Combined Sciatic and Lumbar Plexus Nerve Blocks for the Analgesic Management of Hip Arthroscopy Procedures: A Retrospective Review.

PubMed

Jaffe, J Douglas; Morgan, Theodore Ross; Russell, Gregory B

2017-06-01

Hip arthroscopy is a minimally invasive alternative to open hip surgery. Despite its minimally invasive nature, there can still be significant reported pain following these procedures. The impact of combined sciatic and lumbar plexus nerve blocks on postoperative pain scores and opioid consumption in patients undergoing hip arthroscopy was investigated. A retrospective analysis of 176 patients revealed that compared with patients with no preoperative peripheral nerve block, significant reductions in pain scores to 24 hours were reported and decreased opioid consumption during the post anesthesia care unit (PACU) stay was recorded; no significant differences in opioid consumption out to 24 hours were discovered. A subgroup analysis comparing two approaches to the sciatic nerve block in patients receiving the additional lumbar plexus nerve block failed to reveal a significant difference for this patient population. We conclude that peripheral nerve blockade can be a useful analgesic modality for patients undergoing hip arthroscopy.

Ultrasound guidance in regional anesthesia: state of the art review through challenging clinical scenarios

PubMed Central

Sites, Brian D; Antonakakis, John G

2009-01-01

Ultrasound guided regional anesthesia (UGRA) for peripheral nerve blockade is becoming increasingly popular. The advantage of ultrasound technology is that it affords the anesthesiologist the real time ability to visualize neural structures, needle advancement, and local anesthetic spread. Recent data suggest that UGRA generates improved success rates and reductions in performance times in comparison to traditional approaches. Further, the use of ultrasound technology in peripheral nerve blocks has provided insight into needle–nerve interactions, revealing distinct limitations of nerve stimulator techniques. Given that UGRA requires a unique set of skills, formal standards and guidelines are currently being developed by leadership societies in order to foster education and training. This review article, in a case vignette format, highlights important techniques, concepts, and limitations regarding the use of ultrasound to facilitate regional anesthesia. Clinically relevant aspects of ultrasound physics are also discussed. PMID:22915860

A prospective, randomized comparison between single- and multiple-injection techniques for ultrasound-guided subgluteal sciatic nerve block.

PubMed

Yamamoto, Hiroto; Sakura, Shinichi; Wada, Minori; Shido, Akemi

2014-12-01

It is believed that local anesthetic injected to obtain circumferential spread around nerves produces a more rapid onset and successful blockade after some ultrasound-guided peripheral nerve blocks. However, evidence demonstrating this point is limited only to the popliteal sciatic nerve block, which is relatively easy to perform by via a high-frequency linear transducer. In the present study, we tested the hypothesis that multiple injections of local anesthetic to make circumferential spread would improve the rate of sensory and motor blocks compared with a single-injection technique for ultrasound-guided subgluteal sciatic nerve block, which is considered a relatively difficult block conducted with a low-frequency, curved-array transducer. Ninety patients undergoing knee surgery were divided randomly into 2 groups to receive the ultrasound-guided subgluteal approach to sciatic nerve block with 20 mL of 1.5% mepivacaine with epinephrine. For group M (the multiple-injection technique), the local anesthetic was injected to create circumferential spread around the sciatic nerve without limitation on the number of needle passes. For group S (the single-injection technique), the number of needle passes was limited to 1, and the local anesthetic was injected to create spread along the dorsal surface of the sciatic nerve, during which no adjustment of the needle tip was made. Sensory and motor blockade were assessed in double-blind fashion for 30 minutes after completion of the block. The primary outcome was sensory blockade of all sciatic components tested, including tibial, superficial peroneal, and sural nerves at 30 minutes after injection. Data from 86 patients (43 in each group) were analyzed. Block execution took more time for group M than group S. The proportion of patients with complete sensory blockade of all sciatic components at 30 minutes after injection was significantly larger for group M than group S (41.9% vs 16.3%, P = 0.018). Complete motor blockade of foot and toes extension also was observed more frequently in group M than in group S (67.4% vs 34.9%, P = 0.005 and 51.2% vs 25.6%, P = 0.027, respectively). When ultrasound-guided subgluteal sciatic nerve block is conducted, multiple injections of local anesthetic to make a circumferential spread around the sciatic nerve improve the rate of sensory and motor blocks compared with a single injection.

Norepinephrine reuptake inhibition promotes mobilization in mice: potential impact to rescue low stem cell yields

PubMed Central

Lucas, Daniel; Bruns, Ingmar; Battista, Michela; Mendez-Ferrer, Simon; Magnon, Claire; Kunisaki, Yuya

2012-01-01

The mechanisms mediating hematopoietic stem and progenitor cell (HSPC) mobilization by G-CSF are complex. We have found previously that G-CSF–enforced mobilization is controlled by peripheral sympathetic nerves via norepinephrine (NE) signaling. In the present study, we show that G-CSF likely alters sympathetic tone directly and that methods to increase adrenergic activity in the BM microenvironment enhance progenitor mobilization. Peripheral sympathetic nerve neurons express the G-CSF receptor and ex vivo stimulation of peripheral sympathetic nerve neurons with G-CSF reduced NE reuptake significantly, suggesting that G-CSF potentiates the sympathetic tone by increasing NE availability. Based on these data, we investigated the NE reuptake inhibitor desipramine in HSPC mobilization. Whereas desipramine did not by itself elicit circulating HSPCs, it increased G-CSF–triggered mobilization efficiency significantly and rescued mobilization in a model mimicking “poor mobilizers.” Therefore, these data suggest that blockade of NE reuptake may be a novel therapeutic target to increase stem cell yield in patients. PMID:22422821

Sonographic identification of peripheral nerves in the forearm

PubMed Central

Jackson, Saundra A.; Derr, Charlotte; De Lucia, Anthony; Harris, Marvin; Closser, Zuheily; Miladinovic, Branko; Mhaskar, Rahul; Jorgensen, Theresa; Green, Lori

2016-01-01

Background: With the growing utilization of ultrasonography in emergency medicine combined with the concern over adequate pain management in the emergency department (ED), ultrasound guidance for peripheral nerve blockade in ED is an area of increasing interest. The medical literature has multiple reports supporting the use of ultrasound guidance in peripheral nerve blocks. However, to perform a peripheral nerve block, one must first be able to reliably identify the specific nerve before the procedure. Objective: The primary purpose of this study is to describe the number of supervised peripheral nerve examinations that are necessary for an emergency medicine physician to gain proficiency in accurately locating and identifying the median, radial, and ulnar nerves of the forearm via ultrasound. Methods: The proficiency outcome was defined as the number of attempts before a resident is able to correctly locate and identify the nerves on ten consecutive examinations. Didactic education was provided via a 1 h lecture on forearm anatomy, sonographic technique, and identification of the nerves. Participants also received two supervised hands-on examinations for each nerve. Count data are summarized using percentages or medians and range. Random effects negative binomial regression was used for modeling panel count data. Results: Complete data for the number of attempts, gender, and postgraduate year (PGY) training year were available for 38 residents. Nineteen males and 19 females performed examinations. The median PGY year in practice was 3 (range 1–3), with 10 (27%) in year 1, 8 (22%) in year 2, and 19 (51%) in year 3 or beyond. The median number (range) of required supervised attempts for radial, median, and ulnar nerves was 1 (0–12), 0 (0–10), and 0 (0–17), respectively. Conclusion: We can conclude that the maximum number of supervised attempts to achieve accurate nerve identification was 17 (ulnar), 12 (radial), and 10 (median) in our study. The only significant association was found between years in practice and proficiency (P = 0.025). We plan to expound upon this research with an additional future study that aims to assess the physician's ability to adequately perform peripheral nerve blocks in efforts to decrease the need for more generalized procedural sedation. PMID:27904260

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

PubMed

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

2016-09-01

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

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 concerns for side effects and potential toxicity persist. PMID:26355598

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

PubMed

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

2007-04-01

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

General toxicity and peripheral nerve alterations induced by chronic vincristine treatment in the rabbit.

PubMed

Norido, F; Finesso, M; Fiorito, C; Marini, P; Favaro, G; Fusco, M; Tessari, F; Prosdocimi, M

1988-05-01

The effects of five 0.3 mg/kg intravenous administrations of vincristine (VCR) at weekly intervals were studied in the rabbit. Body weight gain was impaired starting from the first injection, while gross signs of motor paralysis and hair loss initiated from the third week. At the end of the observation period blood analysis revealed normocytic normochromic anemia, elevated serum creatine kinase, and low serum alkaline phosphatase, whereas all the tested parameters related to liver and kidney functions where within normal limits. The decreased number of red blood cells was the consequence of a complete, although reversible, blockade of staminal hematopoietic activity. Two important indexes of peripheral nerve function were clearly altered at the end of the treatment: (i) the sciatic nerve conduction velocity in vitro was 27% reduced and (ii) the latency between sciatic nerve stimulation and extensor digitorum longus (EDL) twitch in vivo was 34% prolonged. The usefulness of the rabbit as an animal model to study side-effects of VCR treatment is discussed.

Additives to local anesthetics for peripheral nerve blocks: Evidence, limitations, and recommendations.

PubMed

Bailard, Neil S; Ortiz, Jaime; Flores, Roland A

2014-03-01

The therapeutic rationale, clinical effectiveness, and potential adverse effects of medications used in combination with local anesthetics for peripheral nerve block therapy are reviewed. A wide range of agents have been tested as adjuncts to peripheral nerve blocks, which are commonly performed for regional anesthesia during or after hand or arm surgery, neck or spine surgery, and other procedures. Studies to determine the comparative merits of nerve block adjuncts are complicated by the wide variety of coadministered local anesthetics and sites of administration and by the heterogeneity of primary endpoints. Sodium bicarbonate has been shown to speed the onset of mepivacaine nerve blocks but delay the onset of others. Epinephrine has been shown to prolong sensory nerve blockade and delay systemic uptake of local anesthetics, thus reducing the risk of anesthetic toxicity. Tramadol, buprenorphine, dexamethasone, and clonidine appear to be effective additives in some situations. Midazolam, magnesium, dexmedetomidine, and ketamine cannot be routinely recommended as nerve block additives due to a dearth of supportive data, modest efficacy, and (in the case of ketamine) significant adverse effects. Recent studies suggest that administering additives intravenously or intramuscularly can provide many of the benefits of perineural administration while reducing the potential for neurotoxicity, contamination, and other hazards. Some additives to local anesthetics can hasten the onset of nerve block, prolong block duration, or reduce toxicity. On the other hand, poorly selected or unnecessary additives may not have the desired effect and may even expose patients to unnecessary risks.

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

PubMed

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

2007-04-01

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

Ultrasound-guided block of sciatic and femoral nerves: an anatomical study.

PubMed

Waag, Sonja; Stoffel, Michael H; Spadavecchia, Claudia; Eichenberger, Urs; Rohrbach, Helene

2014-04-01

The sheep is a popular animal model for human biomechanical research involving invasive surgery on the hind limb. These painful procedures can only be ethically justified with the application of adequate analgesia protocols. Regional anaesthesia as an adjunct to general anaesthesia may markedly improve well-being of these experimental animals during the postoperative period due to a higher analgesic efficacy when compared with systemic drugs, and may therefore reduce stress and consequently the severity of such studies. As a first step 14 sheep cadavers were used to establish a new technique for the peripheral blockade of the sciatic and the femoral nerves under sonographic guidance and to evaluate the success rate by determination of the colorization of both nerves after an injection of 0.5 mL of a 0.1% methylene blue solution. First, both nerves were visualized sonographically. Then, methylene blue solution was injected and subsequently the length of colorization was measured by gross anatomical dissection of the target nerves. Twenty-four sciatic nerves were identified sonographically in 12 out of 13 cadavers. In one animal, the nerve could not be ascertained unequivocally and, consequently, nerve colorization failed. Twenty femoral nerves were located by ultrasound in 10 out of 13 cadavers. In three cadavers, signs of autolysis impeded the scan. This study provides a detailed anatomical description of the localization of the sciatic and the femoral nerves and presents an effective and safe yet simple and rapid technique for performing peripheral nerve blocks with a high success rate.

Phrenic Nerve Palsy and Regional Anesthesia for Shoulder Surgery: Anatomical, Physiologic, and Clinical Considerations.

