without slippage, and nerves were deformed by actuating a telescoping internal fixator. Poly(lactic co-glycolic) acid (PLGA) constructs mounted on the telescoping rods were apposed to the nerve stumps to guide axonal outgrowth. Neuronal cells were exposed to PLGA using direct contact and extract methods, and they exhibited no signs of cytotoxic effects in terms of cell morphology and viability. We confirmed the feasibility of implanting and actuating our device within a sciatic nerve gap and observed axonal outgrowth following device implantation. The successful fabrication and implementation of our device provides a novel method for examining mechanical influences on nerve regeneration. PMID

  19. [Methodological considerations concerning peripheral nerve morphometry].

    PubMed

    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. PMID:8597982

  20. How electrodiagnosis predicts clinical outcome of focal peripheral nerve lesions.

    PubMed

    Robinson, Lawrence R

    2015-09-01

    This article reviews the electrodiagnostic (EDX) prognostic factors for focal traumatic and nontraumatic peripheral nerve injuries. Referring physicians and patients often benefit from general and nerve-specific prognostic information from the EDX consultant. Knowing the probable outcome from a nerve injury allows the referring physician to choose the best treatment options for his/her patients. Nerve injuries are variable in their mechanism, location, and pathophysiology. The general effects of the injuries on nerve and muscle are well known, but more research is needed for nerve-specific information. Several factors currently known to influence prognosis include: nature of the nerve trauma, amount of axon loss, recruitment in muscles supplied by the nerve, the extent of demyelination, and the distance to reinnervate functional muscles. This article reviews these general concepts and also nerve-specific EDX measures that predict outcome after focal neuropathies.

  1. A Bionic Neural Link for peripheral nerve repair.

    PubMed

    Xu, Yong Ping; Yen, Shih-Cheng; Ng, Kian Ann; Liu, Xu; Tan, Ter Chyan

    2012-01-01

    Peripheral nerve injuries with large gaps and long nerve regrowth paths are difficult to repair using existing surgical techniques, due to nerve degeneration and muscle atrophy. This paper proposes a Bionic Neural Link (BNL) as an alternative way for peripheral nerve repair. The concept of the BNL is described, along with the hypothetical benefits. A prototype monolithic single channel BNL has been developed, which consists of 16 neural recording channels and one stimulation channel, and is implemented in a 0.35-µm CMOS technology. The BNL has been tested in in-vivo animal experiments. Full function of the BNL chip has been demonstrated.

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

    PubMed

    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.

  3. Uncompacted myelin lamellae in peripheral nerve biopsy.

    PubMed

    Vital, Claude; Vital, Anne; Bouillot, Sandrine; Favereaux, Alexandre; Lagueny, Alain; Ferrer, Xavier; Brechenmacher, Christiane; Petry, Klaus G

    2003-01-01

    Since 1979, the authors have studied 49 peripheral nerve biopsies presenting uncompacted myelin lamellae (UML). Based on the ultrastructural pattern of UML they propose a 3-category classification. The first category includes cases displaying regular UML, which was observed in 43 cases; it was more frequent in 9 cases with polyneuropathy organomegaly endocrinopathy m-protein skin changes (POEMS) syndrome as well as in 1 case of Charcot-Marie-Tooth 1B with a novel point mutation in the P0 gene. The second category consists of cases showing irregular UML, observed in 4 cases with IgM monoclonal gammopathy and anti-myelin-associated glycoprotein (MAG) activity. This group included 1 benign case and 3 B-cell malignant lymphomas. The third category is complex UML, which was present in 2 unrelated patients with an Arg 98 His missense mutation in the P0 protein gene. Irregular and complex UML are respectively related to MAG and P0, which play a crucial role in myelin lamellae compaction and adhesion.

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

    PubMed Central

    Iijima, Yuki; Murayama, Akira; Takeshita, Katsushi

    2016-01-01

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

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

    EPA Science Inventory

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

  6. Biomaterials for the Development of Peripheral Nerve Guidance Conduits

    PubMed Central

    Nectow, Alexander R.; Marra, Kacey G.

    2012-01-01

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

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

    PubMed

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

    2016-01-01

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

  8. Advances and Future Applications of Augmented Peripheral Nerve Regeneration

    PubMed Central

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

    2016-01-01

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

  9. Tissue-engineered nerve constructs under a microgravity system for peripheral nerve regeneration.

    PubMed

    Luo, Hailang; Zhu, Bin; Zhang, Yongjie; Jin, Yan

    2015-01-01

    Mesenchymal stem cells (MSCs) seeded in a 3D scaffold often present characteristics of low proliferation and migration, which affect the microstructure of tissue-engineered nerves (TENs) and impair the therapeutic effects of nerve defects. By promoting MSC differentiation and mass/nutrient transport, rotary cell culture systems (RCCSs) display potential for advancing the construction of MSC-based TENs. Thus, in this study, we attempted to construct a TEN composed of adipose-derived mesenchymal stem cells (ADSCs) and acellular nerve graft (ANG) utilizing an RCCS. Compared to TENs prepared in a static 3D approach, MTT and cell count results displayed an increased number of ADSCs for TENs in an RCCS. The similarity in cell cycle states and high rates of apoptosis in the static 3D culture demonstrated that the higher proliferation in the RCCS was not due to microgravity regulation but a result of preferential mass/nutrient transport. Quantitative PCR and ELISA indicated that the RCCS promoted the expression of ADSC neural differentiation-associated genes compared to the static 3D culture. Furthermore, this difference was eliminated by adding the Notch1 signaling pathway inhibitor DAPT to the 3D static culture. TEM, axon immunostaining, and retrograde labeling analysis after sciatic nerve transplantation indicated that the TENs prepared in the RCCS exhibited more regenerative characteristics for repairing peripheral nerves than those prepared in a static 3D approach. Therefore, these findings suggest that the RCCS can modulate the construction, morphology, and function of engineered nerves as a promising alternative for nerve regeneration. PMID:25088840

  10. The role of exosomes in peripheral nerve regeneration

    PubMed Central

    Ching, Rosanna C.; Kingham, Paul J.

    2015-01-01

    Peripheral nerve injuries remain problematic to treat, with poor functional recovery commonly observed. Injuries resulting in a nerve gap create specific difficulties for axonal regeneration. Approaches to address these difficulties include autologous nerve grafts (which are currently the gold standard treatment) and synthetic conduits, with the latter option being able to be impregnated with Schwann cells or stem cells which provide an appropriate micro-environment for neuronal regeneration to occur. Transplanting stem cells, however, infers additional risk of malignant transformation as well as manufacturing difficulties and ethical concerns, and the use of autologous nerve grafts and Schwann cells requires the sacrifice of a functioning nerve. A new approach utilizing exosomes, secreted extracellular vesicles, could avoid these complications. In this review, we summarize the current literature on exosomes, and suggest how they could help to improve axonal regeneration following peripheral nerve injury. PMID:26109947

  11. Practical magnetic resonance imaging evaluation of peripheral nerves in children: magnetic resonance neurography.

    PubMed

    Cortes, Cesar; Ramos, Yanerys; Restrepo, Ricardo; Restrepo, Jose Andres; Grossman, John A I; Lee, Edward Y

    2013-07-01

    Magnetic resonance (MR) imaging is an excellent tool for the evaluation of peripheral nerves in children not only because of its excellent soft tissue contrast resolution but also because it is noninvasive and does not use ionizing radiation. In nonconclusive cases, MR neurography can be complementary to physical examination and electromyography in identifying a specific affected nerve and the site of the lesion. This article reviews the MR imaging technique used in the evaluation of peripheral nerves (ie, MR neurography), its major indications, and the common pathologic conditions encountered in the pediatric population.

  12. Nerve transfers and neurotization in peripheral nerve injury, from surgery to rehabilitation.

    PubMed

    Korus, Lisa; Ross, Douglas C; Doherty, Christopher D; Miller, Thomas A

    2016-02-01

    Peripheral nerve injury (PNI) and recent advances in nerve reconstruction (such as neurotization with nerve transfers) have improved outcomes for patients suffering peripheral nerve trauma. The purpose of this paper is to bridge the gap between the electromyographer/clinical neurophysiologist and the peripheral nerve surgeon. Whereas the preceding literature focuses on either the basic science behind nerve injury and reconstruction, or the surgical options and algorithms, this paper demonstrates how electromyography is not just a 'decision tool' when deciding whether to operate but is also essential to all phases of PNI management including surgery and rehabilitation. The recent advances in the reconstruction and rehabilitation of PNI is demonstrated using case examples to assist the electromyographer to understand modern surgical techniques and the unique demands they ask from electrodiagnostic testing.

  13. 21 CFR 868.2775 - Electrical peripheral nerve stimulator.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... a device used to apply an electrical current to a patient to test the level of pharmacological... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Electrical peripheral nerve stimulator. 868.2775... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Monitoring Devices § 868.2775 Electrical peripheral...

  14. 21 CFR 868.2775 - Electrical peripheral nerve stimulator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... a device used to apply an electrical current to a patient to test the level of pharmacological... 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...

  15. 21 CFR 868.2775 - Electrical peripheral nerve stimulator.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... a device used to apply an electrical current to a patient to test the level of pharmacological... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Electrical peripheral nerve stimulator. 868.2775... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Monitoring Devices § 868.2775 Electrical peripheral...

  16. 21 CFR 868.2775 - Electrical peripheral nerve stimulator.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... a device used to apply an electrical current to a patient to test the level of pharmacological... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Electrical peripheral nerve stimulator. 868.2775... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Monitoring Devices § 868.2775 Electrical peripheral...

  17. 21 CFR 868.2775 - Electrical peripheral nerve stimulator.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... a device used to apply an electrical current to a patient to test the level of pharmacological... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Electrical peripheral nerve stimulator. 868.2775... (CONTINUED) MEDICAL DEVICES ANESTHESIOLOGY DEVICES Monitoring Devices § 868.2775 Electrical peripheral...

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

    PubMed

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

    2016-03-01

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

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

    PubMed

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

    2016-03-01

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

  20. Redoxins in peripheral neurons after sciatic nerve injury.

    PubMed

    Valek, Lucie; Kanngießer, Maike; Häussler, Annett; Agarwal, Nitin; Lillig, Christopher Horst; Tegeder, Irmgard

    2015-12-01

    Peripheral nerve injury causes redox stress in injured neurons by upregulations of pro-oxidative enzymes, but most neurons survive suggesting an activation of endogenous defense against the imbalance. As potential candidates we assessed thioredoxin-fold proteins, called redoxins, which maintain redox homeostasis by reduction of hydrogen peroxide or protein dithiol-disulfide exchange. Using a histologic approach, we show that the peroxiredoxins (Prdx1-6), the glutaredoxins (Glrx1, 2, 3 and 5), thioredoxin (Txn1 and 2) and their reductases (Txnrd1 and 2) are expressed in neurons, glial and/or vascular cells of the dorsal root ganglia (DRGs) and in the spinal cord. They show distinct cellular and subcellular locations in agreement with the GO terms for "cellular component". The expression and localization of Glrx, Txn and Txnrd proteins was not affected by sciatic nerve injury but peroxiredoxins were upregulated in the DRGs, Prdx1 and Prdx6 mainly in non-neuronal cells and Prdx4 and Prdx5 in DRG neurons, the latter associated with an increase of respective mRNAs and protein accumulation in peripheral and/or central fibers. The upregulation of Prdx4 and Prdx5 in DRG neurons was reduced in mice with a cre-loxP mediated deficiency of hypoxia inducible factor 1 alpha (HIF1α) in these neurons. The results identify Prdx4 and Prdx5 as endogenous HIF1α-dependent, transcriptionally regulated defenders of nerve injury evoked redox stress that may be important for neuronal survival and regeneration.

  1. Upper extremity peripheral nerve entrapments among wheelchair athletes: prevalence, location, and risk factors.

    PubMed

    Burnham, R S; Steadward, R D

    1994-05-01

    Wheelchair athletes commonly experience hand pain and numbness. This investigation studied the prevalence, location, and risk factors of upper extremity peripheral nerve entrapment among wheelchair athletes. Clinical and electrodiagnostic assessments were performed on both upper extremities of 28 wheelchair athletes and 30 able-bodied controls. Included in the assessment were short-segment stimulation techniques of the median nerve across the carpal tunnel and the ulnar nerve across the elbow. By clinical criteria, the prevalence of nerve entrapment among the wheelchair athletes was 23%, whereas it was 64% electrodiagnostically. The most common electrodiagnostic dysfunction was of the median nerve at the carpal tunnel (46%), and the portion of the nerve within the proximal carpal tunnel was most frequently affected. Ulnar neuropathy was the second most common entrapment electrodiagnostically (39%) and occurred at the wrist and forearm segments. Disability duration correlated significantly with electrophysiologic median nerve dysfunction.

  2. Peripheral Nerve Injury: Principles for Repair and Regeneration

    PubMed Central

    M.F, Griffin; M, Malahias; S, Hindocha; Khan, Wasim S

    2014-01-01

    Peripheral Nerve Injuries are one of the most common causes of hand dysfunction caused by upper limb trauma but still current management has remained suboptimal. This review aims to explain the traditional view of pathophysiology of nerve repair and also describe why surgical management is still inadequate in using the new biological research that has documented the changes that occur after the nerve injury, which, could cause suboptimal clinical outcomes. Subsequently presentation and diagnosis will be described for peripheral nerve injuries. When traditional surgical repair using end-to-end anastomosis is not adequate nerve conduits are required with the gold standard being the autologous nerve. Due to associated donor site morbidity and poor functional outcome documented with autologous nerve repair several new advancements for alternatives to bridge the gap are being investigated. We will summarise the new and future advancements of non-biological and biological replacements as well as gene therapy, which are being considered as the alternatives for peripheral nerve repair. PMID:25067975

  3. Peripheral nerve injury: principles for repair and regeneration.

    PubMed

    M F, Griffin; M, Malahias; S, Hindocha; Khan, Wasim S

    2014-01-01

    Peripheral Nerve Injuries are one of the most common causes of hand dysfunction caused by upper limb trauma but still current management has remained suboptimal. This review aims to explain the traditional view of pathophysiology of nerve repair and also describe why surgical management is still inadequate in using the new biological research that has documented the changes that occur after the nerve injury, which, could cause suboptimal clinical outcomes. Subsequently presentation and diagnosis will be described for peripheral nerve injuries. When traditional surgical repair using end-to-end anastomosis is not adequate nerve conduits are required with the gold standard being the autologous nerve. Due to associated donor site morbidity and poor functional outcome documented with autologous nerve repair several new advancements for alternatives to bridge the gap are being investigated. We will summarise the new and future advancements of non-biological and biological replacements as well as gene therapy, which are being considered as the alternatives for peripheral nerve repair. PMID:25067975

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

    PubMed

    Tao, Xing; Ma, Tie-ming

    2016-02-01

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

  5. Peripheral nerve injuries attributable to sport and recreation.

    PubMed

    Toth, Cory

    2009-02-01

    Many different sports and recreational activities are associated with injuries to the peripheral nervous system (PNS). Although some of those injuries are specific to an individual sport, other peripheral nerve injuries occur ubiquitously within many sporting activities. This review of sport-specific PNS injuries should assist in the understanding of morbidity associated with particular sporting activities, professional or amateur. Proper recognition of these syndromes can prevent unnecessary diagnostic testing and delays in proper diagnosis. The sports most commonly associated with peripheral nerve injuries are likely football, hockey, and baseball, but many other sports have unique associations with peripheral nerve injury. This article should be of assistance for the neurologist, neurosurgeon, orthopedic surgeon, physiatrist, sports medicine doctor, and general physician in contact with athletes at risk for neurologic injuries.

  6. Peripheral nerve injuries attributable to sport and recreation.

    PubMed

    Toth, Cory

    2008-02-01

    Many different sports and recreational activities are associated with injuries to the peripheral nervous system (PNS). Although some of those injuries are specific to an individual sport, other peripheral nerve injuries occur ubiquitously within many sporting activities. This review of sport-specific PNS injuries should assist in the understanding of morbidity associated with particular sporting activities, professional or amateur. Proper recognition of these syndromes can prevent unnecessary diagnostic testing and delays in proper diagnosis. The sports most commonly associated with peripheral nerve injuries are likely football, hockey, and baseball, but many other sports have unique associations with peripheral nerve injury. This article should be of assistance for the neurologist, neurosurgeon, orthopedic surgeon, physiatrist, sports medicine doctor, and general physician in contact with athletes at risk for neurologic injuries.

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

    PubMed

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

    2016-05-01

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

  8. AFM combines functional and morphological analysis of peripheral myelinated and demyelinated nerve fibers.

    PubMed

    Heredia, Alejandro; Bui, Chin Chu; Suter, Ueli; Young, Peter; Schäffer, Tilman E

    2007-10-01

    Demyelination of the myelinated peripheral or central axon is a common pathophysiological step in the clinical manifestation of several human diseases of the peripheral and the central nervous system such as the majority of Charcot-Marie-Tooth syndromes and multiple sclerosis, respectively. The structural degradation of the axon insulating myelin sheath has profound consequences for ionic conduction and nerve function in general, but also affects the micromechanical properties of the nerve fiber. We have for the first time investigated mechanical properties of rehydrated, isolated peripheral nerve fibers from mouse using atomic force microscopy (AFM). We have generated quantitative maps of elastic modulus along myelinated and demyelinated axons, together with quantitative maps of axon topography. This study shows that AFM can combine functional and morphological analysis of neurological tissue at the level of single nerve fibers.

  9. Dynamic Regulation of Schwann Cell Enhancers after Peripheral Nerve Injury*

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  12. Aligned natural-synthetic polyblend nanofibers for peripheral nerve regeneration.

    PubMed

    Wang, Chun-Yang; Zhang, Kui-Hua; Fan, Cun-Yi; Mo, Xiu-Mei; Ruan, Hong-Jiang; Li, Feng-Feng

    2011-02-01

    Peripheral nerve regeneration remains a significant clinical challenge to researchers. Progress in the design of tissue engineering scaffolds provides an alternative approach for neural regeneration. In this study aligned silk fibroin (SF) blended poly(L-lactic acid-co-ε-caprolactone) (P(LLA-CL)) nanofibrous scaffolds were fabricated by electrospinning methods and then reeled into aligned nerve guidance conduits (NGC) to promote nerve regeneration. The aligned SF/P(LLA-CL) NGC was used as a bridge implanted across a 10mm defect in the sciatic nerve of rats and the outcome in terms of of regenerated nerve at 4 and 8 weeks was evaluated by a combination of electrophysiological assessment and histological and immunohistological analysis, as well as electron microscopy. The electrophysiological examination showed that functional recovery of the regenerated nerve in the SF/P(LLA-CL) NGC group was superior to that in the P(LLA-CL) NGC group. The morphological analysis also indicated that the regenerated nerve in the SF/P(LLA-CL) NGC was more mature. All the results demonstrated that the aligned SF/P(LLA-CL) NGC promoted peripheral nerve regeneration significantly better in comparison with the aligned P(LLA-CL) NGC, thus suggesting a potential application in nerve regeneration.

  13. Neural tissue engineering options for peripheral nerve regeneration.

    PubMed

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

    2014-08-01

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

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

    PubMed

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

    2006-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2011-06-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    Restrepo, José Félix; Rondón, Federico; Matteson, Eric L.; Colegial, Carlos H.; Quintana, Gerardo; Iglesias-Gamarra, Antonio

    2009-01-01

    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. PMID:20204175

  18. 21 CFR 882.5870 - Implanted peripheral nerve stimulator for pain relief.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Implanted peripheral nerve stimulator for pain....5870 Implanted peripheral nerve stimulator for pain relief. (a) Identification. An implanted peripheral nerve stimulator for pain relief is a device that is used to stimulate electrically a peripheral...

  19. 21 CFR 882.5870 - Implanted peripheral nerve stimulator for pain relief.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Implanted peripheral nerve stimulator for pain....5870 Implanted peripheral nerve stimulator for pain relief. (a) Identification. An implanted peripheral nerve stimulator for pain relief is a device that is used to stimulate electrically a peripheral...

  20. 21 CFR 882.5870 - Implanted peripheral nerve stimulator for pain relief.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Implanted peripheral nerve stimulator for pain....5870 Implanted peripheral nerve stimulator for pain relief. (a) Identification. An implanted peripheral nerve stimulator for pain relief is a device that is used to stimulate electrically a peripheral...

  1. 21 CFR 882.5870 - Implanted peripheral nerve stimulator for pain relief.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Implanted peripheral nerve stimulator for pain....5870 Implanted peripheral nerve stimulator for pain relief. (a) Identification. An implanted peripheral nerve stimulator for pain relief is a device that is used to stimulate electrically a peripheral...

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

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  3. Shockwave-induced compound action potentials in the peripheral nerve.

    PubMed

    Wehner, H D; Sellier, K

    1981-01-01

    To verify a presumed interaction between shockwaves arisen by impacts of high velocity projectiles and nervous tissue an electrophysiological experiment is performed with the following results: In peripheral nerves regular compound action potentials (CAPs) are provoked by shockwaves the amplitudes of which are increased corresponding to the pressure intensity of the shockwaves. The nerve shows no electrical activity below a certain pressure threshold (0.75 bar). Saturation of the CAP amplitude occurs beyond a pressure limit of 8 bar.

  4. Preclinical evaluations of acellular biological conduits for peripheral nerve regeneration

    PubMed Central

    Liao, I-Chien; Wan, Hua; Qi, Shijie; Cui, Cunqi; Patel, Paarun; Sun, Wendell

    2013-01-01

    Various types of natural biological conduits have been investigated as alternatives to the current surgical standard approach for peripheral nerve injuries. Autologous nerve graft, the current gold standard for peripheral nerve damage, is limited by clinical challenges such as donor-site morbidity and limited availability. The purpose of this study was to evaluate the efficacy of using acellular xenographic conduits (nerve, artery, and dermis) for the repair of a 1.2 cm critical size defect of peripheral nerve in a rodent model. Four months post surgery, the animal group receiving acellular artery as a nerve conduit showed excellent physiological outcome in terms of the prevention of muscle atrophy and foot ulcer. Histological assessment of the bridged site revealed excellent axon regeneration, as opposed to the nonrepaired control group or the group receiving dermal conduit. Finally, the study evaluated the potential improvement via the addition of undifferentiated mesenchymal stem cells into the artery conduit during the bridging procedure. The mesenchymal stem cell–dosed artery conduit group resulted in significantly higher concentration of regenerated axons over artery conduit alone, and exhibited accelerated muscle atrophy rescue. Our results demonstrated that xenographic artery conduits promoted excellent axonal regeneration with highly promising clinical relevance. PMID:23532671

  5. Pulsed laser versus electrical energy for peripheral nerve stimulation

    PubMed Central

    Wells, Jonathon; Konrad, Peter; Kao, Chris; Jansen, E. Duco; Mahadevan-Jansen, Anita

    2010-01-01

    Transient optical neural stimulation has previously been shown to elicit highly controlled, artifact-free potentials within the nervous system in a non-contact fashion without resulting in damage to tissue. This paper presents the physiologic validity of elicited nerve and muscle potentials from pulsed laser induced stimulation of the peripheral nerve in a comparative study with the standard method of electrically evoked potentials. Herein, the fundamental physical properties underlying the two techniques are contrasted. Key laser parameters for efficient optical stimulation of the peripheral nerve are detailed. Strength response curves are shown to be linear for each stimulation modality, although fewer axons can be recruited with optically evoked potentials. Results compare the relative transient energy requirements for stimulation using each technique and demonstrate that optical methods can selectively excite functional nerve stimulation. Adjacent stimulation and recording of compound nerve potentials in their entirety from optical and electrical stimulation are presented, with optical responses shown to be free of any stimulation artifact. Thus, use of a pulsed laser exhibits some advantages when compared to standard electrical means for excitation of muscle potentials in the peripheral nerve in the research domain and possibly for clinical diagnostics in the future. PMID:17537515

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

    PubMed Central

    Liao, Joseph C; Curtin, Catherine M

    2015-01-01

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

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

    PubMed

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

    2016-01-01

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

  8. WATER TRANSPORT IN INVERTEBRATE PERIPHERAL NERVE FIBERS

    PubMed Central

    Nevis, Arnold H.

    1958-01-01

    Osmotic and diffusion permeabilities (Pf and Pd) of invertebrate nerve fibers to tritiated water were measured to determine what water flux studies could reveal about "the nerve membrane" and to directly test the possibility of active transport of water into or out of invertebrate nerve fibers. Pf/Pd ratios for lobster walking leg nerve fibers were found to be about 20 ± 7 at 14°C. Pd measurements were made for squid giant axons at 25°C. and found to yield a value of 4 x 10–4 cm.–1 sec.–1. When combined with the data of D. K. Hill for Pf, a Pf/Pd ratio of 21 ± 5 is obtained. These Pf/Pd ratios correspond to "effective pore radii" of about 16 ± 4 angstrom units, according to theories developed by Koefoed-Johnsen and Ussing and independently by Pappenheimer and his colleagues. Variations of water flux ratios with temperatures were studied and apparent activation energies calculated for both diffusion experiments and osmotic filtration experiments using the Arrhenius equation, and found to be close to 3 to 5 cal. per mole of water transferred. Cyanide (5 x 10–3 molar) and iodoacetate (1 x 10–3 molar) poisoned lobster leg nerve fibers showed no appreciable change in diffusion or osmotic filtration water effluxes. Caution in interpreting these proposed channels as simple pores was emphasized, but the possibility that such channels exist and are related to ionic flow is not incompatible with electrophysiological data. PMID:13525675

  9. Nanotechnology and bio-functionalisation for peripheral nerve regeneration

    PubMed Central

    Sedaghati, Tina; Seifalian, Alexander M.

    2015-01-01

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

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

    SciTech Connect

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

    1990-01-01

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

  11. Adrenergic vasoconstriction in peripheral nerves of the rabbit

    SciTech Connect

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

    1985-01-01

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

  12. Peripheral nerve injuries in athletes. Treatment and prevention.

    PubMed

    Lorei, M P; Hershman, E B

    1993-08-01

    Peripheral nerve lesions are uncommon but serious injuries which may delay or preclude an athlete's safe return to sports. Early, accurate anatomical diagnosis is essential. Nerve lesions may be due to acute injury (e.g. from a direct blow) or chronic injury secondary to repetitive microtrauma (entrapment). Accurate diagnosis is based upon physical examination and a knowledge of the relative anatomy. Palpation, neurological testing and provocative manoeuvres are mainstays of physical diagnosis. Diagnostic suspicion can be confirmed by electrophysiological testing, including electromyography and nerve conduction studies. Proper equipment, technique and conditioning are the keys to prevention. Rest, anti-inflammatories, physical therapy and appropriate splinting are the mainstays of treatment. In the shoulder, spinal accessory nerve injury is caused by a blow to the neck and results in trapezius paralysis with sparing of the sternocleidomastoid muscle. Scapular winging results from paralysis of the serratus anterior because of long thoracic nerve palsy. A lesion of the suprascapular nerve may mimic a rotator cuff tear with pain a weakness of the rotator cuff. Axillary nerve injury often follows anterior shoulder dislocation. In the elbow region, musculocutaneous nerve palsy is seen in weightlifters with weakness of the elbow flexors and dysesthesias of the lateral forearm. Pronator syndrome is a median nerve lesion occurring in the proximal forearm which is diagnosed by several provocative manoeuvres. Posterior interosseous nerve entrapment is common among tennis players and occurs at the Arcade of Froshe--it results in weakness of the wrist and metacarpophalangeal extensors. Ulnar neuritis at the elbow is common amongst baseball pitchers. Carpal tunnel syndrome is a common neuropathy seen in sport and is caused by median nerve compression in the carpal tunnel. Paralysis of the ulnar nerve at the wrist is seen among bicyclists resulting in weakness of grip and

  13. Laminin-based Nanomaterials for Peripheral Nerve Tissue Engineering

    NASA Astrophysics Data System (ADS)

    Neal, Rebekah Anne

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  16. Peripheral nerve injuries in baseball players.

    PubMed

    Cummins, Craig A; Schneider, David S

    2009-02-01

    Baseball players place significant stress across their shoulders and elbows during the throwing motion, causing unique patterns of injuries in the overhead throwing athlete. Specific nerve injuries include suprascapular neuropathy, quadrilateral space syndrome, and cubital tunnel syndrome. Nonoperative treatment includes cessation of throwing and symptom management. As symptoms improve, athletes should start rehabilitation, focusing on restoring shoulder and trunk flexibility and strength. The final rehabilitation phase involves an interval throwing program with attention directed at proper mechanics, with the goal of returning the athlete to competitive throwing. Surgery may assist in a positive outcome in particular patients who fail to improve with nonoperative treatment. Additional indications for surgery may include more profound neuropathy and nerve compression by a mass lesion.

  17. Peripheral nerve injuries in baseball players.

    PubMed

    Cummins, Craig A; Schneider, David S

    2008-02-01

    Baseball players place significant stress across their shoulders and elbows during the throwing motion, causing unique patterns of injuries in the overhead throwing athlete. Specific nerve injuries include suprascapular neuropathy, quadrilateral space syndrome, and cubital tunnel syndrome. Nonoperative treatment includes cessation of throwing and symptom management. As symptoms improve, athletes should start rehabilitation, focusing on restoring shoulder and trunk flexibility and strength. The final rehabilitation phase involves an interval throwing program with attention directed at proper mechanics, with the goal of returning the athlete to competitive throwing. Surgery may assist in a positive outcome in particular patients who fail to improve with nonoperative treatment. Additional indications for surgery may include more profound neuropathy and nerve compression by a mass lesion.

  18. Aligned SF/P(LLA-CL)-blended nanofibers encapsulating nerve growth factor for peripheral nerve regeneration.

    PubMed

    Kuihua, Zhang; Chunyang, Wang; Cunyi, Fan; Xiumei, Mo

    2014-08-01

    Artificial nerve guidance conduits (NGCs) containing bioactive neurotrophic factors and topographical structure to biomimic native tissues are essential for efficient regeneration of nerve gaps. In this study, aligned SF/P(LLA-CL) nanofibers encapsulating nerve growth factor (NGF), which was stabilized by SF in core, were fabricated via a coaxial electrospinning technique. The controlled release of NGF from the nanofibers was evaluated using enzyme-linked immune sorbent assay (ELISA) and PC12 cell-based bioassay over a 60-day time period. The results demonstrated that NGF presented a sustained release and remained biological activity over 60 days. Nerve guidance conduits (NGCs) were fabricated by reeling the aligned SF/P(LLA-CL) nanofibrous scaffolds encapsulating NGF and then used as a bridge implanted across a 15-mm defect in the sciatic nerve of rats to promote nerve regeneration. The outcome in terms of regenerated nerve at 12 weeks was evaluated by a combination of electrophysiological assessment, histochemistry, and electron microscopy. All results clarified that the NGF-encapsulated-aligned SF/P(LLA-CL) NGCs promoted peripheral nerve regeneration significantly better than the aligned SF/P(LLA-CL) NGCs, suggesting that the released NGF from nanofibers could effectively promote the regeneration of peripheral nerve.

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

    PubMed

    Tabarki, B

    2014-10-01

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

  20. Intelligence, Reaction Times, and Peripheral Nerve Conduction Velocity.

    ERIC Educational Resources Information Center

    Vernon, Philip A.; Mori, Monica

    1992-01-01

    In 2 studies with 85 and 88 undergraduates, respectively, peripheral nerve conduction velocity (NCV) was significantly correlated with IQ score and reaction times, and NCV and reaction time contributed significantly, in combination, to prediction of IQ. Results are interpreted in terms of a neural efficiency model of intelligence. (Author/SLD)

  1. Magnetoneurography: theory and application to peripheral nerve disorders.

    PubMed

    Mackert, Bruno-Marcel

    2004-12-01

    Magnetoneurography (MNG) is a non-invasive method to trace and visualize three-dimensionally the propagation path of compound action currents (CAC) along peripheral nerves. The basic physical and physiological principle is the mapping of extremely weak magnetic fields generated by the intraaxonal longitudinal ion flows of evoked nerval CAC using SQUID sensors (Superconducting Quantum Interference Devices). During recent years, MNG protocols have been established which allow for a non-invasive spatiotemporal tracing of impulse propagation along peripheral nerves in humans and in particular along proximal nerve segments in a clinical setting. Thereby, the three-dimensional path, the local nerve conduction velocity, the length and strength of the CAC de- and repolarization phase have been reconstructed. First recordings in patients demonstrated that the method is sensitive enough to detect and to localize nerve conduction anomalities along nerve roots, as, e.g. caused by lumbosacral disc herniation. This review on MNG will focus on those studies which provide data from humans and thereby reveal perspectives for its future clinical applications. PMID:15546775

  2. Magnetoneurography: theory and application to peripheral nerve disorders.

    PubMed

    Mackert, Bruno-Marcel

    2004-12-01

    Magnetoneurography (MNG) is a non-invasive method to trace and visualize three-dimensionally the propagation path of compound action currents (CAC) along peripheral nerves. The basic physical and physiological principle is the mapping of extremely weak magnetic fields generated by the intraaxonal longitudinal ion flows of evoked nerval CAC using SQUID sensors (Superconducting Quantum Interference Devices). During recent years, MNG protocols have been established which allow for a non-invasive spatiotemporal tracing of impulse propagation along peripheral nerves in humans and in particular along proximal nerve segments in a clinical setting. Thereby, the three-dimensional path, the local nerve conduction velocity, the length and strength of the CAC de- and repolarization phase have been reconstructed. First recordings in patients demonstrated that the method is sensitive enough to detect and to localize nerve conduction anomalities along nerve roots, as, e.g. caused by lumbosacral disc herniation. This review on MNG will focus on those studies which provide data from humans and thereby reveal perspectives for its future clinical applications.

  3. 3D multi-channel bi-functionalized silk electrospun conduits for peripheral nerve regeneration.

    PubMed

    Dinis, T M; Elia, R; Vidal, G; Dermigny, Q; Denoeud, C; Kaplan, D L; Egles, C; Marin, F

    2015-01-01

    Despite technological advances over the past 25 years, a complete recovery from peripheral nerve injuries remains unsatisfactory today. The autograft is still considered the "gold standard" in clinical practice; however, postoperative complications and limited availability of nerve tissue have motivated the development of alternative approaches. Among them, the development of biomimetic nerve graft substitutes is one of the most promising strategies. In this study, multichanneled silk electrospun conduits bi-functionalized with Nerve Growth Factor (NGF) and Ciliary Neurotropic Factor (CNTF) were fabricated to enhance peripheral nerve regeneration. These bioactive guides consisting of longitudinally oriented channels and aligned nanofibers were designed in order to mimic the fascicular architecture and fibrous extracellular matrix found in native nerve. The simple use of the electrospinning technique followed by a manual manipulation to manufacture these conduits provides tailoring of channel number and diameter size to create perineurium-like structures. Functionalization of the silk fibroin nanofiber did not affect its secondary structure and chemical property. ELISA assays showed the absence of growth factors passive release from the functionalized fibers avoiding the topical accumulation of proteins. In addition, our biomimetic multichanneled functionalized nerve guides displayed a mechanical behavior comparable to that of rat sciatic nerve with an ultimate peak stress of 4.0 ± 0.6 MPa and a corresponding elongation at failure of 156.8 ± 46.7%. Taken together, our results demonstrate for the first time our ability to design and characterize a bi-functionalized nerve conduit consisting of electrospun nanofibers with multichannel oriented and nanofibers aligned for peripheral regeneration. Our bioactive silk tubes thus represent a new and promising technique towards the creation of a biocompatible nerve guidance conduit. PMID:25460402

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

    PubMed

    Kaiser, Radek

    2016-01-01

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

  5. Contactin orchestrates assembly of the septate-like junctions at the paranode in myelinated peripheral nerve.

    PubMed

    Boyle, M E; Berglund, E O; Murai, K K; Weber, L; Peles, E; Ranscht, B

    2001-05-01

    Rapid nerve impulse conduction depends on specialized membrane domains in myelinated nerve, the node of Ranvier, the paranode, and the myelinated internodal region. We report that GPI-linked contactin enables the formation of the paranodal septate-like axo-glial junctions in myelinated peripheral nerve. Contactin clusters at the paranodal axolemma during Schwann cell myelination. Ablation of contactin in mutant mice disrupts junctional attachment at the paranode and reduces nerve conduction velocity 3-fold. The mutation impedes intracellular transport and surface expression of Caspr and leaves NF155 on apposing paranodal myelin disengaged. The contactin mutation does not affect sodium channel clustering at the nodes of Ranvier but alters the location of the Shaker-type Kv1.1 and Kv1.2 potassium channels. Thus, contactin is a crucial part in the machinery that controls junctional attachment at the paranode and ultimately the physiology of myelinated nerve. PMID:11395001

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

    PubMed

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

    2014-09-01

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

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

    PubMed

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

    2015-03-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  10. Morphometric and ultrastructural changes with ageing in mouse peripheral nerve

    PubMed Central

    CEBALLOS, DOLORES; CUADRAS, JORDI; VERDÚ, ENRIQUE; NAVARRO, XAVIER

    1999-01-01

    Qualitative and quantitative information is reported on the morphological changes that occur in nerve fibres and nonneuronal cells of peripheral nerve during the lifetime of the mouse. Tibial nerves of mice aged 6–33 mo were studied. With ageing, collagen accumulates in the perineurium and lipid droplets in the perineurial cells. Macrophages and mast cells increase in number, and onion bulbs and collagen pockets are frequently present. Schwann cells associated with myelinated fibres (MF) slightly decrease in number in parallel with an increase of the internodal length from 6 to 12 mo, but increase in older nerves when demyelination and remyelination are common. The unmyelinated axon to myelinated fibre (UA/MF) ratio was about 2 until 12 mo, decreasing to 1.6 by 27 mo. In older mice, the loss of nerve fibres involves UA (50% loss of 27–33 mo cf. 6 mo) more markedly than MF (35%). In aged nerves wide incisures and infolded or outfolded myelin loops are frequent, resulting in an increased irregularity in the morphology of fibres along the internodes. In the mouse there is an adult time period, 12–20 mo, during which several features of degeneration progressively appear, and an ageing period from 20 mo upwards when the nerve suffers a general disorganisation and marked fibre loss. PMID:10634695

  11. Peripheral communications of intercostobrachial nerve Peripheral communications of the intercostobrachial nerve in relation to the alar thoracic artery

    PubMed Central

    Rustagi, Shaifaly Madan; Sharma, Mona; Singh, Nidhi; Mehta, Vandana; Suri, Rajesh K; Rath, Gayatri

    2015-01-01

    The intercostobrachial nerve (ICBN) is often encountered during axillary dissection for axillary lymph node dissection (ALND) for diagnostic and therapeutic surgery for mastectomy. The present report is a case observed in the Department of Anatomy at Vardhman Mahavir Medical College, Delhi during routine dissection of the upper extremity of a male cadaver for first year undergraduate medical students. On the right side, the medial cord of brachial plexus gave two medial cutaneous nerves of arm. Both the nerves were seen communicating with the branches of the ICBN. The ICBN and one of its branches were surrounding the termination of an alar thoracic artery. These peripheral neural connections of the ICBN with the branches of the medial cord can be a cause of sensory impairment during axillary procedures done for mastectomy or exploration of long thoracic nerves. The alar thoracic artery found in relation to the ICBN could further be a cause of vascular complications during such procedures. PMID:25802820

  12. Peripheral communications of intercostobrachial nerve Peripheral communications of the intercostobrachial nerve in relation to the alar thoracic artery.