PubMed

El-Boghdadly, Kariem; Chin, Ki Jinn; Chan, Vincent W S

2017-07-01

Regional anesthesia has an established role in providing perioperative analgesia for shoulder surgery. However, phrenic nerve palsy is a significant complication that potentially limits the use of regional anesthesia, particularly in high-risk patients. The authors describe the anatomical, physiologic, and clinical principles relevant to phrenic nerve palsy in this context. They also present a comprehensive review of the strategies for reducing phrenic nerve palsy and its clinical impact while ensuring adequate analgesia for shoulder surgery. The most important of these include limiting local anesthetic dose and injection volume and performing the injection further away from the C5-C6 nerve roots. Targeting peripheral nerves supplying the shoulder, such as the suprascapular and axillary nerves, may be an effective alternative to brachial plexus blockade in selected patients. The optimal regional anesthetic approach in shoulder surgery should be tailored to individual patients based on comorbidities, type of surgery, and the principles described in this article.

Increased expression of CaV3.2 T-type calcium channels in damaged DRG neurons contributes to neuropathic pain in rats with spared nerve injury.

PubMed

Kang, Xue-Jing; Chi, Ye-Nan; Chen, Wen; Liu, Feng-Yu; Cui, Shuang; Liao, Fei-Fei; Cai, Jie; Wan, You

2018-01-01

Ion channels are very important in the peripheral sensitization in neuropathic pain. Our present study aims to investigate the possible contribution of Ca V 3.2 T-type calcium channels in damaged dorsal root ganglion neurons in neuropathic pain. We established a neuropathic pain model of rats with spared nerve injury. In these model rats, it was easy to distinguish damaged dorsal root ganglion neurons (of tibial nerve and common peroneal nerve) from intact dorsal root ganglion neurons (of sural nerves). Our results showed that Ca V 3.2 protein expression increased in medium-sized neurons from the damaged dorsal root ganglions but not in the intact ones. With whole cell patch clamp recording technique, it was found that after-depolarizing amplitudes of the damaged medium-sized dorsal root ganglion neurons increased significantly at membrane potentials of -85 mV and -95 mV. These results indicate a functional up-regulation of Ca V 3.2 T-type calcium channels in the damaged medium-sized neurons after spared nerve injury. Behaviorally, blockade of Ca V 3.2 with antisense oligodeoxynucleotides could significantly reverse mechanical allodynia. These results suggest that Ca V 3.2 T-type calcium channels in damaged medium-sized dorsal root ganglion neurons might contribute to neuropathic pain after peripheral nerve injury.

Parecoxib added to ropivacaine prolongs duration of axillary brachial plexus blockade and relieves postoperative pain.

PubMed

Liu, Xiaoming; Zhao, Xuan; Lou, Jian; Wang, Yingwei; Shen, Xiaofang

2013-02-01

Cyclooxygenase (COX)-2 antagonist is widely used for intravenous postoperative pain relief. Recent studies reported COX-2 in the spinal dorsal horn could modulate spinal nociceptive processes. Epidural parecoxib in rats showed no neurotoxicity. These findings suggested applying a COX-2 antagonist directly to the central or peripheral nerve might provide better analgesia. We therefore determined: (1) whether the addition of parecoxib to ropivacaine injected locally on the nerve block affected the sensory and motor block times of the brachial plexus nerve block; and (2) whether parecoxib injected locally on the nerve or intravenously had a similar analgesic adjuvant effect. We conducted a randomized controlled trial from January 2009 to November 2010 with 150 patients scheduled for elective forearm surgery, using a multiple-nerve stimulation technique. Patients were randomly allocated into one of three groups: Group A (n = 50) received ropivacaine 0.25% alone on the brachial plexus nerve; Group B (n = 50) received ropivacaine together with 20 mg parecoxib locally on the nerve block; and Group C (n = 50) received 20 mg parecoxib intravenously. We recorded the duration of the sensory and motor blocks, and the most severe pain score during a 24-hour postoperative period. Parecoxib added locally on the nerve block prolonged the motor and sensory block times compared with Group A. However, parecoxib injected intravenously had no such effect. Pain intensity scores in Group B were lower than those in Groups A and C. Parecoxib added to ropivacaine locally on the nerve block prolonged the duration of the axillary brachial plexus blockade and relieved postoperative pain for patients having forearm orthopaedic surgery. Level I, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Selective antagonism of muscarinic receptors is neuroprotective in peripheral neuropathy

PubMed Central

Smith, Darrell R.; Frizzi, Katie; Sabbir, Mohammad Golam; Chowdhury, Subir K. Roy; Mixcoatl-Zecuatl, Teresa; Saleh, Ali; Muttalib, Nabeel; Van der Ploeg, Randy; Ochoa, Joseline; Gopaul, Allison; Tessler, Lori; Wess, Jürgen; Jolivalt, Corinne G.

2017-01-01

Sensory neurons have the capacity to produce, release, and respond to acetylcholine (ACh), but the functional role of cholinergic systems in adult mammalian peripheral sensory nerves has not been established. Here, we have reported that neurite outgrowth from adult sensory neurons that were maintained under subsaturating neurotrophic factor conditions operates under cholinergic constraint that is mediated by muscarinic receptor–dependent regulation of mitochondrial function via AMPK. Sensory neurons from mice lacking the muscarinic ACh type 1 receptor (M1R) exhibited enhanced neurite outgrowth, confirming the role of M1R in tonic suppression of axonal plasticity. M1R-deficient mice made diabetic with streptozotocin were protected from physiological and structural indices of sensory neuropathy. Pharmacological blockade of M1R using specific or selective antagonists, pirenzepine, VU0255035, or muscarinic toxin 7 (MT7) activated AMPK and overcame diabetes-induced mitochondrial dysfunction in vitro and in vivo. These antimuscarinic drugs prevented or reversed indices of peripheral neuropathy, such as depletion of sensory nerve terminals, thermal hypoalgesia, and nerve conduction slowing in diverse rodent models of diabetes. Pirenzepine and MT7 also prevented peripheral neuropathy induced by the chemotherapeutic agents dichloroacetate and paclitaxel or HIV envelope protein gp120. As a variety of antimuscarinic drugs are approved for clinical use against other conditions, prompt translation of this therapeutic approach to clinical trials is feasible. PMID:28094765

Superior perioperative analgesia with combined femoral-obturator-sciatic nerve block in comparison with posterior lumbar plexus and sciatic nerve block for ACL reconstructive surgery.

PubMed

Bareka, Metaxia; Hantes, Michael; Arnaoutoglou, Eleni; Vretzakis, George

2018-02-01

The purpose of this randomized controlled study is to compare and evaluate the intraoperative and post-operative outcome of PLPS nerve block and that of femoral, obturator and sciatic (FOS) nerve block as a method of anaesthesia, in performing ACL reconstruction. Patients referred for elective arthroscopic ACL reconstruction using hamstring autograft were divided in two groups. The first group received combined femoral-obturator-sciatic nerve block (FOS Group) under dual guidance, whereas the second group received posterior lumbar plexus block under neurostimulation and sciatic nerve block (PLPS Group) under dual guidance. The two groups were comparable in terms of age, sex, BMI and athletic activity. The time needed to perform the nerve blocks was significantly shorter for the FOS group (p < 0.005). Similarly, VAS scores during tourniquet inflation and autograft harvesting were significantly higher (p < 0.005) in the PLPS group and this is also reflected in the intraoperative fentanyl consumption and conversion to general anaesthesia. Finally, patients in this group also reported higher post-operative VAS scores and consumed more morphine. Peripheral nerve blockade of FOS nerve block under dual guidance for arthroscopic ACL reconstructive surgery is a safe and tempting anaesthetic choice. The success rate of this technique is higher in comparison with PLPS and results in less peri- and post-operative pain with less opioid consumption. This study provides support for the use of peripheral nerve blocks as an exclusive method for ACL reconstructive surgery in an ambulatory setting with almost no complications. I.

Central muscarinic cholinergic regulation of the systemic inflammatory response during endotoxemia

PubMed Central

Pavlov, Valentin A.; Ochani, Mahendar; Gallowitsch-Puerta, Margot; Ochani, Kanta; Huston, Jared M.; Czura, Christopher J.; Al-Abed, Yousef; Tracey, Kevin J.

2006-01-01

TNF has a critical mediator role in inflammation and is an important therapeutic target. We recently discovered that TNF production is regulated by neural signals through the vagus nerve. Activation of this “cholinergic antiinflammatory pathway” inhibits the production of TNF and other cytokines and protects animals from the inflammatory damage caused by endotoxemia and severe sepsis. Here, we describe a role for central muscarinic acetylcholine receptors in the activation of the cholinergic antiinflammatory pathway. Central muscarinic cholinergic activation by muscarine, the M1 receptor agonist McN-A-343, and the M2 receptor antagonist methoctramine inhibited serum TNF levels significantly during endotoxemia. Centrally administered methoctramine stimulated vagus-nerve activity measured by changes in instantaneous heart-rate variability. Blockade of peripheral muscarinic receptors did not abolish antiinflammatory signaling through the vagus nerve, indicating that peripheral muscarinic receptors on immune cells are not required for the cytokine-regulating activities of the cholinergic antiinflammatory pathway. The role of central muscarinic receptors in activating the cholinergic antiinflammatory pathway is of interest for the use of centrally acting muscarinic cholinergic enhancers as antiinflammatory agents. PMID:16549778

Desert hedgehog is a mediator of demyelination in compression neuropathies.

PubMed

Jung, James; Frump, Derek; Su, Jared; Wang, Weiping; Mozaffar, Tahseen; Gupta, Ranjan

2015-09-01

The secreted protein desert hedgehog (dhh) controls the formation of the nerve perineurium during development and is a key component of Schwann cells that ensures peripheral nerve survival. We postulated that dhh may play a critical role in maintaining myelination and investigated its role in demyelination-induced compression neuropathies by using a post-natal model of a chronic nerve injury in wildtype and dhh(-/-) mice. We evaluated demyelination using electrophysiological, morphological, and molecular approaches. dhh transcripts and protein are down-regulated early after injury in wild-type mice, suggesting an intimate relationship between the hedgehog pathway and demyelination. In dhh(-/-) mice, nerve injury induced more prominent and severe demyelination relative to their wild-type counterparts, suggesting a protective role of dhh. Alterations in nerve fiber characteristics included significant decreases in nerve conduction velocity, increased myelin debris, and substantial decreases in internodal length. Furthermore, in vitro studies showed that dhh blockade via either adenovirus-mediated (shRNA) or pharmacological inhibition both resulted in severe demyelination, which could be rescued by exogenous Dhh. Exogenous Dhh was protective against this demyelination and maintained myelination at baseline levels in a custom in vitro bioreactor to applied biophysical forces to myelinated DRG/Schwann cell co-cultures. Together, these results demonstrate a pivotal role for dhh in maintaining myelination. Furthermore, dhh signaling reveals a potential target for therapeutic intervention to prevent and treat demyelination of peripheral nerves in compression neuropathies. Copyright © 2015 Elsevier Inc. All rights reserved.

The Effect of Intra-articular Cocktail Versus Femoral Nerve Block for Patients Undergoing Hip Arthroscopy.

PubMed

Childs, Sean; Pyne, Sonia; Nandra, Kiritpaul; Bakhsh, Wajeeh; Mustafa, S Atif; Giordano, Brian D

2017-12-01

To compare clinical efficacy and complication rate as measured by postoperative falls and development of peripheral neuritis between intra-articular blockade and femoral nerve block in patients undergoing arthroscopic hip surgery. An institutional review board approved retrospective review was conducted on a consecutive series of patients who underwent elective arthroscopic hip surgery by a single surgeon, between November 2013 and April 2015. Subjects were stratified into 2 groups: patients who received a preoperative femoral nerve block for perioperative pain control, and patients who received an intra-articular "cocktail" injection postoperatively. Demographic data, perioperative pain scores, narcotic consumption, incidence of falls, and iatrogenic peripheral neuritis were collected for analysis. Postoperative data were then collected at routine clinical visits. A total of 193 patients were included in this study (65 males, 125 females). Of them, 105 patients received preoperative femoral nerve blocks and 88 patients received an intraoperative intra-articular "cocktail." There were no significant differences in patient demographics, history of chronic pain (P = .35), worker's compensation (P = .24), preoperative pain scores (P = .69), or intraoperative doses of narcotics (P = .40). Patients who received preoperative femoral nerve blocks reported decreased pain during their time in PACU (P = .0001) and on hospital discharge (P = .28); however, there were no statistically significant differences in patient-reported pain scores at postoperative weeks 1 (P = .34), 3 (P = .64), and 6 (P = .70). Administration of an intra-articular block was associated with a significant reduction in the rate of postoperative falls (P = .009) and iatrogenic peripheral neuritis (P = .0001). Preoperative femoral nerve blocks are associated with decreased immediate postoperative pain, whereas intraoperative intra-articular anesthetic injections provide effective postoperative pain control in patients undergoing arthroscopic hip surgery and result in a significant reduction in the rate of postoperative falls and iatrogenic peripheral neuritis. Level III, retrospective comparative study. Copyright © 2017 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Is Local Infiltration Analgesia Superior to Peripheral Nerve Blockade for Pain Management After THA: A Network Meta-analysis.