    PubMed

    Rustagi, Shaifaly Madan; Sharma, Mona; Singh, Nidhi; Mehta, Vandana; Suri, Rajesh K; Rath, Gayatri

    2015-01-01

    The intercostobrachial nerve (ICBN) is often encountered during axillary dissection for axillary lymph node dissection (ALND) for diagnostic and therapeutic surgery for mastectomy. The present report is a case observed in the Department of Anatomy at Vardhman Mahavir Medical College, Delhi during routine dissection of the upper extremity of a male cadaver for first year undergraduate medical students. On the right side, the medial cord of brachial plexus gave two medial cutaneous nerves of arm. Both the nerves were seen communicating with the branches of the ICBN. The ICBN and one of its branches were surrounding the termination of an alar thoracic artery. These peripheral neural connections of the ICBN with the branches of the medial cord can be a cause of sensory impairment during axillary procedures done for mastectomy or exploration of long thoracic nerves. The alar thoracic artery found in relation to the ICBN could further be a cause of vascular complications during such procedures.

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

    PubMed

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

    2016-06-01

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

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

    PubMed Central

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

    2016-01-01

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

  15. Comparison of nerve, vessel, and cartilage grafts in promoting peripheral nerve regeneration.

    PubMed

    Firat, Cemal; Geyik, Ylmaz; Aytekin, Ahmet Hamdi; Gül, Mehmet; Kamşl, Suat; Yiğitcan, Birgül; Ozcan, Cemal

    2014-07-01

    Peripheral nerve injury primarily occurs due to trauma as well as factors such as tumors, inflammatory diseases, congenital deformities, infections, and surgical interventions. The surgical procedure to be performed as treatment depends on the etiology, type of injury, and the anatomic region. The goal of treatment is to minimize loss of function due to motor and sensory nerve loss at the distal part of the injury. Regardless of the cause of the injury, the abnormal nerve regeneration due to incomplete nerve regeneration, optimal treatment of peripheral nerve injuries should provide adequate coaptation of proximal and distal sides without tension, preserving the neurotrophic factors within the repair line. The gold standard for the treatment of nerve defects is the autograft; however, due to denervation of the donor site, scarring, and neuroma formation, many studies have aimed to develop simpler methods, better functional results, and less morbidity. In this study, a defect 1 cm in length was created on the sciatic nerve of rats. The rats were treated with the following procedures: group 1, autograft; group 2, allogeneic aorta graft; group 3, diced cartilage graft in allogeneic aorta graft; and group 4, tubularized cartilage graft in allogeneic aorta graft. Group 5 was the control group. The effects of cartilage tissue in nerve regeneration were evaluated by functional and histomorphological methods.Group 1, for which the repair was performed with an autograft, was evaluated to be the most similar to the control group. There was not a statistically significant difference in myelination and Schwann cell rates between group 2, in which an allogeneic aorta graft was used, and group 3, in which diced cartilage in an allogeneic aorta graft was used. In group 4, myelination and Schwann cell formation were observed; however, they were scattered and irregular, likely due to increased fibrosis.In all of the groups, nerve regeneration at various rates was observed both

  16. Selective recovery of fascicular activity in peripheral nerves

    NASA Astrophysics Data System (ADS)

    Wodlinger, B.; Durand, D. M.

    2011-10-01

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

  17. Ethical considerations in elective amputation after traumatic peripheral nerve injuries

    PubMed Central

    Myers, Keith P.; Holloway, Robert G.; Landau, Mark E.

    2014-01-01

    Summary Traumatic peripheral nerve injuries often complicate extremity trauma, and may cause substantial functional deficits. We have encountered patients who request amputation of such injured extremities, with the goal of prosthetic replacement as a means to restore function. Data on long-term outcomes of limb salvage vs amputation are limited and somewhat contradictory, leaving how to respond to such requests in the hands of the treating physician. We present example cases, drawn from our experience with wounded soldiers in a peripheral nerve injury clinic, in order to facilitate discussion of the ways in which these patients stress the system of medical decision-making while identifying ethical questions central to responding to these requests. PMID:25279253

  18. Peripheral nerve conduction and central motor conduction after magnetic stimulation of the brain in myotonic dystrophy.

    PubMed

    Cruz Martínez, A

    1992-06-01

    Central motor conduction time was calculated after magnetic stimulation of the brain in 15 patients with myotonic dystrophy and in 38 healthy voluntaries of the same age. Conventional electromyography and motor and sensory conduction velocities were also performed. Central motor conduction time from vertex to C8 was within the normal range in all patients whereas motor conduction velocity of the peripheral nerve and amplitude of the nerve evoked potentials were slightly reduced in 3 and 2 cases respectively, supporting peripheral nerve involvement in some subjects. Our results suggest that the reported central nervous system involvement in myotonic dystrophy, including the nonspecific white matter lesions showed by magnetic resonance imaging, would not affect the conduction of the corticospinal tracts. Magnetic stimulation on the motor cortex is a painless method to study the central nervous system and apports a satisfactory approximation to central motor pathways conduction.

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

    PubMed Central

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

    2013-01-01

    To evaluate ultrasonographic (US) cross-sectional areas (CSAs) of peripheral nerves, indexes of the differences between CSAs at the same point (∆CSAs) and between tunnel (T) and pre-tunnel (PT) ulnar CSAs (∆TPTs) in leprosy patients (LPs) and healthy volunteers (HVs). Seventy-seven LPs and 49 HVs underwent bilateral US at PT and T ulnar points, as well as along the median (M) and common fibular (CF) nerves, to calculate the CSAs, ∆CSAs and ∆TPTs. The CSA values in HVs were lower than those in LPs (p < 0.0001) at the PT (5.67/9.78 mm2) and T (6.50/10.94 mm2) points, as well as at the M (5.85/8.48 mm2) and CF (8.17/14.14 mm2) nerves. The optimum CSA- receiver operating characteristic (ROC) points and sensitivities/specificities were, respectively, 6.85 mm2 and 68-85% for the PT point, 7.35 mm2 and 71-78% for the T point, 6.75 mm2 and 62-75% for the M nerve and 9.55 mm2 and 81-72% for the CF nerve. The ∆CSAs of the LPs were greater than those of the HVs at the PT point (4.02/0.85; p = 0.007), T point (3.71/0.98; p = 0.0005) and CF nerve (2.93/1.14; p = 0.015), with no difference found for the M nerve (1.41/0.95; p = 0.17). The optimum ∆CSA-ROC points, sensitivities, specificities and p-values were, respectively, 1.35, 49%, 80% and 0.003 at the PT point, 1.55, 55-85% and 0.0006 at the T point, 0.70, 58-50% and 0.73 for the M nerve and 1.25, 54-67% and 0.022 for the CF nerve. The ∆TPT in the LPs was greater than that in the HVs (4.43/1.44; p <0.0001). The optimum ∆TPT-ROC point was 2.65 (90% sensitivity/41% specificity, p < 0.0001). The ROC analysis of CSAs showed the highest specificity and sensitivity at the PT point and CF nerve, respectively. The PT and T ∆CSAs had high specificities (> 80%) and ∆TPT had the highest specificity (> 90%). New sonographic peripheral nerve measurements (∆CSAs and ∆TPT) provide an important methodological improvement in the detection of leprosy neuropathy. PMID:23778664

  20. How to measure outcomes of peripheral nerve surgery.

    PubMed

    Wang, Yirong; Sunitha, Malay; Chung, Kevin C

    2013-08-01

    Evaluation of outcomes after peripheral nerve surgeries include several assessment methods that reflect different aspects of recovery, including reinnervation, tactile gnosis, integrated sensory and motor function, pain and discomfort, and neurophysiologic and patient-reported outcomes. This review lists measurements addressing these aspects as well as the advantages and disadvantages of each tool. Because of complexities of neurophysiology, assessment remains a difficult process, which requires researchers to focus on measurements best relevant to specific conditions and research questions. PMID:23895715

  1. How to measure outcomes of peripheral nerve surgery.

    PubMed

    Wang, Yirong; Sunitha, Malay; Chung, Kevin C

    2013-08-01

    Evaluation of outcomes after peripheral nerve surgeries include several assessment methods that reflect different aspects of recovery, including reinnervation, tactile gnosis, integrated sensory and motor function, pain and discomfort, and neurophysiologic and patient-reported outcomes. This review lists measurements addressing these aspects as well as the advantages and disadvantages of each tool. Because of complexities of neurophysiology, assessment remains a difficult process, which requires researchers to focus on measurements best relevant to specific conditions and research questions.

  2. Modeling Electric Fields of Peripheral Nerve Block Needles.

    NASA Astrophysics Data System (ADS)

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

    2006-03-01

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

  3. Modeling Electric Fields of Peripheral Nerve Block Needles.

    NASA Astrophysics Data System (ADS)

    Davis, James Ch.; Ramirez, Jason G.

    2005-11-01

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

  4. Ewing sarcoma mimicking a peripheral nerve sheath tumor.

    PubMed

    Mitchell, B D; Fox, B D; Viswanathan, A; Mitchell, A H; Powell, S Z; Cech, D A

    2010-10-01

    We describe the first patient with an extradural, extramedullary Ewing's sarcoma tumor mimicking a nerve sheath tumor with no overt evidence of metastasis. A 28-year-old woman with no past medical history presented with a progressive 3-year history of low back pain and right-sided lower extremity radiculopathy after having failed conservative therapies. MRI of the lumbar spine revealed a right-sided enhancing, dumbbell-shaped lesion at the right neural foramen appearing to originate from the L4 nerve root, suspicious for a peripheral nerve sheath tumor or schwannoma. The patient and findings are discussed in the context of the literature, including an update on the relatively recent diagnostic redesignation of the Ewing's sarcoma family tumors.

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

    PubMed Central

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

    2016-01-01

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

  6. Fabrication and characterization of polyacrylamide/silk fibroin hydrogels for peripheral nerve regeneration.

    PubMed

    Li, Guicai; Kong, Yan; Zhao, Yinxin; Zhao, Yahong; Zhang, Luzhong; Yang, Yumin

    2015-01-01

    Various hydrogels have been used for repairing peripheral nerve injury; however, the silk fibroin (SF)-based hydrogels in peripheral nerve regeneration are still rarely reported. In this study, the SF/pAM hydrogels with different SF concentrations and ethanol treatment time were developed by solution blending and in situ radical polymerization. The physiochemical properties of composite hydrogels were measured, the cytotoxicity of hydrogels was evaluated by L929 fibroblasts, and the effect on peripheral nerve regeneration was evaluated via Schwann cells culture in vitro. The results showed that the physiochemical properties of SF/pAM hydrogels could be changed by varying SF concentration and ethanol treatment time, and the mechanical property was enhanced with increasing SF concentration, while the presence of SF in pAM hydrogels and ethanol treatment does not affect hydrogels structure in per se. All the composite hydrogels displayed no obvious cytotoxicity, while the SF/pAM composite hydrogels with 10% SF and 60-min ethanol treatment could obviously accelerate the attachment and proliferation of Schwann cells. Therefore, the SF/pAM composite hydrogels possessed the beneficial properties required for in situ cell scaffolding and may have potential application in peripheral nerve regeneration.

  7. The Effects of Impact Vibration on Peripheral Blood Vessels and Nerves

    PubMed Central

    KRAJNAK, Kristine M.; WAUGH, Stacey; JOHNSON, Claud; MILLER, G. Roger; XU, Xueyan; WARREN, Christopher; DONG, Ren G.

    2013-01-01

    Research regarding the risk of developing hand-arm vibration syndrome after exposure to impact vibration has produced conflicting results. This study used an established animal model of vibration-induced dysfunction to determine how exposure to impact vibration affects peripheral blood vessels and nerves. The tails of male rats were exposed to a single bout of impact vibration (15 min exposure, at a dominant frequency of 30 Hz and an unweighted acceleration of approximately 345 m/s2) generated by a riveting hammer. Responsiveness of the ventral tail artery to adrenoreceptor-mediated vasoconstriction and acetylcholine-mediated re-dilation was measured ex vivo. Ventral tail nerves and nerve endings in the skin were assessed using morphological and immunohistochemical techniques. Impact vibration did not alter vascular responsiveness to any factors or affect trunk nerves. However, 4 days following exposure there was an increase in protein-gene product (PGP) 9.5 staining around hair follicles. A single exposure to impact vibration, with the exposure characteristics described above, affects peripheral nerves but not blood vessels. PMID:24077447

  8. Adjuvant neurotrophic factors in peripheral nerve repair with chondroitin sulfate proteoglycan-reduced acellular nerve allografts

    PubMed Central

    Boyer, Richard B.; Sexton, Kevin W.; Rodriguez-Feo, Charles L.; Nookala, Ratnam; Pollins, Alonda C.; Cardwell, Nancy L.; Tisdale, Keonna Y.; Nanney, Lillian B.; Shack, R. Bruce; Thayer, Wesley P.

    2014-01-01

    Background Acellular nerve allografts are now standard tools in peripheral nerve repair due to decreased donor site morbidity and operative time savings. Preparation of nerve allografts involves several steps of decellularization and modification of extracellular matrix to remove chondroitin sulfate proteoglycans (CSPGs), which have been shown to inhibit neurite outgrowth through a poorly understood mechanism involving RhoA and ECM-integrin interactions. Chondroitinase ABC (ChABC) is an enzyme that degrades CSPG molecules and has been shown to promote neurite outgrowth following injury of the central and peripheral nervous systems. Variable results following chondroitinase ABC treatment make it difficult to predict the effects of this drug in human nerve allografts, especially in the presence of native extracellular signaling molecules. Several studies have shown cross-talk between neurotrophic factor and CSPG signaling pathways, but their interaction remains poorly understood. In this study, we examined the adjuvant effects of nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF) on neurite outgrowth post-injury in CSPG-reduced substrates and acellular nerve allografts. Materials and Methods E12 chicken DRG explants were cultured in medium containing ChABC, ChABC + NGF, ChABC + GDNF or control media. Explants were imaged at 3 d and neurite outgrowths measured. The rat sciatic nerve injury model involved a 1-cm sciatic nerve gap that was microsurgically repaired with ChABC pre-treated acellular nerve allografts. Prior to implantation, nerve allografts were incubated in NGF, GDNF or sterile water. Nerve histology was evaluated at 5d and 8wk post-injury. Results The addition of GDNF in vitro produced significant increase in sensory neurite length at 3 d compared to ChABC alone (P < 0.01), while NGF was not significantly different from control. In vivo adjuvant NGF produced increases in total myelinated axon count (P < 0.005) and motor axon

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

    NASA Astrophysics Data System (ADS)

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

    2013-02-01

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

  10. A case of malignant atrophic papulosis with cranial nerve and peripheral nerve impairment*

    PubMed Central

    Liu, Fang; Liu, Haibo; Zhang, Min; Yan, Wenliang; Sang, Hong

    2015-01-01

    Malignant atrophic papulosisis is a rare, multisystem obliterative vasculopathy of unknown etiology, occasionally involving the cranial nerve. We describe the first case of malignant atrophic papulosisis with cranial nerve and peripheral nerve involvement in China. A 47-year-old woman presented to our hospital with atrophic porcelain white papules over the trunk and extremities, numbness in the right calf, vision decrease and impaired movement of the right eye. She was diagnosed with malignant atrophic papulosisis, based on characteristic symptoms and histopathologic examination. The patient was treated with dipyridamole and aspirin for 9 months, but later died of gastrointestinal hemorrhage. We reviewed currently available case reports on cranial nerve involvement in malignant atrophic papulosisis and emphasized the importance of skin biopsy in diagnosing this disease. PMID:26312664

  11. A case of malignant atrophic papulosis with cranial nerve and peripheral nerve impairment.

    PubMed

    Liu, Fang; Liu, Haibo; Zhang, Min; Yan, Wenliang; Sang, Hong

    2015-01-01

    Malignant atrophic papulosisis is a rare, multisystem obliterative vasculopathy of unknown etiology, occasionally involving the cranial nerve. We describe the first case of malignant atrophic papulosisis with cranial nerve and peripheral nerve involvement in China. A 47-year-old woman presented to our hospital with atrophic porcelain white papules over the trunk and extremities, numbness in the right calf, vision decrease and impaired movement of the right eye. She was diagnosed with malignant atrophic papulosisis, based on characteristic symptoms and histopathologic examination. The patient was treated with dipyridamole and aspirin for 9 months, but later died of gastrointestinal hemorrhage. We reviewed currently available case reports on cranial nerve involvement in malignant atrophic papulosisis and emphasized the importance of skin biopsy in diagnosing this disease. PMID:26312664

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

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

    2007-01-01

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

  14. Peripheral nerve injury activates convergent nociceptive input to dorsal horn neurons from neighboring intact nerve.

    PubMed

    Terayama, Ryuji; Yamamoto, Yuya; Kishimoto, Noriko; Maruhama, Kotaro; Mizutani, Masahide; Iida, Seiji; Sugimoto, Tomosada

    2015-04-01

    Previous studies demonstrated that peripheral nerve injury induced excessive nociceptive response of spinal cord dorsal horn neurons and such change has been proposed to reflect the development of neuropathic pain state. The aim of this study was to examine the spinal dorsal horn for convergence of nociceptive input to second-order neurons deafferented by peripheral nerve injury. Double immunofluorescence labeling for c-Fos and phosphorylated extracellular signal-regulated kinase (p-ERK) was performed to detect convergent synaptic input to spinal dorsal horn neurons after the saphenous nerve injury. c-Fos expression and the phosphorylation of ERK were induced by noxious heat stimulation of the hindpaw and by electrical stimulation of the injured or uninjured saphenous nerve, respectively. Within the central terminal field of the saphenous nerve, the number of c-Fos protein-like immunoreactive (c-Fos-IR) cell profiles was significantly decreased at 3 days and returned to the control level by 14 days after the injury. p-ERK immunoreactive (p-ERK-IR) cell profiles were distributed in the central terminal field of the saphenous nerve, and the topographic distribution pattern and number of such p-ERK-IR cell profiles remained unchanged after the nerve injury. The time course of changes in the number of double-labeled cell profiles was similar to that of c-Fos-IR cell profiles after the injury. These results indicate that convergent primary nociceptive input through neighboring intact nerves contributes to increased responsiveness of spinal dorsal horn nociceptive neurons.

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

    PubMed

    Chiono, Valeria; Tonda-Turo, Chiara

    2015-08-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-05-01

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

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

    PubMed Central

    Krasteva, Vessela TZ; Papazov, Sava P; Daskalov, Ivan K

    2003-01-01

    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. PMID:14693034

  18. Primary malignant peripheral nerve sheath tumor at unusual location

    PubMed Central

    Panigrahi, Souvagya; Mishra, Sudhansu Sekhar; Das, Srikant; Dhir, Manmath Kumar

    2013-01-01

    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. PMID:24174807

  19. Integrated electronics for peripheral nerve recording and signal processing.

    PubMed

    Limnuson, Kanokwan; Tyler, Dustin J; Mohseni, Pedram

    2009-01-01

    This paper describes the integrated circuit implementation of an electronic system for peripheral nerve recording and signal processing. Specifically, the system aims to record and condition neural activity from the phrenic nerve as a good indicator for breathing, and generate a stimulus trigger signal for a laryngeal pacemaker device to reanimate a paralyzed muscle with electrical stimulation paced with respiration. The 2.2 x 2.2-mm(2) integrated circuit is fabricated using the AMI 1.5 microm 2P/2M n-well CMOS process, and consumes 1 mW from +/-1.5 V. System architecture, circuit design, simulation results, and measurement data in benchtop experiments are presented.

  20. Peripheral facial nerve paralysis after upper third molar extraction.

    PubMed

    Cakarer, Sirmahan; Can, Taylan; Cankaya, Burak; Erdem, Mehmet Ali; Yazici, Sinem; Ayintap, Emre; Özden, Ali Veysel; Keskin, Cengizhan

    2010-11-01

    Peripheral facial nerve paralysis (PFNP) after mandibular interventions has been reported in the literature. In most cases, paralysis begins immediately after the injection of the mandibular anesthesia, and duration of facial weakness is less than 12 hours. However, there are few documented cases of PFNP after maxillary dental or surgical procedures. A variety of mechanisms have been associated to PFNP, including viral reactivation, demyelination, edema, vasospasm, and trauma. The purpose of this presentation was to report a rare case of facial paralysis that occurred after an upper third molar extraction. The cause of the PFNP and the importance of the multidisciplinary approach in the management are emphasized.

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

    PubMed Central

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

    2014-01-01

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

  2. The influence of predegenerated nerve grafts on axonal regeneration from prelesioned peripheral nerves.

    PubMed Central

    Hasan, N A; Neumann, M M; de Souky, M A; So, K F; Bedi, K S

    1996-01-01

    Recent in vitro work has indicated that predegenerated segments of peripheral nerve are more capable of supporting neurite growth from adult neurons than fresh segments of nerve, whereas previous in vivo studies which investigated whether predegenerated nerve segments used as grafts are capable of enhancing axonal regeneration produced conflicting results. We have reinvestigated this question by using predegenerated nerve grafts in combination with conditioning lesions of the host nerve to determine the optimal conditions for obtaining the maximal degree of regeneration of myelinated axons. The sciatic nerve of adult Dark Agouti rats were sectioned at midthigh level, and the distal portion was allowed to predegenerate for 0, 6 or 12 d in situ. 10-15 mm lengths of these distal nerve segments were then syngenically grafted onto the central stumps of sciatic nerves which had themselves received a conditioning lesion 0, 6, and 12 d previously, making a total of 9 different donor-host combinations. The grafts were assessed histologically 3 or 8 wk after grafting. Axonal regeneration in the 9 different donor-host combinations was determined by counting the numbers of myelinated axons in transverse sections through the grafts. All grafts examined contained regenerating myelinated axons. The rats given a 3 wk postgrafting survival period had an average of between 1400 and 5300 such axons. The rats given an 8 wk postgrafting survival period had between about 13,000 and 25,000 regenerating myelinated axons. Analysis of variance revealed significant main effects for both the Donor and Host conditions as well as Weeks (i.e. survival period after grafting). These results indicate that both a conditioning lesion of the host neurons and the degree of predegeneration of peripheral nerve segments to be used as grafts are of importance in influencing the degree of axonal regeneration. Of these 2 factors the conditioning lesion of the host appears to have the greater effect on the

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  6. The Effect of Pulsed Radiofrequency Applied to the Peripheral Nerve in Chronic Constriction Injury Rat Model

    PubMed Central

    Lee, Jun-Beom; Byun, Jeong-Hyun; Kim, Young; Lee, Ji Shin

    2015-01-01

    Objective To investigate the effect of pulsed radiofrequency (PRF) applied proximal to the injured peripheral nerve on the expression of tumor necrosis factor-α (TNF-α) in a neuropathic pain rat model. Methods Nineteen male Sprague-Dawley rats were used in the study. All rats underwent chronic constriction injury (CCI) procedure. After 7 days of CCI, withdrawal frequency of affected hind paw to mechanical stimuli and withdrawal latency of affected hind paw to heat stimulus were measured. They were randomly divided into two groups: group A, CCI group (n=9) and group B, CCI treated with PRF group (n=10). Rats of group B underwent PRF procedure on the sciatic nerve. Withdrawal frequency and withdrawal latency were measured at 12 hours, and 7 days after PRF. Immunohistochemistry and Western blot analysis were performed using a TNF-α antibody. Results Before PRF, withdrawal frequency and withdrawal latency were not different in both groups. After PRF, withdrawal frequency decreased and withdrawal latency prolonged over time in group B. There was significant interaction between time and group for each withdrawal frequency and withdrawal latency. Group B showed decreased TNF-α immunoreactivity of the spinal cord and sciatic nerve at 7 days. Conclusion PRF applied proximal to the peripheral nerve injury is potentially helpful for the reduction of neuropathic pain by neuromodulation of inflammatory markers. PMID:26605164

  7. [A case of Sotos syndrome associated with peripheral nerve involvements].

    PubMed

    Funakawa, I; Katoh, H; Hara, K; Yasuda, T; Terao, A

    1992-03-01

    A case of the Sotos syndrome associated with peripheral nerve involvements was reported. A 52-year-old male was admitted to Kawasaki Medical School Hospital because of gait disturbance, muscle atrophy, and weakness in both hands. This case was diagnosed as the Sotos syndrome based on the following symptoms and findings, acromegaloid features, hypertrophic changes in the hands and feet, a history of epileptic episodes, a low IQ, a normal growth hormone value, and no tumor lesion in the pituitary gland. Radiological examination disclosed a cauliflower-like appearance of the finger tips and thickness of the heel pads. Brain CT and MRI revealed diffuse mild brain atrophy. An electroencephalogram showed diffuse theta waves with sharp waves in the right parietal region. A needle electromyogram revealed neurogenic change in both upper and lower limbs. A nerve conduction study disclosed the carpal tunnel syndrome and cubital tunnel syndrome. These findings suggest that, as in the case of acromegaly, entrapment neuropathy and peripheral neuropathy can also be induced in the Sotos syndrome.

  8. [A case of Sotos syndrome associated with peripheral nerve involvements].

    PubMed

    Funakawa, I; Katoh, H; Hara, K; Yasuda, T; Terao, A

    1992-03-01

    A case of the Sotos syndrome associated with peripheral nerve involvements was reported. A 52-year-old male was admitted to Kawasaki Medical School Hospital because of gait disturbance, muscle atrophy, and weakness in both hands. This case was diagnosed as the Sotos syndrome based on the following symptoms and findings, acromegaloid features, hypertrophic changes in the hands and feet, a history of epileptic episodes, a low IQ, a normal growth hormone value, and no tumor lesion in the pituitary gland. Radiological examination disclosed a cauliflower-like appearance of the finger tips and thickness of the heel pads. Brain CT and MRI revealed diffuse mild brain atrophy. An electroencephalogram showed diffuse theta waves with sharp waves in the right parietal region. A needle electromyogram revealed neurogenic change in both upper and lower limbs. A nerve conduction study disclosed the carpal tunnel syndrome and cubital tunnel syndrome. These findings suggest that, as in the case of acromegaly, entrapment neuropathy and peripheral neuropathy can also be induced in the Sotos syndrome. PMID:1321017

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2014-01-01

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

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

    PubMed

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

    2014-01-01

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

  12. Glycomimetic functionalized collagen hydrogels for peripheral nerve repair

    NASA Astrophysics Data System (ADS)

    Masand, Shirley Narain

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

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

    PubMed

    Lu, Ye-Chen; Liu, Han-Qiu; Hua, Xu-Yun; Shen, Yun-Dong; Xu, Wen-Dong; Xu, Jian-Guang; Gu, Yu-Dong

    2016-04-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  16. In vivo characterization of regenerative peripheral nerve interface function

    NASA Astrophysics Data System (ADS)

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

    2016-04-01

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

  17. Glycogen function in adult central and peripheral nerves.

    PubMed

    Evans, Richard D; Brown, Angus M; Ransom, Bruce R

    2013-08-01

    We studied the roles of glycogen in axonal pathways of the central nervous system (CNS) and peripheral nervous system (PNS). By using electrophysiological recordings, in combination with biochemical glycogen assay, it was possible to determine whether glycogen was crucial to axon function under different conditions. Glycogen was present both in mouse optic nerve (MON) and in mouse sciatic nerve (MSN). Aglycemia caused loss of the compound action potential (CAP) in both pathways after a latency of 15 min (MON) and 120 min for myelinated axons (A fibers) in the MSN. With the exception of unmyelinated axons (C fibers) in the MSN, CAP decline began when usable glycogen was exhausted. Glycogen was located in astrocytes in the MON and in myelinating Schwann cells in the MSN; it was absent from the Schwann cells surrounding unmyelinated C fibers. In MON, astrocytic glycogen is metabolized to lactate and "shuttled" to axons to support metabolism. The ability of lactate to support A fiber conduction in the absence of glucose suggests a common pathway in both the CNS and the PNS. Lactate is released from MON and MSN in substantial quantities. That lactate levels fall in MSN in the presence of diaminobenzidine, which inhibits glycogen phosphorylase, strongly suggests that glycogen metabolism contributes to lactate release under resting conditions. Glycogen is a "backup" energy substrate in both the CNS and the PNS and, beyond sustaining excitability during glucose deprivation, has the capacity to subsidize the axonal energy demands during times of intense activity in the presence of glucose.

  18. Paranodal dysmyelination in peripheral nerves of Trembler mice.

    PubMed

    Rosenbluth, Jack; Bobrowski-Khoury, Natasha

    2014-04-01

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

  19. The utility of ultrasound in the assessment of traumatic peripheral nerve lesions: report of 4 cases.

    PubMed

    Zeidenberg, Joshua; Burks, S Shelby; Jose, Jean; Subhawong, Ty K; Levi, Allan D

    2015-09-01

    Ultrasound technology continues to improve with better image resolution and availability. Its use in evaluating peripheral nerve lesions is increasing. The current review focuses on the utility of ultrasound in traumatic injuries. In this report, the authors present 4 illustrative cases in which high-resolution ultrasound dramatically enhanced the anatomical understanding and surgical planning of traumatic peripheral nerve lesions. Cases include a lacerating injury of the sciatic nerve at the popliteal fossa, a femoral nerve injury from a pseudoaneurysm, an ulnar nerve neuroma after attempted repair with a conduit, and, finally, a spinal accessory nerve injury after biopsy of a supraclavicular fossa lesion. Preoperative ultrasound images and intraoperative pictures are presented with a focus on how ultrasound aided with surgical decision making. These cases are set into context with a review of the literature on peripheral nerve ultrasound and a comparison between ultrasound and MRI modalities.

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

    PubMed Central

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

    2014-01-01

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

  1. Peripheral nerve injury is accompanied by chronic transcriptome-wide changes in the mouse prefrontal cortex

    PubMed Central

    2013-01-01

    Background Peripheral nerve injury can have long-term consequences including pain-related manifestations, such as hypersensitivity to cutaneous stimuli, as well as affective and cognitive disturbances, suggesting the involvement of supraspinal mechanisms. Changes in brain structure and cortical function associated with many chronic pain conditions have been reported in the prefrontal cortex (PFC). The PFC is implicated in pain-related co-morbidities such as depression, anxiety and impaired emotional decision-making ability. We recently reported that this region is subject to significant epigenetic reprogramming following peripheral nerve injury, and normalization of pain-related structural, functional and epigenetic abnormalities in the PFC are all associated with effective pain reduction. In this study, we used the Spared Nerve Injury (SNI) model of neuropathic pain to test the hypothesis that peripheral nerve injury triggers persistent long-lasting changes in gene expression in the PFC, which alter functional gene networks, thus providing a possible explanation for chronic pain associated behaviors. Results SNI or sham surgery where performed in male CD1 mice at three months of age. Six months after injury, we performed transcriptome-wide sequencing (RNAseq), which revealed 1147 differentially regulated transcripts in the PFC in nerve-injured vs. control mice. Changes in gene expression occurred across a number of functional gene clusters encoding cardinal biological processes as revealed by Ingenuity Pathway Analysis. Significantly altered biological processes included neurological disease, skeletal muscular disorders, behavior, and psychological disorders. Several of the changes detected by RNAseq were validated by RT-QPCR and included transcripts with known roles in chronic pain and/or neuronal plasticity including the NMDA receptor (glutamate receptor, ionotropic, NMDA; grin1), neurite outgrowth (roundabout 3; robo3), gliosis (glial fibrillary acidic protein

  2. A laminin-2-derived peptide promotes early-stage peripheral nerve regeneration in a dual-component artificial nerve graft.

    PubMed

    Seo, S Y; Min, S-K; Bae, H K; Roh, D; Kang, H K; Roh, S; Lee, S; Chun, G-S; Chung, D-J; Min, B-M

    2013-10-01

    The DLTIDDSYWYRI motif (Ln2-P3) of human laminin-2 has been reported to promote PC12 cell attachment through syndecan-1; however, the in vivo effects of Ln2-P3 have not been studied. In Schwann cells differentiated from skin-derived precursors, the peptide was effective in promoting cell attachment and spreading in vitro. To examine the effects of Ln2-P3 in peripheral nerve regeneration in vivo, we developed a dual-component poly(p-dioxanone) (PPD)/poly(lactic-co-glycolic acid) (PLGA) artificial nerve graft. The novel graft was coated with scrambled peptide or Ln2-P3 and used to bridge a 10 mm defect in rat sciatic nerves. The dual-component nerve grafts provided tensile strength comparable to that of a real rat nerve trunk. The Ln2-P3-treated grafts promoted early-stage peripheral nerve regeneration by enhancing the nerve regeneration rate and significantly increased the myelinated fibre density compared with scrambled peptide-treated controls. These findings indicate that Ln2-P3, combined with tissue-engineering scaffolds, has potential biomedical applications in peripheral nerve injury repair. PMID:22438104

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

    PubMed

    del Valle, Jaume; Navarro, Xavier

    2013-01-01

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

  4. Dorsal root ganglion myeloid zinc finger protein 1 contributes to neuropathic pain after peripheral nerve trauma.

    PubMed

    Li, Zhisong; Gu, Xiyao; Sun, Linlin; Wu, Shaogen; Liang, Lingli; Cao, Jing; Lutz, Brianna Marie; Bekker, Alex; Zhang, Wei; Tao, Yuan-Xiang

    2015-04-01

    Peripheral nerve injury-induced changes in gene transcription and translation in primary sensory neurons of the dorsal root ganglion (DRG) are considered to contribute to neuropathic pain genesis. Transcription factors control gene expression. Peripheral nerve injury increases the expression of myeloid zinc finger protein 1 (MZF1), a transcription factor, and promotes its binding to the voltage-gated potassium 1.2 (Kv1.2) antisense (AS) RNA gene in the injured DRG. However, whether DRG MZF1 participates in neuropathic pain is still unknown. Here, we report that blocking the nerve injury-induced increase of DRG MZF1 through microinjection of MZF1 siRNA into the injured DRG attenuated the initiation and maintenance of mechanical, cold, and thermal pain hypersensitivities in rats with chronic constriction injury (CCI) of the sciatic nerve, without affecting locomotor functions and basal responses to acute mechanical, heat, and cold stimuli. Mimicking the nerve injury-induced increase of DRG MZF1 through microinjection of recombinant adeno-associated virus 5 expressing full-length MZF1 into the DRG produced significant mechanical, cold, and thermal pain hypersensitivities in naive rats. Mechanistically, MZF1 participated in CCI-induced reductions in Kv1.2 mRNA and protein and total Kv current and the CCI-induced increase in neuronal excitability through MZF1-triggered Kv1.2 AS RNA expression in the injured DRG neurons. MZF1 is likely an endogenous trigger of neuropathic pain and might serve as a potential target for preventing and treating this disorder. PMID:25630025

  5. Promoting peripheral nerve regeneration with biodegradable poly (DL-lactic acid) films

    PubMed Central

    Li, Ruijun; Chen, Lei; Fu, Jinling; Liu, Zhigang; Wang, Shuang; Pan, Yuehai

    2015-01-01

    Regeneration and repair of peripheral nerve injury has always been a major problem in the clinic. The conventional technique based on suturing the nerve ends to each other coupled with the implantation of nerve conduits outside is associated with postoperative adhesions and scar problems. Recently, a novel biodegradable poly (DL-lactic acid) (PDLLA) film has been introduced. This novel anti-adhesion film has a porous structure with better mechanical properties, better flexibility, and more controllable degradation as compared to traditional non-porous nerve conduits. However, little is known about the effects of such PDLLA films on regeneration and repair of peripheral nerve injury in vivo. In this study, we evaluated the effects of PDLLA films implantation after sciatic nerve transection and anastomosis on subsequent sciatic nerve regeneration in vivo, using a rat sciatic nerve injury model. Sciatic nerve transection surgery coupled with direct suturing only, suturing and wrapping with traditional nerve conduits, or suturing and wrapping with PDLLA films was performed on adult Wistar rats. The additional wrapping with PDLLA films inhibited the nerve adhesion after 12 weeks recovery from surgery. It also increased the compound muscle action potentials and tibialis and gastrocnemius muscle wet weight ratio following 8 weeks recovery from surgery. Regenerated nerve fibers were relatively straight and the aligned structure was complete in rats with implantations of PDLLA films. The results suggested that PDLLA films can improve the nutritional status in the muscles innervated by the damaged nerves and promote nerve regeneration in vivo. PMID:26339372

  6. Cellular reactions of the choroid plexus induced by peripheral nerve injury.

    PubMed

    Joukal, Marek; Klusáková, Ilona; Solár, Peter; Kuklová, Adéla; Dubový, Petr

    2016-08-15

    The choroid plexus (CP) of brain ventricles forms the blood-cerebrospinal fluid (blood-CSF) barrier that is involved in many diseases affecting the central nervous system (CNS). We used ED1 and ED2 immunostaining to investigate epiplexus cell changes in rat CP after chronic constriction injury (CCI). In contrast to naïve CP, the CP of sham-operated rats showed an increase in the number of ED1+ cells of a similar magnitude during all periods of survival up to 3 weeks, while the number of ED2+ increased only at 3 days from operation. In comparison to naïve and sham-operated animals, the number of ED1+ and ED2+ cells in the epiplexus position increased with the duration of nerve compression. We detected no or negligible cell proliferation in the CP after sham- or CCI-operation. This suggests that increased number of ED1+ and ED2+ cells in the epiplexus position of the CP is derived from peripheral monocytes passing through altered blood-CSF barrier. The changes in epiplexus cells indicate that the CP reacts to tissue injury after the surgical approach itself and that the response to peripheral nerve lesion is greater. This suggests a role for an altered blood-CSF barrier allowing for propagation of signal molecules from damaged tissue and nerve to the CNS. PMID:27291457

  7. Short-interval intracortical inhibition is modulated by high-frequency peripheral mixed nerve stimulation.

    PubMed

    Murakami, Takenobu; Sakuma, Kenji; Nomura, Takashi; Nakashima, Kenji

    2007-06-01

    Cortical excitability can be modulated by manipulation of afferent input. We investigated the influence of peripheral mixed nerve stimulation on the excitability of the motor cortex. Motor evoked potentials (MEPs), short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) in the right abductor pollicis brevis (APB), extensor carpi radialis (ECR) and first dorsal interosseous (FDI) muscles were evaluated using paired-pulse transcranial magnetic stimulation (TMS) before and after high-frequency peripheral mixed nerve stimulation (150 Hz, 30 min) over the right median nerve at the wrist. The MEP amplitude and SICI of the APB muscle decreased transiently 0-10 min after the intervention, whereas the ICF did not change. High-frequency peripheral mixed nerve stimulation reduced the excitability of the motor cortex. The decrement in the SICI, which reflects the function of GABA(A)ergic inhibitory interneurons, might compensate for the reduced motor cortical excitability after high-frequency peripheral mixed nerve stimulation.