PubMed

Jiménez-Almonte, José H; Wyles, Cody C; Wyles, Saranya P; Norambuena-Morales, German A; Báez, Pedro J; Murad, Mohammad H; Sierra, Rafael J

2016-02-01

Local infiltration analgesia and peripheral nerve blocks are common methods for pain management in patients after THA but direct head-to-head, randomized controlled trials (RCTs) have not been performed. A network meta-analysis allows indirect comparison of individual treatments relative to a common comparator; in this case placebo (or no intervention), epidural analgesia, and intrathecal morphine, yielding an estimate of comparative efficacy. We asked, when compared with a placebo, (1) does use of local infiltration analgesia reduce patient pain scores and opioid consumption, (2) does use of peripheral nerve blocks reduce patient pain scores and opioid consumption, and (3) is local infiltration analgesia favored over peripheral nerve blocks for postoperative pain management after THA? We searched six databases, from inception through June 30, 2014, to identify RCTs comparing local infiltration analgesia or peripheral nerve block use in patients after THA. A total of 35 RCTs at low risk of bias based on the recommended Cochrane Collaboration risk assessment tool were included in the network meta-analysis (2296 patients). Primary outcomes for this review were patient pain scores at rest and cumulative opioid consumption, both assessed at 24 hours after THA. Because of substantial heterogeneity (variation of outcomes between studies) across included trials, a random effect model for meta-analysis was used to estimate the weighted mean difference (WMD) and 95% CI. The gray literature was searched with the same inclusion criteria as published trials. Only one unpublished trial (published abstract) fulfilled our criteria and was included in this review. All other studies included in this systematic review were full published articles. Bayesian network meta-analysis included all RCTs that compared local infiltration analgesia or peripheral nerve blocks with placebo (or no intervention), epidural analgesia, and intrathecal morphine. Compared with placebo, local infiltration analgesia reduced patient pain scores (WMD, -0.61; 95% CI, -0.97 to -0.24; p = 0.001) and opioid consumption (WMD, -7.16 mg; 95% CI, -11.98 to -2.35; p = 0.004). Peripheral nerve blocks did not result in lower pain scores or reduced opioid consumption compared with placebo (WMD, -0.43; 95% CI, -0.99 to 0.12; p = 0.12 and WMD, -3.14 mg, 95% CI, -11.30 to 5.02; p = 0.45). However, network meta-analysis comparing local infiltration analgesia with peripheral nerve blocks through common comparators showed no differences between postoperative pain scores (WMD, -0.36; 95% CI, -1.06 to 0.31) and opioid consumption (WMD, -4.59 mg; 95% CI, -9.35 to 0.17), although rank-order analysis found local infiltration analgesia to be ranked first in more simulations than peripheral nerve blocks, suggesting that it may be more effective. Using the novel statistical network meta-analysis approach, we found no differences between local infiltration analgesia and peripheral nerve blocks in terms of analgesia or opioid consumption 24 hours after THA; there was a suggestion of a slight advantage to peripheral nerve blocks based on rank-order analysis, but the effect size in question is likely not large. Given the slight difference between interventions, clinicians may choose to focus on other factors such as cost and intervention-related complications when debating which analgesic treatment to use after THA. Level I, therapeutic study.

Antinociceptive effect of vinpocetine--a comprehensive survey.

PubMed

Csillik, Bertalan; Mihály, András; Knyihár-Csillik, Elizabeth

2010-05-30

Blockade of retrograde transport of nerve growth factor (NGF) in a peripheral sensory nerve is known to induce transganglionic degenerative atrophy (TDA) of central sensory terminals in the upper dorsal horn of the related, ipsilateral segments(s) of the spinal cord. The ensuing temporary blockade of transmission of nociceptive impulses has been utilized in the therapy of intractable pain, using transcutaneous iontophoresis of the microtubule inhibitors vincristin and vinblastin, drugs which inhibit retrograde transport of NGF. Since microtubule inhibition might inhibit (at least theoretically) mitotic processes in general, we sought to find a drug which inhibits retrograde transport of NGF without microtubule inhibition. Vinpocetine, a derivate of vincamine, which does not interfere with microtubular function, was found to inhibit retrograde axoplasmic transport of NGF in peripheral sensory nerves, similarly to vincristin and vinblastin. Blockade of NGF transport is followed by transganglionic degenerative atrophy in the segmentally related, ipsilateral superficial spinal dorsal horn, characterized by depletion of the marker enzymes of nociception, fluoride resistant acid phosphatase (FRAP) and thiamine monophosphatase (TMP) from the Rolando substance and by decrease of the pain-related neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) from lamina I-II-III. Based upon these findings, it has been suggested that vinpocetine may result in a locally restricted decrease of nociception. Herewith, the structural and behavioral effects of perineurally administered vinpocetine are discussed. Nociception, induced by intraplantar injection of formalin, was mitigated by perineural application of vinpocetine; also formalin-induced expression of c-fos in the ipsilateral, segmentally related superficial dorsal horn, was prevented by this treatment. Since vinpocetine is not a microtubule inhibitor, its mode of action is enigmatic. It is assumed that the effect of vinpocetine might be related to interaction with membrane-trafficking proteins, such as signalling endosomes and the endocytosis-mediating "pincher" protein, involved in retrograde axoplasmic transport of NGF, or to interaction with glial elements, recently reported to be involved in the modulation of pain in the spinal cord. Based on animal experiments it is assumed that the temporary, locally restricted decrease of nociception, induced by vinpocetine applied via transcutaneous iontophoresis, might open up new avenues in the clinical treatment of intractable pain.

Effectiveness of spinal anesthesia combined with obturator nerve blockade in preventing adductor muscle contraction during transurethral resection of bladder tumor

PubMed Central

Alavi, Cyrus Emir; Asgari, Seyed Alaeddin; Falahatkar, Siavash; Rimaz, Siamak; Naghipour, Mohammadreza; Khoshrang, Hossein; Jafari, Mehdi; Herfeh, Nadia

2017-01-01

Objective To determine whether spinal anesthesia combined with obturator nerve blockade (SOB) is effective in preventing obturator nerve stimulation, jerking and bladder perforation during transurethral resection of bladder tumor (TURBT). Material and methods In this clinical trial, 30 patients were randomly divided into two groups: spinal anesthesia (SA) and SOB. In SA group, 2.5 cc of 0.5% bupivacaine was injected intrathecally using a 25-gauge spinal needle and in SOB after spinal anesthesia, a classic obturator nerve blockade was performed by using nerve stimulation technique. Results There was a statistically significant difference between jerking in both groups (p=0.006). During the TURBT, surgeon satisfaction was significantly higher in SOB group compared to SA group (p=0.006). There was no significant correlation between sex, patient age and location of bladder tumor between the groups (p>0.05). Conclusion Obturator nerve blockade by using 15 cc lidocaine 1% is effective in preventing adductor muscle spasms during TURBT. PMID:29201516

Upper Extremity Regional Anesthesia

PubMed Central

Neal, Joseph M.; Gerancher, J.C.; Hebl, James R.; Ilfeld, Brian M.; McCartney, Colin J.L.; Franco, Carlo D.; Hogan, Quinn H.

2009-01-01

Brachial plexus blockade is the cornerstone of the peripheral nerve regional anesthesia practice of most anesthesiologists. As part of the American Society of Regional Anesthesia and Pain Medicine’s commitment to providing intensive evidence-based education related to regional anesthesia and analgesia, this article is a complete update of our 2002 comprehensive review of upper extremity anesthesia. The text of the review focuses on (1) pertinent anatomy, (2) approaches to the brachial plexus and techniques that optimize block quality, (4) local anesthetic and adjuvant pharmacology, (5) complications, (6) perioperative issues, and (6) challenges for future research. PMID:19282714

New modalities of pain treatment after outpatient orthopaedic surgery.

PubMed

Beaussier, M; Sciard, D; Sautet, A

2016-02-01

Postoperative pain relief is one of the cornerstones of success of orthopaedic surgery. Development of new minimally-invasive surgical procedures, as well as improvements in pharmacological and local and regional techniques should result in optimal postoperative pain control for all patients. The analgesic strategy has to be efficient, with minimal side effects, and be easy to manage at home. Multimodal analgesia allows for a reduction of opiate use and thereby its side effects. Local and regional analgesia is a major component of this multimodal strategy, associated with optimal pain relief, even upon mobilization, and it has beneficial effects on postoperative recovery. Ultrasound guidance improves the success rate of distal nerve blocks and makes distal selective blockade possible, helping to preserve the limb's motility. Besides peripheral nerve blocks, local infiltration (incisional and/or intra-articular) is also important to consider. Duration of the nerve blockade is limited after a single injection. This must be taken into consideration to avoid the recurrence of pain when the patient returns home. Continuous perineural blocks using catheters are an option that can be easily managed at home with monitoring by home-care nurses. Extended-release liposomal bupivacaine and adjuvants such as dexamethasone could significantly enhance the duration of the sensory block, thereby reducing the indications for pain pumps. Non-pharmacological approaches, such as cryotherapy, hypnosis and acupuncture should not be ignored. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Analgesia after total knee replacement: local infiltration versus epidural combined with a femoral nerve blockade: a prospective, randomised pragmatic trial.

PubMed

Yadeau, J T; Goytizolo, E A; Padgett, D E; Liu, S S; Mayman, D J; Ranawat, A S; Rade, M C; Westrich, G H

2013-05-01

In a randomised controlled pragmatic trial we investigated whether local infiltration analgesia would result in earlier readiness for discharge from hospital after total knee replacement (TKR) than patient-controlled epidural analgesia (PCEA) plus femoral nerve block. A total of 45 patients with a mean age of 65 years (49 to 81) received a local infiltration with a peri-articular injection of bupivacaine, morphine and methylprednisolone, as well as adjuvant analgesics. In 45 PCEA+femoral nerve blockade patients with a mean age of 67 years (50 to 84), analgesia included a bupivacaine nerve block, bupivacaine/hydromorphone PCEA, and adjuvant analgesics. The mean time until ready for discharge was 3.2 days (1 to 14) in the local infiltration group and 3.2 days (1.8 to 7.0) in the PCEA+femoral nerve blockade group. The mean pain scores for patients receiving local infiltration were higher when walking (p = 0.0084), but there were no statistically significant differences at rest. The mean opioid consumption was higher in those receiving local infiltration. The choice between these two analgesic pathways should not be made on the basis of time to discharge after surgery. Most secondary outcomes were similar, but PCEA+femoral nerve blockade patients had lower pain scores when walking and during continuous passive movement. If PCEA+femoral nerve blockade is not readily available, local infiltration provides similar length of stay and similar pain scores at rest following TKR.

Analgesia after total knee replacement: local infiltration versus epidural combined with a femoral nerve blockade. A prospective, randomised pragmatic trial

PubMed Central

Goytizolo, Enrique A.; Padgett, Douglas E.; Liu, Spencer S.; Mayman, David J.; Ranawat, Amar S.; Rade, Matthew C.; Westrich, Geoffrey H.

2014-01-01

In a randomised controlled pragmatic trial we investigated whether local infiltration analgesia would result in earlier readiness for discharge from hospital after total knee replacement (TKR) than patient-controlled epidural analgesia (PCEA) plus femoral nerve block. A total of 45 patients with a mean age of 65 years (49 to 81) received a local infiltration with a peri-articular injection of bupivacaine, morphine, and methylprednisolone, as well as adjuvant analgesics. In 45 PCEA+femoral nerve blockade patients with a mean age of 67 years (50 to 84), analgesia included a bupivacaine nerve block, bupivacaine/hydromorphone PCEA, and adjuvant analgesics. The mean time until ready for discharge was 3.2 days (1 to 14) in the local infiltration group and 3.2 days (1.8 to 7.0) in the PCEA+femoral nerve blockade group. The mean pain scores for patients receiving local infiltration were higher when walking (p = 0.0084), but there were no statistically significant differences at rest. The mean opioid consumption was higher in those receiving local infiltration. The choice between these two analgesic pathways should not be made on the basis of time to discharge after surgery. Most secondary outcomes were similar, but PCEA+femoral nerve blockade patients had lower pain scores when walking and during continuous passive movement. If PCEA+femoral nerve blockade is not readily available, local infiltration provides similar length of stay and similar pain scores at rest following TKR. PMID:23632672

The ovine fetal endocrine reflex responses to haemorrhage are not mediated by cardiac nerves

PubMed Central

Wood, Charles E

2002-01-01

This study was designed to test the hypothesis that cardiac receptors tonically inhibit the secretion of renin, arginine vasopressin (AVP) and adrenocorticotropic hormone (ACTH) in late-gestation fetal sheep. Eight chronically catheterised fetal sheep between 122 and 134 days gestation were subjected to injection or infusion of saline or 4 % procaine into the pericardial space. Fetal blood pressure and heart rate were monitored and fetal blood samples were drawn to measure the response to these injections. Injection of procaine into the pericardial space effectively blocked cardiac nerves, as evidenced by a reduction in the variability of fetal heart rate and by the blockade of reflex reductions in fetal heart rate after intravenous injection of phenylephrine (an α-adrenergic agonist which raises blood pressure). Injection of saline had no discernable effects on any of the measured variables. A single injection of procaine, followed by a slow infusion, produced a transient blockade of cardiac nerves. Multiple injections of procaine produced a sustained blockade of cardiac nerves and a sustained rise in fetal plasma renin activity and ACTH. In none of the experiments did procaine significantly alter fetal plasma AVP concentrations. In 11 fetuses between 121 and 134 days gestation, we combined the cardiac nerve blockade with slow haemorrhage to test the cardiac nerves as mediators of the endocrine response to haemorrhage in utero. Cardiac nerve blockade exaggerated the fetal blood gas response to haemorrhage somewhat but did not significantly alter the magnitude of the ACTH, AVP, or plasma renin activity response to haemorrhage. We conclude that cardiac nerves in the late-gestation fetal sheep have minor influences on plasma renin activity and ACTH in normovolaemic fetuses, but that changes in cardiac nerve activity do not mediate the endocrine responsiveness to haemorrhage. PMID:12042365

Clinical Practice Guidelines for Sustained Neuromuscular Blockade in the Adult Critically Ill Patient.

PubMed

Murray, Michael J; DeBlock, Heidi; Erstad, Brian; Gray, Anthony; Jacobi, Judi; Jordan, Che; McGee, William; McManus, Claire; Meade, Maureen; Nix, Sean; Patterson, Andrew; Sands, M Karen; Pino, Richard; Tescher, Ann; Arbour, Richard; Rochwerg, Bram; Murray, Catherine Friederich; Mehta, Sangeeta

2016-11-01

To update the 2002 version of "Clinical practice guidelines for sustained neuromuscular blockade in the adult critically ill patient." A Task Force comprising 17 members of the Society of Critical Medicine with particular expertise in the use of neuromuscular-blocking agents; a Grading of Recommendations Assessment, Development, and Evaluation expert; and a medical writer met via teleconference and three face-to-face meetings and communicated via e-mail to examine the evidence and develop these practice guidelines. Annually, all members completed conflict of interest statements; no conflicts were identified. This activity was funded by the Society for Critical Care Medicine, and no industry support was provided. Using the Grading of Recommendations Assessment, Development, and Evaluation system, the Grading of Recommendations Assessment, Development, and Evaluation expert on the Task Force created profiles for the evidence related to six of the 21 questions and assigned quality-of-evidence scores to these and the additional 15 questions for which insufficient evidence was available to create a profile. Task Force members reviewed this material and all available evidence and provided recommendations, suggestions, or good practice statements for these 21 questions. The Task Force developed a single strong recommendation: we recommend scheduled eye care that includes lubricating drops or gel and eyelid closure for patients receiving continuous infusions of neuromuscular-blocking agents. The Task Force developed 10 weak recommendations. 1) We suggest that a neuromuscular-blocking agent be administered by continuous intravenous infusion early in the course of acute respiratory distress syndrome for patients with a PaO2/FIO2 less than 150. 2) We suggest against the routine administration of an neuromuscular-blocking agents to mechanically ventilated patients with status asthmaticus. 3) We suggest a trial of a neuromuscular-blocking agents in life-threatening situations associated with profound hypoxemia, respiratory acidosis, or hemodynamic compromise. 4) We suggest that neuromuscular-blocking agents may be used to manage overt shivering in therapeutic hypothermia. 5) We suggest that peripheral nerve stimulation with train-of-four monitoring may be a useful tool for monitoring the depth of neuromuscular blockade but only if it is incorporated into a more inclusive assessment of the patient that includes clinical assessment. 6) We suggest against the use of peripheral nerve stimulation with train of four alone for monitoring the depth of neuromuscular blockade in patients receiving continuous infusion of neuromuscular-blocking agents. 7) We suggest that patients receiving a continuous infusion of neuromuscular-blocking agent receive a structured physiotherapy regimen. 8) We suggest that clinicians target a blood glucose level of less than 180 mg/dL in patients receiving neuromuscular-blocking agents. 9) We suggest that clinicians not use actual body weight and instead use a consistent weight (ideal body weight or adjusted body weight) when calculating neuromuscular-blocking agents doses for obese patients. 10) We suggest that neuromuscular-blocking agents be discontinued at the end of life or when life support is withdrawn. In situations in which evidence was lacking or insufficient and the study results were equivocal or optimal clinical practice varies, the Task Force made no recommendations for nine of the topics. 1) We make no recommendation as to whether neuromuscular blockade is beneficial or harmful when used in patients with acute brain injury and raised intracranial pressure. 2) We make no recommendation on the routine use of neuromuscular-blocking agents for patients undergoing therapeutic hypothermia following cardiac arrest. 3) We make no recommendation on the use of peripheral nerve stimulation to monitor degree of block in patients undergoing therapeutic hypothermia. 4) We make no recommendation on the use of neuromuscular blockade to improve the accuracy of intravascular-volume assessment in mechanically ventilated patients. 5) We make no recommendation concerning the use of electroencephalogram-derived parameters as a measure of sedation during continuous administration of neuromuscular-blocking agents. 6) We make no recommendation regarding nutritional requirements specific to patients receiving infusions of neuromuscular-blocking agents. 7) We make no recommendation concerning the use of one measure of consistent weight over another when calculating neuromuscular-blocking agent doses in obese patients. 8) We make no recommendation on the use of neuromuscular-blocking agents in pregnant patients. 9) We make no recommendation on which muscle group should be monitored in patients with myasthenia gravis receiving neuromuscular-blocking agents. Finally, in situations in which evidence was lacking or insufficient but expert consensus was unanimous, the Task Force developed six good practice statements. 1) If peripheral nerve stimulation is used, optimal clinical practice suggests that it should be done in conjunction with assessment of other clinical findings (e.g., triggering of the ventilator and degree of shivering) to assess the degree of neuromuscular blockade in patients undergoing therapeutic hypothermia. 2) Optimal clinical practice suggests that a protocol should include guidance on neuromuscular-blocking agent administration in patients undergoing therapeutic hypothermia. 3) Optimal clinical practice suggests that analgesic and sedative drugs should be used prior to and during neuromuscular blockade, with the goal of achieving deep sedation. 4) Optimal clinical practice suggests that clinicians at the bedside implement measure to attenuate the risk of unintended extubation in patients receiving neuromuscular-blocking agents. 5) Optimal clinical practice suggests that a reduced dose of an neuromuscular-blocking agent be used for patients with myasthenia gravis and that the dose should be based on peripheral nerve stimulation with train-of-four monitoring. 6) Optimal clinical practice suggests that neuromuscular-blocking agents be discontinued prior to the clinical determination of brain death.

Dual mTORC1/2 inhibition induces anti-proliferative effect in NF1-associated plexiform neurofibroma and malignant peripheral nerve sheath tumor cells

PubMed Central

Hivelin, Mikael; Nusbaum, Patrick; Hubas, Arnaud; Laurendeau, Ingrid; Lantieri, Laurent; Wolkenstein, Pierre; Vidaud, Michel; Pasmant, Eric; Chapuis, Nicolas; Parfait, Béatrice

2016-01-01

Approximately 30-50% of individuals with Neurofibromatosis type 1 develop benign peripheral nerve sheath tumors, called plexiform neurofibromas (PNFs). PNFs can undergo malignant transformation to highly metastatic malignant peripheral nerve sheath tumors (MPNSTs) in 5-10% of NF1 patients, with poor prognosis. No effective systemic therapy is currently available for unresectable tumors. In tumors, the NF1 gene deficiency leads to Ras hyperactivation causing the subsequent activation of the AKT/mTOR and Raf/MEK/ERK pathways and inducing multiple cellular responses including cell proliferation. In this study, three NF1-null MPNST-derived cell lines (90-8, 88-14 and 96-2), STS26T sporadic MPNST cell line and PNF-derived primary Schwann cells were used to test responses to AZD8055, an ATP-competitive “active-site” mTOR inhibitor. In contrast to rapamycin treatment which only partially affected mTORC1 signaling, AZD8055 induced a strong inhibition of mTORC1 and mTORC2 signaling in MPNST-derived cell lines and PNF-derived Schwann cells. AZD8055 induced full blockade of mTORC1 leading to an efficient decrease of global protein synthesis. A higher cytotoxic effect was observed with AZD8055 compared to rapamycin in the NF1-null MPNST-derived cell lines with IC50 ranging from 70 to 140 nM and antiproliferative effect was confirmed in PNF-derived Schwann cells. Cell migration was impaired by AZD8055 treatment and cell cycle analysis showed a G0/G1 arrest. Combined effects of AZD8055 and PD0325901 MEK inhibitor as well as BRD4 (BromoDomain-containing protein 4) inhibitors showed a synergistic antiproliferative effect. These data suggest that NF1-associated peripheral nerve sheath tumors are an ideal target for AZD8055 as a single molecule or in combined therapies. PMID:26840085

Comparison of Ultrasound with Peripheral Nerve Stimulator-guided Technique for Supraclavicular Block in Upper Limb Surgeries: A Randomized Controlled Trial.

PubMed

Alfred, Vinu Mervick; Srinivasan, Gnanasekaran; Zachariah, Mamie

2018-01-01

The supraclavicular approach is considered to be the easiest and most effective approach to block the brachial plexus for upper limb surgeries. The classical approach using the anatomical landmark technique was associated with higher failure rates and complications. Ultrasonography (USG) guidance and peripheral nerve stimulator (PNS) have improved the success rates and safety margin. The aim of the present study is to compare USG with PNS in supraclavicular brachial plexus block for upper limb surgeries with respect to the onset of motor and sensory blockade, total duration of blockade, procedure time, and complications. Prospective, randomized controlled study. Sixty patients aged above 18 years scheduled for elective upper limb surgery were randomly allocated into two groups. Group A patients received supraclavicular brachial plexus block under ultrasound guidance and in Group B patients, PNS was used. In both groups, local anesthetic mixture consisting of 15 ml of 0.5% bupivacaine and 10 ml of 2% lignocaine with 1:200,000 adrenaline were used. Independent t -test used to compare mean between groups; Chi-square test for categorical variables. The procedure time was shorter with USG (11.57 ± 2.75 min) compared to PNS (21.73 ± 4.84). The onset time of sensory block (12.83 ± 3.64 min vs. 16 ± 3.57 min) and onset of motor block (23 ± 4.27 min vs. 27 ± 3.85 min) were significantly shorter in Group A compared to Group B ( P < 0.05). The duration of sensory block was significantly prolonged in Group A (8.00 ± 0.891 h) compared to Group B (7.25 ± 1.418 h). None of the patients in either groups developed any complications. The ultrasound-guided supraclavicular brachial plexus block can be done quicker, with a faster onset of sensory and motor block compared to nerve stimulator technique.

Catheter orifice configuration influences the effectiveness of continuous peripheral nerve blockade.