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

    PubMed

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

    2013-02-01

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

  9. Augmented reality guidance system for peripheral nerve blocks

    NASA Astrophysics Data System (ADS)

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

    2010-02-01

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

  10. Reflections on the contributions of Harvey Cushing to the surgery of peripheral nerves.

    PubMed

    Tubbs, R Shane; Patel, Neal; Nahed, Brian Vala; Cohen-Gadol, Aaron A; Spinner, Robert J

    2011-05-01

    By the time Harvey Cushing entered medical school, nerve reconstruction techniques had been developed, but peripheral nerve surgery was still in its infancy. As an assistant surgical resident influenced by Dr. William Halsted, Cushing wrote a series of reports on the use of cocaine for nerve blocks. Following his residency training and a hiatus to further his clinical interests and intellectual curiosity, he traveled to Europe and met with a variety of surgeons, physiologists, and scientists, who likely laid the groundwork for Cushing's increased interest in peripheral nerve surgery. Returning to The Johns Hopkins Hospital in 1901, he began documenting these surgeries. Patient records preserved at Yale's Cushing Brain Tumor Registry describe Cushing's repair of ulnar and radial nerves, as well as his exploration of the brachial plexus for nerve repair or reconstruction. The authors reviewed Harvey Cushing's cases and provide 3 case illustrations not previously reported by Cushing involving neurolysis, nerve repair, and neurotization. Additionally, Cushing's experience with facial nerve neurotization is reviewed. The history, physical examination, and operative notes shed light on Cushing's diagnosis, strategy, technique, and hence, his surgery on peripheral nerve injury. These contributions complement others he made to surgery of the peripheral nervous system dealing with nerve pain, entrapment, and tumor. PMID:21214330

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

    PubMed Central

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

    2016-01-01

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

  12. Reflections on the contributions of Harvey Cushing to the surgery of peripheral nerves.

    PubMed

    Tubbs, R Shane; Patel, Neal; Nahed, Brian Vala; Cohen-Gadol, Aaron A; Spinner, Robert J

    2011-05-01

    By the time Harvey Cushing entered medical school, nerve reconstruction techniques had been developed, but peripheral nerve surgery was still in its infancy. As an assistant surgical resident influenced by Dr. William Halsted, Cushing wrote a series of reports on the use of cocaine for nerve blocks. Following his residency training and a hiatus to further his clinical interests and intellectual curiosity, he traveled to Europe and met with a variety of surgeons, physiologists, and scientists, who likely laid the groundwork for Cushing's increased interest in peripheral nerve surgery. Returning to The Johns Hopkins Hospital in 1901, he began documenting these surgeries. Patient records preserved at Yale's Cushing Brain Tumor Registry describe Cushing's repair of ulnar and radial nerves, as well as his exploration of the brachial plexus for nerve repair or reconstruction. The authors reviewed Harvey Cushing's cases and provide 3 case illustrations not previously reported by Cushing involving neurolysis, nerve repair, and neurotization. Additionally, Cushing's experience with facial nerve neurotization is reviewed. The history, physical examination, and operative notes shed light on Cushing's diagnosis, strategy, technique, and hence, his surgery on peripheral nerve injury. These contributions complement others he made to surgery of the peripheral nervous system dealing with nerve pain, entrapment, and tumor.

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

    NASA Astrophysics Data System (ADS)

    Guo-Xin, Xiong; Lei-lei, Xiong

    2016-08-01

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

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

    PubMed Central

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

    2012-01-01

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

  15. Novel TRPM8 antagonist attenuates cold hypersensitivity after peripheral nerve injury in rats.

    PubMed

    Patel, Ryan; Gonçalves, Leonor; Newman, Robert; Jiang, Feng Li; Goldby, Anne; Reeve, Jennifer; Hendrick, Alan; Teall, Martin; Hannah, Duncan; Almond, Sarah; Brice, Nicola; Dickenson, Anthony H

    2014-04-01

    Abnormal cold sensitivity is a common feature of a range of neuropathies. In the murine somatosensory system, multiple aspects of cold sensitivity are dependent on TRPM8, both short term and in response to peripheral nerve injury. The specialized nature of cold-sensitive afferents and the restricted expression of TRPM8 render it an attractive target for the treatment of cold hypersensitivity. This current study examines the effect of a novel TRPM8 antagonist (M8-An) in naive and spinal nerve-ligated rats through behavioral and in vivo electrophysiological approaches. In vitro, M8-An inhibited icilin-evoked Ca(2+) currents in HEK293 cells stably expressing human TRPM8 with an IC(50) of 10.9 nM. In vivo, systemic M8-An transiently decreased core body temperature. Deep dorsal horn recordings were made in vivo from neurons innervating the hind paw. M8-An inhibited neuronal responses to innocuous and noxious cooling of the receptive field in spinal nerve-ligated rats but not in naive rats. No effect on neuronal responses to mechanical and heat stimulation was observed. In addition, M8-An also attenuated behavioral responses to cold but not mechanical stimulation after nerve ligation without affecting the uninjured contralateral response. The data presented here support a contribution of TRPM8 to the pathophysiology of cold hypersensitivity in this model and highlight the potential of the pharmacological block of TRPM8 in alleviating the associated symptoms. PMID:24472724

  16. Local administration of icariin contributes to peripheral nerve regeneration and functional recovery.

    PubMed

    Chen, Bo; Niu, Su-Ping; Wang, Zhi-Yong; Wang, Zhen-Wei; Deng, Jiu-Xu; Zhang, Pei-Xun; Yin, Xiao-Feng; Han, Na; Kou, Yu-Hui; Jiang, Bao-Guo

    2015-01-01

    Our previous study showed that systemic administration of the traditional Chinese medicine Epimedium extract promotes peripheral nerve regeneration. Here, we sought to explore the therapeutic effects of local administration of icariin, a major component of Epimedium extract, on peripheral nerve regeneration. A poly(lactic-co-glycolic acid) biological conduit sleeve was used to bridge a 5 mm right sciatic nerve defect in rats, and physiological saline, nerve growth factor, icariin suspension, or nerve growth factor-releasing microsphere suspension was injected into the defect. Twelve weeks later, sciatic nerve conduction velocity and the number of myelinated fibers were notably greater in the rats treated with icariin suspension or nerve growth factor-releasing microspheres than those that had received nerve growth factor or physiological saline. The effects of icariin suspension were similar to those of nerve growth factor-releasing microspheres. These data suggest that icariin acts as a nerve growth factor-releasing agent, and indicate that local application of icariin after spinal injury can promote peripheral nerve regeneration. PMID:25788925

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  19. Injury of the peripheral cranial nerves during carotid endarterectomy.

    PubMed

    Theodotou, B; Mahaley, M S

    1985-01-01

    The incidence of local nerve injury among 192 consecutive carotid endarterectomies in 162 patients between 1977-1983 was determined from review of the medical records. Two facial nerve, 5 hypoglossal nerve, and 2 vagus nerve injuries were discovered for a total incidence of 4.7%. Only the 2 facial nerve injuries failed to improve over 2 years. Followup ranged from 1 to 60 months in this group of patients. Careful attention to details of tissue dissection at surgery should lower the incidence of nerve injury during carotid endarterectomy. PMID:4049454

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

    PubMed

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

    2015-01-01

    Peripheral nerve regeneration following injury occurs spontaneously, but many of the processes require metabolic energy. The mechanism of energy supply to axons has not previously been determined. In the central nervous system, monocarboxylate transporter 1 (MCT1), expressed in oligodendroglia, is critical for supplying lactate or other energy metabolites to axons. In the current study, MCT1 is shown to localize within the peripheral nervous system to perineurial cells, dorsal root ganglion neurons, and Schwann cells by MCT1 immunofluorescence in wild-type mice and tdTomato fluorescence in MCT1 BAC reporter mice. To investigate whether MCT1 is necessary for peripheral nerve regeneration, sciatic nerves of MCT1 heterozygous null 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 null mice. In fact, half of the MCT1 heterozygote null 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 null 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 null 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. PMID:25447940

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

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

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

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

    PubMed

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

    2009-01-01

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

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

    PubMed

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

    1991-02-01

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

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

    PubMed

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

    2015-02-01

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

  5. Generalised peripheral nerve dysfunction in acromegaly: a study by conventional and novel neurophysiological techniques.

    PubMed

    Jamal, G A; Kerr, D J; McLellan, A R; Weir, A I; Davies, D L

    1987-07-01

    Twenty four patients with clinical, radiological and biochemical evidence of acromegaly were investigated by a number of independent neurophysiological tests. Two-thirds of the patients showed evidence of generalised peripheral nerve dysfunction. A significant correlation was found between total exchangeable body sodium, an indicator of disease activity, and the severity of the neuropathy. The generalised peripheral nerve abnormality was found to occur independently of the associated carbohydrate intolerance human growth hormone levels and other endocrinological dysfunction in this disorder.

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

    PubMed

    Topp, Kimberly S; Boyd, Benjamin S

    2012-01-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

    Knipfer, Christian; Hadlock, Tessa

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  10. Micro-structural geometry of thin films intended for the inner lumen of nerve conduits affects nerve repair.

    PubMed

    Mobasseri, S A; Terenghi, G; Downes, S

    2013-07-01

    Damage to peripheral nerves can cause significant motor or sensory injuries. In serious cases, a nerve is sacrificed from another part of the body to repair a damaged nerve (autograft). The development of biodegradable polymer conduits may offer an alternative to autografts. This study investigated the surface topography and mechanical properties of smooth, pitted and grooved structures of ultra-thin poly (ε-caprolactone)/poly lactic acid blended, solvent-cast films. We have investigated the effect of the groove shape on cell morphology and alignment. Photolithography and dry/wet etching was used to develop patterned silicon substrates with grooves with accurate geometries (V shaped, sloped walls and square shaped). Using a neural cell line (NG108-15), in vitro experiments confirmed good cell attachment and proliferation on all the polymer scaffolds. Imaging techniques demonstrated that there was different cellular responses and morphology according to the shape of the groove. Studies showed that the geometry, particularly the angle of the slope and the space between grooves, affected cellular responses. In addition, biomechanical studies showed that the patterned films had excellent mechanical properties and were stronger than the natural nerve. The conduit tubes were made by rolling the films around a mandrel and using a thermal welding technique to join the edges. The promising biomechanical and in vitro results demonstrate that nerve cell responses are affected by the shape of longitudinal grooves, and particularly by the angle of the slope of the groove walls. PMID:23572143

  11. Immunohistochemical Analysis of the Structure of Injured Peripheral Nerve Neuroma after Electrosurgical Welding Intervention.

    PubMed

    Korsak, A V; Chaikovskii, Yu B

    2015-10-01

    Immunohistochemical analysis of changes in neuroma after surgical treatment of damaged peripheral nerve with the use of high frequency electrosurgical device for high frequency current welding of soft tissues was carried out. No adverse effects of this technology and the bipolar instrument on degeneration and regeneration of damaged nerve stem were detected.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    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.

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

    PubMed

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

    2015-05-01

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

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

    PubMed

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

    2015-05-01

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

  18. Characterization of Peripheral Nerve Sheath Tumors with 3T Proton MR Spectroscopy

    PubMed Central

    Fayad, L.M.; Wang, X.; Blakeley, J.O.; Durand, D.J.; Jacobs, M.A.; Demehri, S.; Subhawong, T.K.; Soldatos, T.; Barker, P.B.

    2014-01-01

    Background and Purpose The characterization of peripheral nerve sheath tumors is challenging. The purpose here was to investigate the diagnostic value of quantitative proton MR spectroscopy at 3T for the characterization of peripheral nerve sheath tumors as benign or malignant, compared with PET. Materials and Methods Twenty participants with 24 peripheral nerve sheath tumors underwent MR spectroscopy by use of a point-resolved sequence (TE, 135 ms). Six voxels were placed in 4 histologically proven malignant peripheral nerve sheath tumors and 22 voxels in 20 benign peripheral nerve sheath tumors (9 histologically proven, 11 with documented stability). The presence or absence of a trimethylamine signal was evaluated, the trimethylamine concentration estimated by use of phantom replacement methodology, and the trimethylamine fraction relative to Cr measured. MR spectroscopy results for benign and malignant peripheral nerve sheath tumors were compared by use of a Mann-Whitney test, and concordance or discordance with PET findings was recorded. Results In all malignant tumors and in 9 of 18 benign peripheral nerve sheath tumors, a trimethylamine peak was detected, offering the presence of trimethylamine as a sensitive (100%), but not specific (50%), marker of malignant disease. Trimethylamine concentrations (2.2 ± 2.8 vs 6.6 ± 5.8 institutional units; P < .049) and the trimethylamine fraction (27 ± 42 vs 88 ± 22%; P < .012) were lower in benign than malignant peripheral nerve sheath tumors. A trimethylamine fraction threshold of 50% resulted in 100% sensitivity (95% CI, 58.0%–100%) and 72.2% (95% CI, 59.5%–75%) specificity for distinguishing benign from malignant disease. MR spectroscopy and PET results were concordant in 12 of 16 cases, (2 false-positive results for MR spectroscopy and PET each). Conclusions Quantitative measurement of trimethylamine concentration by use of MR spectroscopy is feasible in peripheral nerve sheath tumors and shows promise as a

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

    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

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

    PubMed Central

    Grinsell, D.; Keating, C. P.

    2014-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  3. Spectral and spatial dependence of
diffuse optical signals in response to
peripheral nerve stimulation

    PubMed Central

    Chen, Debbie K.; Erb, M. Kelley; Tong, Yunjie; Yu, Yang; Sassaroli, Angelo; Bergethon, Peter R.; Fantini, Sergio

    2010-01-01

    Using non-invasive, near-infrared spectroscopy we have previously reported optical signals measured at or around peripheral nerves in response to their stimulation. Such optical signals featured amplitudes on the order of 0.1% and peaked about 100 ms after peripheral nerve stimulation in human subjects. Here, we report a study of the spatial and spectral dependence of the optical signals induced by stimulation of the human median and sural nerves, and observe that these optical signals are: (1) unlikely due to either dilation or constriction of blood vessels, (2) not associated with capillary bed hemoglobin, (3) likely due to blood vessel(s) displacement, and (4) unlikely due to fiber-skin optical coupling effects. We conclude that the most probable origin of the optical response to peripheral nerve stimulation is from displacement of blood vessels within the optically probed volume, as a result of muscle twitch in adjacent areas. PMID:21258519

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

    PubMed

    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.

  5. Histone deacetylase inhibitors relieve morphine resistance in neuropathic pain after peripheral nerve injury.

    PubMed

    Uchida, Hitoshi; Matsushita, Yosuke; Araki, Kohei; Mukae, Takehiro; Ueda, Hiroshi

    2015-08-01

    Neuropathic pain is often insensitive to morphine. Our previous study has demonstrated that neuron-restrictive silencer factor represses mu opioid receptor (MOP) gene expression in the dorsal root ganglion (DRG) via histone hypoacetylation-mediated mechanisms after peripheral nerve injury, thereby causing loss of peripheral morphine analgesia. Here, we showed that histone deacetylase (HDAC) inhibitors, such as trichostatin A and valproic acid, restored peripheral and systemic morphine analgesia in neuropathic pain. Also, these agents blocked nerve injury-induced MOP down-regulation in the DRG. These results suggest that HDAC inhibitors could serve as adjuvant analgesics to morphine for the management of neuropathic pain.

  6. Low serum magnesium levels are associated with impaired peripheral nerve function in type 2 diabetic patients

    PubMed Central

    Chu, Chen; Zhao, Weijing; Zhang, Yinan; Li, Lu; Lu, Jingyi; Jiang, Lan; Wang, Congrong; Jia, Weiping

    2016-01-01

    The aim of this study was to explore the relationship between serum magnesium and peripheral nerve function in patients with type 2 diabetes (T2DM). A total of 978 T2DM patients were included in the study. Patients were divided into tertiles according to serum magnesium concentration (low tertile: ≤0.85 mmol/L; medium tertile: 0.85 to 0.92 mmol/L; and high tertile: >0.92 mmol/L). All participants underwent nerve conduction (NC) studies. Composite z scores of conduction velocity, latency, and amplitude were constructed, respectively. The serum magnesium levels were significantly lower in patients with abnormal NC than in those with normal NC (0.87 [0.82, 0.92] vs. 0.88 [0.83, 0.93] mmol/L, P = 0.048). The composite z score of amplitude significantly increased with increasing tertiles of magnesium (−0.60 ± 0.02 vs. −0.57 ± 0.02 vs. −0.48 ± 0.03, P for trend = 0.001). After adjusting for all potential confounders, lower serum magnesium levels were still associated with lower composite z score of amplitude (β = 0.095, P = 0.014). In patients with T2DM, lower serum magnesium levels were significantly associated with lower composite z score of amplitude, indicating magnesium might affect peripheral nerve function through axonal degeneration. PMID:27601013

  7. Low serum magnesium levels are associated with impaired peripheral nerve function in type 2 diabetic patients.

    PubMed

    Chu, Chen; Zhao, Weijing; Zhang, Yinan; Li, Lu; Lu, Jingyi; Jiang, Lan; Wang, Congrong; Jia, Weiping

    2016-01-01

    The aim of this study was to explore the relationship between serum magnesium and peripheral nerve function in patients with type 2 diabetes (T2DM). A total of 978 T2DM patients were included in the study. Patients were divided into tertiles according to serum magnesium concentration (low tertile: ≤0.85 mmol/L; medium tertile: 0.85 to 0.92 mmol/L; and high tertile: >0.92 mmol/L). All participants underwent nerve conduction (NC) studies. Composite z scores of conduction velocity, latency, and amplitude were constructed, respectively. The serum magnesium levels were significantly lower in patients with abnormal NC than in those with normal NC (0.87 [0.82, 0.92] vs. 0.88 [0.83, 0.93] mmol/L, P = 0.048). The composite z score of amplitude significantly increased with increasing tertiles of magnesium (-0.60 ± 0.02 vs. -0.57 ± 0.02 vs. -0.48 ± 0.03, P for trend = 0.001). After adjusting for all potential confounders, lower serum magnesium levels were still associated with lower composite z score of amplitude (β = 0.095, P = 0.014). In patients with T2DM, lower serum magnesium levels were significantly associated with lower composite z score of amplitude, indicating magnesium might affect peripheral nerve function through axonal degeneration. PMID:27601013

  8. Laser-activated protein solder for peripheral nerve repair

    NASA Astrophysics Data System (ADS)

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

    1995-05-01

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

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

    PubMed

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

    2014-08-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2008-03-01

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

  11. Hydrogen sulfide is essential for Schwann cell responses to peripheral nerve injury.

    PubMed

    Park, Byung Sun; Kim, Hyun-Wook; Rhyu, Im Joo; Park, Chan; Yeo, Seung Geun; Huh, Youngbuhm; Jeong, Na Young; Jung, Junyang

    2015-01-01

    Hydrogen sulfide (H2 S) functions as a physiological gas transmitter in both normal and pathophysiological cellular events. H2 S is produced from substances by three enzymes: cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (MST). In human tissues, these enzymes are involved in tissue-specific biochemical pathways for H2 S production. For example, CBS and cysteine aminotransferase/MST are present in the brain, but CSE is not. Thus, we examined the expression of H2 S production-related enzymes in peripheral nerves. Here, we found that CSE and MST/cysteine aminotransferase, but not CBS, were present in normal peripheral nerves. In addition, injured sciatic nerves in vivo up-regulated CSE in Schwann cells during Wallerian degeneration (WD); however, CSE was not up-regulated in peripheral axons. Using an ex vivo sciatic nerve explant culture, we found that the inhibition of H2 S production broadly prevented the process of nerve degeneration, including myelin fragmentation, axonal degradation, Schwann cell dedifferentiation, and Schwann cell proliferation in vitro and in vivo. Thus, these results indicate that H2 S signaling is essential for Schwann cell responses to peripheral nerve injury. Hydrogen sulfide (H2 S) functions as a physiological gas transmitter in both normal and pathophysiological cellular events. H2 S is produced from cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfur transferase (MST). Here, we found that CSE and MST/CAT were present in normal peripheral nerves. Injured static nerves in vivo up-regulated CSE in Schwann cells during Wallerian degeneration, but CSE was not up-regulated in peripheral axons.

  12. Episomal Induced Pluripotent Stem Cells Promote Functional Recovery of Transected Murine Peripheral Nerve

    PubMed Central

    Kao, Huang-Kai; Cardona, Esteban; Chuang, Sheng-Hao

    2016-01-01

    Traumatic peripheral nerve neurotmesis occurs frequently and functional recovery is often slow and impaired. Induced pluripotent stem cells (iPSCs) have shown much promise in recent years due to its regenerative properties similar to that of embryonic stem cells. However, the potential of iPSCs in promoting the functional recovery of a transected peripheral nerve is largely unknown. This study is the first to investigate in vivo effects of episomal iPSCs (EiPSCs) on peripheral nerve regeneration in a murine sciatic nerve transection model. Episomal iPSCs refer to iPSCs that are generated via Oct3/4-Klf4-Sox2 plasmid reprogramming instead of the conventional viral insertion techniques. It represents a relatively safer form of iPSC production without permanent transgene integration which may raise questions regarding risks of genomic mutation. A minimal number of EiPSCs were added directly to the transected nerve. Functional recovery of the EiPSC group was significantly improved compared to the negative control group when assessed via serial five-toe spread measurement and gait analysis of ankle angles. EiPSC promotion of nerve regeneration was also evident on stereographic analysis of axon density, myelin thickness, and axonal cross-sectional surface area. Most importantly, the results observed in EiPSCs are similar to that of the embryonic stem cell group. A roughly ten-fold increase in neurotrophin-3 levels was seen in EiPSCs which could have contributed to peripheral nerve regeneration and recovery. No abnormal masses or adverse effects were noted with EiPSC administration after one year of follow-up. We have hence shown that functional recovery of the transected peripheral nerve can be improved with the use of EiPSC therapy, which holds promise for the future of nerve regeneration. PMID:27736950

  13. Laser-activated protein bands for peripheral nerve repair

    NASA Astrophysics Data System (ADS)

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

    1996-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  16. Types of neural guides and using nanotechnology for peripheral nerve reconstruction

    PubMed Central

    Biazar, Esmaeil; Khorasani, MT; Montazeri, Naser; Pourshamsian, Khalil; Daliri, Morteza; T, Mostafa Rezaei; B, Mahmoud Jabarvand; Khoshzaban, Ahad; K, Saeed Heidari; Jafarpour, Mostafa; Roviemiab, Ziba

    2010-01-01

    Peripheral nerve injuries can lead to lifetime loss of function and permanent disfigurement. Different methods, such as conventional allograft procedures and use of biologic tubes present problems when used for damaged peripheral nerve reconstruction. Designed scaffolds comprised of natural and synthetic materials are now widely used in the reconstruction of damaged tissues. Utilization of absorbable and nonabsorbable synthetic and natural polymers with unique characteristics can be an appropriate solution to repair damaged nerve tissues. Polymeric nanofibrous scaffolds with properties similar to neural structures can be more effective in the reconstruction process. Better cell adhesion and migration, more guiding of axons, and structural features, such as porosity, provide a clearer role for nanofibers in the restoration of neural tissues. In this paper, basic concepts of peripheral nerve injury, types of artificial and natural guides, and methods to improve the performance of tubes, such as orientation, nanotechnology applications for nerve reconstruction, fibers and nanofibers, electrospinning methods, and their application in peripheral nerve reconstruction are reviewed. PMID:21042546

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    Kowalska, Berta; Sudoł-Szopińska, Iwona

    2013-03-01

    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.

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

    PubMed

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

    2016-09-01

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

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

    PubMed

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

    2011-11-01

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

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

    ERIC Educational Resources Information Center

    Gordon, Tessa; Gordon, Karen

    2010-01-01

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

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

    PubMed

    Kowalska, Berta; Sudoł-Szopińska, Iwona

    2012-09-01

    Ultrasound (US) is one of the methods for imaging entrapment neuropathies, post-traumatic 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 assessment 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. Entrapment 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 tunnel 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 Ultrasonography 2012; 12 (49): 120-163 - Normal and sonographic anatomy of selected peripheral nerves. Part I: Sonohistology and general principles of examination, following the example 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 echostructure, thickness (edema and related increase

  3. Effect of Limb Lengthening on Internodal Length and Conduction Velocity of Peripheral Nerve

    PubMed Central

    Gillingwater, Thomas H.; Anderson, Heather; Cottrell, David; Sherman, Diane L.; Ribchester, Richard R.; Brophy, Peter J.

    2013-01-01

    The influences of axon diameter, myelin thickness, and internodal length on the velocity of conduction of peripheral nerve action potentials are unclear. Previous studies have demonstrated a strong dependence of conduction velocity on internodal length. However, a theoretical analysis has suggested that this relationship may be lost above a nodal separation of ∼0.6 mm. Here we measured nerve conduction velocities in a rabbit model of limb lengthening that produced compensatory increases in peripheral nerve growth. Divided tibial bones in one hindlimb were gradually lengthened at 0.7 mm per day using an external frame attached to the bone. This was associated with a significant increase (33%) of internodal length (0.95–1.3 mm) in axons of the tibial nerve that varied in proportion to the mechanical strain in the nerve of the lengthened limb. Axonal diameter, myelin thickness, and g-ratios were not significantly altered by limb lengthening. Despite the substantial increase in internodal length, no significant change was detected in conduction velocity (∼43 m/s) measured either in vivo or in isolated tibial nerves. The results demonstrate that the internode remains plastic in the adult but that increases in internodal length of myelinated adult nerve axons do not result in either deficiency or proportionate increases in their conduction velocity and support the view that the internodal lengths of nerves reach a plateau beyond which their conduction velocities are no longer sensitive to increases in internodal length. PMID:23467369

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

    PubMed Central

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

    2013-01-01

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

  5. Transitional Nerve: A New and Original Classification of a Peripheral Nerve Supported by the Nature of the Accessory Nerve (CN XI)

    PubMed Central

    Benninger, Brion; McNeil, Jonathan

    2010-01-01

    Classically, the accessory nerve is described as having a cranial and a spinal root. Textbooks are inconsistent with regard to the modality of the spinal root of the accessory nerve. Some authors report the spinal root as general somatic efferent (GSE), while others list a special visceral efferent (SVE) modality. We investigated the comparative, anatomical, embryological, and molecular literature to determine which modality of the accessory nerve was accurate and why a discrepancy exists. We traced the origin of the incongruity to the writings of early comparative anatomists who believed the accessory nerve was either branchial or somatic depending on the origin of its target musculature. Both theories were supported entirely by empirical observations of anatomical and embryological dissections. We find ample evidence including very recent molecular experiments to show the cranial and spinal root are separate entities. Furthermore, we determined the modality of the spinal root is neither GSE or SVE, but a unique peripheral nerve with a distinct modality. We propose a new classification of the accessory nerve as a transitional nerve, which demonstrates characteristics of both spinal and cranial nerves. PMID:21318044

  6. Conductive PPY/PDLLA conduit for peripheral nerve regeneration

    PubMed Central

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

    2013-01-01

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

  7. Biosynthesis and transport of gangliosides in peripheral nerve

    SciTech Connect

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

    1984-01-01

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

  8. Effects of laser therapy in peripheral nerve regeneration

    PubMed Central

    Sene, Giovana Almeida Leitão; Sousa, Fausto Fernandes de Almeida; Fazan, Valéria Sassoli; Barbieri, Cláudio Henrique

    2013-01-01

    OBJECTIVE: The influence of dose of low power lasertherapy (AsGaAl, 830 nm) on the regeneration of the fibular nerve of rats after a crush injury was evaluated by means of the functional gait analysis and histomorphometric parameters. METHODS: Controlled crush injury of the right common fibular nerve, immediately followed by increasing doses (G1: no irradiation; G2: simulated; G3: 5 J/cm2; G4: 10 J/cm2; G5: 20 J/cm2) laser irradiation directly on the lesion site for 21 consecutive days. Functional gait analysis was carried out at weekly intervals by measuring the peroneal/fibular functional index (PFI). The animals were killed on the 21st postoperative day for removal of the fibular nerve, which was prepared for the histomorphometric analysis. RESULTS: The PFI progressively increased during the observation period in all groups, without significant differences between them (p>0.05). The transverse nerve area was significantly wider in group 2 than in groups 3 and 4, while fiber density was significantly greater in group 4 than in all remaining groups. CONCLUSION: The low power AsGaAl laser irradiation did not accelerate nerve recovery with any of the doses used. Level of Evidence I, Therapeutic Studies Investigating the Results of Treatment. PMID:24453680

  9. Enhanced Immune Response in Immunodeficient Mice Improves Peripheral Nerve Regeneration Following Axotomy

    PubMed Central

    Bombeiro, André L.; Santini, Júlio C.; Thomé, Rodolfo; Ferreira, Elisângela R. L.; Nunes, Sérgio L. O.; Moreira, Bárbara M.; Bonet, Ivan J. M.; Sartori, Cesar R.; Verinaud, Liana; Oliveira, Alexandre L. R.

    2016-01-01

    Injuries to peripheral nerves cause loss of motor and sensory function, greatly affecting life quality. Successful repair of the lesioned nerve requires efficient cell debris removal, followed by axon regeneration and reinnervation of target organs. Such process is orchestrated by several cellular and molecular events in which glial and immune cells actively participate. It is known that tissue clearance is largely improved by macrophages, which activation is potentiated by cells and molecules of the acquired immune system, such as T helper lymphocytes and antibodies, respectively. In the present work, we evaluated the contribution of lymphocytes in the regenerative process of crushed sciatic nerves of immunocompetent (wild-type, WT) and T and B-deficient (RAG-KO) mice. In Knockout animals, we found increased amount of macrophages under basal conditions and during the initial phase of the regenerative process, that was evaluated at 2, 4, and 8 weeks after lesion (wal). That parallels with faster axonal regeneration evidenced by the quantification of neurofilament and a growth associated protein immunolabeling. The motor function, evaluated by the sciatic function index, was fully recovered in both mouse strains within 4 wal, either in a progressive fashion, as observed for RAG-KO mice, or presenting a subtle regression, as seen in WT mice between 2 and 3 wal. Interestingly, boosting the immune response by early adoptive transference of activated WT lymphocytes at 3 days after lesion improved motor recovery in WT and RAG-KO mice, which was not ameliorated when cells were transferred at 2 wal. When monitoring lymphocytes by in vivo imaging, in both mouse strains, cells migrated to the lesion site shortly after transference, remaining in the injured limb up to its complete motor recovery. Moreover, a first peak of hyperalgesia, determined by von-Frey test, was coincident with increased lymphocyte infiltration in the damaged paw. Overall, the present results suggest

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

    PubMed

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

    2016-09-01

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

  11. Peripheral nerve sheath tumor in a subadult golden eagle (Aquila chrysaetos).

    PubMed

    Wernick, Morena Bernadette; Dennler, Matthias; Beckmann, Kathrin; Schybli, Martina; Albini, Sarah; Hoop, Richard K; Steffen, Frank; Kircher, Patrick; Hatt, Jean-Michel

    2014-03-01

    A 5-year-old, female golden eagle (Aquila chrysaetos) was admitted with tetraplegia that progressed to a nonambulatory, spastic tetraparesis after a few days of treatment. Clinical and radiologic examinations, including radiography, computed tomography scan, and myelography, were indicative of neoplasia involving a spinal nerve root. Postmortem magnetic resonance imaging and necropsy findings confirmed the diagnosis of a peripheral nerve sheath neoplasia, not, to our knowledge, previously reported in a raptor. PMID:24881155

  12. Effects of Acute Organophosphorus Poisoning on Function of Peripheral Nerves: A Cohort Study

    PubMed Central

    Jayasinghe, Sudheera S.; Pathirana, Kithsiri D.; Buckley, Nick A.

    2012-01-01

    Background Following acute organophosphorus (OP) poisoning patients complain of numbness without objective sensory abnormalities or other features of OP induced delayed polyneuropathy. The aim of this study was to measure peripheral nerve function after acute exposure to OP. Methods A cohort study was conducted with age, gender and occupation matched controls. Motor nerve conduction velocity (MNCV), amplitude and area of compound muscle action potential (CMAP), sensory nerve conduction velocity (SNCV), F- waves and electromyography (EMG) on the deltoid and the first dorsal interosseous muscles on the dominant side were performed, following acute OP poisoning. All neurophysiological assessments except EMG were performed on the controls. Assessments were performed on the day of discharge from the hospital (the first assessment) and six weeks (the second assessment) after the exposure. The controls were assessed only once. Results There were 70 patients (50 males) and 70 controls. Fifty-three patients attended for the second assessment. In the first assessment MNCV of all the motor nerves examined, CMAP amplitude and SNCV of ulnar nerve, median and ulnar F-wave occurrence in the patients were significantly reduced compared to the controls. In the second assessment significant reduction was found in SNCV of both sensory nerves examined, MNCV of ulnar nerve, CMAP amplitude of common peroneal nerve, F-wave occurrence of median and ulnar nerves. No abnormalities were detected in the patients when compared to the standard cut-off values of nerve conduction studies except F-wave occurrence. EMG studies did not show any abnormality. Conclusion There was no strong evidence of irreversible peripheral nerve damage following acute OP poisoning, however further studies are required. PMID:23185328

  13. Impact of Aortic Cross-Clamping Time on Peripheral Nerves: Experimental Model

    PubMed Central

    Akdemir, Ovunc; Cavusoglu, Turker; Lineaweaver, William C; Ates, Utku; Zhang, Feng; Erbas, Oytun

    2014-01-01

    Purpose: The present study investigated the correlation between extend aortic cross-clamping time and peripheral nerve injury on rats. Methods: 24 male, Sprague Dawley rats were divided into 3 groups; (a) control group: abdomen was directly closed after reached aorta, and followed by 72 hours, (b) short-term ischaemia-reperfusion group: peripheral nerve ischemia was induced in rats by supraceliac aortic occlusion for 20 min followed by 72 h of reperfusion, (c) long-term ischaemia-reperfusion group: peripheral nerve ischemia was induced for 30 min followed by 72 h of reperfusion. Preoperative and postoperative, electromyography (EMG) recordings were done. End of 72 h, the sciatic nerves were harvested from each animal for histopathological and biochemical analysis. Results: The mean compound muscle action potential (CMAP) amplitude of long-term ischaemia-reperfusion group was statically significant reduced when compared to the control group (p <0.01). However, the mean distal latency value of long-term ischaemia-reperfusion group was statically significant increased (p <0.01). On the other hand, there were statically significant differences between the results of malondialdehyde, edema and ischemia fiber degeneration grades on control and long-term ischaemia-reperfusion group (p <0.001). Conclusion: This study demonstrated that the extending cross clamping time directly harms the peripheral nerve of rats. PMID:24583701

  14. Instability of spatial encoding by CA1 hippocampal place cells after peripheral nerve injury.

    PubMed

    Cardoso-Cruz, Helder; Lima, Deolinda; Galhardo, Vasco

    2011-06-01

    Several authors have shown that the hippocampus responds to painful stimulation and suggested that prolonged painful conditions could lead to abnormal hippocampal functioning. The aim of the present study was to evaluate whether the induction of persistent peripheral neuropathic pain would affect basic hippocampal processing such as the spatial encoding performed by CA1 place cells. These place cells fire preferentially in a certain spatial position in the environment, and this spatial mapping remains stable across multiple experimental sessions even when the animal is removed from the testing environment. To address the effect of prolonged pain on the stability of place cell encoding, we chronically implanted arrays of electrodes in the CA1 hippocampal region of adult rats and recorded the multichannel neuronal activity during a simple food-reinforced alternation task in a U-shaped runway. The activity of place cells was followed over a 3-week period before and after the establishment of an animal model of neuropathy, spared nerve injury. Our results show that the nerve injury increased the number of place fields encoded per cell and the mapping size of the place fields. In addition, there was an increase in in-field coherence while the amount of spatial information content that a single spike conveyed about the animal location decreased over time. Other measures of spatial tuning (in-field firing rate, firing peak and number of spikes) were unchanged between the experimental groups. These results demonstrate that the functioning of spatial place cells is altered during neuropathic pain conditions.

  15. Cellulose/soy protein composite-based nerve guidance conduits with designed microstructure for peripheral nerve regeneration

    NASA Astrophysics Data System (ADS)

    Gan, Li; Zhao, Lei; Zhao, Yanteng; Li, Ke; Tong, Zan; Yi, Li; Wang, Xiong; Li, Yinping; Tian, Weiqun; He, Xiaohua; Zhao, Min; Li, Yan; Chen, Yun

    2016-10-01

    Objective. The objective of this work was to develop nerve guidance conduits from natural polymers, cellulose and soy protein isolate (SPI), by evaluating the effects of cellulose/SPI film-based conduit (CSFC) and cellulose/SPI sponge-based conduit (CSSC) on regeneration of nerve defects in rats. Approach. CSFC and CSSC with the same chemical components were fabricated from cellulose and SPI. Effects of CSSC and CSFC on regeneration of the defective nerve were comparatively investigated in rats with a 10 mm long gap in sciatic nerve. The outcomes of peripheral nerve repair were evaluated by a combination of electrophysiological assessment, Fluoro-Gold retrograde tracing, double NF200/S100 immunofluorescence analysis, toluidine blue staining, and electron microscopy. The probable molecular mechanism was investigated using quantitative real-time PCR (qPCR) analysis. Main results. Compared with CSFC, CSSC had 2.69 times higher porosity and 5.07 times higher water absorption, thus ensuring much higher permeability. The nerve defects were successfully bridged and repaired by CSSC and CSFC. Three months after surgery, the CSSC group had a higher compound muscle action potential amplitude ratio, a higher percentage of positive NF200 and S100 staining, and a higher axon diameter and myelin sheath thickness than the CSFC group, showing the repair efficiency of CSSC was higher than that of CSFC. qPCR analysis indicated the mRNA levels of nerve growth factor, IL-10, IL-6, and growth-associated protein 43 (GAP-43) were higher in the CSSC group. This also indicated that there was better nerve repair with CSSC due to the higher porosity and permeability of CSSC providing a more favourable microenvironment for nerve regeneration than CSFC. Significance. A promising nerve guidance conduit was developed from cellulose/SPI sponge that showed potential for application in the repair of nerve defect. This work also suggests that nerve guidance conduits with better repair efficiency

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

    PubMed Central

    Erkutlu, Ibrahim; Alptekin, Mehmet; Geyik, Sirma; Geyik, Abidin Murat; Gezgin, Inan; Gök, Abdulvahap

    2015-01-01

    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 cyclosporine-A 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. PMID:25883626

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

    NASA Astrophysics Data System (ADS)

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

    2014-08-01

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

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

    PubMed Central

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

    2013-01-01

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

  19. Functional regeneration of severed peripheral nerve using an implantable electrical stimulator.

    PubMed

    Lee, Tae Hyung; Pan, Hui; Kim, In Sook; Hwang, Soon Jung; Kim, Sung June

    2010-01-01

    This paper presents functional regeneration of severed peripheral nerve using a polymer-based implantable electrical stimulator. A polyimide based conduit electrode was made by micro-fabrication and a stimulation chip was designed to generate biphasic current pulse for electrical stimulation. The stimulation chip was packaged with a battery using silicone elastomer, and integrated with the electrode. The implantable electrical stimulator was implanted in the rat sciatic nerve with 7 mm gap. The electrical stimulation was applied for periods of one, two and four weeks between the proximal and the distal nerve stumps. After four weeks of post-operations, the degree of regeneration was evaluated through walking track assessments and by measuring neural response of the regenerated nerve. Based on these results, electrical stimulation, especially for two weeks of stimulation, could accelerate functional regeneration of the severed nerve.

  20. Method for morphometric analysis of axons in experimental peripheral nerve reconstruction.

    PubMed

    Heijke, G C; Klopper, P J; Baljet, B; Van Doorn, I B; Dutrieux, R P

    2000-01-01

    A new method for morphometric analysis of axons in experimental peripheral nerve reconstruction is presented. Twelve adult female rabbits were used. In nine animals the saphenous nerve was transected and stitched epineurially. Three animals functioned as control. After 3, 6, and 12 months, the nerves were harvested, fixed in Kryofix and embedded in Histowax. Transverse sections of 6 microm were cut, immunohistochemically stained for NF 90, and counterstained by Sirius Red. Quantification of nerve fibers in cross sections was performed by using a confocal laser scanning microscope (CLSM), and the images were stored digitally. Data analyzing was performed by the Optimas program (5.2). Calculations were done with Microsoft Excel. The total number of axons, the mean axon diameter and the percentage axon area/fascicle area were evaluated statistically. This method for morphologic analysis provides automatically complete registration of axons and so different methods of experimental nerve reconstruction can be compared in a fast and reliable way.

  1. The border between the central and the peripheral nervous system in the cat cochlear nerve: a light and scanning electron microscopical study.