PubMed

Fredrickson, Michael J; Ball, Craig M; Dalgleish, Adam J

2011-01-01

We investigated perineural catheter threading distance and orifice configuration during continuous interscalene analgesia. One hundred fifty-three patients receiving an anterolateral interscalene catheter (catheter needle and nerve/plexus in a similar alignment) for elective shoulder surgery were randomized to 1 of 3 groups: following out-of-plane ultrasound confirmation of the needle tip immediately lateral to the C5/6 roots, a nonstimulating catheter was blindly advanced 0.5 cm (end-hole; n = 50), 2.5 cm (multiorifice; n = 50) or 5 cm (multiorifice; n = 53) beyond the needle tip. Ropivacaine 0.75% + lidocaine 1% (50:50) 20 mL was administered preoperatively via the catheter before surgery under general anesthesia. A ropivacaine 0.2% 2 mL/hr elastomeric infusion with mandatory 6 hourly (and on demand) 5-mL boluses was continued for more than 48 hrs with tramadol available as rescue. Patients were questioned in the recovery room, at 24 and 48 hrs for numerical rating pain score (0-10), ropivacaine bolus, and tramadol consumption. Patients were more frequently pain-free in the recovery room in the multiorifice 2.5 and 5 cm groups compared with the end-hole 0.5 cm group (94%, 91% vs 66%; P < 0.001). During the first 24 hrs, the end-hole group demonstrated an earlier time to first pain (median, 10 vs17, 15 hrs; P < 0.001), higher "average pain" (median, 3 vs 1, 2, P = 0.004), and more ropivacaine bolus (median, 5 vs 3, 3; P < 0.001) and tramadol consumption (P = 0.01). Groups 2.5 and 5 cm did not significantly differ in any outcomes. These results suggest that multiorifice catheters provide superior intermittent bolus continuous peripheral nerve blockade compared with end-hole catheters. For anterolateral approach interscalene catheter placement, there is minimal benefit, either way, to 2.5- or 5-cm blind catheter advancement.

Efficacy of ultrasound and nerve stimulation guidance in peripheral nerve block: A systematic review and meta-analysis.

PubMed

Wang, Zhi-Xue; Zhang, De-Li; Liu, Xin-Wei; Li, Yan; Zhang, Xiao-Xia; Li, Ru-Hong

2017-09-01

Evidence was controversial about whether nerve stimulation (NS) can optimize ultrasound guidance (US)-guided nerve blockade for peripheral nerve block. This review aims to explore the effects of the two combined techniques. We searched EMBASE (from 1974 to March 2015), PubMed (from 1966 to Mar 2015), Medline (from 1966 to Mar 2015), the Cochrane Central Register of Controlled Trials and clinicaltrials.gov. Finally, 15 randomized trials were included into analysis involving 1,019 lower limb and 696 upper limb surgery cases. Meta-analysis indicated that, compared with US alone, USNS combination had favorable effects on overall block success rate (risk ratio [RR] 1.17; confidence interval [CI] 1.05 to 1.30, P = 0.004), sensory block success rate (RR 1.56; CI 1.29 to 1.89, P < 0.00001), and block onset time (mean difference [MD] -3.84; CI -5.59 to -2.08, P < 0.0001). USNS guidance had a longer procedure time in both upper and lower limb nerve block (MD 1.67; CI 1.32 to 2.02, P < 0.00001; MD 1.17; CI 0.95 to 1.39, P < 0.00001) and more patients with anesthesia supplementation (RR 2.5; CI 1.02 to 6.13, P = 0.05). USNS guidance trends to result in a shorter block onset time than US alone as well as higher block success rate, but no statistical difference was demonstrated, as more data are required. © 2017 IUBMB Life, 69(9):720-734, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

Benefit-risk assessment of ropivacaine in the management of postoperative pain.

PubMed

Zink, Wolfgang; Graf, Bernhard M

2004-01-01

Ropivacaine is a long-acting amide-type local anaesthetic, released for clinical use in 1996. In comparison with bupivacaine, ropivacaine is equally effective for subcutaneous infiltration, epidural and peripheral nerve block for surgery, obstetric procedures and postoperative analgesia. Nevertheless, ropivacaine differs from bupivacaine in several aspects: firstly, it is marketed as a pure S(-)-enantiomer and not as a racemate, and secondly, its lipid solubility is markedly lower. These features have been suggested to significantly improve the safety profile of ropivacaine, and indeed, numerous studies have shown that ropivacaine has less cardiovascular and CNS toxicity than racemic bupivacaine in healthy volunteers. Extensive clinical data have demonstrated that epidural 0.2% ropivacaine is nearly identical to 0.2% bupivacaine with regard to onset, quality and duration of sensory blockade for initiation and maintenance of labour analgesia. Ropivacaine also provides effective pain relief after abdominal or orthopaedic surgery, especially when given in conjunction with opioids or other adjuvants. Nevertheless, epidurally administered ropivacaine causes significantly less motor blockade at low concentrations. Whether the greater degree of blockade of nerve fibres involved in pain transmission (Adelta- and C-fibres) than of those controlling motor function (Aalpha- and Abeta-fibres) is due to a lower relative potency compared with bupivacaine or whether other physicochemical properties or stereoselectivity are involved, is still a matter of intense debate. Recommended epidural doses for postoperative or labour pain are 20-40 mg as bolus with 20-30 mg as top-up dose, with an interval of >or=30 minutes. Alternatively, 0.2% ropivacaine can be given as continuous epidural infusion at a rate of 6-14 mL/h (lumbar route) or 4-10 mL/h (thoracic route). Preoperative or postoperative subcutaneous wound infiltration, during cholecystectomy or inguinal hernia repair, with ropivacaine 100-175 mg has been shown to be more effective than placebo and as effective as bupivacaine in reducing wound pain, whereby the vasoconstrictive potency of ropivacaine may be involved. Similar results were found in peripheral blockades on upper and lower limbs. Ropivacaine shows an identical efficacy and potency to that of bupivacaine, with similar analgesic duration over hours using single shot or continuous catheter techniques. In summary, ropivacaine, a newer long-acting local anaesthetic, has an efficacy generally similar to that of the same dose of bupivacaine with regard to postoperative pain relief, but causes less motor blockade and stronger vasoconstriction at low concentrations. Despite a significantly better safety profile of the pure S(-)-isomer of ropivacaine, the increased cost of ropivacaine may presently limit its clinical utility in postoperative pain therapy.

Preventive Analgesia by Local Anesthetics: The Reduction of Postoperative Pain by Peripheral Nerve Blocks and Intravenous Drugs

PubMed Central

Barreveld, Antje; Witte, Jürgen; Chahal, Harkirat; Durieux, Marcel E.; Strichartz, Gary

2012-01-01

The use of local anesthetics to reduce acute postoperative pain has a long history, but recent reports have not been systematically reviewed. In addition, the need to include only those clinical studies that meet minimum standards for randomization and blinding must be adhered to. In this review we have applied stringent clinical study design standards to identify publications on the use of perioperative local anesthetics. We first examined several types of peripheral nerve blocks, covering a variety of surgical procedures, and second, for effects of intentionally administered IV local anesthetic (lidocaine) for suppression of postoperative pain. Thirdly, we have examined publications in which vascular concentrations of local anesthetics were measured at different times after peripheral nerve block procedures, noting the incidence when those levels reached ones achieved during intentional IV administration. Importantly, the very large number of studies using neuraxial blockade techniques (epidural, spinal) has not been included in this review but will be dealt with separately in a later review. The overall results showed a strongly positive effect of local anesthetics, by either route, for suppressing postoperative pain scores and analgesic (opiate) consumption. In only a few situations were the effects equivocal. Enhanced effectiveness with the addition of adjuvants was not uniformly apparent. The differential benefits between drug delivery before, during, or immediately after a surgical procedure are not obvious, and a general conclusion is that the significant antihyperalgesic effects occur when the local anesthetic is present during the acute postoperative period, and its presence during surgery is not essential for this action. PMID:23408672

Peripheral Nerve Block as a Supplement to Light or Deep General Anesthesia in Elderly Patients Receiving Total Hip Arthroplasty: A Prospective Randomized Study.

PubMed

Mei, Bin; Zha, Hanning; Lu, Xiaolong; Cheng, Xinqi; Chen, Shishou; Liu, Xuesheng; Li, Yuanhai; Gu, Erwei

2017-12-01

Peripheral nerve block combined with general anesthesia is a preferable anesthesia method for elderly patients receiving hip arthroplasty. The depth of sedation may influence patient recovery. Therefore, we investigated the influence of peripheral nerve blockade and different intraoperative sedation levels on the short-term recovery of elderly patients receiving total hip arthroplasty. Patients aged 65 years and older undergoing total hip arthroplasty were randomized into 3 groups: a general anesthesia without lumbosacral plexus block group, and 2 general anesthesia plus lumbosacral plexus block groups, each with a different level of sedation (light or deep). The extubation time and intraoperative consumption of propofol, sufentanil, and vasoactive agent were recorded. Postoperative delirium and early postoperative cognitive dysfunction were assessed using the Confusion Assessment Method and Mini-Mental State Examination, respectively. Postoperative analgesia was assessed by the consumption of patient-controlled analgesics and visual analog scale scores. Discharge time and complications over a 30-day period were also recorded. Lumbosacral plexus block reduced opioid intake. With lumbosacral plexus block, intraoperative deep sedation was associated with greater intake of propofol and vasoactive agent. In contrast, patients with lumbosacral plexus block and intraoperative light sedation had lower incidences of postoperative delirium and postoperative cognitive decline, and earlier discharge readiness times. The 3 groups showed no difference in complications within 30 days of surgery. Lumbosacral plexus block reduced the need for opioids and offered satisfactory postoperative analgesia. It led to better postoperative outcomes in combination with intraoperative light sedation (high bispectral index).

Activation of the sympathetic nervous system mediates hypophagic and anxiety-like effects of CB₁ receptor blockade.

PubMed

Bellocchio, Luigi; Soria-Gómez, Edgar; Quarta, Carmelo; Metna-Laurent, Mathilde; Cardinal, Pierre; Binder, Elke; Cannich, Astrid; Delamarre, Anna; Häring, Martin; Martín-Fontecha, Mar; Vega, David; Leste-Lasserre, Thierry; Bartsch, Dusan; Monory, Krisztina; Lutz, Beat; Chaouloff, Francis; Pagotto, Uberto; Guzman, Manuel; Cota, Daniela; Marsicano, Giovanni

2013-03-19

Complex interactions between periphery and the brain regulate food intake in mammals. Cannabinoid type-1 (CB1) receptor antagonists are potent hypophagic agents, but the sites where this acute action is exerted and the underlying mechanisms are not fully elucidated. To dissect the mechanisms underlying the hypophagic effect of CB1 receptor blockade, we combined the acute injection of the CB1 receptor antagonist rimonabant with the use of conditional CB1-knockout mice, as well as with pharmacological modulation of different central and peripheral circuits. Fasting/refeeding experiments revealed that CB1 receptor signaling in many specific brain neurons is dispensable for the acute hypophagic effects of rimonabant. CB1 receptor antagonist-induced hypophagia was fully abolished by peripheral blockade of β-adrenergic transmission, suggesting that this effect is mediated by increased activity of the sympathetic nervous system. Consistently, we found that rimonabant increases gastrointestinal metabolism via increased peripheral β-adrenergic receptor signaling in peripheral organs, including the gastrointestinal tract. Blockade of both visceral afferents and glutamatergic transmission in the nucleus tractus solitarii abolished rimonabant-induced hypophagia. Importantly, these mechanisms were specifically triggered by lipid-deprivation, revealing a nutrient-specific component acutely regulated by CB1 receptor blockade. Finally, peripheral blockade of sympathetic neurotransmission also blunted central effects of CB1 receptor blockade, such as fear responses and anxiety-like behaviors. These data demonstrate that, independently of their site of origin, important effects of CB1 receptor blockade are expressed via activation of peripheral sympathetic activity. Thus, CB1 receptors modulate bidirectional circuits between the periphery and the brain to regulate feeding and other behaviors.

Activation of the sympathetic nervous system mediates hypophagic and anxiety-like effects of CB1 receptor blockade

PubMed Central

Bellocchio, Luigi; Soria-Gómez, Edgar; Quarta, Carmelo; Metna-Laurent, Mathilde; Cardinal, Pierre; Binder, Elke; Cannich, Astrid; Delamarre, Anna; Häring, Martin; Martín-Fontecha, Mar; Vega, David; Leste-Lasserre, Thierry; Bartsch, Dusan; Monory, Krisztina; Lutz, Beat; Chaouloff, Francis; Pagotto, Uberto; Guzman, Manuel; Cota, Daniela; Marsicano, Giovanni

2013-01-01

Complex interactions between periphery and the brain regulate food intake in mammals. Cannabinoid type-1 (CB1) receptor antagonists are potent hypophagic agents, but the sites where this acute action is exerted and the underlying mechanisms are not fully elucidated. To dissect the mechanisms underlying the hypophagic effect of CB1 receptor blockade, we combined the acute injection of the CB1 receptor antagonist rimonabant with the use of conditional CB1-knockout mice, as well as with pharmacological modulation of different central and peripheral circuits. Fasting/refeeding experiments revealed that CB1 receptor signaling in many specific brain neurons is dispensable for the acute hypophagic effects of rimonabant. CB1 receptor antagonist-induced hypophagia was fully abolished by peripheral blockade of β-adrenergic transmission, suggesting that this effect is mediated by increased activity of the sympathetic nervous system. Consistently, we found that rimonabant increases gastrointestinal metabolism via increased peripheral β-adrenergic receptor signaling in peripheral organs, including the gastrointestinal tract. Blockade of both visceral afferents and glutamatergic transmission in the nucleus tractus solitarii abolished rimonabant-induced hypophagia. Importantly, these mechanisms were specifically triggered by lipid-deprivation, revealing a nutrient-specific component acutely regulated by CB1 receptor blockade. Finally, peripheral blockade of sympathetic neurotransmission also blunted central effects of CB1 receptor blockade, such as fear responses and anxiety-like behaviors. These data demonstrate that, independently of their site of origin, important effects of CB1 receptor blockade are expressed via activation of peripheral sympathetic activity. Thus, CB1 receptors modulate bidirectional circuits between the periphery and the brain to regulate feeding and other behaviors. PMID:23487769

Raman spectroscopic detection of peripheral nerves towards nerve-sparing surgery

NASA Astrophysics Data System (ADS)

Minamikawa, Takeo; Harada, Yoshinori; Takamatsu, Tetsuro

2017-02-01

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

Ultrasound-guided axillary nerve block for ED incision and drainage of deltoid abscess.

PubMed

Lyons, Claire; Herring, Andrew A

2017-07-01

Deltoid abscesses are common and painful, often a consequence of injection drug use and seen frequently in emergency departments (EDs). The required incision and drainage can be completed successfully with effective pain relief using a peripheral nerve block. The brachial plexus nerve block works well, however it is technically complex with a low, but potentially serious, risk of complications such as phrenic nerve paralysis. Selective blockade of the axillary nerve eliminates the risks associated with a brachial plexus block, while providing more specific anesthesia for the deltoid region. Our initial experience suggests that the axillary nerve block (ANB) is a technically simple, safe, and effective way to manage the pain of deltoid abscesses and the necessary incision and drainage (I&D). The block involves using ultrasound guidance to inject a 20mL bolus of local anesthetic into the quadrangular space surrounding the axillary nerve (inferior to the posterolateral aspect of the acromion, near the overlap of the long head of triceps brachii and teres minor). Once injected the local will anesthetize the axillary nerve resulting in analgesia of the cutaneous area of the lateral shoulder and the deeper tissues including the deltoid muscle. Further research will clarify questions about the volume and concentration of local anesthetic, the role of injected adjuncts, and expected duration of analgesia and anesthesia. Herein we present a description of an axillary nerve block successfully used for deltoid abscess I&D in the ED. Copyright © 2017 Elsevier Inc. All rights reserved.

Kinetics of Uptake and Washout of Lidocaine in Rat Sciatic Nerve In Vitro

PubMed Central

Leeson, Stanley; Strichartz, Gary

2012-01-01

Background The potency and efficacy of local anesthetics injected clinically for peripheral nerve block depends strongly on the rate of neural drug uptake. However, since diffusion into surrounding tissues and removal by the vascular system are major factors in the overall distribution of lidocaine in vivo, true kinetics of drug/neural tissue interactions must be studied in the absence of those confounding factors. Methods Uptake: Ensheathed or desheathed isolated rat sciatic nerves were exposed to [14C]-lidocaine for 0-180min and then removed and the lidocaine content of nerve and sheath analyzed. Washout: Isolated nerves were soaked in [14C]-lidocaine for 60min and then placed in lidocaine-free solution for 0-30min, with samples removed at different times to assess the drug content. Experimental variables included the effects of the ensheathing epineurium, lidocaine concentration, pH, presence of CO2-bicarbonate, and incubation duration. Results The equilibrium uptake of lidocaine increased with incubation time, concentration and the fraction of molecules in the non-ionized form. The uptake rate was unaffected by drug concentration, but was about halved by the presence of the epineurial sheath, with the washout rate slowed less. Slight alkalinization, from pH 6.8 to pH 7.4, by bicarbonate-CO2 buffer or a non-bicarbonate buffer, enhanced the neural uptake, and to the same degree. The washout of lidocaine was faster after shorter incubations at high concentrations than when equal amounts of lidocaine were taken up after long incubations at low lidocaine concentrations. Conclusion Lidocaine enters a nerve by a process other than free diffusion, through an epineurial sheath that is a slight obstacle. Given the rapid entry in vitro compared to the much smaller and transient content measured in vivo, it seems highly unlikely that lidocaine equilibrates with the nerve during a peripheral blockade. PMID:23400993

Naloxone Antagonizes Soman-induced Central Respiratory Depression in Rats.

PubMed

Škrbić, Ranko; Stojiljković, Miloš P; Ćetković, Slavko S; Dobrić, Silva; Jeremić, Dejan; Vulović, Maja

2017-06-01

The influence of naloxone on respiration impaired by the highly toxic organophosphate nerve agent soman in anaesthetized rats was investigated. Soman, administered in a dose that was ineffective in blocking the electrically induced contractions of the phrenic nerve-diaphragm preparation in situ, induced a complete block of the spontaneous respiratory movements of the diaphragm, indicating the domination of central over the peripheral effects. Naloxone dose-dependently antagonized the soman-induced respiratory blockade. Atropine, at a dose that was per se ineffective in counteracting soman-induced respiratory depression, potentiated the protective effects of naloxone and completely restored respiration. Naloxone remained completely ineffective in antagonizing respiratory depression induced by the muscarinic receptor agonist the oxotremorine. It is assumed that naloxone antagonizes soman-induced respiratory inhibition by blocking endogenous opioidergic respiratory control pathways that are independent of the stimulation of muscarinic receptors. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Oral Microbiome Link to Neurodegeneration in Glaucoma

PubMed Central

Astafurov, Konstantin; Elhawy, Eman; Ren, Lizhen; Dong, Cecilia Q.; Igboin, Christina; Hyman, Leslie; Griffen, Ann; Mittag, Thomas; Danias, John

2014-01-01

Background Glaucoma is a progressive optic nerve degenerative disease that often leads to blindness. Local inflammatory responses are implicated in the pathology of glaucoma. Although inflammatory episodes outside the CNS, such as those due to acute systemic infections, have been linked to central neurodegeneration, they do not appear to be relevant to glaucoma. Based on clinical observations, we hypothesized that chronic subclinical peripheral inflammation contributes to neurodegeneration in glaucoma. Methods Mouthwash specimens from patients with glaucoma and control subjects were analyzed for the amount of bacteria. To determine a possible pathogenic mechanism, low-dose subcutaneous lipopolysaccharide (LPS) was administered in two separate animal models of glaucoma. Glaucomatous neurodegeneration was assessed in the retina and optic nerve two months later. Changes in gene expression of toll-like receptor 4 (TLR4) signaling pathway and complement as well as changes in microglial numbers and morphology were analyzed in the retina and optic nerve. The effect of pharmacologic blockade of TLR4 with naloxone was determined. Findings Patients with glaucoma had higher bacterial oral counts compared to control subjects (p<0.017). Low-dose LPS administration in glaucoma animal models resulted in enhancement of axonal degeneration and neuronal loss. Microglial activation in the optic nerve and retina as well as upregulation of TLR4 signaling and complement system were observed. Pharmacologic blockade of TLR4 partially ameliorated the enhanced damage. Conclusions The above findings suggest that the oral microbiome contributes to glaucoma pathophysiology. A plausible mechanism by which increased bacterial loads can lead to neurodegeneration is provided by experiments in animal models of the disease and involves activation of microglia in the retina and optic nerve, mediated through TLR4 signaling and complement upregulation. The finding that commensal bacteria may play a role in the development and/or progression of glaucomatous pathology may also be relevant to other chronic neurodegenerative disorders. PMID:25180891

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 nerve...

Targeting the colony stimulating factor 1 receptor alleviates two forms of Charcot-Marie-Tooth disease in mice.

PubMed

Klein, Dennis; Patzkó, Ágnes; Schreiber, David; van Hauwermeiren, Anemoon; Baier, Michaela; Groh, Janos; West, Brian L; Martini, Rudolf

2015-11-01

See Scherer (doi:10.1093/awv279) for a scientific commentary on this article.Charcot-Marie-Tooth type 1 neuropathies are inherited disorders of the peripheral nervous system caused by mutations in Schwann cell-related genes. Typically, no causative cure is presently available. Previous preclinical data of our group highlight the low grade, secondary inflammation common to distinct Charcot-Marie-Tooth type 1 neuropathies as a disease amplifier. In the current study, we have tested one of several available clinical agents targeting macrophages through its inhibition of the colony stimulating factor 1 receptor (CSF1R). We here show that in two distinct mouse models of Charcot-Marie-Tooth type 1 neuropathies, the systemic short- and long-term inhibition of CSF1R by oral administration leads to a robust decline in nerve macrophage numbers by ∼70% and substantial reduction of the typical histopathological and functional alterations. Interestingly, in a model for the dominant X-linked form of Charcot-Marie-Tooth type 1 neuropathy, the second most common form of the inherited neuropathies, macrophage ablation favours maintenance of axonal integrity and axonal resprouting, leading to preserved muscle innervation, increased muscle action potential amplitudes and muscle strengths in the range of wild-type mice. In another model mimicking a mild, demyelination-related Charcot-Marie-Tooth type 1 neuropathy caused by reduced P0 (MPZ) gene dosage, macrophage blockade causes an improved preservation of myelin, increased muscle action potential amplitudes, improved nerve conduction velocities and ameliorated muscle strength. These observations suggest that disease-amplifying macrophages can produce multiple adverse effects in the affected nerves which likely funnel down to common clinical features. Surprisingly, treatment of mouse models mimicking Charcot-Marie-Tooth type 1A neuropathy also caused macrophage blockade, but did not result in neuropathic or clinical improvements, most likely due to the late start of treatment of this early onset disease model. In summary, our study shows that targeting peripheral nerve macrophages by an orally administered inhibitor of CSF1R may offer a highly efficacious and safe treatment option for at least two distinct forms of the presently non-treatable Charcot-Marie-Tooth type 1 neuropathies. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Ultrasound-Guided Treatment of Peripheral Nerve Pathology.

PubMed

Dettori, Nathan; Choudur, Hema; Chhabra, Avneesh

2018-07-01

High-resolution ultrasound serves as a fast, accessible, reliable, and radiation-free tool for anatomical and dynamic evaluation of various peripheral nerves. It can be used not only to identify and diagnose peripheral nerve and perineural pathology accurately but also to guide various nerve and perineural interventions. We describe the normal and pathologic appearances of peripheral nerves, the pathologies commonly affecting the individual peripheral nerves, and the current ultrasound-guided peripheral nerve interventions and techniques. Future directions are also highlighted. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Our experience with facial nerve monitoring in vestibular schwannoma surgery under partial neuromuscular blockade.

PubMed

Vega-Céliz, Jorge; Amilibia-Cabeza, Emili; Prades-Martí, José; Miró-Castillo, Nuria; Pérez-Grau, Marta; Pintanel Rius, Teresa; Roca-Ribas Serdà, Francesc

2015-01-01

Facial nerve monitoring is fundamental in the preservation of the facial nerve in vestibular schwannoma surgery. Our objective was to analyse the usefulness of facial nerve monitoring under partial neuromuscular blockade. This was a retrospective analysis of 69 patients operated in a tertiary hospital. We monitored 100% of the cases. In 75% of the cases, we could measure an electromyographic response after tumour resection. In 17 cases, there was an absence of electromyographic response. Fifteen of them had an anatomic lesion with loss of continuity of the facial nerve and, in 2 cases, there was a lesion with preservation of the nerve. Preoperative facial palsy (29% 7%; P=.0349), large tumour size (88 vs. 38%; P=.0276), and a non-functional audition (88 vs. 51%; P=.0276) were significantly related with an absence of electromyographic response. Facial nerve monitoring under neuromuscular blockade is possible and safe in patients without previous facial palsy. If the patient had an electromyographic response after tumour excision, they developed better facial function in the postoperative period and after a year of follow up. Copyright © 2014 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Patología Cérvico-Facial. All rights reserved.