    PubMed

    Osen, Kirsten K; Furness, David N; Hackney, Carole M

    2011-07-01

    The transition between the central (CNS) and peripheral nervous system (PNS) in cranial and spinal nerve roots, referred to here as the CNS-PNS border, is of relevance to nerve root disorders and factors that affect peripheral-central regeneration. Here, this border is described in the cat cochlear nerve using light microscopical sections, and scanning electron microscopy of the CNS-PNS interfaces exposed by fracture of the nerve either prior to or following critical point drying. The CNS-PNS border represents an abrupt change in type of myelin, supporting elements, and vascularization. Because central myelin is formed by oligodendrocytes and peripheral myelin by Schwann cells, the myelinated fibers are as a rule equipped with a node of Ranvier at the border passage. The border is shallower and smoother in cat cochlear nerve than expected from other nerves, and the borderline nodes are largely in register. The loose endoneurial connective tissue of the PNS compartment is closed at the border by a compact glial membrane, the mantle zone, of the CNS compartment. The mantle zone is penetrated by the nerve fibers, but is otherwise composed of astrocytes and their interwoven processes like the external limiting membrane of the brain surface with which it is continuous. The distal surface of the mantle zone is covered by a fenestrated basal lamina. Only occasional vessels traverse the border. From an anatomical point of view, the border might be expected to be a weak point along the cochlear nerve and thus vulnerable to trauma. In mature animals, the CNS-PNS border presents a barrier to regrowth of regenerating nerve fibers and to invasion of the CNS by Schwann cells. An understanding of this region in the cochlear nerve is therefore relevant to head injuries that lead to hearing loss, to surgery on acoustic Schwannomas, and to the possibility of cochlear nerve regeneration.

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  6. Optimal freezing and thawing for the survival of peripheral nerves in severed rabbit limbs.

    PubMed

    Zhu, Zexing; Qiao, Lin; Zhao, Yandong; Zhang, Shuming

    2014-01-01

    This study aimed to investigate the optimal freezing and thawing procedures for the survival of peripheral nerves in severed rabbit limbs. Twenty New Zealand White rabbits were randomized into four groups: normal control, slow-freezing fast-thawing, slow-freezing slow-thawing, fast-freezing fast-thawing, with five animals in each group. The hind limbs of the rabbits were severed at 1 cm above the knee joint. The severed limbs were cryopreserved with various freezing and thawing procedures. The sciatic nerves were harvested and trypsinized into single nerve fibers for morphological evaluation. The cell viability of the nerve fibers was examined by staining with Calcein-AM and propidium iodide. The fluorescent intensity of the nerve fibers was measured with a laser scanning confocal microscope. The morphology of the nerve fibers in the slow-freezing fast-thawing group was very similar with that of the normal control group, with only mild demyelination. The slow-freezing fast-thawing group and slow-freezing slow-thawing group showed severely damaged nerve fibers. The fluorescent intensities of the nerve fibers was significantly different among the four groups, with a decreasing order of normal control, slow-freezing fast-thawing, slow-freezing slow-thawing, and fast-freezing fast-thawing (P < 0.05). Of the various cryopreservative procedures, slow-freezing fast thawing has the minimal effects on the survival of nerve fibers in severed rabbit limbs.

  7. Netrin-1 overexpression in bone marrow mesenchymal stem cells promotes functional recovery in a rat model of peripheral nerve injury

    PubMed Central

    Ke, Xianjin; Li, Qian; Xu, Li; Zhang, Ying; Li, Dongmei; Ma, Jianhua; Mao, Xiaoming

    2015-01-01

    Abstract Transplantation of bone marrow mesenchymal stem cells (BMSCs) has been developed as a new method of treating diseases of the peripheral nervous system. While netrin-1 is a critical molecule for axonal path finding and nerve growth, it may also affect vascular network formation. Here, we investigated the effect of transplanting BMSCs that produce netrin-1 in a rat model of sciatic nerve crush injury. We introduced a sciatic nerve crush injury, and then injected 1×106 BMSCs infected by a recombinant adenovirus expressing netrin-1 Ad5-Netrin-1-EGFP or culture medium into the injured part in the next day. At day 7, 14 and 28 after injection, we measured motor nerve conduction and detected mRNA expressions of netrin-1 receptors UNC5B and Deleted in Colorectal Cancer (DCC), and neurotrophic factors brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) by real-time PCR. We also detected protein expressions of BDNF and NGF by Western blotting assays and examined BMSCs that incorporated into myelin and vascellum. The results showed that BMSCs infected by Ad5-Netrin-1-EGFP significantly improved the function of the sciatic nerve, and led to increased expression of BDNF and NGF (P<0.05). Moreover, 28 days after injury, more Schwann cells were found in BMSCs infected by Ad5-Netrin-1-EGFP compared to control BMSCs. In conclusion, transplantation of BMSCs that produce netrin-1 improved the function of the sciatic nerve after injury. This method may be a new treatment of nerve injury. PMID:26445571

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

    PubMed

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

    2011-04-01

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

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

    PubMed

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

    2016-08-01

    The objective of this study is to systematically review the relationship between lower-extremity peripheral nerve function and mobility in older adults. The National Library of Medicine (PubMed) was searched on March 23, 2015 with no limits on publication dates. One reviewer selected original research studies of older adults (≥65 years) that assessed the relationship between lower-extremity peripheral nerve function and mobility-related outcomes. Participants, study design and methods of assessing peripheral nerve impairment were evaluated and results were reported and synthesized. Eight articles were identified, including 6 cross-sectional and 2 longitudinal studies. These articles investigated 6 elderly cohorts (4 from the U.S. and 2 from Italy): 3 community-dwelling (including 1 with only disabled women and 1 without mobility limitations at baseline), 1 with both community-dwelling and institutionalized residents, 1 from a range of residential locations, and 1 of patients with peripheral arterial disease. Mean ages ranged from 71-82 years. Nerve function was assessed by vibration threshold (n=2); sensory measures and clinical signs and symptoms of neuropathy (n=2); motor nerve conduction (n=1); and a combination of both sensory measures and motor nerve conduction (n=3). Each study found that worse peripheral nerve function was related to poor mobility, although relationships varied based on the nerve function measure and mobility domain assessed. Six studies found that the association between nerve function and mobility persisted despite adjustment for diabetes. Evidence suggests that peripheral nerve function impairment at various levels of severity is related to poor mobility independent of diabetes. Relationships varied depending on peripheral nerve measure, which may be particularly important when investigating specific biological mechanisms. Future research needs to identify risk factors for peripheral nerve decline beyond diabetes, especially those

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

    PubMed

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

    2016-08-01

    The objective of this study is to systematically review the relationship between lower-extremity peripheral nerve function and mobility in older adults. The National Library of Medicine (PubMed) was searched on March 23, 2015 with no limits on publication dates. One reviewer selected original research studies of older adults (≥65 years) that assessed the relationship between lower-extremity peripheral nerve function and mobility-related outcomes. Participants, study design and methods of assessing peripheral nerve impairment were evaluated and results were reported and synthesized. Eight articles were identified, including 6 cross-sectional and 2 longitudinal studies. These articles investigated 6 elderly cohorts (4 from the U.S. and 2 from Italy): 3 community-dwelling (including 1 with only disabled women and 1 without mobility limitations at baseline), 1 with both community-dwelling and institutionalized residents, 1 from a range of residential locations, and 1 of patients with peripheral arterial disease. Mean ages ranged from 71-82 years. Nerve function was assessed by vibration threshold (n=2); sensory measures and clinical signs and symptoms of neuropathy (n=2); motor nerve conduction (n=1); and a combination of both sensory measures and motor nerve conduction (n=3). Each study found that worse peripheral nerve function was related to poor mobility, although relationships varied based on the nerve function measure and mobility domain assessed. Six studies found that the association between nerve function and mobility persisted despite adjustment for diabetes. Evidence suggests that peripheral nerve function impairment at various levels of severity is related to poor mobility independent of diabetes. Relationships varied depending on peripheral nerve measure, which may be particularly important when investigating specific biological mechanisms. Future research needs to identify risk factors for peripheral nerve decline beyond diabetes, especially those

  11. Involvement of Peripheral Nerves in the Transgenic PLP-α-Syn Model of Multiple System Atrophy: Extending the Phenotype

    PubMed Central

    Kuzdas-Wood, Daniela; Irschick, Regina; Theurl, Markus; Malsch, Philipp; Mair, Norbert; Mantinger, Christine; Wanschitz, Julia; Klimaschewski, Lars; Poewe, Werner; Stefanova, Nadia; Wenning, Gregor K.

    2015-01-01

    Multiple system atrophy (MSA) is a fatal, rapidly progressive neurodegenerative disease with (oligodendro-)glial cytoplasmic α-synuclein (α-syn) inclusions (GCIs). Peripheral neuropathies have been reported in up to 40% of MSA patients, the cause remaining unclear. In a transgenic MSA mouse model featuring GCI-like inclusion pathology based on PLP-promoter driven overexpression of human α-syn in oligodendroglia motor and non-motor deficits are associated with MSA-like neurodegeneration. Since α-syn is also expressed in Schwann cells we aimed to investigate whether peripheral nerves are anatomically and functionally affected in the PLP-α-syn MSA mouse model. Results To this end, heat/cold as well as mechanical sensitivity tests were performed. Furthermore, in vivo and ex vivo nerve conduction and the G-ratios of the sciatic nerve were analyzed, and thermosensitive ion channel mRNA expression in dorsal root ganglia (DRG) was assessed. The presence of human α-syn in Schwann cells was associated with subtle behavioral impairments. The G-ratio of the sciatic nerve, the conduction velocity of myelinated and unmyelinated primary afferents and the expression of thermosensitive ion channels in the sensory neurons, however, were similar to wildtype mice. Conclusion Our results suggest that the PNS appears to be affected by Schwann cell α-syn deposits in the PLP-α-syn MSA mouse model. However, there was no consistent evidence for functional PNS perturbations resulting from such α-syn aggregates suggesting a more central cause of the observed behavioral abnormalities. Nonetheless, our results do not exclude a causal role of α-syn in the pathogenesis of MSA associated peripheral neuropathy. PMID:26496712

  12. Molecular examination of bone marrow stromal cells and chondroitinase ABC-assisted acellular nerve allograft for peripheral nerve regeneration

    PubMed Central

    Wang, Ying; Jia, Hua; Li, Wen-Yuan; Guan, Li-Xin; Deng, Lingxiao; Liu, Yan-Cui; Liu, Gui-Bo

    2016-01-01

    The present study aimed to evaluate the molecular mechanisms underlying combinatorial bone marrow stromal cell (BMSC) transplantation and chondroitinase ABC (Ch-ABC) therapy in a model of acellular nerve allograft (ANA) repair of the sciatic nerve gap in rats. Sprague Dawley rats (n=24) were used as nerve donors and Wistar rats (n=48) were randomly divided into the following groups: Group I, Dulbecco's modified Eagle's medium (DMEM) control group (ANA treated with DMEM only); Group II, Ch-ABC group (ANA treated with Ch-ABC only); Group III, BMSC group (ANA seeded with BMSCs only); Group IV, Ch-ABC + BMSCs group (Ch-ABC treated ANA then seeded with BMSCs). After 8 weeks, the expression of nerve growth factor, brain-derived neurotrophic factor and vascular endothelial growth factor in the regenerated tissues were detected by reverse transcription-quantitative polymerase chain reaction and immunohistochemistry. Axonal regeneration, motor neuron protection and functional recovery were examined by immunohistochemistry, horseradish peroxidase retrograde neural tracing and electrophysiological and tibialis anterior muscle recovery analyses. It was observed that combination therapy enhances the growth response of the donor nerve locally as well as distally, at the level of the spinal cord motoneuron and the target muscle organ. This phenomenon is likely due to the propagation of retrograde and anterograde transport of growth signals sourced from the graft site. Collectively, growth improvement on the donor nerve, target muscle and motoneuron ultimately contribute to efficacious axonal regeneration and functional recovery. Thorough investigation of molecular peripheral nerve injury combinatorial strategies are required for the optimization of efficacious therapy and full functional recovery following ANA. PMID:27698684

  13. Molecular examination of bone marrow stromal cells and chondroitinase ABC-assisted acellular nerve allograft for peripheral nerve regeneration

    PubMed Central

    Wang, Ying; Jia, Hua; Li, Wen-Yuan; Guan, Li-Xin; Deng, Lingxiao; Liu, Yan-Cui; Liu, Gui-Bo

    2016-01-01

    The present study aimed to evaluate the molecular mechanisms underlying combinatorial bone marrow stromal cell (BMSC) transplantation and chondroitinase ABC (Ch-ABC) therapy in a model of acellular nerve allograft (ANA) repair of the sciatic nerve gap in rats. Sprague Dawley rats (n=24) were used as nerve donors and Wistar rats (n=48) were randomly divided into the following groups: Group I, Dulbecco's modified Eagle's medium (DMEM) control group (ANA treated with DMEM only); Group II, Ch-ABC group (ANA treated with Ch-ABC only); Group III, BMSC group (ANA seeded with BMSCs only); Group IV, Ch-ABC + BMSCs group (Ch-ABC treated ANA then seeded with BMSCs). After 8 weeks, the expression of nerve growth factor, brain-derived neurotrophic factor and vascular endothelial growth factor in the regenerated tissues were detected by reverse transcription-quantitative polymerase chain reaction and immunohistochemistry. Axonal regeneration, motor neuron protection and functional recovery were examined by immunohistochemistry, horseradish peroxidase retrograde neural tracing and electrophysiological and tibialis anterior muscle recovery analyses. It was observed that combination therapy enhances the growth response of the donor nerve locally as well as distally, at the level of the spinal cord motoneuron and the target muscle organ. This phenomenon is likely due to the propagation of retrograde and anterograde transport of growth signals sourced from the graft site. Collectively, growth improvement on the donor nerve, target muscle and motoneuron ultimately contribute to efficacious axonal regeneration and functional recovery. Thorough investigation of molecular peripheral nerve injury combinatorial strategies are required for the optimization of efficacious therapy and full functional recovery following ANA.

  14. 3D-engineering of Cellularized Conduits for Peripheral Nerve Regeneration.

    PubMed

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

    2016-01-01

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

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

    SciTech Connect

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

    2013-12-15

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

  16. 3D-engineering of Cellularized Conduits for Peripheral Nerve Regeneration

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-04-01

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

  18. 3D-engineering of Cellularized Conduits for Peripheral Nerve Regeneration.

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  20. Peripheral Nerve Regeneration – an Appraisal of the Current Treatment Options

    PubMed Central

    CINTEZA, Dragos; PERSINARU, Iulia; MACIUCEANU ZARNESCU, Bogdan Mircea; IONESCU, Dan; LASCAR, Ioan

    2015-01-01

    During the last decades significant progress was made in the understanding of the physiopathology of the peripheral nerve regeneration. Although the evolution of therapy is not as spectacular, a series of new treatment solutions were developed. The gold standard in therapy remains the use of autografts. We present the current concepts and therapeutic options available. PMID:26225155

  1. Doxycycline-regulated GDNF expression promotes axonal regeneration and functional recovery in transected peripheral nerve.

    PubMed

    Shakhbazau, Antos; Mohanty, Chandan; Shcharbin, Dzmitry; Bryszewska, Maria; Caminade, Anne-Marie; Majoral, Jean-Pierre; Alant, Jacob; Midha, Rajiv

    2013-12-28

    Increased production of neurotrophic factors (NTFs) is one of the key responses seen following peripheral nerve injury, making them an attractive choice for pro-regenerative gene therapies. However, the downside of over-expression of certain NTFs, including glial cell line-derived neurotrophic factor (GDNF), was earlier found to be the trapping and misdirection of regenerating axons, the so-called 'candy-store' effect. We report a proof-of-principle study on the application of conditional GDNF expression system in injured peripheral nerve. We engineered Schwann cells (SCs) using dendrimers or lentiviral transduction with the vector providing doxycycline-regulated GDNF expression. Injection of GDNF-modified cells into the injured peripheral nerve followed by time-restricted administration of doxycycline demonstrated that GDNF expression in SCs can also be controlled locally in the peripheral nerves of the experimental animals. Cell-based GDNF therapy was shown to increase the extent of axonal regeneration, while controlled deactivation of GDNF effectively prevented trapping of regenerating axons in GDNF-enriched areas, and was associated with improved functional recovery.

  2. Rac1-regulated dendritic spine remodeling contributes to neuropathic pain after peripheral nerve injury.

    PubMed

    Tan, Andrew M; Chang, Yu-Wen; Zhao, Peng; Hains, Bryan C; Waxman, Stephen G

    2011-12-01

    Although prior studies have implicated maladaptive remodeling of dendritic spines on wide-dynamic range dorsal horn neurons as a contributor to pain after spinal cord injury, there have been no studies on dendritic spines after peripheral nerve injury. To determine whether dendritic spine remodeling contributes to neuronal hyperexcitability and neuropathic pain after peripheral nerve injury, we analyzed dendritic spine morphology and functional influence in lamina IV-V dorsal horn neurons after sham, chronic constriction injury (CCI) of the sciatic nerve, and CCI treatment with NSC23766, a selective inhibitor of Rac1, which has been implicated in dendritic spine development. 10 days after CCI, spine density increased with mature, mushroom-shaped spines preferentially distributed along dendritic branch regions closer to the cell body. Because spine morphology is strongly correlated with synaptic function and transmission, we recorded the response of single units to innocuous and noxious peripheral stimuli and performed behavioral assays for tactile allodynia and thermal hyperalgesia. Wide dynamic range dorsal horn neurons of CCI animals exhibited hyperexcitable responses to a range of stimuli. They also showed reduced nociceptive thresholds in the ipsilateral hind paw. 3-day treatment with NSC23766 significantly reduced post-CCI spine dimensions and densities, and attenuated injury-induced hyperexcitability. Drug treatment reduced behavioral measures of tactile allodynia, but not for thermal hyperalgesia. Together, our results demonstrate that peripheral nerve injury induces Rac1-regulated remodeling of dendritic spines on dorsal horn neurons, and suggest that this spine remodeling contributes to neuropathic pain.

  3. Peripheral Nerve Dysfunction in Middle-Aged Subjects Born with Thalidomide Embryopathy

    PubMed Central

    Nicotra, Alessia; Newman, Claus; Johnson, Martin; Eremin, Oleg; Friede, Tim; Malik, Omar; Nicholas, Richard

    2016-01-01

    Background Phocomelia is an extremely rare congenital malformation that emerged as one extreme of a range of defects resulting from 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. Methods 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. Results 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)). Conclusions 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. PMID:27100829

  4. Bioactive poly(L-lactic acid) conduits seeded with Schwann cells for peripheral nerve regeneration.

    PubMed

    Evans, Gregory R D; Brandt, Keith; Katz, Steven; Chauvin, Priscilla; Otto, Lisa; Bogle, Melissa; Wang, Bao; Meszlenyi, Rudolph K; Lu, Lichun; Mikos, Antonios G; Patrick, Charles W

    2002-02-01

    This study attempted to enhance the efficacy of peripheral nerve regeneration using our previously tested poly(L-lactic acid) (PLLA) conduits by incorporating them with allogeneic Schwann cells (SCs). The SCs were harvested, cultured to obtain confluent monolayers and two concentrations (1 x 10(4) and 1 x 10(6) SC/ml) were combined with a collagen matrix (Vitrogen) and injected into the PLLA conduits. The conduits were then implanted into a 12 mm right sciatic nerve defect in rats. Three control groups were used: isografts, PLLA conduits filled with collagen alone and empty silicone tubes. The sciatic functional index (SFI) was calculated monthly through four months. At the end of second and fourth months, the gastrocnemius muscle was harvested and weighed for comparison and the graft conduit and distal nerve were harvested for histomorphologic analysis. The mean SFI demonstrated no group differences from isograft control. By four months, there was no significant difference in gastrocnemius muscle weight between the experimental groups compared to isograft controls. At four months, the distal nerve demonstrated a statistically lower number of axons mm2 for the high and low SC density groups and collagen control. The nerve fiber density was significantly lower in all of the groups compared to isograft controls by four months. The development of a "bioactive" nerve conduit using tissue engineering to replace autogenous nerve grafts offers a potential approach to improved patient care. Although equivalent nerve regeneration to autografts was not achieved, this study provides promising results for further investigation.

  5. Equine laryngeal hemiplegia. Part II. An electron microscopic study of peripheral nerves.

    PubMed

    Cahill, J I; Goulden, B E

    1986-10-01

    The recurrent laryngeal nerves were examined by electron microscopy in five control, four subclinical and four clinical laryngeal hemiplegic horses. In addition, the peroneal nerve was examined in two horses in the latter group. The distally distributed loss of large myelinated fibres in the left recurrent laryngeal nerve seen by light microscopy was confirmed. In addition, active axonal pathology was found to be more evident than indicated by light microscopic investigations. The onion bulb formations observed indicated the repetitive nature of the damaging influence to nerve fibres. Although the pathological changes were most obvious in the distal left recurrent laryngeal nerve, alterations similar in type and distribution were present in other areas of the left and right nerves, and in the distal hindlimb nerves. The observation of fibres with inappropriately thick myelin sheaths relative to their axonal calibre, was confirmed statistically by determining the regressions of axis cylinder perimeter against the number of myelin lamellae. In conclusion, the peripheral nerve pathology of equine laryngeal hemiplegia was demonstrated to be a distally distributed loss of myelinated fibres, with considerable active axonal damage, in conjunction with axonal atrophy. These features suggest that this disease may be classified as a distal axonopathy.

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

    NASA Astrophysics Data System (ADS)

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

    2014-04-01

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

  7. Vibration-induced disruption of retrograde axoplasmic transport in peripheral nerve.

    PubMed

    Yan, Ji-Geng; Matloub, Hani S; Sanger, James R; Zhang, Lin-Ling; Riley, Danny A

    2005-10-01

    Hand-arm vibration syndrome (HAVS) results from excessive exposure to hand-transmitted vibration. Whether the peripheral nerve damage characteristic of HAVS is a direct result of vibration or is secondary to vascular insufficiency remains unclear. The purpose of this study was to explore the effect of vibration exposure on axoplasmic transport in peripheral nerves and soleus motor neurons. Sciatic nerves and motor neurons from rats following two 5-h periods of vibration exposure demonstrated disruption in retrograde transport compared to normal. After 10 days of vibration (5 h/day), axoplasmic transport failed to recover within 24-48 h in most rats. This study demonstrates that disrupted axoplasmic transport is an early consequence of short-term vibration exposure. The effects of vibration on axoplasmic transport also appear to be cumulative. This study provides a new biological way to evaluate measures to prevent early vibration injury.

  8. Signals regulating myelination in peripheral nerves and the Schwann cell response to injury

    PubMed Central

    Glenn, Thomas D.; Talbot, William S.

    2013-01-01

    In peripheral nerves, Schwann cells form myelin, which facilitates the rapid conduction of action potentials along axons in the vertebrate nervous system. Myelinating Schwann cells are derived from neural crest progenitors in a step-wise process that is regulated by extracellular signals and transcription factors. In addition to forming the myelin sheath, Schwann cells orchestrate much of the regenerative response that occurs after injury to peripheral nerves. In response to injury, myelinating Schwann cells dedifferentiate into repair cells that are essential for axonal regeneration, and then redifferentiate into myelinating Schwann cells to restore nerve function. Although this remarkable plasticity has long been recognized, many questions remain unanswered regarding the signaling pathways regulating both myelination and the Schwann cell response to injury. PMID:23896313

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

    NASA Technical Reports Server (NTRS)

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

    1998-01-01

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

  10. Development of a simple low noise amplifier for recording of sensory mass signals from peripheral nerves.

    PubMed

    Stieglitz, Thomas; Klausmann, Dominic; Krueger, Thilo B

    2009-02-01

    In the present work, a simple low noise amplifier system with relatively few components for the recording of peripheral nerve signals via electrodes, such as cuff electrodes, was developed. The amplifier system was developed with the aid of a computer-aided characterization tool, which allowed the characterization of bioelectric signal amplifiers and the identification of system parameters. Three commercially available amplifier systems were investigated with this tool regarding their technical parameters. In addition, peripheral sensory nerve mass signals were analyzed to validate the target specifications for the amplifier to be designed with regard to amplitude and frequency range. An amplifier was designed and developed according to these specifications, characterized in comparison to the commercial amplifiers, and successfully applied in pilot experiments on the sciatic nerve in a rat animal model. PMID:19182867

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

    PubMed

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

    2016-03-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

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

  13. Role of macrophages in Wallerian degeneration and axonal regeneration after peripheral nerve injury.

    PubMed

    Chen, Peiwen; Piao, Xianhua; Bonaldo, Paolo

    2015-11-01

    The peripheral nervous system (PNS) has remarkable regenerative abilities after injury. Successful PNS regeneration relies on both injured axons and non-neuronal cells, including Schwann cells and immune cells. Macrophages are the most notable immune cells that play key roles in PNS injury and repair. Upon peripheral nerve injury, a large number of macrophages are accumulated at the injury sites, where they not only contribute to Wallerian degeneration, but also are educated by the local microenvironment and polarized to an anti-inflammatory phenotype (M2), thus contributing to axonal regeneration. Significant progress has been made in understanding how macrophages are educated and polarized in the injured microenvironment as well as how they contribute to axonal regeneration. Following the discussion on the main properties of macrophages and their phenotypes, in this review, we will summarize the current knowledge regarding the mechanisms of macrophage infiltration after PNS injury. Moreover, we will discuss the recent findings elucidating how macrophages are polarized to M2 phenotype in the injured PNS microenvironment, as well as the role and underlying mechanisms of macrophages in peripheral nerve injury, Wallerian degeneration and regeneration. Furthermore, we will highlight the potential application by targeting macrophages in treating peripheral nerve injury and peripheral neuropathies.

  14. Amplitude of sensory nerve action potential in early stage diabetic peripheral neuropathy: an analysis of 500 cases.

    PubMed

    Zhang, Yunqian; Li, Jintao; Wang, Tingjuan; Wang, Jianlin

    2014-07-15

    Early diagnosis of diabetic peripheral neuropathy is important for the successful treatment of diabetes mellitus. In the present study, we recruited 500 diabetic patients from the Fourth Affiliated Hospital of Kunming Medical University in China from June 2008 to September 2013: 221 cases showed symptoms of peripheral neuropathy (symptomatic group) and 279 cases had no symptoms of peripheral impairment (asymptomatic group). One hundred healthy control subjects were also recruited. Nerve conduction studies revealed that distal motor latency was longer, sensory nerve conduction velocity was slower, and sensory nerve action potential and amplitude of compound muscle action potential were significantly lower in the median, ulnar, posterior tibial and common peroneal nerve in the diabetic groups compared with control subjects. Moreover, the alterations were more obvious in patients with symptoms of peripheral neuropathy. Of the 500 diabetic patients, neural conduction abnormalities were detected in 358 cases (71.6%), among which impairment of the common peroneal nerve was most prominent. Sensory nerve abnormality was more obvious than motor nerve abnormality in the diabetic groups. The amplitude of sensory nerve action potential was the most sensitive measure of peripheral neuropathy. Our results reveal that varying degrees of nerve conduction changes are present in the early, asymptomatic stage of diabetic peripheral neuropathy.

  15. Peripheral nerve explants grafted into the vitreous body of the eye promote the regeneration of retinal ganglion cell axons severed in the optic nerve.

    PubMed

    Berry, M; Carlile, J; Hunter, A

    1996-02-01

    We have conducted experiments in the adult rat visual system to assess the relative importance of an absence of trophic factors versus the presence of putative growth inhibitory molecules for the failure of regeneration of CNS axons after injury. The experiments comprised three groups of animals in which all optic nerves were crushed intra-orbitally: an optic nerve crush group had a sham implant-operation on the eye; the other two groups had peripheral nerve tissue introduced into the vitreous body; in an acellular peripheral nerve group, a frozen/thawed teased sciatic nerve segment was grafted, and in a cellular peripheral nerve group, a predegenerate teased segment of sciatic nerve was implanted. The rats were left for 20 days and their optic nerves and retinae prepared for immunohistochemical examination of both the reaction to injury of axons and glia in the nerve and also the viability of Schwann cells in the grafts. Anterograde axon tracing with rhodamine-B provided unequivocal qualitative evidence of regeneration in each group, and retrograde HRP tracing gave a measure of the numbers of axons growing across the lesion by counting HRP filled retinal ganglion cells in retinal whole mounts after HRP injection into the optic nerve distal to the lesion. No fibres crossed the lesion in the optic nerve crush group and dense scar tissue was formed in the wound site. GAP-43-positive and rhodamine-B filled axons in the acellular peripheral nerve and cellular peripheral nerve groups traversed the lesion and grew distally. There were greater numbers of regenerating fibres in the cellular peripheral nerve compared to the acellular peripheral nerve group. In the former, 0.6-10% of the retinal ganglion cell population regenerated axons at least 3-4 mm into the distal segment. In both the acellular peripheral nerve and cellular peripheral nerve groups, no basal lamina was deposited in the wound. Thus, although astrocyte processes were stacked around the lesion edge, a glia

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2015-05-01

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

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

    PubMed Central

    Beggs, Simon; Salter, Michael W.

    2016-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-05-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

    Bhangra, Kulraj Singh; Busuttil, Francesca

    2016-01-01

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

  3. Action of therapeutic laser and ultrasound in peripheral nerve regeneration

    PubMed Central

    Oliveira, Fabrício Borges; Pereira, Valéria Martins Dias; da Trindade, Ana Paula Nassif Tondato; Shimano, Antônio Carlos; Gabriel, Ronaldo Eugênio Calçada Dias; Borges, Ana Paula Oliveira

    2012-01-01

    Objective To assess the efficacy of early therapeutic laser and ultrasound in the regeneration process of an injury in rats. Methods We used 24 rats. Eighteen underwent surgery for sciatic nerve compression by a hemostat above the popliteal fossa. The animals were divided into three groups of six animals each. Normal control group. GI: Injured control without therapeutic intervention. GII: laser ArGaAl therapeutic intervention. GIII: therapeutic intervention of Pulsed Ultrasound. We begin therapeutic interventions 24 hours after injury, with daily applications for a period of fourteen consecutive days. Results In assessing the girth of the muscles of the right they, the following average decrease (in mm) for each GI: 0.45, GII: 0.42, GIII: 0.40 In relation to travel time, both GII and GIII presented significant difference when compared to GI. In the final evaluation of the IFC, GII excelled in the GIII. As for the healing observed, a major great improvement was observed in GII and GIII. Conclusion The results showed that nerve recovery was higher with the laser application. Level of evidence II, Therapeutic Studies - Investigation of the results of treatment. PMID:24453589

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

    PubMed Central

    Patel, Yogi A.

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-02-01

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

  7. Use of 5% lidocaine medicated plaster to treat localized neuropathic pain secondary to traumatic injury of peripheral nerves

    PubMed Central

    Correa-Illanes, Gerardo; Roa, Ricardo; Piñeros, José Luis; Calderón, Wilfredo

    2012-01-01

    Objective 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. PMID:23152700

  8. Arachidonic Acid Derivatives and Their Role in Peripheral Nerve Degeneration and Regeneration

    PubMed Central

    Camara-Lemarroy, Carlos Rodrigo; Gonzalez-Moreno, Emmanuel Irineo; Guzman-de la Garza, Francisco Javier; Fernandez-Garza, Nancy Esthela

    2012-01-01

    After peripheral nerve injury, a process of axonal degradation, debris clearance, and subsequent regeneration is initiated by complex local signaling, called Wallerian degeneration (WD). This process is in part mediated by neuroglia as well as infiltrating inflammatory cells and regulated by inflammatory mediators such as cytokines, chemokines, and the activation of transcription factors also related to the inflammatory response. Part of this neuroimmune signaling is mediated by the innate immune system, including arachidonic acid (AA) derivatives such as prostaglandins and leukotrienes. The enzymes responsible for their production, cyclooxygenases and lipooxygenases, also participate in nerve degeneration and regeneration. The interactions between signals for nerve regeneration and neuroinflammation go all the way down to the molecular level. In this paper, we discuss the role that AA derivatives might play during WD and nerve regeneration, and the therapeutic possibilities that arise. PMID:22997489

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

    SciTech Connect

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

    1988-02-01

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

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

    SciTech Connect

    Wadhwani, K.C.

    1986-01-01

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

  11. Survivin Expression and Prognostic Significance in Pediatric Malignant Peripheral Nerve Sheath Tumors (MPNST)

    PubMed Central

    Boldrin, Daniela; Merlo, Anna; Gambini, Claudio; Ferrari, Andrea; Dall'Igna, Patrizia; Coffin, Cheryl M.; Martines, Annalisa; Bonaldi, Laura; De Salvo, Gian Luca; Zanovello, Paola; Rosato, Antonio

    2013-01-01

    Malignant peripheral nerve sheath tumors (MPNST) are very aggressive malignancies comprising approximately 5–10% of all soft tissue sarcomas. In this study, we focused on pediatric MPNST arising in the first 2 decades of life, as they represent one the most frequent non-rhabdomyosarcomatous soft tissue sarcomas in children. In MPNST, several genetic alterations affect the chromosomal region 17q encompassing the BIRC5/SURVIVIN gene. As cancer-specific expression of survivin has been found to be an effective marker for cancer detection and outcome prediction, we analyzed survivin expression in 35 tumor samples derived from young patients affected by sporadic and neurofibromatosis type 1-associated MPNST. Survivin mRNA and protein expression were assessed by Real-Time PCR and immunohistochemical staining, respectively, while gene amplification was analyzed by FISH. Data were correlated with the clinicopathological characteristics of patients. Survivin mRNA was overexpressed in pediatric MPNST and associated to a copy number gain of BIRC5; furthermore, increased levels of transcripts correlated with a higher FNCLCC tumor grade (grade 1 and 2 vs. 3, p = 0.0067), and with a lower survival probability (Log-rank test, p = 0.0038). Overall, these data support the concept that survivin can be regarded as a useful prognostic marker for pediatric MPNST and a promising target for therapeutic interventions. PMID:24303016

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

    PubMed

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

    2011-09-01

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

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

    PubMed

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

    2015-02-20

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

  14. Downregulation of ClC-3 in dorsal root ganglia neurons contributes to mechanical hypersensitivity following peripheral nerve injury.

    PubMed

    Pang, Rui-Ping; Xie, Man-Xiu; Yang, Jie; Shen, Kai-Feng; Chen, Xi; Su, Ying-Xue; Yang, Chao; Tao, Jing; Liang, Si-Jia; Zhou, Jia-Guo; Zhu, He-Quan; Wei, Xu-Hong; Li, Yong-Yong; Qin, Zhi-Hai; Liu, Xian-Guo

    2016-11-01

    ClC-3 chloride channel/antiporter has been demonstrated to play an important role in synaptic transmission in central nervous system. However, its expression and function in sensory neurons is poorly understood. In present work, we found that ClC-3 is expressed at high levels in dorsal root ganglia (DRG). Co-immunofluorescent data showed that ClC-3 is mainly distributed in A- and C-type nociceptive neurons. ClC-3 expression in DRG is decreased in the spared nerve injury (SNI) model of neuropathic pain. Knockdown of local ClC-3 in DRG neurons with siRNA increased mechanical sensitivity in naïve rats, while overexpression of ClC-3 reversed the hypersensitivity to mechanical stimuli after peripheral nerve injury. In addition, genetic deletion of ClC-3 enhances mouse mechanical sensitivity but did not affect thermal and cold threshold. Restoration of ClC-3 expression in ClC-3 deficient mice reversed the mechanical sensitivity. Mechanistically, loss of ClC-3 enhanced mechanical sensitivity through increasing the excitability of DRG neurons. These data indicate that ClC-3 is an endogenous inhibitor of neuropathic pain development. Downregulation of ClC-3 by peripheral nerve injury is critical for mechanical hypersensitivity. Our findings suggest that ClC-3 is a novel therapeutic target for treating neuropathic pain. PMID:27460962

  15. Downregulation of ClC-3 in dorsal root ganglia neurons contributes to mechanical hypersensitivity following peripheral nerve injury.

    PubMed

    Pang, Rui-Ping; Xie, Man-Xiu; Yang, Jie; Shen, Kai-Feng; Chen, Xi; Su, Ying-Xue; Yang, Chao; Tao, Jing; Liang, Si-Jia; Zhou, Jia-Guo; Zhu, He-Quan; Wei, Xu-Hong; Li, Yong-Yong; Qin, Zhi-Hai; Liu, Xian-Guo

    2016-11-01

    ClC-3 chloride channel/antiporter has been demonstrated to play an important role in synaptic transmission in central nervous system. However, its expression and function in sensory neurons is poorly understood. In present work, we found that ClC-3 is expressed at high levels in dorsal root ganglia (DRG). Co-immunofluorescent data showed that ClC-3 is mainly distributed in A- and C-type nociceptive neurons. ClC-3 expression in DRG is decreased in the spared nerve injury (SNI) model of neuropathic pain. Knockdown of local ClC-3 in DRG neurons with siRNA increased mechanical sensitivity in naïve rats, while overexpression of ClC-3 reversed the hypersensitivity to mechanical stimuli after peripheral nerve injury. In addition, genetic deletion of ClC-3 enhances mouse mechanical sensitivity but did not affect thermal and cold threshold. Restoration of ClC-3 expression in ClC-3 deficient mice reversed the mechanical sensitivity. Mechanistically, loss of ClC-3 enhanced mechanical sensitivity through increasing the excitability of DRG neurons. These data indicate that ClC-3 is an endogenous inhibitor of neuropathic pain development. Downregulation of ClC-3 by peripheral nerve injury is critical for mechanical hypersensitivity. Our findings suggest that ClC-3 is a novel therapeutic target for treating neuropathic pain.

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

    SciTech Connect

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

    2015-02-20

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

  17. Effect of Tongxinluo on nerve regeneration in mice with diabetic peripheral neuropathy.

    PubMed

    Li, X; Zhang, J; Zhao, W; Yang, H; Ma, J; Qi, Y; Wu, S

    2015-01-01

    Diabetic peripheral neuropathy (DPN) is a common complication of diabetes. This study aims to investigate the effects of Tongxinluo on the nerve regeneration in diabetic peripheral neuropathy mice. Forty Specefic Pathogen Free (SPF) male KK/Upj—Ay mice were divided into diabetes group, diabetes with high dose Tongxinluo (4g/kg) (D+H), diabetes with mid dose Tongxinluo (2g/kg) (D+M), and diabetes with low dose Tongxinluo (1g/kg) (D+L) groups. Fasting blood glucose (FPG), heat pain threshold, motor nerve conduction velocity (MNCV), insulin—like growth factor—1 (IGF1), activator protein 1 (c—fos), nerve growth factor (NGF), and basic fibroblast growth factor (BFGF) were measured. Results indicated that FPG of diabetes group was significantly higher than that of control group. Heat pain threshold and MNCV were significantly lowered in diabetes group. Expression levels of IGF1, NGF and BFGF were significantly lower than that of control, whereas c—fos expression was significantly higher than that of control group. Tongxinluo treatment (D+M and D+H) significantly up—regulated heat pain threshold, MNCV, and IGF1, NGF and BFGF expression, but decreased c—fos expresson when compared to that of diabetes group. In conclusion, Tongxinluo can ameliorate diabetic peripheral neuropathy, improve MNCV, and promote nerve regeneration. The underlying mechanism needs to be further elucidated. PMID:26522065

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Cabaj, Anna; Zmyslowski, Wojciech

    2011-01-01

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

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

    PubMed

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

    2010-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    1998-07-01

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

  5. A new computerized morphometric analysis for peripheral nerve study.

    PubMed

    Tobin, Chase A; Wang, Ziyi; Zhang, Lin-Ling; Agresti, Michael; Grewal, Prabhjot; Matloub, Hani S; Yan, Ji-Geng

    2014-02-01

    The commonly used methods to quantify axon numbers and mean area include manual and semiautomated procedures. The authors introduce a new fully automated method of morphometric analysis using ImageJ and Paint.net software to improve efficiency and accuracy. A total of six rat sciatic nerves were examined for their axon numbers and mean axon area by comparing the manual method or semiautomated MetaVue method with the new ImageJ method. It was observed that the number of axons for manual counting and ImageJ were 4,630 ± 403 and 4,779 ± 352, respectively, and the difference was not statistically significant (p > 0.5, t-test). The mean axon area measured was 13.44 ± 2.62 µm2 for MetaVue and 8.87 ± 0.78 µm2 for ImageJ, respectively, and the difference was statistically significant (p < 0.01, t-test). The standard error and coefficient of variation of MetaVue were 1.07 and 0.195; and for ImageJ were 0.32 and 0.087. The authors conclude that their new approach demonstrates improved convenience, time efficiency, accuracy, and less operator error or bias.