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

PubMed

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

2018-02-01

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

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".

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

PubMed Central

Sudoł-Szopińska, Iwona

2012-01-01

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”. PMID:26674560

Vestibulo-oculomotor behaviour in rats following a transient unilateral vestibular loss induced by lidocaine.

PubMed

Magnusson, A K; Tham, R

2003-01-01

The effects of a transient vestibular nerve blockade, achieved by intra-tympanic instillation of lidocaine, were studied in rats by recording horizontal eye movements in darkness. Evaluation of the dose-response relationship showed that a maximal effect was attained with a concentration of 4% lidocaine. Within 15 min of lidocaine instillation, a vigorous spontaneous nystagmus was observed which reached maximal frequency and velocity of the slow phase after about 20 min. Subsequently, the nystagmus failed for approximately half an hour before it reappeared. This could be avoided by providing visual feedback in between the recordings in darkness or by a contralateral instillation of 2.5% lidocaine. It is suggested that the failure reflects an overload of the vestibulo-oculomotor circuits. After recovery from the nerve blockade, when the gaze was stable, dynamic vestibular tests were performed. They revealed that a decrease of the slow phase velocity gain and the dominant time constant during, respectively, sinusoidal- and step stimulation toward the unanaesthetised side, had developed with the nerve blockade. These modulations were impaired by a nodulo-uvulectomy but not by bilateral flocculectomy, which is consistent with the concept of vestibular habituation. A GABA(B) receptor antagonist, CGP 56433A, given systemically during the nerve blockade, aggravated the vestibular asymmetry. The same effect has previously been demonstrated in both short- (days) and long-term (months) compensated rats, by antagonising the GABA(B) receptor. In summary, this study provides the first observations of vestibulo-oculomotor disturbances during the first hour after a rapid and transient unilateral vestibular loss in the rat. By using this method, it is possible to study immediate behavioural consequences and possible neural changes that might outlast the nerve blockade.

Current Strategies in Anesthesia and Analgesia for Total Knee Arthroplasty.

PubMed

Moucha, Calin Stefan; Weiser, Mitchell C; Levin, Emily J

2016-02-01

Total knee arthroplasty is associated with substantial postoperative pain that may impair mobility, reduce the ability to participate in rehabilitation, lead to chronic pain, and reduce patient satisfaction. Traditional general anesthesia with postoperative epidural and patient-controlled opioid analgesia is associated with an undesirable adverse-effect profile, including postoperative nausea and vomiting, hypotension, urinary retention, respiratory depression, delirium, and an increased infection rate. Multimodal anesthesia--incorporating elements of preemptive analgesia, neuraxial perioperative anesthesia, peripheral nerve blockade, periarticular injections, and multimodal oral opioid and nonopioid medications during the perioperative and postoperative periods--can provide superior pain control while minimizing opioid-related adverse effects, improving patient satisfaction, and reducing the risk of postoperative complications.

Intraoperative Ultrasound for Peripheral Nerve Applications.

PubMed

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

2017-10-01

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

Extraneural findings during peripheral nerve ultrasound: Prevalence and further assessment.

PubMed

Bignotti, Bianca; Zaottini, Federico; Airaldi, Sonia; Martinoli, Carlo; Tagliafico, Alberto

2018-01-01

In this study we evaluated the frequency and further assessment of extraneural findings encountered during peripheral nerve ultrasound (US). Our retrospective review identified 278 peripheral nerve US examinations of 229 patients performed between December 2014 and December 2015. Reports were reviewed to assess the number of studies without peripheral nerve abnormalities and the frequency and further assessment of extraneural findings. A total of 107 peripheral nerve US examinations of 90 patients (49 men and 41 women, mean age 55 ± 16 years) did not report peripheral nerve abnormalities. Extraneural findings were observed in 24 of 107 (22.4%) studies. Fifteen of the 278 [5.4% (95% confidence interval 2.7%-8.1%)] studies led to a recommendation for additional imaging or clinical evaluation of an extraneural finding. At least 5.4% (15 of 278) of peripheral nerve US studies led to additional clinical or imaging assessment. Muscle Nerve 57: 65-69, 2018. © 2017 Wiley Periodicals, Inc.

Evidence that spinal segmental nitric oxide mediates tachyphylaxis to peripheral local anesthetic nerve block.

PubMed

Wang, C; Sholas, M G; Berde, C B; DiCanzio, J; Zurakowski, D; Wilder, R T

2001-09-01

Tachyphylaxis to sciatic nerve blockade in rats correlates with hyperalgesia. Spinal inhibition of nitric oxide synthase with N(G)nitro-L-arginine methyl ester (L-NAME) has been shown to prevent hyperalgesia. Given systemically, L-NAME also prevents tachyphylaxis. The action of L-NAME in preventing tachyphylaxis therefore may be mediated at spinal sites. We compared systemic versus intrathecal potency of L-NAME in modulating tachyphylaxis to sciatic nerve block. Rats were prepared with intrathecal catheters. Three sequential sciatic nerve blocks were placed. Duration of block of thermal nocifensive, proprioceptive and motor responses was recorded. We compared spinal versus systemic dose-response to L-NAME, and examined effects of intrathecal arginine on tachyphylaxis. An additional group of rats underwent testing after T10 spinal cord transection. In these rats duration of sciatic nerve block was assessed by determining the heat-induced flexion withdrawal reflex. L-NAME was 25-fold more potent in preventing tachyphylaxis given intrathecally than intraperitoneally. Intrathecal arginine augmented tachyphylaxis. Spinalized rats exhibited tachyphylaxis to sciatic block. The increased potency of intrathecal versus systemic L-NAME suggests a spinal site of action in inhibiting tachyphylaxis. Descending pathways are not necessary for the development of tachyphylaxis since it occurs even after T10 spinal cord transection. Thus tachyphylaxis, like hyperalgesia, is mediated at least in part by a spinal site of action.

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

PubMed

Hontanilla, B; Vidal, A

2000-01-01

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

Electrophysiological characterization of the rat trigeminal caudalis (Vc) neurons following intramuscular injection of capsaicin

PubMed Central

Chun, Yang H; Ro, Jin Y

2009-01-01

Extracellular single unit recording experiments were performed to examine response characteristics of wide dynamic range neurons in the Vc that receive masseter afferent input in Sprague Dawley rats. Capsaicin, or its vehicle, was directly administered into the masseter muscle and changes in resting discharge, responses to mechanical stimulation on the cutaneous receptive field and the electrical threshold for masseter nerve stimulation were assessed. Intramuscular capsaicin induced significant increase in the background discharge and mechanical hypersensitivity to the cutaneous stimulation and lowered the threshold masseter nerve stimulation evoked responses in the majority of neurons. The capsaicin-induced increase in evoked responses, but not the resting discharge, was partially attenuated when the muscle was pretreated with a mGluR antagonist. The present study suggests that injury or inflammation in the masseter muscle induce generalized hyperexcitability of central trigeminal neurons and that the blockade of peripherally localized mGluR5 can effectively attenuate muscular hypersensitivity. PMID:19818833

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

PubMed Central

Nevo, Zvi

2014-01-01

Objective. Guiding Regeneration Gel (GRG) was developed in response to the clinical need of improving treatment for peripheral nerve injuries and helping patients regenerate massive regional losses in peripheral nerves. The efficacy of GRG based on tissue engineering technology for the treatment of complete peripheral nerve injury with significant loss defect was investigated. Background. Many severe peripheral nerve injuries can only be treated through surgical reconstructive procedures. Such procedures are challenging, since functional recovery is slow and can be unsatisfactory. One of the most promising solutions already in clinical practice is synthetic nerve conduits connecting the ends of damaged nerve supporting nerve regeneration. However, this solution still does not enable recovery of massive nerve loss defect. The proposed technology is a biocompatible and biodegradable gel enhancing axonal growth and nerve regeneration. It is composed of a complex of substances comprising transparent, highly viscous gel resembling the extracellular matrix that is almost impermeable to liquids and gasses, flexible, elastic, malleable, and adaptable to various shapes and formats. Preclinical study on rat model of peripheral nerve injury showed that GRG enhanced nerve regeneration when placed in nerve conduits, enabling recovery of massive nerve loss, previously unbridgeable, and enabled nerve regeneration at least as good as with autologous nerve graft “gold standard” treatment. PMID:25105121

Overlapping Mechanisms of Peripheral Nerve Regeneration and Angiogenesis Following Sciatic Nerve Transection

PubMed Central

Wang, Hongkui; Zhu, Hui; Guo, Qi; Qian, Tianmei; Zhang, Ping; Li, Shiying; Xue, Chengbin; Gu, Xiaosong

2017-01-01

Peripheral nervous system owns the ability of self-regeneration, mainly in its regenerative microenvironment including vascular network reconstruction. More recently, more attentions have been given to the close relationship between tissue regeneration and angiogenesis. To explore the overlap of molecular mechanisms and key regulation molecules between peripheral nerve regeneration and angiogenesis post peripheral nerve injury, integrative and bioinformatic analysis was carried out for microarray data of proximal stumps after sciatic nerve transection in SD rats. Nerve regeneration and angiogenesis were activated at 1 day immediately after sciatic nerve transection simultaneously. The more obvious changes of transcription regulators and canonical pathways suggested a phase transition between 1 and 4 days of both nerve regeneration and angiogenesis after sciatic nerve transection. Furthermore, 16 differentially expressed genes participated in significant biological processes of both nerve regeneration and angiogenesis, a few of which were validated by qPCR and immunofluorescent staining. It was demonstrated that STAT3, EPHB3, and Cdc42 co-expressed in Schwann cells and vascular endothelial cells to play a key role in regulation of nerve regeneration and angiogenesis simultaneously response to sciatic nerve transection. We provide a framework for understanding biological processes and precise molecular correlations between peripheral nerve regeneration and angiogenesis after peripheral nerve transection. Our work serves as an experimental basis and a valuable resource to further understand molecular mechanisms that define nerve injury-induced micro-environmental variation for achieving desired peripheral nerve regeneration. PMID:29085283

Overlapping Mechanisms of Peripheral Nerve Regeneration and Angiogenesis Following Sciatic Nerve Transection.

PubMed

Wang, Hongkui; Zhu, Hui; Guo, Qi; Qian, Tianmei; Zhang, Ping; Li, Shiying; Xue, Chengbin; Gu, Xiaosong

2017-01-01

Peripheral nervous system owns the ability of self-regeneration, mainly in its regenerative microenvironment including vascular network reconstruction. More recently, more attentions have been given to the close relationship between tissue regeneration and angiogenesis. To explore the overlap of molecular mechanisms and key regulation molecules between peripheral nerve regeneration and angiogenesis post peripheral nerve injury, integrative and bioinformatic analysis was carried out for microarray data of proximal stumps after sciatic nerve transection in SD rats. Nerve regeneration and angiogenesis were activated at 1 day immediately after sciatic nerve transection simultaneously. The more obvious changes of transcription regulators and canonical pathways suggested a phase transition between 1 and 4 days of both nerve regeneration and angiogenesis after sciatic nerve transection. Furthermore, 16 differentially expressed genes participated in significant biological processes of both nerve regeneration and angiogenesis, a few of which were validated by qPCR and immunofluorescent staining. It was demonstrated that STAT3, EPHB3, and Cdc42 co-expressed in Schwann cells and vascular endothelial cells to play a key role in regulation of nerve regeneration and angiogenesis simultaneously response to sciatic nerve transection. We provide a framework for understanding biological processes and precise molecular correlations between peripheral nerve regeneration and angiogenesis after peripheral nerve transection. Our work serves as an experimental basis and a valuable resource to further understand molecular mechanisms that define nerve injury-induced micro-environmental variation for achieving desired peripheral nerve regeneration.

Rearrangement of potassium ions and Kv1.1/Kv1.2 potassium channels in regenerating axons following end-to-end neurorrhaphy: ionic images from TOF-SIMS.