  6. [Application of ENMG-controlled electrostimulation of peripheral nerves in the treatment of compression radiculopathies].

    PubMed

    Zakharov, Ia Iu; Shirokov, V A

    2009-01-01

    A clinical experiment on a group of 22 patients, aged 45,4+/-6,2 years, with compression radiculopathies L(5)-S(1) has proved the possibility of optimized therapeutic electrostimulation of peripheral nerves under the control of F-waves on ENMG. Parameters of electrostimulation were specified as follows: rectangular impulses of positive polarity and duration of 500-1000 ms, frequency 1-10 Hz and submaximal intensity of current. The positive effect of electrostimulation on the conductivity of nerve fibers and excitability of spinal motor neurons was found.

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

    PubMed

    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.

  8. Reproducibility of normal facial motor nerve conduction studies and their relevance in the electrophysiological assessment of peripheral facial paralysis.

    PubMed

    Di Bella, P; Logullo, F; Lagalla, G; Sirolla, C; Provinciali, L

    1997-09-01

    To determine the intra-examiner intertrial reproducibility of normal facial motor nerve conduction studies (FNCS) and their relevance in electrophysiological assessments of peripheral facial paralysis, 52 patients with acute unilateral Bell's palsy were examined on two separate occasions 1 months apart. Three electroneurographic methods were assessed. On the unaffected side of the face, FNCS are reliable when performed by a single examiner over time. Nevertheless, compound muscle action potential (CMAP) baseline-to-peak and peak-to-peak amplitude showed a rather high intertrial variability. Reproducibility of the assessed surface electrode recording procedures was similar. Regarding the affected side, in patients with mild axonotmesis of the facial nerve variations of electroneurographic parameters 1 months apart fell within the range of normal intertrial variability. In patients with severe or moderate axonotmesis, the distal latency and the M wave amplitude variations showed significant intertrial variations. Reproducibility of FNCS appears to be similar to that found in limb motor nerves. Normal variability curtails the sensitivity of FNCS in detecting mild facial nerve axonotmesis, although this technique remains useful in severe cases.

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

    NASA Astrophysics Data System (ADS)

    FitzGerald, James J.

    2016-04-01

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

  10. Normal and sonographic anatomy of selected peripheral nerves. Part I: Sonohistology and general principles of examination, following the example of the median nerve

    PubMed Central

    Sudoł-Szopińska, Iwona

    2012-01-01

    Ultrasonography is an established method for imaging peripheral nerves. It serves to supplement the physical examination, electromyography, and magnetic resonance imaging. It enables the identification of post-traumatic changes of nerves, neuropathies secondary to compression syndromes, inflammatory or neoplastic nerve lesions as well as the evaluation of postoperative complications. In certain situations, this technique is the imaging method of choice. It is increasingly used in anesthesiology for regional anesthesia. As in the case of other ultrasound imaging studies, the examination of peripheral nerves is non-invasive, well-tolerated by patients, and relatively inexpensive. This article presents the histological structure of peripheral nerves and their appearance in ultrasonography. It also presents the examination technique, following the example of the median nerve, and includes a series of diagrams and ultrasound images. The interpretation of the shape, echogenicity, thickness and vascularity of nerves is described, as well as their relation to the surrounding tissues. The “elevator technique”, which consists of locating a set nerve at a characteristic anatomic point, and following it proximally or distally, has been explained. The undisputed benefits of the ultrasound examination have been presented, including its advantages over other diagnostic methods. These advantages include the dynamic component of the ultrasound examination and the possibility of correlating the patient's symptoms with the ultrasound images. As an example, the proper anatomy and the ultrasonographic appearance of the median nerve were described. This nerve's course is presented, its divisions, and characteristic reference points, so as to facilitate its location and identification, and enable subsequent use of the aforementioned “elevator technique”. This article opens a series of publications concerning anatomy, technique of examination and pathologies of peripheral nerves

  11. Nerve compression activates selective nociceptive pathways and upregulates peripheral sodium channel expression in Schwann cells.

    PubMed

    Frieboes, Laura Rummler; Palispis, Winnie Anne; Gupta, Ranjan

    2010-06-01

    Chronic nerve compression (CNC) injuries, such as carpal tunnel syndrome, are common musculoskeletal conditions that affect patients with debilitating loss of sensory function and pain. Although early detection and treatment are important, our understanding of pain-related molecular mechanisms remains largely unclear. Here we investigate these mechanisms using an animal model for CNC injury. To confirm that CNC injury induces pain, we assessed expression of c-fos, a gene that is rapidly expressed in spinal sensory afferents in response to painful peripheral stimuli, and TNF-alpha and IL-6, two proinflammatory cytokines that are crucial to development of inflammatory-mediated pain. Results show c-fos upregulation 1-2 weeks postinjury in the absence of TNF-alpha or IL-6 expression, indicating increased neural sensitivity without an inflammatory response. This is consistent with previous studies that showed no morphologic evidence of inflammation in the CNC model. Surprisingly, we also found de novo expression of Na(V)1.8, a sodium channel linked to the development of neuropathic pain, in endoneurial Schwann cells following injury. Until now, Na(V)1.8 expression was thought to be restricted to sensory neurons. CNC injury appears to be a unique model of noninflammatory neuropathic pain. Further investigation of the underlying molecular basis could yield promising targets for early diagnosis and treatment.

  12. Chromosomal imbalances in malignant peripheral nerve sheath tumor detected by metaphase and microarray comparative genomic hybridization.

    PubMed

    Nakagawa, Yasuko; Yoshida, Aki; Numoto, Kunihiko; Kunisada, Toshiyuki; Wai, Daniel; Ohata, Norihide; Takeda, Ken; Kawai, Akira; Ozaki, Toshifumi

    2006-02-01

    Malignant peripheral nerve sheath tumors (MPNSTs) are highly malignant tumors affecting adolescents and adults. There have been a few reports on chromosomal aberrations of MPNSTs; however, the tumor-specific alteration remains unknown. We characterized the genomic alterations in 8 MPNSTs and 8 schwannomas by metaphase comparative genomic hybridization (CGH). In 5 of 8 MPNSTs, microarray CGH was added for more detailed analyses. Frequent gains were identified on 3q13-26, 5p13-14, and 12q11-23 and frequent losses were at 1p31, 10p, 11q24-qter, 16, and 17. Microarray CGH revealed frequent gains of EGFR, DAB2, MSH2, KCNK12, DDX15, CDK6, and LAMA3, and losses of CDH1, GLTSCR2, EGR1, CTSB, GATA3, and SULT2A1. These genes seem to be responsible for developing MPNSTs. The concordance rate between metaphase CGH and microarray CGH was 66%. Metaphase CGH was useful for identifying chromosomal alterations before applying microarray CGH. PMID:16391845

  13. The effect of pregabalin - codeine combination on partial sciatic nerve ligation - induced peripheral mononeuropathy in rats.

    PubMed

    Popa, G; Mititelu Tartau, L; Stoleriu, I; Lupusoru, R V; Lupusoru, C E; Ochiuz, L

    2016-06-01

    The present study investigates the effects of pregabalin (PGB) and codeine (COD) combination on neuropathic hyperalgesia in an animal model of peripheral nerve injury represented by partial sciatic nerve ligation. Hot plate and analgesimeter tests were performed to evaluate the influence of PGB, COD and their combination on thermal and mechanical hyperalgesia in the hind paw with partial sciatic nerve ligation. Reactivity was evaluated by measuring the latency to withdrawal of the operated hind paw from the noxious heat and pressure stimulation. Nociceptive thresholds were evaluated before (baseline) and in the 1(st), 3(rd), 5(th) and 7(th) day after surgical procedure. The investigation demonstrates that the treatment with PGB attenuated partial sciatic nerve ligation development of thermal and mechanical hyperalgesia in rats operated hind paw. The oral administration, during 14 consecutive days of PGB-COD combination significantly reduced the degree of both thermal and mechanical hyperalgesia in the hind paw with partial sciatic nerve ligation. These results suggest that the association of PGB with COD exerted ameliorative effect on partial sciatic nerve ligation-induced neuropathic pain in rats. PMID:27512007

  14. Neuroprotective Effect of Natural Products on Peripheral Nerve Degeneration: A Systematic Review.

    PubMed

    Araújo-Filho, Heitor G; Quintans-Júnior, Lucindo J; Barreto, André S; Almeida, Jackson R G S; Barreto, Rosana S S; Quintans, Jullyana S S

    2016-04-01

    Peripheral nerve injury (PNI) is a serious public health problem that is linked with motor, sensory and autonomic deficits. Given the fact that this type of disorder leads to a decreased quality of life in most patients and adherence of available drugs is limited and have adverse effects, we investigated the efficacy of natural products in a PNI model. The search terms plants, medicinal, nerve regeneration, nerve crush, sciatic nerve as well as MeSH terms or free-text words were used to retrieve English language articles in PubMed, Scopus, Web of Science and LILACS published until July 2015. After sciatic nerve crush, natural products have improved significantly motor performance, sensory function and electrical conductance measured over weeks. Among the pharmacological targets suggested by the action of natural products, there were citations on the activation of the antiapoptotic signaling pathway, modulation in the expression of pro-inflammatory cytokines and neurotrophic factors. The systematic review provides scientific evidence that natural products are pharmacologically effective in the treatment of PNI such as sciatic nerve crush.

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

    PubMed Central

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

    2008-01-01

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

  16. Enhancement of Peripheral Nerve Regrowth by the Purine Nucleoside Analog and Cell Cycle Inhibitor, Roscovitine

    PubMed Central

    Law, Vincent; Dong, Sophie; Rosales, Jesusa L.; Jeong, Myung-Yung; Zochodne, Douglas; Lee, Ki-Young

    2016-01-01

    Peripheral nerve regeneration is a slow process that can be associated with limited outcomes and thus a search for novel and effective therapy for peripheral nerve injury and disease is crucial. Here, we found that roscovitine, a synthetic purine nucleoside analog, enhances neurite outgrowth in neuronal-like PC12 cells. Furthermore, ex vivo analysis of pre-injured adult rat dorsal root ganglion (DRG) neurons showed that roscovitine enhances neurite regrowth in these cells. Likewise, in vivo transected sciatic nerves in rats locally perfused with roscovitine had augmented repopulation of new myelinated axons beyond the transection zone. By mass spectrometry, we found that roscovitine interacts with tubulin and actin. It interacts directly with tubulin and causes a dose-dependent induction of tubulin polymerization as well as enhances Guanosine-5′-triphosphate (GTP)-dependent tubulin polymerization. Conversely, roscovitine interacts indirectly with actin and counteracts the inhibitory effect of cyclin-dependent kinases 5 (Cdk5) on Actin-Related Proteins 2/3 (Arp2/3)-dependent actin polymerization, and thus, causes actin polymerization. Moreover, in the presence of neurotrophic factors such as nerve growth factor (NGF), roscovitine-enhanced neurite outgrowth is mediated by increased activation of the extracellular signal-regulated kinases 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK) pathways. Since microtubule and F-actin dynamics are critical for axonal regrowth, the ability of roscovitine to activate the ERK1/2 and p38 MAPK pathways and support polymerization of tubulin and actin indicate a major role for this purine nucleoside analog in the promotion of axonal regeneration. Together, our findings demonstrate a therapeutic potential for the purine nucleoside analog, roscovitine, in peripheral nerve injury. PMID:27799897

  17. Histopathological Effects of Tissue Adhesives on Experimental Peripheral Nerve Transection Model in Rats

    PubMed Central

    Çıralık, Harun

    2015-01-01

    Objective Our aim was to evaluate the histopathological effects of tissue adhesives on peripheral nerve regeneration after experimental sciatic nerve transection in rats and to search whether these tissue adhesives may possess a therapeutic potential in peripheral nerve injuries. Methods This experimental study was performed using 42 female Wistar-Albino rats distributed in 6 groups subsequent to transection of right sciatic nerves. Group I underwent external circumferential neurolysis; Group II received suture repair; Group III had local polymeric hydrogel based tissue adhesive administration; Group IV received suture repair and polymeric hydrogel based tissue adhesive application together; Group V had gelatin based tissue adhesive application and Group VI had suture repair and gelatin based tissue adhesive together. After a 6-week follow-up period, biopsies were obtained from site of neural injury and groups were compared with respect to histopathological scoring based on inflammatory, degenerative, necrotic and fibrotic changes. Results There were remarkable differences between control group and study groups with respect to inflammation (p=0.001), degeneration (p=0.002), necrosis (p=0.007), fibrosis (p<0.001) and vascularity (p=0.001). Histopathological scores were similar between study groups and the only noteworthy difference was that Group V displayed a lower score for necrosis and higher score in terms of vascularization. Conclusion Our results imply that tissue adhesives can be useful in repair of peripheral nerve injuries by decreasing the surgical trauma and shortening the duration of intervention. Results with gelatin based tissue adhesive are especially promising since more intense vascularity was observed in tissue after application. However, trials on larger series with longer durations of follow-up are essential for reaching more reliable conclusions. PMID:26819683

  18. Combining Peripheral Nerve Grafts and Chondroitinase Promotes Functional Axonal Regeneration in the Chronically Injured Spinal Cord

    PubMed Central

    Tom, Veronica J.; Sandrow-Feinberg, Harra R.; Miller, Kassi; Santi, Lauren; Connors, Theresa; Lemay, Michel A.; Houlé, John D.

    2010-01-01

    Because there currently is no treatment for spinal cord injury, most patients are living with long-standing injuries. Therefore, strategies aimed at promoting restoration of function to the chronically injured spinal cord have high therapeutic value. For successful regeneration, long-injured axons must overcome their poor intrinsic growth potential as well as the inhibitory environment of the glial scar established around the lesion site. Acutely injured axons that regenerate into growth-permissive peripheral nerve grafts (PNGs) reenter host tissue to mediate functional recovery if the distal graft– host interface is treated with chondroitinase ABC (ChABC) to cleave inhibitory chondroitin sulfate proteoglycans in the scar matrix. To determine whether a similar strategy is effective for a chronic injury, we combined grafting of a peripheral nerve into a highly relevant, chronic, cervical contusion site with ChABC treatment of the glial scar and glial cell line-derived neurotrophic factor (GDNF) stimulation of long-injured axons. We tested this combination in two grafting paradigms: (1) a peripheral nerve that was grafted to span a chronic injury site or (2) a PNG that bridged a chronic contusion site with a second, more distal injury site. Unlike GDNF–PBS treatment, GDNF–ChABC treatment facilitated axons to exit the PNG into host tissue and promoted some functional recovery. Electrical stimulation of axons in the peripheral nerve bridge induced c-Fos expression in host neurons, indicative of synaptic contact by regenerating fibers. Thus, our data demonstrate, for the first time, that administering ChABC to a distal graft interface allows for functional axonal regeneration by chronically injured neurons. PMID:19940184

  19. Sjögren-Larsson syndrome in two sibs with peripheral nerve involvement and bisalbuminaemia

    PubMed Central

    Maia, Maria

    1974-01-01

    Two sibs are described with Sjögren-Larsson syndrome. Another sib died in early life with signs which appear to be indicative of the same condition. In the two cases studied we have documented signs of peripheral nerve involvement (not previously reported in the literature) which point towards a pathological process acting on ectodermal structures to a greater extent than has previously been considered. Images PMID:4448995

  20. [Modern aspects of pathogenesis of the trauma of the spinal cord and trunks of peripheral nerves].

    PubMed

    Shul'ga, A E; Norkin, I A; Ninel', V G; Puchin'ian, D M; Zaretskov, V V; Korshunova, G A; Ostrovskiĭ, V V; Smol'kin, A A

    2014-02-01

    In pathogenesis of the traumatic disease of the spinal cord, two mechanisms of the injuries of its neuronal apparatus are defined: primary (necrosis) and secondary (apoptosis). In the work a participation of a number of internal causes in the progression of apoptosis in injury of the spinal cord and peripheral nerve trunks, the role of those remains little-studied up to date, is discussed.

  1. Combining peripheral nerve grafts and chondroitinase promotes functional axonal regeneration in the chronically injured spinal cord.

    PubMed

    Tom, Veronica J; Sandrow-Feinberg, Harra R; Miller, Kassi; Santi, Lauren; Connors, Theresa; Lemay, Michel A; Houlé, John D

    2009-11-25

    Because there currently is no treatment for spinal cord injury, most patients are living with long-standing injuries. Therefore, strategies aimed at promoting restoration of function to the chronically injured spinal cord have high therapeutic value. For successful regeneration, long-injured axons must overcome their poor intrinsic growth potential as well as the inhibitory environment of the glial scar established around the lesion site. Acutely injured axons that regenerate into growth-permissive peripheral nerve grafts (PNGs) reenter host tissue to mediate functional recovery if the distal graft-host interface is treated with chondroitinase ABC (ChABC) to cleave inhibitory chondroitin sulfate proteoglycans in the scar matrix. To determine whether a similar strategy is effective for a chronic injury, we combined grafting of a peripheral nerve into a highly relevant, chronic, cervical contusion site with ChABC treatment of the glial scar and glial cell line-derived neurotrophic factor (GDNF) stimulation of long-injured axons. We tested this combination in two grafting paradigms: (1) a peripheral nerve that was grafted to span a chronic injury site or (2) a PNG that bridged a chronic contusion site with a second, more distal injury site. Unlike GDNF-PBS treatment, GDNF-ChABC treatment facilitated axons to exit the PNG into host tissue and promoted some functional recovery. Electrical stimulation of axons in the peripheral nerve bridge induced c-Fos expression in host neurons, indicative of synaptic contact by regenerating fibers. Thus, our data demonstrate, for the first time, that administering ChABC to a distal graft interface allows for functional axonal regeneration by chronically injured neurons.

  2. Effects of ionic strength of immersion medium on the structure of peripheral nerve myelin.

    PubMed

    FINEAN, J B; MILLINGTON, P F

    1957-01-25

    A study of the effects of hypertonic solutions on the structure of peripheral nerve myelin reveals an expansion rather than a contraction of the layer spacing. This suggests the absence of "free" water between the myelin layers. Hypotonic solutions bring about a change in radial repeat period from 171 A to 250 to 270 A. These findings are of significance in relation to the structure of myelin.

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

    PubMed

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

    2016-03-01

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

  4. Morphology and Nanomechanics of Sensory Neurons Growth Cones following Peripheral Nerve Injury

    PubMed Central

    Szabo, Vivien; Végh, Attila-Gergely; Lucas, Olivier; Cloitre, Thierry; Scamps, Frédérique; Gergely, Csilla

    2013-01-01

    A prior peripheral nerve injury in vivo, promotes a rapid elongated mode of sensory neurons neurite regrowth in vitro. This in vitro model of conditioned axotomy allows analysis of the cellular and molecular mechanisms leading to an improved neurite re-growth. Our differential interference contrast microscopy and immunocytochemistry results show that conditioned axotomy, induced by sciatic nerve injury, did not increase somatic size of adult lumbar sensory neurons from mice dorsal root ganglia sensory neurons but promoted the appearance of larger neurites and growth cones. Using atomic force microscopy on live neurons, we investigated whether membrane mechanical properties of growth cones of axotomized neurons were modified following sciatic nerve injury. Our data revealed that neurons having a regenerative growth were characterized by softer growth cones, compared to control neurons. The increase of the growth cone membrane elasticity suggests a modification in the ratio and the inner framework of the main structural proteins. PMID:23418549

  5. Equine laryngeal hemiplegia. Part I. A light microscopic study of peripheral nerves.

    PubMed

    Cahill, J I; Goulden, B E

    1986-10-01

    This light microscopic investigation of 15 Thoroughbred horses provided substantial evidence for the classification of equine laryngeal hemiplegia as a distal axonopathy. Morphologic and morphometric examinations were performed on resin embedded recurrent laryngeal nerves from control, subclinical and clinical laryngeal hemiplegic animals. In the latter group of animals some distal hindlimb nerves were also examined. A distally graded loss of myelinated fibres selectively affecting those of large diameter was demonstrated in both left and right recurrent laryngeal nerves. Morphologic evidence of similar pathological changes in long hindlimb nerves was also present. An explanation for the early involvement of the cricoarytenoideus lateralis muscle in the course of laryngeal hemiplegia, was offered by the demonstration of more large diameter fibres in the branch of the recurrent laryngeal nerve innervating it, thus making it more susceptible to the disease process.

  6. Central sensory motor pathways are less affected than peripheral in chronic renal failure.

    PubMed

    Kalita, J; Misra, U K; Rajani, M; Kumar, A

    2004-01-01

    In chronic renal failure, peripheral neuropathy although is well recognised but there are only a few studies on the evaluation of central sensory pathways and none on central motor pathways. This study is aimed at the evaluation of peripheral and central sensory motor pathways. In this prospective hospital based study, 19 patients with chronic renal failure on regular hemodialysis were included. They were subjected to detailed clinical evaluation and blood urea nitrogen, serum creatinine, serum protein, haemoglobin and vasculitic profile were carried out in all the patients. Peroneal motor conduction, sural sensory conduction, tibial somatosensory evoked potential (SEP) and motor evoked potential to tibialis anterior (CMCT-TA) were carried out in all the patients and the results correlated with clinical and biochemical parameters. The mean age of the patients was 34.6 y and 1 of them was female. The duration of renal failure ranged between 0.3 and 5 years. Nerve conduction studies were abnormal in 12 patients of whom sural nerve conduction was abnormal in 10 and peroneal in 8 patients. Central conduction, motor or sensory or both were abnormal in 5 patients. Central motor conduction time to tibialis anterior was marginally prolonged in 3 patients and tibial SEPs were recordable in 2 and prolonged in 1 patient. The central and peripheral conduction did not correlate with duration of illness, serum creatinine and hemoglobin levels. It is concluded that central pathways are less frequently and less severely affected than the peripheral in chronic renal failure. PMID:15008018

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

    PubMed

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

    2011-03-15

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

  8. Mesenchymal stem cells as a source of Schwann cells: their anticipated use in peripheral nerve regeneration.

    PubMed

    Wakao, Shohei; Matsuse, Dai; Dezawa, Mari

    2014-01-01

    Schwann cells form myelin, sustain axons and provide the microenvironment for nerve fibers, thereby playing a key role in the peripheral nervous system (PNS). Schwann cells also provide support for the damaged PNS by producing factors that strongly promote axonal regrowth and contribute to remyelination, which is crucial for the recovery of neural function. These advantages are not confined to the PNS and also apply to the central nervous system. Many diseases, including peripheral nerve injury, neuropathy, multiple sclerosis and spinal cord injury, are targets for Schwann cell therapy. The collection of Schwann cells, however, causes new damage to other peripheral nerve segments. Furthermore, the doubling time of Schwann cells is not very fast, and thus adequate amounts of Schwann cells for clinical use cannot be collected within a reasonable amount of time. Mesenchymal stem cells, which are highly proliferative, are easily accessible from various types of mesenchymal tissues, such as the bone marrow, umbilical cord and fat tissue. Because these cells have the ability to cross oligolineage boundaries between mesodermal to ectodermal lineages, they are capable of differentiating into Schwann cells with step-by-step cytokine stimulation. In this review, we summarize the properties of mesenchymal stem cell-derived Schwann cells, which are comparable to authentic Schwann cells, and discuss future perspectives.

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

    PubMed Central

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

    2016-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2011-07-01

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

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

    NASA Technical Reports Server (NTRS)

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

    2011-01-01

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

  12. Mice Lacking GD3 Synthase Display Morphological Abnormalities in the Sciatic Nerve and Neuronal Disturbances during Peripheral Nerve Regeneration

    PubMed Central

    Ribeiro-Resende, Victor Túlio; Gomes, Tiago Araújo; de Lima, Silmara; Nascimento-Lima, Maiara; Bargas-Rega, Michele; Santiago, Marcelo Felipe; Reis, Ricardo Augusto de Melo; de Mello, Fernando Garcia

    2014-01-01

    The ganglioside 9-O-acetyl GD3 is overexpressed in peripheral nerves after lesioning, and its expression is correlated with axonal degeneration and regeneration in adult rodents. However, the biological roles of this ganglioside during the regenerative process are unclear. We used mice lacking GD3 synthase (Siat3a KO), an enzyme that converts GM3 to GD3, which can be further converted to 9-O-acetyl GD3. Morphological analyses of longitudinal and transverse sections of the sciatic nerve revealed significant differences in the transverse area and nerve thickness. The number of axons and the levels of myelin basic protein were significantly reduced in adult KO mice compared to wild-type (WT) mice. The G-ratio was increased in KO mice compared to WT mice based on quantification of thin transverse sections stained with toluidine blue. We found that neurite outgrowth was significantly reduced in the absence of GD3. However, addition of exogenous GD3 led to neurite growth after 3 days, similar to that in WT mice. To evaluate fiber regeneration after nerve lesioning, we compared the regenerated distance from the lesion site and found that this distance was one-fourth the length in KO mice compared to WT mice. KO mice in which GD3 was administered showed markedly improved regeneration compared to the control KO mice. In summary, we suggest that 9-O-acetyl GD3 plays biological roles in neuron-glia interactions, facilitating axonal growth and myelination induced by Schwann cells. Moreover, exogenous GD3 can be converted to 9-O-acetyl GD3 in mice lacking GD3 synthase, improving regeneration. PMID:25330147

  13. Can "dor to dor+rec neurorrhaphy" by biodegradable chitin conduit be a new method for peripheral nerve injury?

    PubMed

    Yin, Xiao Feng; Kou, Yu Hui; Wang, Yan Hua; Zhang, Peixun; Zhang, Dian Yin; Fu, Zhong Guo; Zhang, Hong Bo; Jiang, Bao Guo

    2011-04-01

    This study aims to estimate the effects of using one donor nerve to repair the injured nerve and itself simultaneously by biodegradable chitin conduit. Proximal median nerve served as donor nerve to repair the distal median and whole ulnar nerve. Four months postoperation, the number of myelinated axons and nerve conduction velocities of the distal median and ulnar nerve were (2085 ± 215 and 24.4 ± 5.9 m/s), and (1193 ± 102 and 30.7 ± 11.2 m/s). Recovery of the tetanic muscle forces of the reinvervated muscles were also observed. It suggests that Dor to Dor+Rec neurorrhaphy is a practical method for severe peripheral nerve injury.

  14. The effect of exercise on the peripheral nerve in streptozotocin (STZ)-induced diabetic rats.

    PubMed

    Jin, Heung Yong; Lee, Kyung Ae; Park, Tae Sun

    2015-04-01

    The exact effectiveness of supportive care activities, such as exercise, in diabetes patients has yet to be elucidated in the diabetic peripheral neuropathy (DPN) field. Therefore, this study was designed to investigate the effect of regular exercise on the peripheral nerves of streptozotocin-induced diabetic rats. The animals were divided as follows into six groups according to exercise combination and glucose control: Normal group, normal group with exercise (EXE), diabetic group (DM), DM group with EXE, DM+glucose control with insulin (INS), and DM+INS+EXE. Animals in the exercise groups were made to walk on a treadmill machine everyday for 30 min at a setting of 8 m/min without inclination. After 8 weeks, sensory parameters were evaluated, and after 16 weeks, biochemicals and peripheral nerves were quantified by immunohistochemistry and compared among experimental groups. The resulting data showed that fasting blood glucose levels and HbA1c levels were not influenced significantly by exercise in normal and DM groups. However, the current perception threshold and the von Frey stimulation test revealed higher thresholds in the DM+INS+EXE group than in the DM+INS group (P<0.05). Significantly lower thresholds were observed in untreated DM groups (DM or DM+EXE) compared to the normal and insulin-treated DM groups (P<0.05). Intra-epidermal nerve fiber density was reduced in a lesser degree in the DM+INS+EXE group than in the DM+INS group (9.8±0.4 vs. 9.1±0.5, P<0.05). Exercise alone was not associated with a significant protective effect on the peripheral nerve in the normal or DM groups; however, a beneficial effect from exercise was observed when hyperglycemia was controlled with insulin in the DM group. These findings suggest that exercise has a potential protective effect against DPN based on the preferential effort for glucose control, although exercise alone cannot prevent peripheral nerve damage from hyperglycemia. PMID:25253638

  15. Myelination and nodal formation of regenerated peripheral nerve fibers following transplantation of acutely prepared olfactory ensheathing cells.

    PubMed

    Dombrowski, Mary A; Sasaki, Masanori; Lankford, Karen L; Kocsis, Jeffery D; Radtke, Christine

    2006-12-13

    Transplantation of olfactory ensheathing cells (OECs) into injured spinal cord results in improved functional outcome. Mechanisms suggested to account for this functional improvement include axonal regeneration, remyelination and neuroprotection. OECs transplanted into transected peripheral nerve have been shown to modify peripheral axonal regeneration and functional outcome. However, little is known of the detailed integration of OECs at the transplantation site in peripheral nerve. To address this issue, cell populations enriched in OECs were isolated from the olfactory bulbs of adult green fluorescent protein (GFP)-expressing transgenic rats and transplanted into a sciatic nerve crush lesion which transects all axons. Five weeks to 6 months after transplantation, the nerves were studied histologically. GFP-expressing OECs survived in the lesion and distributed longitudinally across the lesion zone. The internodal regions of individual teased fibers distal to the transection site were characterized by GFP expression in the cytoplasmic and nuclear compartments of cells surrounding the axons. Immunoelectron microscopy for GFP indicated that the transplanted OECs formed peripheral type myelin. Immunostaining for sodium channel and Caspr revealed a high density of Na(v)1.6 at the newly formed nodes of Ranvier which were flanked by paranodal Caspr staining. These results indicate that transplanted OECs extensively integrate into transected peripheral nerve and form myelin on regenerated peripheral nerve fibers, and that nodes of Ranvier of these axons display proper sodium channel organization. PMID:17112480

  16. Multiwalled CNT-pHEMA composite conduit for peripheral nerve repair.

    PubMed

    Arslantunali, D; Budak, G; Hasirci, V

    2014-03-01

    A nerve conduit is designed to improve peripheral nerve regeneration by providing guidance to the nerve cells. Conductivity of such guides is reported to enhance this process. In the current study, a nerve guide was constructed from poly(2-hydroxyethyl methacrylate) (pHEMA), which was loaded with multiwalled carbon nanotubes (mwCNT) to introduce conductivity. PHEMA hydrogels were designed to have a porous structure to facilitate the transportation of the compounds needed for cell nutrition and growth and also for waste removal. We showed that when loaded with relatively high concentrations of mwCNTs (6%, w/w in hydrogels), the pHEMA guide was more conductive and more hydrophobic than pristine pHEMA hydrogel. The mechanical properties of the composites were better when they carried mwCNT. Elastic modulus of 6% mwCNT loaded pHEMA was twofold higher (0.32 ± 0.06 MPa) and similar to that of the soft tissues. Electrical conductivity was significantly improved (11.4-fold) from 7 × 10(-3) Ω(-1).cm(-1) (pHEMA) to 8.0 × 10(-2) Ω(-1).cm(-1) (6% mwCNT loaded pHEMA). On application of electrical potential, the SHSY5Y neuroblastoma cells seeded on mwCNTs carrying pHEMA maintained their viability, whereas those on pure pHEMA could not, indicating that mwCNT helped conduct electricity and make them more suitable as nerve conduits. PMID:23554154

  17. Exogenous tissue plasminogen activator enhances peripheral nerve regeneration and functional recovery after injury in mice.

    PubMed

    Zou, Tie; Ling, Changchun; Xiao, Yao; Tao, Xianmei; Ma, Duan; Chen, Zu-Lin; Strickland, Sidney; Song, Houyan

    2006-01-01

    Tissue plasminogen activator (tPA) is an essential component of the proteolytic cascade that lyses blood clots. Various studies also suggest that tPA plays important roles in the nervous system. We show that exogenous tPA or tPA/plasminogen (plg) promotes axonal regeneration, remyelination, and functional recovery after sciatic nerve injury in the mouse. Local application of tPA or tPA/plg 7 days after sciatic nerve crush significantly increased the total number of axons and myelinated axons, which is accompanied by enhanced expression of neurofilament. Treatment with tPA or tPA/plg reduced the deposition of fibrin(ogen) after nerve injury. Moreover, tPA or tPA/plg increased the number of macrophages and induced MMP-9 expression at the injury site, coincident with reduced collagen scar formation and accelerated clearance of myelin and lipid debris after treatment. Consequently, tPA or tPA/plg treatment protected muscles from atrophy after nerve injury, indicating better functional recovery. These results suggest that administration of exogenous tPA or tPA/plg promotes axonal regeneration and remyelination through removal of fibrin deposition and activation of MMP-9-positive macrophages, which may be responsible for myelin debris clearance and preventing collagen scar formation. Therefore, tPA may be useful for treatment of peripheral nerve injury.

  18. Preparation and characterization of electrical conductive PVA based materials for peripheral nerve tube-guides.

    PubMed

    Gonçalves, C; Ribeiro, J; Pereira, T; Luís, A L; Mauricio, A C; Santos, J D; Lopes, M A

    2016-08-01

    Peripheral nerve regeneration is a serious clinical problem. Presently, there are several nerve tube-guides available in the market, however with some limitations. The goal of this work was the development of a biomaterial with high electrical conductivity to produce tube-guides for nerve regeneration after neurotmesis injuries whenrver an end-to-end suture without tension is not possible. A matrix of poly(vinyl alcohol) (PVA) was used loaded with the following electrical conductive materials: COOH-functionalized multiwall carbon nanotubes (MWCNTs), poly(pyrrole) (PPy), magnesium chloride (MgCl2 ), and silver nitrate (AgNO3 ). The tube-guide production was carried out by a freezing/thawing process (physical crosslinking) with a final annealing treatment. After producing the tube-guide for nerve regeneration, the physicochemical characterization was performed. The most interesting results were achieved by loading PVA with 0.05% of PPy or COOH- functionalized CNTs. These tubes combined the electrical conductivity of carbon nanotubes (CNTs) and PPy with the biocompatibility of PVA matrix, with potential clinical application for nerve regeneration. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1981-1987, 2016. PMID:27027727

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

    NASA Astrophysics Data System (ADS)

    Silva, Susana F.; Gouveia, Sofia; Gomes, Leonor; Negrão, Luís; João Quadrado, Maria; Domingues, José Paulo; Morgado, António Miguel

    2015-05-01

    Diabetic peripheral neuropathy (DPN) is one common complication of diabetes. Early diagnosis of DPN often fails due to the non-availability of a simple, reliable, non-invasive method. Several published studies show that corneal confocal microscopy (CCM) can identify small nerve fibre damage and quantify the severity of DPN, using nerve morphometric parameters. Here, we used image texture features, extracted from corneal sub-basal nerve plexus images, obtained in vivo by CCM, to identify DPN patients, using classification techniques. A SVM classifier using image texture features was used to identify (DPN vs. No DPN) DPN patients. The accuracies were 80.6%, when excluding diabetic patients without neuropathy, and 73.5%, when including diabetic patients without diabetic neuropathy jointly with healthy controls. The results suggest that texture analysis might be used as a complementing technique for DPN diagnosis, without requiring nerve segmentation in CCM images. The results also suggest that this technique has enough sensitivity to detect early disorders in the corneal nerves of diabetic patients.

  20. Omega-6 and omega-3 fatty acids predict accelerated decline of peripheral nerve function in older persons.

    PubMed

    Lauretani, F; Bandinelli, S; Bartali, B; Benedetta, B; Cherubini, A; Iorio, A D; Blè, A; Giacomini, V; Corsi, A M; Guralnik, J M; Ferrucci, L

    2007-07-01

    Pre-clinical studies suggest that both omega-6 and omega-3 fatty acids have beneficial effects on peripheral nerve function. Rats feed a diet rich in polyunsaturated fatty acids (PUFAs) showed modification of phospholipid fatty acid composition in nerve membranes and improvement of sciatic nerve conduction velocity (NCV). We tested the hypothesis that baseline plasma omega-6 and omega-3 fatty acids levels predict accelerated decline of peripheral nerve function. Changes between baseline and the 3-year follow-up in peripheral nerve function was assessed by standard surface ENG of the right peroneal nerve in 384 male and 443 female participants of the InCHIANTI study (age range: 24-97 years). Plasma concentrations of selected fatty acids assessed at baseline by gas chromatography. Independent of confounders, plasma omega-6 fatty acids and linoleic acid were significantly correlated with peroneal NCV at enrollment. Lower plasma PUFA, omega-6 fatty acids, linoleic acid, ratio omega-6/omega-3, arachidonic acid and docosahexanoic acid levels were significantly predicted a steeper decline in nerve function parameters over the 3-year follow-up. Low plasma omega-6 and omega-3 fatty acids levels were associated with accelerated decline of peripheral nerve function with aging.

  1. Neuroinflammation in the peripheral nerve: Cause, modulator, or bystander in peripheral neuropathies?

    PubMed Central

    2015-01-01

    The role of innate and adaptive inflammation as a primary driver or modifier of neuropathy in premorbidly normal nerves, and as a critical player in amplifying neuropathies of other known causes (e.g., genetic, metabolic) is incompletely understood and under‐researched, despite unmet clinical need. Also, cellular and humoral components of the adaptive and innate immune system are substantial disease modifying agents in the context of neuropathies and, at least in some neuropathies, there is an identified tight interrelationship between both compartments of the immune system. Additionally, the quadruple relationship between Schwann cell, axon, macrophage, and endoneurial fibroblast, with their diverse membrane bound and soluble signalling systems, forms a distinct focus for investigation in nerve diseases with inflammation secondary to Schwann cell mutations and possibly others. Identification of key immunological effector pathways that amplify neuropathic features and associated clinical symptomatology including pain should lead to realistic and timely possibilities for translatable therapeutic interventions using existing immunomodulators, alongside the development of novel therapeutic targets. GLIA 2016;64:475–486 PMID:26250643

  2. Permanent implantation of peripheral nerve stimulator for combat injury-related ilioinguinal neuralgia.

    PubMed

    Banh, Diem Phuc T; Moujan, Pablo M; Haque, Quazi; Han, Tae-Hyung

    2013-01-01

    A peripheral nerve stimulator (PNS) can be an alternative for long-term pain relief refractory to conventional therapeutic modalities. We present a case of chronic incapacitating ilioinguinal neuralgia, which was successfully managed with permanent implantation of a peripheral nerve stimulator. A 26-year-old active duty African American man was referred to the University Pain Clinic with left ilioinguinal neuralgia due to shrapnel injury during his military service 6 years prior to his visit. Most of the shrapnel were surgically removed, but the patient subsequently developed left lower abdominal pain. Multiple surgeries, including inguinal herniorrhaphy, varicocelectomy, and orchiectomy, failed to provide satisfactory relief of his neuralgia. Other therapies tried resulting in limited outcomes were multiple ilioinguinal nerve blocks and cryoanalgesia. A trial of PNS was successful and the implantation of permanent leads was carried out. At his 3-month visit, the patient reported to have minimal pain, was tapered off oral analgesics, was able to return to work, and had resumed his normal daily activities. Recent technological advances in programming software and surgical techniques have led to renewed interest in PNS for the treatment of chronic refractory peripheral nerve injury. Despite our limited understanding of its exact mechanism of action, it can be considered as a therapeutic potential for a few carefully selected, intractable cases. Its minimally invasive and reversible features make PNS a favorable option for these patients. The stringent and rigorous screening procedures for suitable candidacy, documentation of previously failed treatments, psychiatric evaluation, and 3-5 days of preplacement trial, improve the success rate. PMID:24284860

  3. Small-molecule trkB agonists promote axon regeneration in cut peripheral nerves

    PubMed Central

    English, Arthur W.; Liu, Kevin; Nicolini, Jennifer M.; Mulligan, Amanda M.; Ye, Keqiang

    2013-01-01

    Treatments with two-small molecule tropomyosin receptor kinase B (trkB) ligands, 7,8 dihydroxyflavone (7,8 DHF) and deoxygedunin, were evaluated for their ability to promote the regeneration of cut axons in injured peripheral nerves in mice in which sensory and motor axons are marked by YFP. Peripheral nerves were cut and repaired with grafts from strain-matched, nonfluorescent donors and secured in place with fibrin glue. Lengths of profiles of regenerating YFP+ axons were measured 2 wk later from confocal images. Axon regeneration was enhanced when the fibrin glue contained dilutions of 500-nM solution of either small-molecule trkB agonist. In mice in which the neurotrophin receptor trkB is knocked out selectively in neurons, axon regeneration is very weak, and topical treatment with 7,8 DHF had no effect on axon regeneration. Similar treatments with deoxygedunin had only a modest effect. In conditional BDNF knockout mice, topical treatments with either 7,8 DHF or deoxygedunin resulted in a reversal of the poor regeneration found in controls and produced significant enhancement of regeneration. In WT mice treated with 2 wk of daily i.p. injections of either 7,8 DHF or deoxygedunin (5 mg/kg), regenerating axon profiles were nearly twice as long as in controls. Restoration of direct muscle responses evoked by sciatic nerve stimulation to pretransection levels over an 8-wk survival period was found only in the treated mice. Treatments with either small-molecule trkB agonist enhanced axon regeneration and muscle reinnervation after peripheral nerve injuries. PMID:24043773

  4. Small-molecule trkB agonists promote axon regeneration in cut peripheral nerves.

    PubMed

    English, Arthur W; Liu, Kevin; Nicolini, Jennifer M; Mulligan, Amanda M; Ye, Keqiang

    2013-10-01

    Treatments with two-small molecule tropomyosin receptor kinase B (trkB) ligands, 7,8 dihydroxyflavone (7,8 DHF) and deoxygedunin, were evaluated for their ability to promote the regeneration of cut axons in injured peripheral nerves in mice in which sensory and motor axons are marked by YFP. Peripheral nerves were cut and repaired with grafts from strain-matched, nonfluorescent donors and secured in place with fibrin glue. Lengths of profiles of regenerating YFP(+) axons were measured 2 wk later from confocal images. Axon regeneration was enhanced when the fibrin glue contained dilutions of 500-nM solution of either small-molecule trkB agonist. In mice in which the neurotrophin receptor trkB is knocked out selectively in neurons, axon regeneration is very weak, and topical treatment with 7,8 DHF had no effect on axon regeneration. Similar treatments with deoxygedunin had only a modest effect. In conditional BDNF knockout mice, topical treatments with either 7,8 DHF or deoxygedunin resulted in a reversal of the poor regeneration found in controls and produced significant enhancement of regeneration. In WT mice treated with 2 wk of daily i.p. injections of either 7,8 DHF or deoxygedunin (5 mg/kg), regenerating axon profiles were nearly twice as long as in controls. Restoration of direct muscle responses evoked by sciatic nerve stimulation to pretransection levels over an 8-wk survival period was found only in the treated mice. Treatments with either small-molecule trkB agonist enhanced axon regeneration and muscle reinnervation after peripheral nerve injuries. PMID:24043773

  5. Alignment and composition of laminin–polycaprolactone nanofiber blends enhance peripheral nerve regeneration

    PubMed Central

    Neal, Rebekah A.; Tholpady, Sunil S.; Foley, Patricia L.; Swami, Nathan; Ogle, Roy C.; Botchwey, Edward A.

    2012-01-01

    Peripheral nerve transection occurs commonly in traumatic injury, causing deficits distal to the injury site. Conduits for repair currently on the market are hollow tubes; however, they often fail due to slow regeneration over long gaps. To facilitate increased regeneration speed and functional recovery, the ideal conduit should provide biochemically relevant signals and physical guidance cues, thus playing an active role in regeneration. To that end, laminin and laminin–polycaprolactone (PCL) blend nanofibers were fabricated to mimic peripheral nerve basement membrane. In vitro assays established 10% (wt) laminin content is sufficient to retain neurite-promoting effects of laminin. In addition, modified collector plate design to introduce an insulating gap enabled the fabrication of aligned nanofibers. The effects of laminin content and fiber orientation were evaluated in rat tibial nerve defect model. The lumens of conduits were filled with nanofiber meshes of varying laminin content and alignment to assess changes in motor and sensory recovery. Retrograde nerve conduction speed at 6 weeks was significantly faster in animals receiving aligned nanofiber conduits than in those receiving random nanofiber conduits. Animals receiving nanofiber-filled conduits showed some conduction in both anterograde and retrograde directions, whereas in animals receiving hollow conduits, no impulse conduction was detected. Aligned PCL nanofibers significantly improved motor function; aligned laminin blend nanofibers yielded the best sensory function recovery. In both cases, nanofiber-filled conduits resulted in better functional recovery than hollow conduits. These studies provide a firm foundation for the use of natural–synthetic blend electrospun nanofibers to enhance existing hollow nerve guidance conduits. PMID:22106069

  6. Radiosensitizing activity and pharmacokinetics of multiple dose administered KU-2285 in peripheral nerve tissue in mice

    SciTech Connect

    Iwai, Hiroyuki; Matsuno, Etsuko ); Sasai, Keisuke; Abe, Mitsuyuki; Shibamoto, Yuta )

    1994-06-15

    In a clinical trial in which a 2-nitroimidazole radiosensitizer was administered repeatedly, the dose-limiting toxicity was found to be peripheral neuropathy. In the present study, the in vivo radiosensitizing activity of KU-2285 in combination with radiation dose fractionation, and the pharmacokinetics of cumulative dosing of KU-2285 in the peripheral nerves were examined. The ability of three nitroimidazoles, misonidazole (MISO), etanidazole (SR-2508) and KU-2285, to sensitize SCCVII tumors to radiation treatment has been compared for drug doses in the range 0-200 mg/kg. Single radiation doses or two different fractionation schedules (6 Gy/fractions [times] three fractions/48 h or 5 Gy/fractions [times] five fractions/48 h) were used; the tumor cell survival was determined using an in vivo/in vitro colony assay. The pharmacokinetics in the sciatic nerves were undertaken, when KU-2285 or etanidazole were injected at a dose of 200 mg/kg intravenously one, two, three, or four times at 2-h intervals. At less than 100 mg/kg, KU-2285 sensitized SCCVII tumors more than MISO and SR-2508 by fractionated irradiation. Evaluation of pharmacokinetics in the peripheral nerves showed that the apparent biological half-life of SR-2508 increased with the increases in the number of administrations, whereas that of KU-2285 became shorter. Since most clinical radiotherapy is given in small multiple fractions, KU-2285 appears to be a hypoxic cell radiosensitizer that could be useful in such regimens, and that poses no risk of chronic peripheral neurotoxicity. 12 refs., 5 figs., 1 tab.

  7. Electrospun and woven silk fibroin/poly(lactic-co-glycolic acid) nerve guidance conduits for repairing peripheral nerve injury

    PubMed Central

    Wang, Ya-ling; Gu, Xiao-mei; Kong, Yan; Feng, Qi-lin; Yang, Yu-min

    2015-01-01

    We have designed a novel nerve guidance conduit (NGC) made from silk fibroin and poly(lactic-co-glycolic acid) through electrospinning and weaving (ESP-NGCs). Several physical and biological properties of the ESP-NGCs were assessed in order to evaluate their biocompatibility. The physical properties, including thickness, tensile stiffness, infrared spectroscopy, porosity, and water absorption were determined in vitro. To assess the biological properties, Schwann cells were cultured in ESP-NGC extracts and were assessed by morphological observation, the MTT assay, and immunohistochemistry. In addition, ESP-NGCs were subcutaneously implanted in the backs of rabbits to evaluate their biocompatibility in vivo. The results showed that ESP-NGCs have high porosity, strong hydrophilicity, and strong tensile stiffness. Schwann cells cultured in the ESP-NGC extract fluids showed no significant differences compared to control cells in their morphology or viability. Histological evaluation of the ESP-NGCs implanted in vivo indicated a mild inflammatory reaction and high biocompatibility. Together, these data suggest that these novel ESP-NGCs are biocompatible, and may thus provide a reliable scaffold for peripheral nerve repair in clinical application. PMID:26692862

  8. Electrospun and woven silk fibroin/poly(lactic-co-glycolic acid) nerve guidance conduits for repairing peripheral nerve injury.

    PubMed

    Wang, Ya-Ling; Gu, Xiao-Mei; Kong, Yan; Feng, Qi-Lin; Yang, Yu-Min

    2015-10-01

    We have designed a novel nerve guidance conduit (NGC) made from silk fibroin and poly(lactic-co-glycolic acid) through electrospinning and weaving (ESP-NGCs). Several physical and biological properties of the ESP-NGCs were assessed in order to evaluate their biocompatibility. The physical properties, including thickness, tensile stiffness, infrared spectroscopy, porosity, and water absorption were determined in vitro. To assess the biological properties, Schwann cells were cultured in ESP-NGC extracts and were assessed by morphological observation, the MTT assay, and immunohistochemistry. In addition, ESP-NGCs were subcutaneously implanted in the backs of rabbits to evaluate their biocompatibility in vivo. The results showed that ESP-NGCs have high porosity, strong hydrophilicity, and strong tensile stiffness. Schwann cells cultured in the ESP-NGC extract fluids showed no significant differences compared to control cells in their morphology or viability. Histological evaluation of the ESP-NGCs implanted in vivo indicated a mild inflammatory reaction and high biocompatibility. Together, these data suggest that these novel ESP-NGCs are biocompatible, and may thus provide a reliable scaffold for peripheral nerve repair in clinical application. PMID:26692862

  9. Peripheral nerve injury sensitizes neonatal dorsal horn neurons to tumor necrosis factor-α

    PubMed Central

    Li, Jie; Xie, Wenrui; Zhang, Jun-Ming; Baccei, Mark L

    2009-01-01

    Background Little is known about whether peripheral nerve injury during the early postnatal period modulates synaptic efficacy in the immature superficial dorsal horn (SDH) of the spinal cord, or whether the neonatal SDH network is sensitive to the proinflammatory cytokine TNFα under neuropathic conditions. Thus we examined the effects of TNFα on synaptic transmission and intrinsic membrane excitability in developing rat SDH neurons in the absence or presence of sciatic nerve damage. Results The spared nerve injury (SNI) model of peripheral neuropathy at postnatal day (P)6 failed to significantly alter miniature excitatory (mEPSCs) or inhibitory (mIPSCs) postsynaptic currents in SDH neurons at P9-11. However, SNI did alter the sensitivity of excitatory synapses in the immature SDH to TNFα. While TNFα failed to influence mEPSCs or mIPSCs in slices from sham-operated controls, it significantly increased mEPSC frequency and amplitude following SNI without modulating synaptic inhibition onto the same neurons. This was accompanied by a significant decrease in the paired-pulse ratio of evoked EPSCs, suggesting TNFα increases the probability of glutamate release in the SDH under neuropathic conditions. Similarly, while SNI alone did not alter action potential (AP) threshold or rheobase in SDH neurons at this age, TNFα significantly decreased AP threshold and rheobase in the SNI group but not in sham-operated littermates. However, unlike the adult, the expression of TNFα in the immature dorsal horn was not significantly elevated during the first week following the SNI. Conclusion Developing SDH neurons become susceptible to regulation by TNFα following peripheral nerve injury in the neonate. This may include both a greater efficacy of glutamatergic synapses as well as an increase in the intrinsic excitability of immature dorsal horn neurons. However, neonatal sciatic nerve damage alone did not significantly modulate synaptic transmission or neuronal excitability in

  10. Peripheral neuropathy

    MedlinePlus

    Peripheral neuritis; Neuropathy - peripheral; Neuritis - peripheral; Nerve disease; Polyneuropathy ... Neuropathy is very common. There are many types and causes. Often, no cause can be found. Some ...

  11. Development of a Regenerative Peripheral Nerve Interface for Control of a Neuroprosthetic Limb

    PubMed Central

    Frost, Christopher M.; Martin, David C.; Larkin, Lisa M.

    2016-01-01

    Background. The purpose of this experiment was to develop a peripheral nerve interface using cultured myoblasts within a scaffold to provide a biologically stable interface while providing signal amplification for neuroprosthetic control and preventing neuroma formation. Methods. A Regenerative Peripheral Nerve Interface (RPNI) composed of a scaffold and cultured myoblasts was implanted on the end of a divided peroneal nerve in rats (n = 25). The scaffold material consisted of either silicone mesh, acellular muscle, or acellular muscle with chemically polymerized poly(3,4-ethylenedioxythiophene) conductive polymer. Average implantation time was 93 days. Electrophysiological tests were performed at endpoint to determine RPNI viability and ability to transduce neural signals. Tissue samples were examined using both light microscopy and immunohistochemistry. Results. All implanted RPNIs, regardless of scaffold type, remained viable and displayed robust vascularity. Electromyographic activity and stimulated compound muscle action potentials were successfully recorded from all RPNIs. Physiologic efferent motor action potentials were detected from RPNIs in response to sensory foot stimulation. Histology and transmission electron microscopy revealed mature muscle fibers, axonal regeneration without neuroma formation, neovascularization, and synaptogenesis. Desmin staining confirmed the preservation and maturation of myoblasts within the RPNIs. Conclusions. RPNI demonstrates significant myoblast maturation, innervation, and vascularization without neuroma formation. PMID:27294122

  12. Responses to magnetic stimuli recorded in peripheral nerves in the marine nudibranch mollusk Tritonia diomedea.

    PubMed

    Pavlova, Galina A; Glantz, Raymon M; Dennis Willows, A O

    2011-10-01

    Prior behavioral and neurophysiological studies provide evidence that the nudibranch mollusk Tritonia orients to the earth's magnetic field. Earlier studies of electrophysiological responses in certain neurons of the brain to changing ambient magnetic fields suggest that although certain identified brain cells fire impulses when the ambient field is changed, these neuron somata and their central dentritic and axonal processes are themselves not primary magnetic receptors. Here, using semi-intact animal preparations from which the brain was removed, we recorded from peripheral nerve trunks. Using techniques to count spikes in individual nerves and separately also to identify, then count individual axonal spikes in extracellular records, we found both excitatory and inhibitory axonal responses elicited by changes in the direction of ambient earth strength magnetic fields. We found responses in nerves from many locations throughout the body and in axons innervating the body wall and rhinophores. Our results indicate that primary receptors for geomagnetism in Tritonia are not focally concentrated in any particular organ, but appear to be widely dispersed in the peripheral body tissues. PMID:21717186

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

    PubMed

    Dong, Han-Yu; Jiang, Xin-Mei; Niu, Chun-Bo; Du, Lin; Feng, Jun-Yan; Jia, Fei-Yong

    2016-01-01

    To examine the effects of Cerebrolysin on the treatment of diabetic peripheral neuropathy, we first established a mouse model of type 2 diabetes mellitus by administering a high-glucose, high-fat diet and a single intraperitoneal injection of streptozotocin. Mice defined as diabetic in this model were then treated with 1.80, 5.39 or 8.98 mL/kg of Cerebrolysin via intraperitoneal injections for 10 consecutive days. Our results demonstrated that the number, diameter and area of myelinated nerve fibers increased in the sciatic nerves of these mice after administration of Cerebrolysin. The results of several behavioral tests showed that Cerebrolysin dose-dependently increased the slope angle in the inclined plane test (indicating an improved ability to maintain body position), prolonged tail-flick latency and foot-licking time (indicating enhanced sensitivity to thermal and chemical pain, respectively, and reduced pain thresholds), and increased an index of sciatic nerve function in diabetic mice compared with those behavioral results in untreated diabetic mice. Taken together, the anatomical and functional results suggest that Cerebrolysin ameliorated peripheral neuropathy in a mouse model of type 2 diabetes mellitus.

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

    PubMed Central

    Dong, Han-yu; Jiang, Xin-mei; Niu, Chun-bo; Du, Lin; Feng, Jun-yan; Jia, Fei-yong

    2016-01-01

    To examine the effects of Cerebrolysin on the treatment of diabetic peripheral neuropathy, we first established a mouse model of type 2 diabetes mellitus by administering a high-glucose, high-fat diet and a single intraperitoneal injection of streptozotocin. Mice defined as diabetic in this model were then treated with 1.80, 5.39 or 8.98 mL/kg of Cerebrolysin via intraperitoneal injections for 10 consecutive days. Our results demonstrated that the number, diameter and area of myelinated nerve fibers increased in the sciatic nerves of these mice after administration of Cerebrolysin. The results of several behavioral tests showed that Cerebrolysin dose-dependently increased the slope angle in the inclined plane test (indicating an improved ability to maintain body position), prolonged tail-flick latency and foot-licking time (indicating enhanced sensitivity to thermal and chemical pain, respectively, and reduced pain thresholds), and increased an index of sciatic nerve function in diabetic mice compared with those behavioral results in untreated diabetic mice. Taken together, the anatomical and functional results suggest that Cerebrolysin ameliorated peripheral neuropathy in a mouse model of type 2 diabetes mellitus. PMID:26981106

  15. A novel therapeutic target for peripheral nerve injury-related diseases: aminoacyl-tRNA synthetases

    PubMed Central

    Park, Byung Sun; Yeo, Seung Geun; Jung, Junyang; Jeong, Na Young

    2015-01-01

    Aminoacyl-tRNA synthetases (AminoARSs) are essential enzymes that perform the first step of protein synthesis. Beyond their original roles, AminoARSs possess non-canonical functions, such as cell cycle regulation and signal transduction. Therefore, AminoARSs represent a powerful pharmaceutical target if their non-canonical functions can be controlled. Using AminoARSs-specific primers, we screened mRNA expression in the spinal cord dorsal horn of rats with peripheral nerve injury created by sciatic nerve axotomy. Of 20 AminoARSs, we found that phenylalanyl-tRNA synthetase beta chain (FARSB), isoleucyl-tRNA synthetase (IARS) and methionyl-tRNA synthetase (MARS) mRNA expression was increased in spinal dorsal horn neurons on the injured side, but not in glial cells. These findings suggest the possibility that FARSB, IARS and MARS, as a neurotransmitter, may transfer abnormal sensory signals after peripheral nerve damage and become a new target for drug treatment. PMID:26692865

  16. Genome-wide analysis of EGR2/SOX10 binding in myelinating peripheral nerve

    PubMed Central

    Srinivasan, Rajini; Sun, Guannan; Keles, Sunduz; Jones, Erin A.; Jang, Sung-Wook; Krueger, Courtney; Moran, John J.; Svaren, John

    2012-01-01

    Myelin is essential for the rapidity of saltatory nerve conduction, and also provides trophic support for axons to prevent axonal degeneration. Two critical determinants of myelination are SOX10 and EGR2/KROX20. SOX10 is required for specification of Schwann cells from neural crest, and is required at every stage of Schwann cell development. Egr2/Krox20 expression is activated by axonal signals in myelinating Schwann cells, and is required for cell cycle arrest and myelin formation. To elucidate the integrated function of these two transcription factors during peripheral nerve myelination, we performed in vivo ChIP-Seq analysis of myelinating peripheral nerve. Integration of these binding data with loss-of-function array data identified a range of genes regulated by these factors. In addition, although SOX10 itself regulates Egr2/Krox20 expression, leading to coordinate activation of several major myelin genes by the two factors, there is a large subset of genes that are activated independent of EGR2. Finally, the results identify a set of SOX10-dependent genes that are expressed in early Schwann cell development, but become subsequently repressed by EGR2/KROX20. PMID:22492709

  17. Solution space reduction in the peripheral nerve source localization problem using forward field similarities

    NASA Astrophysics Data System (ADS)

    Zariffa, José; Popovic, Milos R.

    2008-06-01

    Improving our ability to localize bioelectric sources within a peripheral nerve would help us to monitor the control signals flowing to and from any limb or organ. This technology would provide a useful neuroscience tool, and could perhaps be incorporated into a neuroprosthesis interface. We propose to use measurements from a multi-contact nerve cuff to solve an inverse problem of bioelectric source localization within the peripheral nerve. Before the inverse problem can be addressed, the forward problem is solved using finite element modeling. A fine mesh improves the accuracy of the forward problem solution, but increases the number of variables to be solved for in the inverse problem. To alleviate this problem, variables corresponding to mesh elements that are not distinguishable by the measurement setup are grouped together, thus reducing the dimension of the inverse problem without impacting on the forward problem accuracy. A quantitative criterion for element distinguishability is derived using the columns of the leadfield matrix and information about the uncertainty in the measurements. Our results indicate that the number of variables in the inverse problem can be reduced by more than half using the proposed method, without having a detrimental impact on the quality of the localization.

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

    PubMed

    Dong, Han-Yu; Jiang, Xin-Mei; Niu, Chun-Bo; Du, Lin; Feng, Jun-Yan; Jia, Fei-Yong

    2016-01-01

    To examine the effects of Cerebrolysin on the treatment of diabetic peripheral neuropathy, we first established a mouse model of type 2 diabetes mellitus by administering a high-glucose, high-fat diet and a single intraperitoneal injection of streptozotocin. Mice defined as diabetic in this model were then treated with 1.80, 5.39 or 8.98 mL/kg of Cerebrolysin via intraperitoneal injections for 10 consecutive days. Our results demonstrated that the number, diameter and area of myelinated nerve fibers increased in the sciatic nerves of these mice after administration of Cerebrolysin. The results of several behavioral tests showed that Cerebrolysin dose-dependently increased the slope angle in the inclined plane test (indicating an improved ability to maintain body position), prolonged tail-flick latency and foot-licking time (indicating enhanced sensitivity to thermal and chemical pain, respectively, and reduced pain thresholds), and increased an index of sciatic nerve function in diabetic mice compared with those behavioral results in untreated diabetic mice. Taken together, the anatomical and functional results suggest that Cerebrolysin ameliorated peripheral neuropathy in a mouse model of type 2 diabetes mellitus. PMID:26981106

  19. Late-onset Tay-Sachs disease: the spectrum of peripheral neuropathy in 30 affected patients.

    PubMed

    Shapiro, Barbara E; Logigian, Eric L; Kolodny, Edwin H; Pastores, Gregory M

    2008-08-01

    Late-onset Tay-Sachs (LOTS) disease is a chronic, progressive, lysosomal storage disorder caused by a partial deficiency of beta-hexosaminidase A (HEXA) activity. Deficient levels of HEXA result in the intracellular accumulation of GM2-ganglioside, resulting in toxicity to nerve cells. Clinical manifestations primarily involve the central nervous system (CNS) and lower motor neurons, and include ataxia, weakness, spasticity, dysarthria, dysphagia, dystonia, seizures, psychosis, mania, depression, and cognitive decline. The prevalence of peripheral nervous system (PNS) involvement in LOTS has not been well documented, but it has traditionally been thought to be very low. We examined a cohort of 30 patients with LOTS who underwent clinical and electrophysiologic examination, and found evidence of a predominantly axon loss polyneuropathy affecting distal nerve segments in the lower and upper extremities in eight patients (27%). PMID:18642377

  20. The Semaphorin 3A Inhibitor SM-345431 Accelerates Peripheral Nerve Regeneration and Sensitivity in a Murine Corneal Transplantation Model

    PubMed Central

    Miyashita, Hideyuki; Kawakita, Tetsuya; Yoshida, Kenji; Kishino, Akiyoshi; Kimura, Toru; Shibata, Shinsuke; Tsubota, Kazuo; Okano, Hideyuki; Shimmura, Shigeto

    2012-01-01

    Background Peripheral nerve damage of the cornea is a complication following surgery or infection which may lead to decreased visual function. We examined the efficacy of the semaphorin 3A inhibitor, SM-345431, in promoting regeneration of peripheral nerves in a mouse corneal transplantation model. Methodology/Principal Findings P0-Cre/Floxed-EGFP mice which express EGFP in peripheral nerves cells were used as recipients of corneal transplantation with syngeneic wild-type mouse cornea donors. SM-345431 was administered subconjunctivally every 2 days while control mice received vehicle only. Mice were followed for 3 weeks and the length of regenerating nerves was measured by EGFP fluorescence and immunohistochemistry against βIII tubulin. Cornea sensitivity was also measured by the Cochet-Bonnet esthesiometer. CD31 staining was used to determine corneal neovascularization as a possible side effect of SM-345431. Regeneration of βIII tubulin positive peripheral nerves was significantly higher in SM-345431 treated mice compared to control. Furthermore, corneal sensitivity significantly improved in the SM-345431 group by 3 weeks after transplantation. Neovascularization was limited to the peripheral cornea with no difference between SM-345431 group and control. Conclusions/Significance Subconjunctival injections of SM-345431 promoted a robust network of regenerating nerves as well as functional recovery of corneal sensation in a mouse keratoplasty model, suggesting a novel therapeutic strategy for treating neurotrophic corneal disease. PMID:23152758

  1. Comparative outcomes of peripheral nerve blocks versus general anesthesia for hip fractures in geriatric Chinese patients

    PubMed Central

    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

  2. Clinical toxicity of peripheral nerve to intraoperative radiotherapy in a canine model

    SciTech Connect

    Johnstone, P.A.S.; DeLuca, A.M.; Terrill, R.E.

    1995-07-15

    The clinical late effects of intraoperative radiotherapy (IORT) on peripheral nerve were investigated in a foxhound model. Between 1982 and 1987, 40 animals underwent laparotomy with intraoperative radiotherapy of doses from 0-75 Gy administered to the right lumbosacral plexus. Subsequently, all animals were monitored closely and sacrificed to assess clinical effects to peripheral nerve. This analysis reports final clinical results of all animals, with follow-up to 5 years. All animals treated with {>=} 25 Gy developed ipsilateral neuropathy. An inverse relationship was noted between intraoperative radiotherapy dose and time to neuropathy, with an effective dose for 50% paralysis (ED{sub 50}) of 17.2 Gy. One of the animals treated with 15 Gy IORT developed paralysis, after a much longer latency than the other animals. Doses of 15 Gy delivered intraoperatively may be accompanied by peripheral neuropathy with long-term follow-up. This threshold is less than that reported with shorter follow-up. The value of ED{sub 50} determined here is in keeping with data from other animal trials, and from clinical trials in humans. 11 refs., 2 figs.

  3. Clinical implications of peripheral myelin protein 22 for nerve compression and neural regeneration: a review.

    PubMed

    Hui-Chou, Helen G; Hashemi, Sharyhar S; Hoke, Ahmet; Dellon, A Lee

    2011-01-01

    Peripheral myelin protein 22 (PMP22) is a major component of the peripheral myelin sheath. The PMP22 gene is located on chromosome 17p11.2, and defects in PMP22 gene have been implicated in several common inherited peripheral neuropathies. Hereditary neuropathy with liability to pressure palsies (HNPP), Charcot-Marie Tooth disease type 1A (CMT1A), Dejerine-Sottas syndrome, and congenital hypomyelinating neuropathy are all associated with defects in PMP22 gene. The disease phenotypes mirror the range of expression of PMP22 due to the corresponding genetic defect. HNPP, characterized by a milder recurrent episodic focal demyelinating neuropathy, is attributed to a deletion leading to PMP22 underexpression. On the other end of the spectrum, CMT1A leads to a more uniform demyelination and axonal loss, resulting in severe progressive distal weakness and paresthesias; it is due to a duplication at 17p11.2 leading to PMP22 overexpression. Additional point mutations result in varying phenotypes due to dysfunction of the resultant PMP22 protein. All inherited neuropathies are diagnosed with a combination of physical findings on examination, electromyography, sural nerve biopsies, and genetic testing. Treatment and management of these disorders differ depending on the underlying genetic defect, nerves involved, and resulting functional impairments. A review of current literature elucidates clinical, microsurgical implications, and management of patients with PMP22-related neuropathy. PMID:20976668

  4. Processed allografts and type I collagen conduits for repair of peripheral nerve gaps.

    PubMed

    Whitlock, Elizabeth L; Tuffaha, Sami H; Luciano, Janina P; Yan, Ying; Hunter, Daniel A; Magill, Christina K; Moore, Amy M; Tong, Alice Y; Mackinnon, Susan E; Borschel, Gregory H

    2009-06-01

    Autografting is the gold standard in the repair of peripheral nerve injuries that are not amenable to end-to-end coaptation. However, because autografts result in donor-site defects and are a limited resource, an effective substitute would be valuable. In a rat model, we compared isografts with Integra NeuraGen (NG) nerve guides, which are a commercially available type I collagen conduit, with processed rat allografts comparable to AxoGen's Avance human decellularized allograft product. In a 14-mm sciatic nerve gap model, isograft was superior to processed allograft, which was in turn superior to NG conduit at 6 weeks postoperatively (P < 0.05 for number of myelinated fibers both at midgraft and distal to the graft). At 12 weeks, these differences were no longer apparent. In a 28-mm graft model, isografts again performed better than processed allografts at both 6 and 22 weeks; regeneration through the NG conduit was often insufficient for analysis in this long graft model. Functional tests confirmed the superiority of isografts, although processed allografts permitted successful reinnervation of distal targets not seen in the NG conduit groups. Processed allografts were inherently non-immunogenic and maintained some internal laminin structure. We conclude that, particularly in a long gap model, nerve graft alternatives fail to confer the regenerative advantages of an isograft. However, AxoGen processed allografts are superior to a currently available conduit-style nerve guide, the Integra NeuraGen. They provide an alternative for reconstruction of short nerve gaps where a conduit might otherwise be used.

  5. NT-3 modulates NPY expression in primary sensory neurons following peripheral nerve injury

    PubMed Central

    STERNE, G. D.; BROWN, R. A.; GREEN, C. J.; TERENGHI, G.

    1998-01-01

    Peripheral nerve transection induces significant changes in neuropeptide expression and content in injured primary sensory neurons, possibly due to loss of target derived neurotrophic support. This study shows that neurotrophin-3 (NT-3) delivery to the injured nerve influences neuropeptide Y (NPY) expression within dorsal root ganglia (DRG) neurons. NT-3 was delivered by grafting impregnated fibronectin (500 ng/ml; NT group) in the axotomised sciatic nerve. Animals grafted with plain fibronectin mats (FN) or nerve grafts (NG) were used as controls. L4 and L5 DRG from operated and contralateral sides were harvested between 5 and 240 d. Using immunohistochemistry and computerised image analysis the percentage, diameter and optical density of neurons expressing calcitonin gene-related peptide (CGRP), substance P (SP), vasoactive intestinal peptide (VIP) and NPY were quantified. Sciatic nerve axotomy resulted in significant reduction in expression of CGRP and SP, and significant upregulation of VIP and NPY (P<0.05 for ipsilateral vs contralateral DRG). By d 30, exogenous NT-3 and nerve graft attenuated the upregulation of NPY (P<0.05 for NT and NG vs FN). However, NT-3 administration did not influence the expression of CGRP, SP or VIP. The mean cell diameter of NPY immunoreactive neurons was significantly smaller in the NT-3 group (P<0.05 for NT vs FN and NG) suggesting a differential influence of NT-3 on larger neurons. The optical densities of NPY immunoreactive neurons of equal size were the same in each group at any time point, indicating that the neurons responding to NT-3 downregulate NPY expression to levels not detectable by immunohistochemistry. These results demonstrate that targeted administration of NT-3 regulates the phenotype of a NPY-immunoreactive neuronal subpopulation in the dorsal root ganglia, a further evidence of the trophic role of neurotrophins on primary sensory neurons. PMID:9827642

  6. Dorsal root ganglion transcriptome analysis following peripheral nerve injury in mice

    PubMed Central

    Wu, Shaogen; Marie Lutz, Brianna; Miao, Xuerong; Liang, Lingli; Mo, Kai; Chang, Yun-Juan; Du, Peicheng; Soteropoulos, Patricia; Tian, Bin; Kaufman, Andrew G.; Bekker, Alex; Hu, Yali

    2016-01-01

    Background Peripheral nerve injury leads to changes in gene expression in primary sensory neurons of the injured dorsal root ganglia. These changes are believed to be involved in neuropathic pain genesis. Previously, these changes have been identified using gene microarrays or next generation RNA sequencing with poly-A tail selection, but these approaches cannot provide a more thorough analysis of gene expression alterations after nerve injury. Methods The present study chose to eliminate mRNA poly-A tail selection and perform strand-specific next generation RNA sequencing to analyze whole transcriptomes in the injured dorsal root ganglia following spinal nerve ligation. Quantitative real-time reverse transcriptase polymerase chain reaction assay was carried out to verify the changes of some differentially expressed RNAs in the injured dorsal root ganglia after spinal nerve ligation. Results Our results showed that more than 50 million (M) paired mapped sequences with strand information were yielded in each group (51.87 M–56.12 M in sham vs. 51.08 M–57.99 M in spinal nerve ligation). Six days after spinal nerve ligation, expression levels of 11,163 out of a total of 27,463 identified genes in the injured dorsal root ganglia significantly changed, of which 52.14% were upregulated and 47.86% downregulated. The largest transcriptional changes were observed in protein-coding genes (91.5%) followed by noncoding RNAs. Within 944 differentially expressed noncoding RNAs, the most significant changes were seen in long interspersed noncoding RNAs followed by antisense RNAs, processed transcripts, and pseudogenes. We observed a notable proportion of reads aligning to intronic regions in both groups (44.0% in sham vs. 49.6% in spinal nerve ligation). Using quantitative real-time polymerase chain reaction, we confirmed consistent differential expression of selected genes including Kcna2, Oprm1 as well as lncRNAs Gm21781 and 4732491K20Rik following spinal nerve

  7. Peripheral nerve regeneration in the MRL/MpJ ear wound model.

    PubMed

    Buckley, Gemma; Metcalfe, Anthony D; Ferguson, Mark W J

    2011-02-01

    The MRL/MpJ mouse displays an accelerated ability to heal ear punch wounds without scar formation (whereas wounds on the dorsal surface of the trunk heal with scar formation), offering a rare opportunity for studying tissue regeneration in adult mammals. A blastema-like structure develops and subsequently the structure of the wounded ear is restored, including cartilage, skin, hair follicles and adipose tissue. We sought to assess if the MRL/MpJ strain also possessed an enhanced capacity for peripheral nerve regeneration. Female MRL/MpJ and C57BL/6 mice were wounded with a 2-mm excisional biopsy punch to the centre of each ear and two 4-mm excisional biopsy punches to the dorsal skin. Immunohistochemical dual staining of pan-neurofilament and CD31 markers was used to investigate reinnervation and vascularisation of both the dorsal surface of the trunk and ear wounds. The MRL/MpJ mouse ear exhibited a significantly (P > 0.01) higher density of regenerated nerves than C57BL/6 between 10 and 21 days post-wounding when the blastema-like structure was forming. Unlike dorsal skin wounds, nerve regeneration in the ear wound preceded vascularisation, recapitulating early mammalian development. Immunohistochemical data suggest that factors within the blastemal mesenchyme, such as aggrecan, may direct nerve regrowth in the regenerating ear tissue.

  8. The effects of picric acid (2,4,6-trinitrophenol) and a bite-deterrent chemical (denatonium benzoate) on autotomy in rats after peripheral nerve lesion.

    PubMed

    Firouzi, Matin Sadat; Firouzi, Masoumeh; Nabian, Mohammad Hossein; Zanjani, Leila Oryadi; Zadegan, Shayan Abdollah; Kamrani, Reza Shahryar; Rahimi-Movaghar, Vafa

    2015-04-01

    Denervation of the hind limb is a technique used to study peripheral nerve regeneration. Autotomy or autophagia is an undesirable response to denervation in such studies. Application of a commercially available lotion used to deter nail biting in humans reduced autotomy in rats after denervation but did not completely prevent it. In this study, this authors evaluated the application of picric acid to prevent autotomy in rats in peripheral nerve experiments. They carried out sciatic nerve transection in 41 adult female Wistar rats and then applied either bite-deterrent lotion (n = 26) or saturated picric acid solution (n = 15) topically to the affected hind limb immediately after surgery and every day for 1 month. Autotomy scores were lower for rats treated with picric acid than for rats treated with bite-deterrent lotion 1 week and 2 weeks after surgery but were not different between the two groups 4 weeks after surgery. The authors conclude that application of picric acid could be used as an alternative strategy to prevent autotomy in peripheral nerve studies.

  9. The effects of picric acid (2,4,6-trinitrophenol) and a bite-deterrent chemical (denatonium benzoate) on autotomy in rats after peripheral nerve lesion.

    PubMed

    Firouzi, Matin Sadat; Firouzi, Masoumeh; Nabian, Mohammad Hossein; Zanjani, Leila Oryadi; Zadegan, Shayan Abdollah; Kamrani, Reza Shahryar; Rahimi-Movaghar, Vafa

    2015-04-01

    Denervation of the hind limb is a technique used to study peripheral nerve regeneration. Autotomy or autophagia is an undesirable response to denervation in such studies. Application of a commercially available lotion used to deter nail biting in humans reduced autotomy in rats after denervation but did not completely prevent it. In this study, this authors evaluated the application of picric acid to prevent autotomy in rats in peripheral nerve experiments. They carried out sciatic nerve transection in 41 adult female Wistar rats and then applied either bite-deterrent lotion (n = 26) or saturated picric acid solution (n = 15) topically to the affected hind limb immediately after surgery and every day for 1 month. Autotomy scores were lower for rats treated with picric acid than for rats treated with bite-deterrent lotion 1 week and 2 weeks after surgery but were not different between the two groups 4 weeks after surgery. The authors conclude that application of picric acid could be used as an alternative strategy to prevent autotomy in peripheral nerve studies. PMID:25793680

  10. PGC-1α Mediated Peripheral Nerve Protection of Tongxinluo in STZ-Induced Diabetic Rats.

    PubMed

    Cui, Xiaopei; Feng, Hua; Xu, Xia; Li, Haijun; Zhang, Hongyu

    2016-01-01

    Aim. To investigate the effect of Tongxinluo (Txl), a Chinese herbal compound, on diabetic peripheral neuropathy (DPN). Methods and Results. Diabetic rat model was established by peritoneal injection of streptozotocin (STZ). Txl ultrafine powder treatment for 16 weeks from the baseline significantly reversed the impairment of motor nerve conductive velocity (MNCV), mechanical hyperalgesia, and nerve structure. We further proved that Tongxinluo upregulates PGC-1α and its downstream factors including COX IV and SOD, which were involved in mitochondrial biogenesis. Conclusion. Our study indicates that the protective effect of Txl in diabetic neuropathy may be attributed to the induction of PGC-1α and its downstream targets. This finding may further illustrate the pleiotropic effect of the medicine. PMID:27504136

  11. Multiple orbital neurofibromas, painful peripheral nerve tumors, distinctive face and marfanoid habitus: a new syndrome.

    PubMed

    Babovic-Vuksanovic, D; Messiaen, Ludwine; Nagel, Christoph; Brems, Hilde; Scheithauer, Bernd; Denayer, Ellen; Mao, Rong; Sciot, Raf; Janowski, Karen M; Schuhmann, Martin U; Claes, Kathleen; Beert, Eline; Garrity, James A; Spinner, Robert J; Stemmer-Rachamimov, Anat; Gavrilova, Ralitza; Van Calenbergh, Frank; Mautner, Victor; Legius, Eric

    2012-06-01

    Four unrelated patients having an unusual clinical phenotype, including multiple peripheral nerve sheath tumors, are reported. Their clinical features were not typical of any known familial tumor syndrome. The patients had multiple painful neurofibromas, including bilateral orbital plexiform neurofibromas, and spinal as well as mucosal neurofibromas. In addition, they exhibited a marfanoid habitus, shared similar facial features, and had enlarged corneal nerves as well as neuronal migration defects. Comprehensive NF1, NF2 and SMARCB1 mutation analyses revealed no mutation in blood lymphocytes and in schwann cells cultured from plexiform neurofibromas. Furthermore, no mutations in RET, PRKAR1A, PTEN and other RAS-pathway genes were found in blood leukocytes. Collectively, the clinical and pathological findings in these four cases fit no known syndrome and likely represent a new disorder.

  12. Multiple orbital neurofibromas, painful peripheral nerve tumors, distinctive face and marfanoid habitus: a new syndrome.

    PubMed

    Babovic-Vuksanovic, D; Messiaen, Ludwine; Nagel, Christoph; Brems, Hilde; Scheithauer, Bernd; Denayer, Ellen; Mao, Rong; Sciot, Raf; Janowski, Karen M; Schuhmann, Martin U; Claes, Kathleen; Beert, Eline; Garrity, James A; Spinner, Robert J; Stemmer-Rachamimov, Anat; Gavrilova, Ralitza; Van Calenbergh, Frank; Mautner, Victor; Legius, Eric

    2012-06-01

    Four unrelated patients having an unusual clinical phenotype, including multiple peripheral nerve sheath tumors, are reported. Their clinical features were not typical of any known familial tumor syndrome. The patients had multiple painful neurofibromas, including bilateral orbital plexiform neurofibromas, and spinal as well as mucosal neurofibromas. In addition, they exhibited a marfanoid habitus, shared similar facial features, and had enlarged corneal nerves as well as neuronal migration defects. Comprehensive NF1, NF2 and SMARCB1 mutation analyses revealed no mutation in blood lymphocytes and in schwann cells cultured from plexiform neurofibromas. Furthermore, no mutations in RET, PRKAR1A, PTEN and other RAS-pathway genes were found in blood leukocytes. Collectively, the clinical and pathological findings in these four cases fit no known syndrome and likely represent a new disorder. PMID:22258529

  13. PGC-1α Mediated Peripheral Nerve Protection of Tongxinluo in STZ-Induced Diabetic Rats

    PubMed Central

    Cui, Xiaopei; Feng, Hua; Xu, Xia; Li, Haijun

    2016-01-01

    Aim. To investigate the effect of Tongxinluo (Txl), a Chinese herbal compound, on diabetic peripheral neuropathy (DPN). Methods and Results. Diabetic rat model was established by peritoneal injection of streptozotocin (STZ). Txl ultrafine powder treatment for 16 weeks from the baseline significantly reversed the impairment of motor nerve conductive velocity (MNCV), mechanical hyperalgesia, and nerve structure. We further proved that Tongxinluo upregulates PGC-1α and its downstream factors including COX IV and SOD, which were involved in mitochondrial biogenesis. Conclusion. Our study indicates that the protective effect of Txl in diabetic neuropathy may be attributed to the induction of PGC-1α and its downstream targets. This finding may further illustrate the pleiotropic effect of the medicine. PMID:27504136

  14. Molecular mechanisms of peripheral nerve regeneration: emerging roles of microRNAs

    PubMed Central

    Wu, Di; Murashov, Alexander K.

    2013-01-01

    MicroRNAs are small non-coding RNAs that suppress gene expression through target mRNA degradation or translation repression. Recent studies suggest that miRNA plays an important role in multiple physiological and pathological processes in the nervous system. In this review article, we described what is currently known about the mechanisms in peripheral nerve regeneration on cellular and molecular levels. Recently, changes in microRNA expression profiles have been detected in different injury models, and emerging evidence strongly indicates that these changes promote neurons to survive by shifting their physiology from maintaining structure and supporting synaptic transmission towards a regenerative phenotype. We reviewed the putative mechanisms involved in miRNA mediated post-transcriptional regulation and pointed out several areas where future research is necessary to advance our understanding of how targeting miRNA machinery can be used as a therapeutic approach for treating nerve injuries. PMID:23554595

  15. Reference values and clinical application of magnetic peripheral nerve stimulation in cats.

    PubMed

    Van Soens, Iris; Struys, Michel M R F; Bhatti, Sofie F M; Van Ham, Luc M L

    2012-07-01

    Magnetic stimulation of radial (RN) and sciatic (SN) nerves was performed bilaterally in 40 healthy cats. Reference values for onset latency and peak-to-peak amplitude of magnetic motor evoked potentials (MMEPs) were obtained and compared with values of electric motor evoked potentials (EMEPs) in 10/40 cats. Onset latencies and peak-to-peak amplitudes of the MMEPs of three cats with polyneuropathy (PNP) were compared to the reference values. Magnetic motor evoked responses were easily recorded in all normal cats. Significant differences were found in onset latencies between MMEPs and EMEPs, but peak-to-peak amplitudes were equal. The MMEPs of three cats with PNP can be seen as outliers in comparison to the reference values. MMEPs from the RN and SN were easily obtained and reproducible in normal cats. The technique could represent a useful adjunct in the assessment of peripheral nerve disorders. PMID:22070914

  16. Spinal expression of Hippo signaling components YAP and TAZ following peripheral nerve injury in rats.

    PubMed

    Li, Na; Lim, Grewo; Chen, Lucy; McCabe, Michael F; Kim, Hyangin; Zhang, Shuzhuo; Mao, Jianren

    2013-10-16

    Previous studies have shown that the morphology and number of cells in the spinal cord dorsal horn could change following peripheral nerve injury and that the Hippo signaling pathway plays an important role in cell growth, proliferation, apoptosis, and dendritic remolding. In the present study, we examined whether the expression of YAP and TAZ, two critical components regulated by Hippo signaling, in the spinal cord dorsal horn would be altered by chronic constriction sciatic nerve injury (CCI). We found that (1) YAP was mainly expressed on CGRP- and IB4-immunoreactive primary afferent nerve terminals without noticeable expression on glial cells, whereas TAZ was mainly expressed on spinal cord second order neurons as well as microglia; (2) upregulation of YAP and TAZ expression followed two distinct temporal patterns after CCI, such that the highest expression of YAP and TAZ was on day 14 and day 1 after CCI, respectively; (3) there were also unique topographic patterns of YAP and TAZ distribution in the spinal cord dorsal horn consistent with their distinctive association with primary afferents and second order neurons; (4) changes in the YAP expression were selectively induced by CCI but not CFA-induced hindpaw inflammation; and (5) the number of nuclear profiles of TAZ expression was significantly increased after CCI, indicating translocation of TAZ from the cytoplasma to nucleus. These findings indicate that peripheral nerve injury induced time-dependent and region-specific changes in the spinal YAP and TAZ expression. A role for Hippo signaling in synaptic and structural plasticity is discussed in relation to the cellular mechanism of neuropathic pain.

  17. SUCCESSFUL TRANSPLANTATION OF MOTONEURONS INTO THE PERIPHERAL NERVE DEPENDS ON THE NUMBER OF TRANSPLANTED CELLS

    PubMed Central

    KATO, SHUICHI; KURIMOTO, SHIGERU; NAKANO, TOMONORI; YONEDA, HIDEMASA; ISHII, HISAO; MITA-SUGIURA, SATOKA; HIRATA, HITOSHI

    2015-01-01

    ABSTRACT Transplantation of motoneurons (MN) into the peripheral nerve to provide a source of neurons for muscle reinnervation, termed motoneuron integrated striated muscle (MISM), may provide the potential to restore functional muscle activity, when combined with computer-programmed functional electrical stimulation (FES). The number of MNs required to restore innervation to denervated muscles in adult Fischer 344 rats was investigated by comparing two groups, one transplanted with 2 × 105 cells (group A) and the other with 1 × 106 cells (group B). Twelve weeks after transplantation, electrophysiological analysis, muscle function analysis, and tissue analysis were performed. The mean motor nerve conduction velocity was faster (12.4 ± 1.0 m/s vs. 8.5 ± 0.7 m/s, P = 0.011) and the mean amplitude of compound muscle action potential was larger (1.6 ± 0.4 mV vs. 0.7 ± 0.2 mV, P = 0.034) in group B. The dorsiflexed ankle angle was larger in group B (27 ± 5° vs. 75 ± 8°, P = 0.02). The mean myelinated axon number in the peroneal nerve and the proportion of reinnervated motor end plates were also greater in group B (317 ± 33 vs. 104 ± 17, 87.5 ± 3.4% vs. 40.6 ± 7.7%; P < 0.01, respectively). When sufficient MNs are transplanted into the peripheral nerve, MISM forms functional motor units. MISM, in conjunction with FES, provides a new treatment strategy for paralyzed muscles. PMID:25797991

  18. Potential of boron neutron capture therapy (BNCT) for malignant peripheral nerve sheath tumors (MPNST).

    PubMed

    Fujimoto, Takuya; Andoh, Tooru; Sudo, Tamotsu; Fujita, Ikuo; Fukase, Naomasa; Takeuchi, Tamotsu; Sonobe, Hiroshi; Inoue, Masayoshi; Hirose, Tkanori; Sakuma, Toshiko; Moritake, Hiroshi; Sugimoto, Tohru; Kawamoto, Teruya; Fukumori, Yoshinobu; Yamamoto, Satomi; Atagi, Shinji; Sakurai, Yoshinori; Kurosaka, Masahiro; Ono, Koji; Ichikawa, Hideki; Suzuki, Minoru

    2015-12-01

    Malignant peripheral nerve sheath tumors (MPNST) are relatively rare neoplasms with poor prognosis. At present there is no effective treatment for MPNST other than surgical resection. Nonetheless, the anti-tumor effect of boron neutron capture therapy (BNCT) was recently demonstrated in two patients with MPNST. Subsequently, tumor-bearing nude mice subcutaneously transplanted with a human MPNST cell line were injected with p-borono-L-phenylalanine (L-BPA) and subjected to BNCT. Pathological studies then revealed that the MPNST cells were selectively destroyed by BNCT.

  19. Ultrasound-Guided Pain Interventions - A Review of Techniques for Peripheral Nerves

    PubMed Central

    Soneji, Neilesh

    2013-01-01

    Ultrasound has emerged to become a commonly used modality in the performance of chronic pain interventions. It allows direct visualization of tissue structure while allowing real time guidance of needle placement and medication administration. Ultrasound is a relatively affordable imaging tool and does not subject the practitioner or patient to radiation exposure. This review focuses on the anatomy and sonoanatomy of peripheral non-axial structures commonly involved in chronic pain conditions including the stellate ganglion, suprascapular, ilioinguinal, iliohypogastric, genitofemoral and lateral femoral cutaneous nerves. Additionally, the review discusses ultrasound guided intervention techniques applicable to these structures. PMID:23614071

  20. Uptake of nerve growth factor along peripheral and spinal axons of primary sensory neurons

    SciTech Connect

    Richardson, P.M.; Riopelle, R.J.

    1984-07-01

    To investigate the distribution of nerve growth factor (NGF) receptors on peripheral and central axons, (/sup 125/I)NGF was injected into the sciatic nerve or spinal cord of adult rats. Accumulation of (/sup 125/I)NGF in lumbar dorsal root ganglia was monitored by gamma emission counting and radioautography. (/sup 125/I)NGF, injected endoneurially in small quantities, was taken into sensory axons by a saturable process and was transported retrogradely to their cell bodies at a maximal rate of 2.5 to 7.5 mm/hr. Because very little (/sup 125/I)NGF reached peripheral terminals, the results were interpreted to indicate that receptors for NGF are present on nonterminal segments of sensory axons. The specificity and high affinity of NGF uptake were illustrated by observations that negligible amounts of gamma activity accumulated in lumbar dorsal root ganglia after comparable intraneural injection of (/sup 125/I) cytochrome C or (/sup 125/I)oxidized NGF. Similar techniques were used to demonstrate avid internalization and retrograde transport of (/sup 125/I)NGF by intraspinal axons arising from dorsal root ganglia. Following injection of (/sup 125/I)NGF into lumbar or cervical regions of the spinal cord, neuronal perikarya were clearly labeled in radioautographs of lumbar dorsal root ganglia. Sites for NGF uptake on primary sensory neurons in the adult rat are not restricted to peripheral axon terminals but are extensively distributed along both peripheral and central axons. Receptors on axons provide a mechanism whereby NGF supplied by glia could influence neuronal maintenance or axonal regeneration.

  1. Peripheral nerve blocks in patients with Ehlers-Danlos syndrome, hypermobility type: a report of 2 cases.

    PubMed

    Patzkowski, Michael S

    2016-03-01

    Ehlers-Danlos syndrome is an inherited disorder of collagen production that results in multiorgan dysfunction. Patients with hypermobility type display skin hyperextensibility and joint laxity, which can result in chronic joint instability, dislocation, peripheral neuropathy, and severe musculoskeletal pain. A bleeding diathesis can be found in all subtypes of varying severity despite a normal coagulation profile. There have also been reports of resistance to local anesthetics in these patients. Several sources advise against the use of regional anesthesia in these patients citing the 2 previous features. There have been reports of successful neuraxial anesthesia, but few concerning peripheral nerve blocks, none of which describe nerves of the lower extremity. This report describes 2 cases of successful peripheral regional anesthesia in the lower extremity. In case 1, a 16-year-old adolescent girl with hypermobility type presented for osteochondral grafting of tibiotalar joint lesions. She underwent a popliteal sciatic (with continuous catheter) and femoral nerve block under ultrasound guidance. She proceeded to surgery and tolerated the procedure under regional block and intravenous sedation. She did not require any analgesics for the following 15 hours. In case 2, an 18-year-old woman with hypermobility type presented for medial patellofemoral ligament reconstruction for chronic patella instability. She underwent a saphenous nerve block above the knee with analgesia in the distribution of the saphenous nerve lasting for approximately 18 hours. There were no complications in either case. Prohibitions against peripheral nerve blocks in patients with Ehlers-Danlos syndrome, hypermobility type, appear unwarranted.

  2. Peripheral nerve blocks in patients with Ehlers-Danlos syndrome, hypermobility type: a report of 2 cases.

    PubMed

    Patzkowski, Michael S

    2016-03-01

    Ehlers-Danlos syndrome is an inherited disorder of collagen production that results in multiorgan dysfunction. Patients with hypermobility type display skin hyperextensibility and joint laxity, which can result in chronic joint instability, dislocation, peripheral neuropathy, and severe musculoskeletal pain. A bleeding diathesis can be found in all subtypes of varying severity despite a normal coagulation profile. There have also been reports of resistance to local anesthetics in these patients. Several sources advise against the use of regional anesthesia in these patients citing the 2 previous features. There have been reports of successful neuraxial anesthesia, but few concerning peripheral nerve blocks, none of which describe nerves of the lower extremity. This report describes 2 cases of successful peripheral regional anesthesia in the lower extremity. In case 1, a 16-year-old adolescent girl with hypermobility type presented for osteochondral grafting of tibiotalar joint lesions. She underwent a popliteal sciatic (with continuous catheter) and femoral nerve block under ultrasound guidance. She proceeded to surgery and tolerated the procedure under regional block and intravenous sedation. She did not require any analgesics for the following 15 hours. In case 2, an 18-year-old woman with hypermobility type presented for medial patellofemoral ligament reconstruction for chronic patella instability. She underwent a saphenous nerve block above the knee with analgesia in the distribution of the saphenous nerve lasting for approximately 18 hours. There were no complications in either case. Prohibitions against peripheral nerve blocks in patients with Ehlers-Danlos syndrome, hypermobility type, appear unwarranted. PMID:26897449

  3. Preliminary studies on long distance, retrograde transport of horseradish peroxidase in equine peripheral nerves.

    PubMed

    Fubini, S L; Cummings, J F; Todhunter, R J

    1985-11-01

    As a prelude to studies on retrograde axonal transport of neurotoxin (ie, so-called suicide transport) as a means to prevent post neurectomy neuroma formation, preliminary studies were conducted with an innocuous enzymatic marker, horseradish peroxidase (HRP). The proximal stumps of resected medial and lateral palmar digital nerves in six ponies were injected via a tuberculin syringe and needle with 50 micron 1 of a 30 per cent solution of HRP in order to assess long distance retrograde axonal transport. The dorsal root ganglion of the cervical spinal enlargement (ie, C6, C7, C8, T1, T2) were removed at post injection intervals of two, four, six, eight, 10 and 12 days. These were sectioned serially and reacted by the tetramethylbenzidine method to demonstrate transported enzyme in the ganglionic cell bodies which give rise to sensory fibres of the palmar digital nerves. Enzyme, retrogradely transported over axon lengths of 115 cm, was first demonstrated in spinal ganglia four days after injections of the palmar digital nerves. The calculated transport velocity of 287 mm/day, although almost certainly an underestimate, greatly exceeded rates of 72 to 120 mm/day recorded previously with HRP in the peripheral nerves of small laboratory animals. The intensity of the HRP reaction product in ganglionic neurons was strong at four days and it remained unabated in ganglia examined at six, eight, 10 and 12 days post injection. The major sources of the sensory fibres of the palmar digital nerves appeared to be the ganglia of the C8 and T1 spinal segments which contained more than 90 per cent of all labelled neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Fibre-selective recording from the peripheral nerves of frogs using a multi-electrode cuff

    NASA Astrophysics Data System (ADS)

    Schuettler, Martin; Donaldson, Nick; Seetohul, Vipin; Taylor, John

    2013-06-01

    Objective. We investigate the ability of the method of velocity selective recording (VSR) to determine the fibre types that contribute to a compound action potential (CAP) propagating along a peripheral nerve. Real-time identification of the active fibre types by determining the direction of action potential propagation (afferent or efferent) and velocity might allow future neural prostheses to make better use of biological sensor signals and provide a new and simple tool for use in fundamental neuroscience. Approach. Fibre activity was recorded from explanted Xenopus Laevis frog sciatic nerve using a single multi-electrode cuff that records whole nerve activity with 11 equidistant ring-shaped electrodes. The recorded signals were amplified, delayed against each other with variable delay times, added and band-pass filtered. Finally, the resulting amplitudes were measured. Main Result. Our experiments showed that electrically evoked frog CAP was dominated by two fibre populations, propagating at around 20 and 40 m/s, respectively. The velocity selectivity, i.e. the ability of the system to discriminate between individual populations was increased by applying band-pass filtering. The method extracted an entire velocity spectrum from a 10 ms CAP recording sample in real time. Significance. Unlike the techniques introduced in the 1970s and subsequently, VSR requires only a single nerve cuff and does not require averaging to provide velocity spectral information. This makes it potentially suitable for the generation of highly-selective real-time control-signals for future neural prostheses. In our study, electrically evoked CAPs were analysed and it remains to be proven whether the method can reliably classify physiological nerve traffic. The work presented here was carried out at the laboratories of the Implanted Devices Group, Department of Medical Physics and Bioengineering, University College London, UK.

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

    NASA Astrophysics Data System (ADS)

    Sharma, Anup Dutt

    Peripheral nerve regeneration is a complex biological process responsible for regrowth of neural tissue following a nerve injury. The main objective of this project was to enhance peripheral nerve regeneration using interdisciplinary approaches involving polymeric scaffolds, stem cell therapy, drug delivery and high content screening. Biocompatible and biodegradable polymeric materials such as poly (lactic acid) were used for engineering conduits with micropatterns capable of providing mechanical support and orientation to the regenerating axons and polyanhydrides for fabricating nano/microparticles for localized delivery of neurotrophic growth factors and cytokines at the site of injury. Transdifferentiated bone marrow stromal cells or mesenchymal stem cells (MSCs) were used as cellular replacements for lost native Schwann cells (SCs) at the injured nerve tissue. MSCs that have been transdifferentiated into an SC-like phenotype were tested as a substitute for the myelinating SCs. Also, genetically modified MSCs were engineered to hypersecrete brain- derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) to secrete therapeutic factors which Schwann cell secrete. To further enhance the regeneration, nerve growth factor (NGF) and interleukin-4 (IL4) releasing polyanhydrides nano/microparticles were fabricated and characterized in vitro for their efficacy. Synergistic use of these proposed techniques was used for fabricating a multifunctional nerve regeneration conduit which can be used as an efficient tool for enhancing peripheral nerve regeneration.

  6. Vagus nerve stimulation modulates visceral pain-related affective memory.

    PubMed

    Zhang, Xu; Cao, Bing; Yan, Ni; Liu, Jin; Wang, Jun; Tung, Vivian Oi Vian; Li, Ying

    2013-01-01

    Within a biopsychosocial model of pain, pain is seen as a conscious experience modulated by mental, emotional and sensory mechanisms. Recently, using a rodent visceral pain assay that combines the colorectal distension (CRD) model with the conditioned place avoidance (CPA) paradigms, we measured a learned behavior that directly reflects the affective component of visceral pain, and showed that perigenual anterior cingulate cortex (pACC) activation is critical for memory processing involved in long-term visceral affective state and prediction of aversive stimuli by contextual cue. Electrical vagus nerve stimulation (VNS) has become an established therapy for treatment-resistant epilepsy. VNS has also been shown to enhance memory performance in rats and humans. High-intensity VNS (400 μA) immediately following conditional training significantly increases the CRD-induced CPA scores, and enhanced the pain affective memory retention. In contrast, VNS (400 μA) had no effect on CPA induced by non-nociceptive aversive stimulus (U69,593). Low-intensity VNS (40 μA) had no effect on CRD-induced CPA. Electrophysiological recording showed that VNS (400 μA) had no effect on basal and CRD-induced ACC neuronal firing. Further, VNS did not alter CRD-induced visceral pain responses suggesting high intensity VNS facilitates visceral pain aversive memory independent of sensory discriminative aspects of visceral pain processing. The findings that vagus nerve stimulation facilities visceral pain-related affective memory underscore the importance of memory in visceral pain perception, and support the theory that postprandial factors may act on vagal afferents to modulate ongoing nature of visceral pain-induced affective disorder observed in the clinic, such as irritable bowel syndrome.

  7. [Continuing peripheral nerve blocks - benefit for orthopedic patients with diabetes mellitus?].

    PubMed

    Doležal, David; Saleh, Abdo Islam

    2015-06-01

    There is increasing incidence of diabetes mellitus in population of developed countries. And there is also, together with this fact, an increasing frequency of surgical not only orthopedic procedures for diabetic complications or for other reasons. However, thanks to modern sophisticated perioperative approaches, diabetes itself is no longer main risk factor for worsening of perioperative morbidity and mortality. The organ complications of diabetes still remain the crucial for patients outcome. The individual approach to each patient is important when we are plann-ing anesthesiological perioperative strategy. Assessment of long term diabetes compensation before elective surgical procedures, assessment and optimization of organ functions with searching for possible secondary complications of diabetes is also crucial. Generally, it is necessary to maintain compensation of diabetes through the whole perioperative period, avoid episodes of hypotension and tissue hypoperfusion and all anesthesiological interventions have to be targeted to rapid recovery (chronic medication, oral feeding and early rehabilitation). Technics of regional anesthesia and peripheral nerve blocks particularly, may be very useful for the objective especially for ortho-pedic patients.Key words: anesthesia - diabetes mellitus - perioperative period - peripheral nerve blocks.

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

    PubMed

    Koppisetty, Shalini; Alessio, Ricardo C; Rajpurkar, Atul

    2016-01-01

    Malignant peripheral nerve sheath tumors (MPNSTs) are extremely rare soft tissue sarcomas of ectomesenchymal origin. They are commonly seen in association with neurofibromatosis type 1 (NF-1), but can also occur without a history of NF (isolated MPNST). MPNSTs are most commonly located on the extremities (brachial and sacral plexus), head and neck, and trunk regions and are rarely reported in genitourinary organs. These tumors are aggressive, with a high recurrence rate and distant metastases. MPNST involving the kidney is extremely rare, and review of the literature using PubMed from 2001 to 2014 revealed eight cases of MPNST involving the kidney (seven, primarily involving the kidney and one metastatic MPNST of the kidney). Herein, we describe a case of breast metastases from an MPNST of the kidney without a history of NF-1. The patient was initially diagnosed with a spindle cell neoplasm of the kidney with peripheral nerve sheath differentiation. Eventually, the patient developed a right breast mass that was diagnosed as metastatic MPNST. The patient refused any kind of treatment and died 6 months later in hospice care. PMID:27453670

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

    PubMed Central

    Koppisetty, Shalini; Alessio, Ricardo C.; Rajpurkar, Atul

    2016-01-01

    Malignant peripheral nerve sheath tumors (MPNSTs) are extremely rare soft tissue sarcomas of ectomesenchymal origin. They are commonly seen in association with neurofibromatosis type 1 (NF-1), but can also occur without a history of NF (isolated MPNST). MPNSTs are most commonly located on the extremities (brachial and sacral plexus), head and neck, and trunk regions and are rarely reported in genitourinary organs. These tumors are aggressive, with a high recurrence rate and distant metastases. MPNST involving the kidney is extremely rare, and review of the literature using PubMed from 2001 to 2014 revealed eight cases of MPNST involving the kidney (seven, primarily involving the kidney and one metastatic MPNST of the kidney). Herein, we describe a case of breast metastases from an MPNST of the kidney without a history of NF-1. The patient was initially diagnosed with a spindle cell neoplasm of the kidney with peripheral nerve sheath differentiation. Eventually, the patient developed a right breast mass that was diagnosed as metastatic MPNST. The patient refused any kind of treatment and died 6 months later in hospice care. PMID:27453670

  10. Tailoring of chitosan scaffolds with heparin and γ-aminopropyltriethoxysilane for promoting peripheral nerve regeneration.

    PubMed

    Li, Guicai; Zhang, Luzhong; Yang, Yumin

    2015-10-01

    Chitosan has been well known for promoting peripheral nerve regeneration, however, its effect is still not as good as that of autografts. In this study, the feasibility of using negatively charged heparin and positively charged γ-aminopropyltriethoxysilane (APTE) treatment as biocompatible modification of lyophilized porous chitosanscaffolds was evaluated. The morphology of the prepared chitosan scaffolds as a function of treatment with different charged molecules showed no significant differences, while a skin-like surface was observed for the scaffolds modified with high APTE concentration and heparin. The quantitative and qualitative characterization of heparin and amino densities by Toluidine Blue O (TBO) and Acid Orange (AO) assays confirmed the successful immobilization of heparin and APTE on the chitosan scaffolds. The measurement of surface charge densities indicated that the scaffolds treated with APTE showed increased charge densities while heparin decreased the cationic charge density. Moreover, the fabricated charge processed chitosan scaffolds were stable after immersion in phosphate buffer saline for more than ten days. Further on, the chitosan scaffolds processed with 2 mg/mL heparin did facilitate the attachment, proliferation and maintain the biological function of Schwann cells in vitro. The study demonstrates that chitosan scaffolds treated with suitable heparin concentration provides an effective selection for biomaterials surface modification and shows great potential for the application in peripheral nerve regeneration. PMID:26222407

  11. Tailoring of chitosan scaffolds with heparin and γ-aminopropyltriethoxysilane for promoting peripheral nerve regeneration.

    PubMed

    Li, Guicai; Zhang, Luzhong; Yang, Yumin

    2015-10-01

    Chitosan has been well known for promoting peripheral nerve regeneration, however, its effect is still not as good as that of autografts. In this study, the feasibility of using negatively charged heparin and positively charged γ-aminopropyltriethoxysilane (APTE) treatment as biocompatible modification of lyophilized porous chitosanscaffolds was evaluated. The morphology of the prepared chitosan scaffolds as a function of treatment with different charged molecules showed no significant differences, while a skin-like surface was observed for the scaffolds modified with high APTE concentration and heparin. The quantitative and qualitative characterization of heparin and amino densities by Toluidine Blue O (TBO) and Acid Orange (AO) assays confirmed the successful immobilization of heparin and APTE on the chitosan scaffolds. The measurement of surface charge densities indicated that the scaffolds treated with APTE showed increased charge densities while heparin decreased the cationic charge density. Moreover, the fabricated charge processed chitosan scaffolds were stable after immersion in phosphate buffer saline for more than ten days. Further on, the chitosan scaffolds processed with 2 mg/mL heparin did facilitate the attachment, proliferation and maintain the biological function of Schwann cells in vitro. The study demonstrates that chitosan scaffolds treated with suitable heparin concentration provides an effective selection for biomaterials surface modification and shows great potential for the application in peripheral nerve regeneration.

  12. Localized regulation of axonal RanGTPase controls retrograde injury signaling in peripheral nerve

    PubMed Central

    Yudin, Dmitry; Hanz, Shlomit; Yoo, Soonmoon; Iavnilovitch, Elena; Willis, Dianna; Gradus, Tal; Vuppalanchi, Deepika; Segal-Ruder, Yael; Ben-Yaakov, Keren; Hieda, Miki; Yoneda, Yoshihiro; Twiss, Jeffery L.; Fainzilber, Mike

    2008-01-01

    Summary Peripheral sensory neurons respond to axon injury by activating an importin-dependent retrograde signaling mechanism. How is this mechanism regulated? Here we show that Ran GTPase and its associated effectors RanBP1 and RanGAP regulate the formation of importin signaling complexes in injured axons. A gradient of nuclear RanGTP versus cytoplasmic RanGDP is thought to be fundamental for the organization of eukaryotic cells. Surprisingly, we find RanGTP in sciatic nerve axoplasm, distant from neuronal cell bodies and nuclei, and in association with dynein and importin α. Following injury, localized translation of RanBP1 stimulates RanGTP dissociation from importins and subsequent hydrolysis, thereby allowing binding of newly synthesized importin β to importin α and dynein. Perturbation of RanGTP hydrolysis or RanBP1 blockade at axonal injury sites reduces the neuronal conditioning lesion response. Thus, neurons employ localized mechanisms of Ran regulation to control retrograde injury signaling in peripheral nerve. PMID:18667152

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

    PubMed

    Hanigan, William

    2010-05-01

    Although the clinical and electrical diagnoses and treatments of peripheral nerve injuries (PNIs) had been described prior to World War I, many reports were fragmented and incomplete. Individual physicians' experiences were not extensive, and in 1914 the patient with a PNI remained a subject of medical curiosity, and was hardly a focus of comprehensive care. World War I altered these conditions; casualties with septic wounds and PNIs swamped the general hospitals. By 1915, specialized hospitals or wards were developed to care for neurological injuries. In the United Kingdom, Sir Robert Jones developed the concept of Military Orthopedic Centres, with coordinated specialized care and rehabilitation. Military appointments of neurologists and electrotherapists sharpened clinical diagnoses and examinations. Surgical techniques were introduced, then discarded or accepted as surgeons developed skills to meet the new conditions. The US Surgeon General, William Gorgas, and his consultant in neurosurgery, Charles Frazier, went a step further, with the organization of a research laboratory as well as the establishment of a Peripheral Nerve Commission and Registry. Despite these developments and good intentions, postwar follow-up for PNIs remained incomplete at best. Records were lost, personnel transferred, and patients discharged from the system. The lack of a standardized grading system seriously impaired the ability to record clinical changes and compare outcomes. Nevertheless, specialized treatment of a large number of PNIs during World War I established a foundation for comprehensive care that influenced military medical services in the next world war.

  14. Comprehensive Evaluation of Peripheral Nerve Regeneration in the Acute Healing Phase Using Tissue Clearing and Optical Microscopy in a Rodent Model

    PubMed Central

    Keating, Cameron P.; Senthil-Kumar, Prabhu; Zhao, Jie; Randolph, Mark A.; Winograd, Jonathan M.; Evans, Conor L.

    2014-01-01

    Peripheral nerve injury (PNI), a common injury in both the civilian and military arenas, is usually associated with high healthcare costs and with patients enduring slow recovery times, diminished quality of life, and potential long-term disability. Patients with PNI typically undergo complex interventions but the factors that govern optimal response are not fully characterized. A fundamental understanding of the cellular and tissue-level events in the immediate postoperative period is essential for improving treatment and optimizing repair. Here, we demonstrate a comprehensive imaging approach to evaluate peripheral nerve axonal regeneration in a rodent PNI model using a tissue clearing method to improve depth penetration while preserving neural architecture. Sciatic nerve transaction and end-to-end repair were performed in both wild type and thy-1 GFP rats. The nerves were harvested at time points after repair before undergoing whole mount immunofluorescence staining and tissue clearing. By increasing the optic depth penetration, tissue clearing allowed the visualization and evaluation of Wallerian degeneration and nerve regrowth throughout entire sciatic nerves with subcellular resolution. The tissue clearing protocol did not affect immunofluorescence labeling and no observable decrease in the fluorescence signal was observed. Large-area, high-resolution tissue volumes could be quantified to provide structural and connectivity information not available from current gold-standard approaches for evaluating axonal regeneration following PNI. The results are suggestive of observed behavioral recovery in vivo after neurorrhaphy, providing a method of evaluating axonal regeneration following repair that can serve as an adjunct to current standard outcomes measurements. This study demonstrates that tissue clearing following whole mount immunofluorescence staining enables the complete visualization and quantitative evaluation of axons throughout nerves in a PNI model

  15. Flexible adaptation to an artificial recurrent connection from muscle to peripheral nerve in man.

    PubMed

    Kato, Kenji; Sasada, Syusaku; Nishimura, Yukio

    2016-02-01

    Controlling a neuroprosthesis requires learning a novel input-output transformation; however, how subjects incorporate this into limb control remains obscure. To elucidate the underling mechanisms, we investigated the motor adaptation process to a novel artificial recurrent connection (ARC) from a muscle to a peripheral nerve in healthy humans. In this paradigm, the ulnar nerve was electrically stimulated in proportion to the activation of the flexor carpi ulnaris (FCU), which is ulnar-innervated and monosynaptically innervated from Ia afferents of the FCU, defined as the "homonymous muscle," or the palmaris longus (PL), which is not innervated by the ulnar nerve and produces similar movement to the FCU, defined as the "synergist muscle." The ARC boosted the activity of the homonymous muscle and wrist joint movement during a visually guided reaching task. Participants could control muscle activity to utilize the ARC for the volitional control of wrist joint movement and then readapt to the absence of the ARC to either input muscle. Participants reduced homonymous muscle recruitment with practice, regardless of the input muscle. However, the adaptation process in the synergist muscle was dependent on the input muscle. The activity of the synergist muscle decreased when the input was the homonymous muscle, whereas it increased when it was the synergist muscle. This reorganization of the neuromotor map, which was maintained as an aftereffect of the ARC, was observed only when the input was the synergist muscle. These findings demonstrate that the ARC induced reorganization of neuromotor map in a targeted and sustainable manner. PMID:26631144

  16. Upslope treadmill exercise enhances motor axon regeneration but not functional recovery following peripheral nerve injury.

    PubMed

    Cannoy, Jill; Crowley, Sam; Jarratt, Allen; Werts, Kelly LeFevere; Osborne, Krista; Park, Sohee; English, Arthur W

    2016-09-01

    Following peripheral nerve injury, moderate daily exercise conducted on a level treadmill results in enhanced axon regeneration and modest improvements in functional recovery. If the exercise is conducted on an upwardly inclined treadmill, even more motor axons regenerate successfully and reinnervate muscle targets. Whether this increased motor axon regeneration also results in greater improvement in functional recovery from sciatic nerve injury was studied. Axon regeneration and muscle reinnervation were studied in Lewis rats over an 11 wk postinjury period using stimulus evoked electromyographic (EMG) responses in the soleus muscle of awake animals. Motor axon regeneration and muscle reinnervation were enhanced in slope-trained rats. Direct muscle (M) responses reappeared faster in slope-trained animals than in other groups and ultimately were larger than untreated animals. The amplitude of monosynaptic H reflexes recorded from slope-trained rats remained significantly smaller than all other groups of animals for the duration of the study. The restoration of the amplitude and pattern of locomotor EMG activity in soleus and tibialis anterior and of hindblimb kinematics was studied during treadmill walking on different slopes. Slope-trained rats did not recover the ability to modulate the intensity of locomotor EMG activity with slope. Patterned EMG activity in flexor and extensor muscles was not noted in slope-trained rats. Neither hindblimb length nor limb orientation during level, upslope, or downslope walking was restored in slope-trained rats. Slope training enhanced motor axon regeneration but did not improve functional recovery following sciatic nerve transection and repair. PMID:27466130

  17. Clinical observation of peripheral nerve injury in 2 patients with cancer after radiotherapy

    PubMed Central

    Liang, Li; Jia, Ting-zhen; Zhang, Shu-lan; Wang, Mo-pei; Ma, Li-Wen; Liu, Qiang

    2013-01-01

    Aim of the study This study aims to analyze the clinical manifestations and sequelae of peripheral nerve radiation damage of two cases of cancer patients after radiotherapy at the corresponding sites in clinical practice and to summarize experiences and lesions in order to provide a reference for future tumor radiotherapy. Material and methods Some data of two cases of patients, such as doses of radiotherapy, clinical manifestations and damage occurrence time, were collected and examinations were conducted to define diagnosis. Afterwards, therapies and follow-up were conducted. Results Case 1 (rectal cancer) was diagnosed as mild left lower extremity nerve damage. After the symptomatic treatment, the disease condition was improved, and there was no tumor recurrence sign. Case 2 (breast cancer) was diagnosed as left brachial plexus damage, and left upper extremity movement function was lost completely. While the analgesic treatment was conducted, anti-tumor relevant treatments were being carried out. Conclusions Radiotherapy can cause different extents of radioactive nerve damage. In practice, it is necessary to constantly improve the radiotherapy technology level and actively prevent the occurrence of complications. Once symptoms appear, the diagnosis and treatment should be conducted as early as possible in order to avoid aggravating damage to cause dysfunction and cause lifetime pain to patients. PMID:23788990

  18. Flexible adaptation to an artificial recurrent connection from muscle to peripheral nerve in man.

    PubMed

    Kato, Kenji; Sasada, Syusaku; Nishimura, Yukio

    2016-02-01

    Controlling a neuroprosthesis requires learning a novel input-output transformation; however, how subjects incorporate this into limb control remains obscure. To elucidate the underling mechanisms, we investigated the motor adaptation process to a novel artificial recurrent connection (ARC) from a muscle to a peripheral nerve in healthy humans. In this paradigm, the ulnar nerve was electrically stimulated in proportion to the activation of the flexor carpi ulnaris (FCU), which is ulnar-innervated and monosynaptically innervated from Ia afferents of the FCU, defined as the "homonymous muscle," or the palmaris longus (PL), which is not innervated by the ulnar nerve and produces similar movement to the FCU, defined as the "synergist muscle." The ARC boosted the activity of the homonymous muscle and wrist joint movement during a visually guided reaching task. Participants could control muscle activity to utilize the ARC for the volitional control of wrist joint movement and then readapt to the absence of the ARC to either input muscle. Participants reduced homonymous muscle recruitment with practice, regardless of the input muscle. However, the adaptation process in the synergist muscle was dependent on the input muscle. The activity of the synergist muscle decreased when the input was the homonymous muscle, whereas it increased when it was the synergist muscle. This reorganization of the neuromotor map, which was maintained as an aftereffect of the ARC, was observed only when the input was the synergist muscle. These findings demonstrate that the ARC induced reorganization of neuromotor map in a targeted and sustainable manner.

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

    PubMed Central

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

    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. PMID:25961054

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

    NASA Astrophysics Data System (ADS)

    Desai, Vidhi

    Peripheral nerves offer unique accessibility to the innate motor and sensory pathways that can be interfaced with high degree of selectivity for intuitive and bidirectional control of advanced upper extremity prosthetic limbs. Several peripheral nerve interfaces have been proposed and investigated over the last few decades with significant progress made in the area of sensory feedback. However, clinical translation still remains a formidable challenge due to the lack of long term recordings. Prominent causes include signal degradation, eventual interface failures, and lack of specificity in the low amplitude nerve signals. This dissertation evaluates the capabilities of the newly developed Regenerative Multi-electrode Interface (REMI) by the characterization of signal quality progression, the identification of interfaced axon types, and the demonstration of "functional linkage" between acquired signals and target organs. Chapter 2 details the chronic recording of high quality signals from REMI in sciatic nerve which remained stable over a 120 day implantation period indicative of minimal ongoing tissue response with no detrimental effects on the recording ability. The dominant cause of failures was attributable to abiotic factors pertaining to the connector/wire breakage, observed in 76% of REMI implants. Also, the REMI implants had 20% higher success rate and significantly larger Signal to Noise Ratio (SNR) in comparison to the Utah Slanted Electrode Array (USEA). Chapter 3 describes the successful feasibility of interfacing with motor and sensory axons by REMI implantation in the tibial and sural fascicles of the sciatic nerve. A characteristic sampling bias towards recording signals from medium-to-large diameter axons that are primarily involved in mechanoception and proprioception sensory functions was uncovered. Specific bursting units (Inter Spike Interval of 30-70ms) were observed most frequently from the tibial fascicle during bipedal locomotion. Chapter 4

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

    PubMed Central

    2011-01-01

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

  2. Peripheral nerve blocks on the upper extremity: Technique of landmark-based and ultrasound-guided approaches.

    PubMed

    Steinfeldt, T; Volk, T; Kessler, P; Vicent, O; Wulf, H; Gottschalk, A; Lange, M; Schwartzkopf, P; Hüttemann, E; Tessmann, R; Marx, A; Souquet, J; Häger, D; Nagel, W; Biscoping, J; Schwemmer, U

    2015-11-01

    The German Society of Anaesthesiology and Intensive Care Medicine (Deutsche Gesellschaft für Anästhesiologie und Intensivmedizin, DGAI) established an expert panel to develop preliminary recommendations for the application of peripheral nerve blocks on the upper extremity. The present recommendations state in different variations how ultrasound and/or electrical nerve stimulation guided nerve blocks should be performed. The description of each procedure is rather a recommendation than a guideline. The anaesthesiologist should select the variation of block which provides the highest grade of safety according to his individual opportunities. The first section comprises recommendations regarding dosages of local anaesthetics, general indications and contraindications for peripheral nerve blocks and informations about complications. In the following sections most common blocks techniques on the upper extremity are described. PMID:26408023

  3. Ciguatoxin reduces regenerative capacity of axotomized peripheral neurons and delays functional recovery in pre-exposed mice after peripheral nerve injury.

    PubMed

    Au, Ngan Pan Bennett; Kumar, Gajendra; Asthana, Pallavi; Tin, Chung; Mak, Yim Ling; Chan, Leo Lai; Lam, Paul Kwan Sing; Ma, Chi Him Eddie

    2016-01-01

    Ciguatera fish poisoning (CFP) results from consumption of tropical reef fish containing ciguatoxins (CTXs). Pacific (P)-CTX-1 is among the most potent known CTXs and the predominant source of CFP in the endemic region responsible for the majority of neurological symptoms in patients. Chronic and persistent neurological symptoms occur in some CFP patients, which often result in incomplete functional recovery for years. However, the direct effects of exposure to CTXs remain largely unknown. In present study, we exposed mice to CTX purified from ciguatera fish sourced from the Pacific region. P-CTX-1 was detected in peripheral nerves within hours and persisted for two months after exposure. P-CTX-1 inhibited axonal regrowth from axotomized peripheral neurons in culture. P-CTX-1 exposure reduced motor function in mice within the first two weeks of exposure before returning to baseline levels. These pre-exposed animals exhibited delayed sensory and motor functional recovery, and irreversible motor deficits after peripheral nerve injury in which formation of functional synapses was impaired. These findings are consistent with reduced muscle function, as assessed by electromyography recordings. Our study provides strong evidence that the persistence of P-CTX-1 in peripheral nerves reduces the intrinsic growth capacity of peripheral neurons, resulting in delayed functional recovery after injury. PMID:27229176

  4. Ciguatoxin reduces regenerative capacity of axotomized peripheral neurons and delays functional recovery in pre-exposed mice after peripheral nerve injury

    PubMed Central

    Au, Ngan Pan Bennett; Kumar, Gajendra; Asthana, Pallavi; Tin, Chung; Mak, Yim Ling; Chan, Leo Lai; Lam, Paul Kwan Sing; Ma, Chi Him Eddie

    2016-01-01

    Ciguatera fish poisoning (CFP) results from consumption of tropical reef fish containing ciguatoxins (CTXs). Pacific (P)-CTX-1 is among the most potent known CTXs and the predominant source of CFP in the endemic region responsible for the majority of neurological symptoms in patients. Chronic and persistent neurological symptoms occur in some CFP patients, which often result in incomplete functional recovery for years. However, the direct effects of exposure to CTXs remain largely unknown. In present study, we exposed mice to CTX purified from ciguatera fish sourced from the Pacific region. P-CTX-1 was detected in peripheral nerves within hours and persisted for two months after exposure. P-CTX-1 inhibited axonal regrowth from axotomized peripheral neurons in culture. P-CTX-1 exposure reduced motor function in mice within the first two weeks of exposure before returning to baseline levels. These pre-exposed animals exhibited delayed sensory and motor functional recovery, and irreversible motor deficits after peripheral nerve injury in which formation of functional synapses was impaired. These findings are consistent with reduced muscle function, as assessed by electromyography recordings. Our study provides strong evidence that the persistence of P-CTX-1 in peripheral nerves reduces the intrinsic growth capacity of peripheral neurons, resulting in delayed functional recovery after injury. PMID:27229176

  5. L-Ornithine intake affects sympathetic nerve outflows and reduces body weight and food intake in rats.

    PubMed

    Konishi, Yuuki; Koosaka, Yasutaka; Maruyama, Ryuutaro; Imanishi, Kazuki; Kasahara, Kazuaki; Matsuda, Ai; Akiduki, Saori; Hishida, Yukihiro; Kurata, Yasutaka; Shibamoto, Toshishige; Satomi, Jun; Tanida, Mamoru

    2015-02-01

    Ingesting the amino acid l-ornithine effectively improves lipid metabolism in humans, although it is unknown whether it affects the activities of autonomic nerves that supply the peripheral organs related to lipid metabolism, such as adipose tissues. Thus, we investigated the effects of l-ornithine ingestion on autonomic nerves that innervate adipose tissues and the feeding behaviors of rats. Intragastric injection of l-ornithine (2.5%) in urethane-anesthetized rats activated sympathetic nerve activity to white adipose tissue (WAT-SNA), and stimulated sympathetic nerve activity to brown adipose tissue (BAT-SNA). In addition, WAT-SNA responses to l-ornithine were abolished in rats with ablated abdominal vagal nerves. l-ornithine ingestion for 9 weeks also significantly reduced rats' body weight, food intake, and abdominal fat weight. Proopiomelanocortin (POMC) levels in the hypothalamus and uncoupling protein 1 (UCP1) levels in brown adipose tissue were significantly increased in rats that ingested 2.5% l-ornithine for 9 weeks. These results suggested that ingested l-ornithine was taken up in the gastrointestinal organs and stimulated afferent vagal nerves and activated the central nervous system. Subsequently, increased hypothalamic POMC activated sympathetic neurotransmission to adipose tissues and accelerated energy expenditure. PMID:25526897

  6. Peripheral Nerve Damage Facilitates Functional Innervation of Brain Grafts in Adult Sensory Cortex

    NASA Astrophysics Data System (ADS)

    Ebner, Ford F.; Erzurumlu, Reha S.; Lee, Stefan M.

    1989-01-01

    The neuralb pathways that relay information from cutaneous receptors to the cortex provide the somatic sensory information needed for cortical function. The last sensory relay neurons in this pathway have cell bodies in the thalamus and axons that synapse on neurons in the somatosensory cortex. After cortical lesions that damage mature thalamocortical fibers in the somatosensory cortex, we have attempted to reestablish somatosensory cortical function by grafting embryonic neocortical cells into the lesioned area. Such grafts survive in adult host animals but are not innervated by thalamic neurons, and consequently the grafted neurons show little if any spontaneous activity and no responses to cutaneous stimuli. We have reported that transection of peripheral sensory nerves prior to grafting ``conditions'' or ``primes'' the thalamic neurons in the ventrobasal complex so that they extend axons into grafts subsequently placed in the cortical domain of the cut nerve. In this report we present evidence that the ingrowth of ventrobasal fibers leads to graft neurons that become functionally integrated into the sensory circuitry of the host brain. Specifically, the conditioning lesions made prior to grafting produce graft neurons that are spontaneously active and can be driven by natural activation of cutaneous receptors or electrical stimulation of the transected nerve after it regenerates. Furthermore, oxidative metabolism in these grafts reaches levels that are comparable to normal cortex, whereas without prior nerve cut, oxidative metabolism is abnormally low in neocortical grafts. We conclude that damage to the sensory periphery transsynaptically stimulates reorganization of sensory pathways through mechanisms that include axonal elongation and functional synaptogenesis.

  7. Combined Spinal Cord Stimulation and Peripheral Nerve Stimulation for Brachial Plexopathy: A Case Report.

    PubMed

    Choi, Ji Hye; Choi, Shu Chung; Kim, Dong Kyu; Sung, Choon Ho; Chon, Jin Young; Hong, Sung Jin; Lee, Ji Young; Moon, Ho Sik

    2016-03-01

    Brachial plexopathy usually results from an iatrogenic brachial plexus injury and can sometimes cause severe chronic pain and disability. There are a number of possible treatments for this condition, including medication, physical therapy, nerve blocks, and neuromodulation, but they are not always successful. Recently, combined spinal cord stimulation (SCS) and peripheral nerve stimulation (PNS) have been tried for various chronic pain diseases because of their different mechanisms of action.Here, we describe the case of a 54-year-old man who was diagnosed with brachial plexopathy 8 years ago. He underwent video-assisted thoracoscopic surgery to remove a superior mediastinal mass. However, his brachial plexus was damaged during the surgery. Although he had received various treatments, the pain did not improve. For the management of intractable severe pain, he underwent SCS 2 years ago, which initially reduced his pain from numeric rating scale (NRS) 10/10 to NRS 4 - 5/10, but the pain then gradually increased, reaching NRS 8/10, 6 months ago. At that time, he was refractory to other treatments, and we therefore applied PNS in combination with SCS. The PNS electrode was positioned on the radial nerve under ultrasound guidance. After combined PNS and SCS, his background pain disappeared, although a breakthrough pain (NRS 3 - 4/10) was caused intermittently by light touch. Furthermore, the patient's need for analgesics decreased, and he was satisfied with the outcome of this combined treatment. We concluded that combined SCS and PNS is a very useful treatment modality, which can stimulate the target nerve both directly and indirectly, and hence, relieve pain from brachial plexopathy. PMID:27008302

  8. Axon-Schwann cell interaction in degenerating and regenerating peripheral nerve

    SciTech Connect

    Pellegrino, R.G.

    1984-01-01

    Severance of a peripheral nerve stimulates a characteristic sequence of events in the distal stump, including the dissolution of axons and myelin and the proliferation of Schwann cells within their basal lamina. The first part of this thesis employs the cat tibial nerve to examine the relationship between the spatio-temporal pattern of Schwann cell mitosis, loss of the structural and functional properties of axolemma, synthesis of P/sub 0/, the major myelin glycoprotein, and the clearance of morphological myelin. Induction of S phase was measured by determining the uptake of /sup 3/H thymidine into trichloroacetic acid (TCA) precipitates following a 3 hour in vitro incubation in Krebs-Ringers buffer containing /sup 3/H thymidine. Nerve transection stimulated a monophasic increase in /sup 3/H thymidine uptake that peaked at 4 days post-transection throughout an 80 mm length of distal stump. Light microscope autoradiography revealed prominent incorporation into Schwann cells of myelinated fibers. Nerve transection also produced dramatic changes in the intrafascicular binding of /sup 3/H STX which binds to voltage-sensitive sodium channels STX binding fell precipitously to 20% of normal at 4 days post-transection, concurrent with the peak of /sup 3/H thymidine uptake. In conclusion, these studies suggest: (a) Schwann cells divide more or less contemporaneously throughout the distal stump; (b) changes in axons rather than myelin are likely to stimulate the Schwann cell to divide; (c) mitosis regulates other events during Wallerian degeneration, including myelin degeneration and the clearance of sodium channels from nodal axolemma.

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

    PubMed

    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. PMID:27597256

  10. Unravelling crucial biomechanical resilience of myelinated peripheral nerve fibres provided by the Schwann cell basal lamina and PMP22

    PubMed Central

    Rosso, Gonzalo; Liashkovich, Ivan; Gess, Burkhard; Young, Peter; Kun, Alejandra; Shahin, Victor

    2014-01-01

    There is an urgent need for the research of the close and enigmatic relationship between nerve biomechanics and the development of neuropathies. Here we present a research strategy based on the application atomic force and confocal microscopy for simultaneous nerve biomechanics and integrity investigations. Using wild-type and hereditary neuropathy mouse models, we reveal surprising mechanical protection of peripheral nerves. Myelinated peripheral wild-type fibres promptly and fully recover from acute enormous local mechanical compression while maintaining functional and structural integrity. The basal lamina which enwraps each myelinated fibre separately is identified as the major contributor to the striking fibre's resilience and integrity. In contrast, neuropathic fibres lacking the peripheral myelin protein 22 (PMP22), which is closely connected with several hereditary human neuropathies, fail to recover from light compression. Interestingly, the structural arrangement of the basal lamina of Pmp22−/− fibres is significantly altered compared to wild-type fibres. In conclusion, the basal lamina and PMP22 act in concert to contribute to a resilience and integrity of peripheral nerves at the single fibre level. Our findings and the presented technology set the stage for a comprehensive research of the links between nerve biomechanics and neuropathies. PMID:25446378

  11. Unravelling crucial biomechanical resilience of myelinated peripheral nerve fibres provided by the Schwann cell basal lamina and PMP22.

    PubMed

    Rosso, Gonzalo; Liashkovich, Ivan; Gess, Burkhard; Young, Peter; Kun, Alejandra; Shahin, Victor

    2014-12-02

    There is an urgent need for the research of the close and enigmatic relationship between nerve biomechanics and the development of neuropathies. Here we present a research strategy based on the application atomic force and confocal microscopy for simultaneous nerve biomechanics and integrity investigations. Using wild-type and hereditary neuropathy mouse models, we reveal surprising mechanical protection of peripheral nerves. Myelinated peripheral wild-type fibres promptly and fully recover from acute enormous local mechanical compression while maintaining functional and structural integrity. The basal lamina which enwraps each myelinated fibre separately is identified as the major contributor to the striking fibre's resilience and integrity. In contrast, neuropathic fibres lacking the peripheral myelin protein 22 (PMP22), which is closely connected with several hereditary human neuropathies, fail to recover from light compression. Interestingly, the structural arrangement of the basal lamina of Pmp22(-/-) fibres is significantly altered compared to wild-type fibres. In conclusion, the basal lamina and PMP22 act in concert to contribute to a resilience and integrity of peripheral nerves at the single fibre level. Our findings and the presented technology set the stage for a comprehensive research of the links between nerve biomechanics and neuropathies.

  12. Microsurgical management of giant malignant peripheral nerve sheath tumor of the scalp: two case reports and a literature review.

    PubMed

    Wang, Jun; Ou, Shao-wu; Guo, Zong-ze; Wang, Yun-jie; Xing, De-guang

    2013-10-10

    Malignant peripheral nerve sheath tumors of the scalp are rare lesions of the nervous system. Only 14 cases have been reported to date. The field of neurosurgery has struggled with diagnosing and treating these tumors. In this report, we present two cases of giant malignant peripheral nerve sheath tumors of the scalp and retrospectively analyze the clinical features, imaging findings, pathological features, and prognoses of these two patients. Each underwent microsurgery and radiotherapy. In addition, based on a literature review, we discuss the diagnostic and therapeutic strategies used to treat these unusual lesions.

  13. High-resolution ultrasonographic evaluation of "hourglass-like fascicular constriction" in peripheral nerves: a preliminary report.

    PubMed

    Nakashima, Yuko; Sunagawa, Toru; Shinomiya, Rikuo; Ochi, Mitsu

    2014-07-01

    An hourglass-like constriction is a focal fascicular lesion observed in one or a few places in one or a few fascicles of a peripheral nerve trunk, and usually affects the anterior interosseous (AIN) or posterior interosseous (PIN) nerve. Constrictions have previously been discovered only by surgical exploration, and have been unable to be recognized on pre-operative imaging. We encountered some cases in which the lesion was able to be diagnosed pre-operatively by high-resolution ultrasonography; these findings were then confirmed intra-operatively. Five consecutive cases were included in this study. In three cases with constrictions revealed on pre-operative ultrasound, the findings were confirmed intra-operatively. In the remaining two cases in which no constrictions were detected pre-operatively, no constriction was revealed intra-operatively. High-resolution ultrasonography may play a significant role in the diagnosis of hourglass-like constrictions, and may thus lead to significant changes in treatment strategies for AIN and PIN palsy.

  14. Fibroblast-derived tenascin-C promotes Schwann cell migration through β1-integrin dependent pathway during peripheral nerve regeneration.

    PubMed

    Zhang, Zhanhu; Yu, Bin; Gu, Yun; Zhou, Songlin; Qian, Tianmei; Wang, Yongjun; Ding, Guohui; Ding, Fei; Gu, Xiaosong

    2016-03-01

    Peripheral nerve regeneration requires precise coordination and dynamic interaction among various types of cells in the tissue. It remains unclear, however, whether the cellular crosstalk between fibroblasts and Schwann cells (SCs) is related to phenotype modulation of SCs, a critical cellular process after peripheral nerve injury. In this study, microarray analysis revealed that a total of 6,046 genes were differentially expressed in the proximal nerve segment after sciatic nerve transection in rats, and bioinformatics analysis further identified tenascin-C (TNC), an extracellular matrix (ECM) protein, as a key gene regulator. TNC was abundantly produced by nerve fibroblasts accumulating at the lesion site, rather than by SCs as usually expected. TNC significantly promoted SC migration without effects on SC proliferation in primary culture. In co-culture of fibroblasts and SCs, inhibition of TNC expression either by siRNA transfection or antibody blockade could suppress SC migration, while TNC-stimulated SC migration was mediated by TNC binding to β1-integrin receptor in SCs through activation of Rac1 effectors. The in vivo evidence showed that exogenous TNC protein enhanced SC migration and axonal regrowth. Our results highlight that TNC-mediated cellular interaction between fibroblasts and SCs may regulate SC migration through β1-integrin-dependent pathway during peripheral nerve regeneration.

  15. Large-area irradiated low-level laser effect in a biodegradable nerve guide conduit on neural regeneration of peripheral nerve injury in rats.

    PubMed

    Shen, Chiung-Chyi; Yang, Yi-Chin; Liu, Bai-Shuan

    2011-08-01

    This study used a biodegradable composite containing genipin-cross-linked gelatin annexed with β-tricalcium phosphate ceramic particles (genipin-gelatin-tricalcium phosphate, GGT), developed in a previous study, as a nerve guide conduit. The aim of this study was to analyse the influence of a large-area irradiated aluminium-gallium-indium phosphide (AlGaInP) diode laser (660 nm) on the neural regeneration of the transected sciatic nerve after bridging the GGT nerve guide conduit in rats. The animals were divided into two groups: group 1 comprised sham-irradiated controls and group 2 rats underwent low-level laser (LLL) therapy. A compact multi-cluster laser system with 20 AlGaInP laser diodes (output power, 50mW) was applied transcutaneously to the injured peripheral nerve immediately after closing the wound, which was repeated daily for 5 min for 21 consecutive days. Eight weeks after implantation, walking track analysis showed a significantly higher sciatic function index (SFI) score (P<0.05) and better toe spreading development in the laser-treated group than in the sham-irradiated control group. For electrophysiological measurement, both the mean peak amplitude and nerve conduction velocity of compound muscle action potentials (CMAPs) were higher in the laser-treated group than in the sham-irradiated group. The two groups were found to be significantly different during the experimental period (P<0.005). Histomorphometric assessments revealed that the qualitative observation and quantitative analysis of the regenerated nerve tissue in the laser-treated group were superior to those of the sham-irradiated group. Thus, the motor functional, electrophysiologic and histomorphometric assessments demonstrate that LLL therapy can accelerate neural repair of the corresponding transected peripheral nerve after bridging the GGT nerve guide conduit in rats. PMID:21397226

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

    PubMed

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

    2016-04-12

    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.

  17. Peripheral innervation patterns of vestibular nerve afferents in the bullfrog utriculus

    NASA Technical Reports Server (NTRS)

    Baird, Richard A.; Schuff, N. R.

    1994-01-01

    Vestibular nerve afferents innervating the bullfrog utriculus differ in their response dynamics and sensitivity to natural stimulation. They also supply hair cells that differ markedly in hair bundle morphology. To examine the peripheral innervation patterns of individual utricular afferents more closely, afferent fibers were labeled by the extracellular injection of horseradish peroxidase (HRP) into the vestibular nerve after sectioning the vestibular nerve medial to Scarpa's ganglion to allow the degeneration of sympathetic and efferent fibers. The peripheral arborizations of individual afferents were then correlated with the diameters of their parent axons, the regions of the macula they innervate, and the number and type of hair cells they supply. The utriculus is divided by the striola, a narrow zone of distinctive morphology, into media and lateral parts. Utiricular afferents were classified as striolar or extrastriolar according to the epithelial entrance of their parent axons and the location of their terminal fields. In general, striolar afferents had thicker parent axons, fewer subepithelial bifurcations, larger terminal fields, and more synaptic endings than afferents in extrstriolar regions. Afferents in a juxtastriolar zone, immediately adjacent to the medial striola, had innervation patterns transitional between those in the striola and more peripheral parts of the medial extrastriola. moast afferents innervated only a single macular zone. The terminal fields of striolar afferents, with the notable exception of a few afferents with thin parent axons, were generally confined to one side of the striola. Hair cells in the bullfrog utriculus have perviously been classified into four types based on hair bundle morphology. Afferents in the extrastriolar and juxtastriolar zones largely or exclusively innervated Type B hair cells, the predominant hair cell type in the utricular macula. Striolar afferents supplied a mixture of four hair cell types, but largely

  18. l-Ornithine affects peripheral clock gene expression in mice

    PubMed Central

    Fukuda, Takafumi; Haraguchi, Atsushi; Kuwahara, Mari; Nakamura, Kaai; Hamaguchi, Yutaro; Ikeda, Yuko; Ishida, Yuko; Wang, Guanying; Shirakawa, Chise; Tanihata, Yoko; Ohara, Kazuaki; Shibata, Shigenobu

    2016-01-01

    The peripheral circadian clock is entrained by factors in the external environment such as scheduled feeding, exercise, and mental and physical stresses. In addition, recent studies in mice demonstrated that some food components have the potential to control the peripheral circadian clock during scheduled feeding, although information about these components remains limited. l-Ornithine is a type of non-protein amino acid that is present in foods and has been reported to have various physiological functions. In human trials, for example, l-ornithine intake improved a subjective index of sleep quality. Here we demonstrate, using an in vivo monitoring system, that repeated oral administration of l-ornithine at an early inactive period in mice induced a phase advance in the rhythm of PER2 expression. By contrast, l-ornithine administration to mouse embryonic fibroblasts did not affect the expression of PER2, indicating that l-ornithine indirectly alters the phase of PER2. l-Ornithine also increased plasma levels of insulin, glucose and glucagon-like peptide-1 alongside mPer2 expression, suggesting that it exerts its effects probably via insulin secretion. Collectively, these findings demonstrate that l-ornithine affects peripheral clock gene expression and may expand the possibilities of L-ornithine as a health food. PMID:27703199

  19. Identification of the sensory and motor fascicles in the peripheral nerve: A historical review and recent progress.

    PubMed

    Xianyu, Meng; Zhenggang, Bi; Laijin, Lu

    2016-01-01

    The aim of the study was to critically review the clinical approach to distinguish the sensory and motor nerve fascicles of the peripheral nerve system and to explore potential novel techniques to meet the clinical needs. The principles and shortcomings of the currently used methods for identification of sensory and motor nerve fascicles, including nerve morphology, electrical stimulation, spectroscopy, enzymohistochemistry staining (acetylcholinesterase [AchE], carbonic anhydrase [CA] and choline acetyltransferase [ChAC] histochemistry staining methods), and immunochemical staining were systematically reviewed. The progress in diffusion tensor imaging, proteomic approaches, and quantum dots (QDs) assessment in clinical applications to identify sensory or motor fascicles has been discussed. Traditional methods such as physical and enzymohistochemical methods are not suitable for the precise differentiation of sensory and motor nerve fascicles. Immunohistochemical staining using AchE, CA, and ChAC is promising in differentiation of sensory and motor nerve fascicles. Diffusion tensor imaging can reflect morphological details of nerve fibers. Proteomics can reveal the dynamics of specific proteins discriminating sensory and motor fascicles. QDs, with their size-dependent optical properties, make them the ideal protein markers for identification of the sensory or motor nerves. Diffusion tensor imaging, proteomics and QDs-imaging will facilitate the clinical identification of motor and sensory nerve fascicles, help in improving surgical success rates and assist in postoperative functional recovery. PMID:27625224

  20. Mannose-6-phosphate facilitates early peripheral nerve regeneration in thy-1-YFP-H mice.

    PubMed

    Harding, A J; Christmas, C R; Ferguson, M W J; Loescher, A R; Robinson, P P; Boissonade, F M

    2014-10-24

    The formation of scar tissue following nerve injury has been shown to adversely affect nerve regeneration and evidence suggests that mannose-6-phosphate (M6P), a potential scar reducing agent that affects transforming growth factor (TGF)-β activation, may enhance nerve regeneration. In this study we utilized thy-1-YFP-H mice - a transgenic strain expressing yellow fluorescent protein (YFP) within a subset of axons - to enable visual analysis of axons regenerating through a nerve graft. Using this strain of mouse we have developed analysis techniques to visualize and quantify regeneration of individual axons across the injury site following the application of either M6P or vehicle to the site of nerve injury. No significant differences were found in the proportion of axons regenerating through the graft between M6P- and vehicle-treated grafts at any point along the graft length. Maximal sprouting occurred at 1.0mm from the proximal graft ending in both groups. The maximum change in sprouting levels for both treatment groups occurred between the graft start and 0.5-mm interval for both treatment groups. The difference between repair groups was significant at this point with a greater increase seen in the vehicle group than the M6P group. The average length of axons regenerating across the initial graft entry was significantly shorter in M6P- than in vehicle-treated grafts, indicating that they encountered less impedance. Application of M6P appears to reduce the disruption of regenerating axons and may therefore facilitate quicker recovery; this is likely to result from altered scar tissue formation in M6P grafts in the early stages of recovery. This study also establishes the usefulness of our methods of analysis using the thy-1-YFP-H mouse strain to visualize and quantify regeneration at the level of the individual axon.

  1. Identification of a peripheral nerve neurite growth-promoting activity by development and use of an in vitro bioassay.

    PubMed Central

    Sandrock, A W; Matthew, W D

    1987-01-01

    The effective regeneration of severed neuronal axons in the peripheral nerves of adult mammals may be explained by the presence of molecules in situ that promote the effective elongation of neurites. The absence of such molecules in the central nervous system of these animals may underlie the relative inability of axons to regenerate in this tissue after injury. In an effort to identify neurite growth-promoting molecules in tissues that support effective axonal regeneration, we have developed an in vitro bioassay that is sensitive to substrate-bound factors of peripheral nerve that influence the growth of neurites. In this assay, neonatal rat superior cervical ganglion explants are placed on longitudinal cryostat sections of fresh-frozen sciatic nerve, and the regrowing axons are visualized by catecholamine histofluorescence. Axons are found to regenerate effectively over sciatic nerve tissue sections. When ganglia are similarly explanted onto cryostat sections of adult rat central nervous system tissue, however, axonal regeneration is virtually absent. We have begun to identify the molecules in peripheral nerve that promote effective axonal regeneration by examining the effect of antibodies that interfere with the activity of previously described neurite growth-promoting factors. Axonal elongation over sciatic nerve tissue was found to be sensitive to the inhibitory effects of INO (for inhibitor of neurite outgrowth), a monoclonal antibody that recognizes and inhibits a neurite growth-promoting activity from PC-12 cell-conditioned medium. The INO antigen appears to be a molecular complex of laminin and heparan sulfate proteoglycan. In contrast, a rabbit antiserum that recognizes laminin purified from mouse Engelbreth-Holm-Swarm (EHS) sarcoma, stains the Schwann cell basal lamina of peripheral nerve, and inhibits neurite growth over purified laminin substrata has no detectable effect on the rate of axonal regeneration in our assay. Images PMID:3477817

  2. Malignant peripheral nerve sheath tumor arising in a traumatic neuroma: a case report.

    PubMed

    Kos, Zuzana; Robertson, Susan J; Purgina, Bibianna M; Verma, Shailendra; Gravel, Denis H

    2013-10-01

    A 67-year-old woman with a history of breast cancer presented with a soft tissue mass at the site of a remote, non-neoplastic lumbar surgery. Excisional biopsy revealed a traumatic neuroma. Five years later she re-presented with a rapidly growing, tender nodule at the same site. An excisional biopsy was again performed and revealed a tumor composed of malignant epithelioid and spindle cells merging imperceptibly with residual traumatic neuroma. The malignant cells were positive for vimentin, S-100 and micropthalmia transcription factor. They were negative for cytokeratins, muscle markers, Melan-A, HMB45, glial fibrillary acidic protein, and myelin basic protein. Electron microscopy showed no melanosomes. The diagnosis of malignant peripheral nerve sheath tumor arising within a long-standing traumatic neuroma was rendered and represents a hitherto unreported origin of this rare, aggressive soft tissue sarcoma.

  3. Lithium Enhances Axonal Regeneration in Peripheral Nerve by Inhibiting Glycogen Synthase Kinase 3β Activation

    PubMed Central

    Su, Huanxing; Yuan, Qiuju; Qin, Dajiang; Yang, Xiaoying; So, Kwok-Fai; Wu, Wutian

    2014-01-01

    Brachial plexus injury often involves traumatic root avulsion resulting in permanent paralysis of the innervated muscles. The lack of sufficient regeneration from spinal motoneurons to the peripheral nerve (PN) is considered to be one of the major causes of the unsatisfactory outcome of various surgical interventions for repair of the devastating injury. The present study was undertaken to investigate potential inhibitory signals which influence axonal regeneration after root avulsion injury. The results of the study showed that root avulsion triggered GSK-3β activation in the injured motoneurons and remaining axons in the ventral funiculus. Systemic application of a clinical dose of lithium suppressed activated GSK-3β in the lesioned spinal cord to the normal level and induced extensive axonal regeneration into replanted ventral roots. Our study suggests that GSK-3β activity is involved in negative regulation for axonal elongation and regeneration and lithium, the specific GSK-3β inhibitor, enhances motoneuron regeneration from CNS to PNS. PMID:24967390

  4. Malignant peripheral nerve sheath tumor presenting as orbito temporal lump: Case report and review of literature

    PubMed Central

    Panigrahi, Souvagya; Mishra, Sudhansu S.; Mishra, Sanjib; Das, Srikant

    2016-01-01

    Malignant peripheral nerve sheath tumor (MPNST) is a rare soft tissue sarcoma. The most common anatomical sites include the upper and lower extremities and trunk and less commonly the head and neck. To our knowledge, few patients with a cranial or facial MPNST have been reported. We report such a lesion in a 35-year-old woman who presented with left sided rapidly progressive proptosis and visual loss due to an orbital lump extending up to the temporal lobe. Cranial imaging showed a huge mass invading the orbital wall and temporal bone. The presumptive diagnosis was a malignant orbital tumor. Preoperative fine needle aspiration cytology of the orbital mass came to be neurofibroma. Near total resection of the tumor was done. Histopathology revealed MPNST which was subsequently confirmed on the basis of immunopositivity for S-100. The patient recovered uneventfully and was discharged 8 days after surgery with an advice to attend cancer institute for possible radiotherapy. PMID:27057226

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

    PubMed Central

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

    2016-01-01

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

  6. Malignant peripheral nerve sheath tumor presenting as orbito temporal lump: Case report and review of literature.

    PubMed

    Panigrahi, Souvagya; Mishra, Sudhansu S; Mishra, Sanjib; Das, Srikant

    2016-01-01

    Malignant peripheral nerve sheath tumor (MPNST) is a rare soft tissue sarcoma. The most common anatomical sites include the upper and lower extremities and trunk and less commonly the head and neck. To our knowledge, few patients with a cranial or facial MPNST have been reported. We report such a lesion in a 35-year-old woman who presented with left sided rapidly progressive proptosis and visual loss due to an orbital lump extending up to the temporal lobe. Cranial imaging showed a huge mass invading the orbital wall and temporal bone. The presumptive diagnosis was a malignant orbital tumor. Preoperative fine needle aspiration cytology of the orbital mass came to be neurofibroma. Near total resection of the tumor was done. Histopathology revealed MPNST which was subsequently confirmed on the basis of immunopositivity for S-100. The patient recovered uneventfully and was discharged 8 days after surgery with an advice to attend cancer institute for possible radiotherapy. PMID:27057226

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

    PubMed Central

    Verdiyan, Ekaterina E.; Allakhverdiev, Elvin S.; Maksimov, Georgy V.

    2016-01-01

    In the present paper we consider a new type of mechanism by which neurotransmitter acetylcholine (ACh) regulates the properties of peripheral nerve fibers myelin. Our data show the importance of the relationship between the changes in the number of Schwann cell (SC) acetylcholine receptors (AChRs) and the axon excitation (different intervals between action potentials (APs)). Using Raman spectroscopy, an effect of activation of SC AChRs on the myelin membrane fluidity was investigated. It was found, that ACh stimulates an increase in lipid ordering degree of the myelin lipids, thus providing evidence for specific role of the “axon-SC” interactions at the axon excitation. It was proposed, that during the axon excitation, the SC membrane K+- depolarization and the Ca2+—influx led to phospholipase activation or exocytosis of intracellular membrane vesicles and myelin structure reorganization. PMID:27455410

  8. Publications on Peripheral Nerve Injuries during World War I: A Dramatic Increase in Knowledge.

    PubMed

    Koehler, Peter J

    2016-01-01

    Publications from French (Jules Tinel and Chiriachitza Athanassio-Bénisty), English (James Purves-Stewart, Arthur Henry Evans and Hartley Sidney Carter), German (Otfrid Foerster and Hermann Oppenheim) and American (Charles Harrison Frazier and Byron Stookey) physicians from both sides of the front during World War I (WWI) contributed to a dramatic increase in knowledge about peripheral nerve injuries. Silas Weir Mitchell's original experience with respect to these injuries, and particularly causalgia, during the American Civil War was further expanded in Europe during WWI. Following the translation of one of his books, he was referred to mainly by French physicians. During WWI, several French books were in turn translated into English, which influenced American physicians, as was observed in the case of Byron Stookey. The establishment of neurological centres played an important role in the concentration of experience and knowledge. Several eponyms originated during this period (including the Hoffmann-Tinel sign and the Froment sign). Electrodiagnostic tools were increasingly used.

  9. Malignant peripheral nerve sheath tumour in the nasopharynx of a cow.

    PubMed

    Sydler, T; Lesser, M; Waldern, N; Dennler, M; Bode-Lesniewska, B; Pospischil, A; Braun, U

    2013-11-01

    This case describes the findings in a Swiss Braunvieh cow with a malignant peripheral nerve sheath tumour (MPNST) in the nasopharynx. The major clinical signs were mixed dyspnoea with inspiratory and expiratory noises. Radiographic views of the head revealed an irregular mass with soft-tissue density in the nasopharynx originating from the dorsal pharynx and occupying and restricting the pharyngeal cavity. Endoscopic examination showed a lobulated mass obstructing almost the entire lumen of the aboral nasal passages and nasopharynx. Postmortem examination revealed a lobulated mass in the choanae with a broad attachment to the dorsal pharynx and histologically a soft tissue sarcoma with tumour cells positive for the S-100 and p75NTR (neurotrophin receptor) proteins and negative for CNPase. Electron microscopic examination showed few structures that indicated that the tumour originated from Schwann cells.

  10. The search of the target of promotion: Phenylbenzoate esterase activities in hen peripheral nerve

    SciTech Connect

    Moretto, A. . E-mail: angelo.moretto@icps.it; Nicolli, A.; Lotti, M.

    2007-03-15

    Certain esterase inhibitors, such as carbamates, phosphinates and sulfonyl halides, do not cause neuropathy as some organophosphates, but they may exacerbate chemical or traumatic insults to axons. This phenomenon is called promotion of axonopathies. Given the biochemical and toxicological characteristics of these compounds, the hypothesis was made that the target of promotion is a phenyl valerate (PV) esterase similar to neuropathy target esterase (NTE), the target of organophosphate induced delayed polyneuropathy. However, attempts to identify a PV esterase in hen peripheral nerve have been, so far, unsuccessful. We tested several esters, other than PV, as substrates of esterases from crude homogenate of the hen peripheral nerve. The ideal substrate should be poorly hydrolysed by NTE but extensively by enzyme(s) that are insensitive to non-promoters, such as mipafox, and sensitive to promoters, such as phenyl methane sulfonyl fluoride (PMSF). When phenyl benzoate (PB) was used as substrate, about 65% of total activity was resistant to the non-promoter mipafox (up to 0.5 mM, 20 min, pH 8.0), that inhibits NTE and other esterases. More than 90% of this resistant activity was sensitive to the classical promoter PMSF (1 mM, 20 min, pH 8.0) with an IC{sub 50} of about 0.08 mM (20 min, pH 8.0). On the contrary, the non-promoter p-toluene sulfonyl fluoride caused only about 10% inhibition at 0.5 mM. Several esterase inhibitors including, paraoxon, phenyl benzyl carbamate, di-n-butyl dichlorovinyl phosphate and di-isopropyl fluorophosphate, were tested both in vitro and in vivo for inhibition of this PB activity. Mipafox-resistant PMSF-sensitive PB esterase activity(ies) was inhibited by promoters but not by non promoters and neuropathic compounds.

  11. Galectin-3 Inhibition Is Associated with Neuropathic Pain Attenuation after Peripheral Nerve Injury

    PubMed Central

    Ai, Zisheng; Zheng, Yongjun

    2016-01-01

    Neuropathic pain remains a prevalent and persistent clinical problem because it is often poorly responsive to the currently used analgesics. It is very urgent to develop novel drugs to alleviate neuropathic pain. Galectin-3 (gal3) is a multifunctional protein belonging to the carbohydrate-ligand lectin family, which is expressed by different cells. Emerging studies showed that gal3 elicits a pro-inflammatory response by recruiting and activating lymphocytes, macrophages and microglia. In the study we investigated whether gal3 inhibition could suppress neuroinflammation and alleviate neuropathic pain following peripheral nerve injury. We found that L5 spinal nerve ligation (SNL) increases the expression of gal3 in dorsal root ganglions at the mRNA and protein level. Intrathecal administration of modified citrus pectin (MCP), a gal