PubMed

Liu, Chiung-Hui; Chang, Hung-Ming; Wu, Tsung-Huan; Chen, Li-You; Yang, Yin-Shuo; Tseng, To-Jung; Liao, Wen-Chieh

2017-10-01

The voltage-gated potassium channels Kv1.1 and Kv1.2 that cluster at juxtaparanodal (JXP) regions are essential in the regulation of nerve excitability and play a critical role in axonal conduction. When demyelination occurs, Kv1.1/Kv1.2 activity increases, suppressing the membrane potential nearly to the equilibrium potential of K + , which results in an axonal conduction blockade. The recovery of K + -dependent communication signals and proper clustering of Kv1.1/Kv1.2 channels at JXP regions may directly reflect nerve regeneration following peripheral nerve injury. However, little is known about potassium channel expression and its relationship with the dynamic potassium ion distribution at the node of Ranvier during the regenerative process of peripheral nerve injury (PNI). In the present study, end-to-end neurorrhaphy (EEN) was performed using an in vivo model of PNI. The distribution of K + at regenerating axons following EEN was detected by time-of-flight secondary-ion mass spectrometry. The specific localization and expression of Kv1.1/Kv1.2 channels were examined by confocal microscopy and western blotting. Our data showed that the re-establishment of K + distribution and intensity was correlated with the functional recovery of compound muscle action potential morphology in EEN rats. Furthermore, the re-clustering of Kv1.1/1.2 channels 1 and 3 months after EEN at the nodal region of the regenerating nerve corresponded to changes in the K + distribution. This study provided direct evidence of K + distribution in regenerating axons for the first time. We proposed that the Kv1.1/Kv1.2 channels re-clustered at the JXP regions of regenerating axons are essential for modulating the proper patterns of K + distribution in axons for maintaining membrane potential stability after EEN.

Measurement of wavefront aberrations in cortex and peripheral nerve using a two-photon excitation guidestar

NASA Astrophysics Data System (ADS)

Futia, Gregory L.; Fontaine, Arjun; McCullough, Connor; Ozbay, Baris N.; George, Nickolas M.; Caldwell, John; Restrepo, Diego; Weir, Richard; Gibson, Emily A.

2018-02-01

Neural-machine interfaces using optogenetics are of interest due to their minimal invasiveness and potential for parallel read in and read out of activity. One possible biological target for such an interface is the peripheral nerve, where axonlevel imaging or stimulation could greatly improve interfacing with artificial limbs or enable neuron/fascicle level neuromodulation in the vagus nerve. Two-photon imaging has been successful in imaging brain activity using genetically encoded calcium or voltage indicators, but in the peripheral nerve, this is severely limited by scattering and aberrations from myelin. We employ a Shack-Hartman wavefront sensor and two-photon excitation guidestar to quantify optical scattering and aberrations in peripheral nerves and cortex. The sciatic and vagus nerves, and cortex from a ChAT-Cre ChR-eYFP transgenic mouse were excised and imaged directly. In peripheral nerves, defocus was the strongest aberration followed by astigmatism and coma. Peripheral nerve had orders of magnitude higher aberration compared with cortex. These results point to the potential of adaptive optics for increasing the depth of two-photon access into peripheral nerves.

Ultrasound-guided, percutaneous peripheral nerve stimulation: technical note.

PubMed

Chan, Isaac; Brown, Anthony R; Park, Kenneth; Winfree, Christopher J

2010-09-01

Peripheral nerve stimulation is a form of neuromodulation that applies electric current to peripheral nerves to induce stimulation paresthesias within the painful areas. To report a method of ultrasound-guided, percutaneous peripheral nerve stimulation. This technique utilizes real-time imaging to avoid injury to adjacent vascular structures during minimally invasive placement of peripheral nerve stimulator electrodes. We describe a patient that presented with chronic, bilateral foot pain following multiple foot surgeries, for whom a comprehensive, pain management treatment strategy had failed. We utilized ultrasound-guided, percutaneous tibial nerve stimulation at a thigh level to provide durable pain relief on the right side, and open peripheral nerve stimulation on the left. The patient experienced appropriate stimulation paresthesias and excellent pain relief on the plantar aspect of the right foot with the percutaneous electrode. On the left side, we were unable to direct the stimulation paresthesias to the sole of the foot, despite multiple electrode repositionings. A subsequent, open placement of a left tibial nerve stimulator was performed. This revealed that the correct electrode position against the tibial nerve was immediately adjacent to the popliteal artery, and was thus not appropriate for percutaneous placement. We describe a method of ultrasound-guided peripheral nerve stimulation that avoids the invasiveness of electrode placement via an open procedure while providing excellent pain relief. We further describe limitations of the percutaneous approach when navigating close to large blood vessels, a situation more appropriately managed with open peripheral nerve stimulator placement. Ultrasound-guided placement may be considered for patients receiving peripheral nerve stimulators placed within the deep tissues, and not easily placed in a blind fashion.

3D printing strategies for peripheral nerve regeneration.

PubMed

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

2018-03-23

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

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

PubMed

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

2013-12-01

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

Peripheral, but not central, CB1 antagonism provides food intake-independent metabolic benefits in diet-induced obese rats.

PubMed

Nogueiras, Ruben; Veyrat-Durebex, Christelle; Suchanek, Paula M; Klein, Marcella; Tschöp, Johannes; Caldwell, Charles; Woods, Stephen C; Wittmann, Gabor; Watanabe, Masahiko; Liposits, Zsolt; Fekete, Csaba; Reizes, Ofer; Rohner-Jeanrenaud, Francoise; Tschöp, Matthias H

2008-11-01

Blockade of the CB1 receptor is one of the promising strategies for the treatment of obesity. Although antagonists suppress food intake and reduce body weight, the role of central versus peripheral CB1 activation on weight loss and related metabolic parameters remains to be elucidated. We therefore specifically assessed and compared the respective potential relevance of central nervous system (CNS) versus peripheral CB1 receptors in the regulation of energy homeostasis and lipid and glucose metabolism in diet-induced obese (DIO) rats. Both lean and DIO rats were used for our experiments. The expression of key enzymes involved in lipid metabolism was measured by real-time PCR, and euglycemic-hyperinsulinemic clamps were used for insulin sensitivity and glucose metabolism studies. Specific CNS-CB1 blockade decreased body weight and food intake but, independent of those effects, had no beneficial influence on peripheral lipid and glucose metabolism. Peripheral treatment with CB1 antagonist (Rimonabant) also reduced food intake and body weight but, in addition, independently triggered lipid mobilization pathways in white adipose tissue and cellular glucose uptake. Insulin sensitivity and skeletal muscle glucose uptake were enhanced, while hepatic glucose production was decreased during peripheral infusion of the CB1 antagonist. However, these effects depended on the antagonist-elicited reduction of food intake. Several relevant metabolic processes appear to independently benefit from peripheral blockade of CB1, while CNS-CB1 blockade alone predominantly affects food intake and body weight.

Perioperative Pain Management in Total Hip Arthroplasty: Korean Hip Society Guidelines

PubMed Central

Kim, Yeesuk; Cho, Hong-Man; Park, Kyung-Soon; Yoon, Pil Whan; Nho, Jae-Hwi; Kim, Sang-Min; Lee, Kyung-Jae; Moon, Kyong-Ho

2016-01-01

Effective perioperative pain management techniques and accelerated rehabilitation programs can improve health-related quality of life and functional status of patients after total hip arthroplasty. Traditionally, postoperative analgesia following arthroplasty was provided by intravenous patient-controlled analgesia or epidural analgesia. Recently, peripheral nerve blockade has emerged alternative analgesic approach. Multimodal analgesia strategy combines analgesics with different mechanisms of action to improve pain management. Intraoperative periarticular injection of multimodal drugs is one of the most important procedures in perioperative pain control for total hip arthroplasty. The goal of this review article is to provide a concise overview of the principles of multimodal pain management regimens as a practical guide for the perioperative pain management for total hip arthroplasty. PMID:27536639

Evaluation of pediatric upper extremity peripheral nerve injuries.

PubMed

Ho, Emily S

2015-01-01

The evaluation of motor and sensory function of the upper extremity after a peripheral nerve injury is critical to diagnose the location and extent of nerve injury as well as document functional recovery in children. The purpose of this paper is to describe an approach to the evaluation of the pediatric upper extremity peripheral nerve injuries through a critical review of currently used tests of sensory and motor function. Outcome studies on pediatric upper extremity peripheral nerve injuries in the Medline database were reviewed. The evaluation of the outcome in children less than 10 years of age with an upper extremity peripheral nerve injury includes careful observation of preferred prehension patterns, examination of muscle atrophy and sudomotor function, provocative tests, manual muscle testing and tests of sensory threshold and tactile gnosis. The evaluation of outcome in children with upper extremity peripheral nerve injuries warrants a unique approach. Copyright © 2015 Hanley & Belfus. Published by Elsevier Inc. All rights reserved.

Ultrasound-guided percutaneous injection of methylene blue to identify nerve pathology and guide surgery.

PubMed

Osorio, Joseph A; Breshears, Jonathan D; Arnaout, Omar; Simon, Neil G; Hastings-Robinson, Ashley M; Aleshi, Pedram; Kliot, Michel

2015-09-01

OBJECT The objective of this study was to provide a technique that could be used in the preoperative period to facilitate the surgical exploration of peripheral nerve pathology. METHODS The authors describe a technique in which 1) ultrasonography is used in the immediate preoperative period to identify target peripheral nerves, 2) an ultrasound-guided needle electrode is used to stimulate peripheral nerves to confirm their position, and then 3) a methylene blue (MB) injection is performed to mark the peripheral nerve pathology to facilitate surgical exploration. RESULTS A cohort of 13 patients with varying indications for peripheral nerve surgery is presented in which ultrasound guidance, stimulation, and MB were used to localize and create a road map for surgeries. CONCLUSIONS Preoperative ultrasound-guided MB administration is a promising technique that peripheral nerve surgeons could use to plan and execute surgery.

Polymeric scaffolds for three-dimensional culture of nerve cells: a model of peripheral nerve regeneration

PubMed Central

Ayala-Caminero, Radamés; Pinzón-Herrera, Luis; Martinez, Carol A. Rivera; Almodovar, Jorge

2018-01-01

Understanding peripheral nerve repair requires the evaluation of 3D structures that serve as platforms for 3D cell culture. Multiple platforms for 3D cell culture have been developed, mimicking peripheral nerve growth and function, in order to study tissue repair or diseases. To recreate an appropriate 3D environment for peripheral nerve cells, key factors are to be considered including: selection of cells, polymeric biomaterials to be used, and fabrication techniques to shape and form the 3D scaffolds for cellular culture. This review focuses on polymeric 3D platforms used for the development of 3D peripheral nerve cell cultures. PMID:29515936

Localization and modulation of calcitonin gene-related peptide-receptor component protein-immunoreactive cells in the rat central and peripheral nervous systems.

PubMed

Ma, W; Chabot, J-G; Powell, K J; Jhamandas, K; Dickerson, I M; Quirion, R

2003-01-01

Calcitonin gene-related peptide (CGRP) is widely distributed in the central and peripheral nervous system. Its highly diverse biological activities are mediated via the G protein-coupled receptor that uniquely requires two accessory proteins for optimal function. CGRP receptor component protein (RCP) is a coupling protein necessary for CGRP-receptor signaling. In this study, we established the anatomical distribution of RCP in the rat central and peripheral nervous system and its relationship to CGRP immunoreactivity. RCP-immunoreactive (IR) perikarya are widely and selectively distributed in the cerebral cortex, septal nuclei, hippocampus, various hypothalamic nuclei, amygdala, nucleus colliculus, periaqueductal gray, parabrachial nuclei, locus coeruleus, cochlear nuclei, dorsal raphe nuclei, the solitary tractus nucleus and gracile nucleus, cerebellar cortex, various brainstem motor nuclei, the spinal dorsal and ventral horns. A sub-population of neurons in the dorsal root ganglia (DRG) and trigeminal ganglia were strongly RCP-IR. Overall, the localization of RCP-IR closely matched with that of CGRP-IR. We also determined whether RCP in DRG and dorsal horn neurons can be modulated by CGRP receptor blockade and pain-related pathological stimuli. The intrathecal injection of the antagonist CGRP(8-37) markedly increased RCP expression in the lumbar DRG and spinal dorsal horn. Carrageenan-induced plantar inflammation produced a dramatic bilateral increase in RCP expression in the dorsal horn while a partial sciatic nerve ligation reduced RCP expression in the ipsilateral superficial dorsal horn. Our data suggest that the distribution of RCP immunoreactivity is closely matched with CGRP immunoreactivity in most of central and peripheral nervous systems. The co-localization of RCP and CGRP in motoneurons and primary sensory neurons suggests that CGRP has an autocrine or paracrine effect on these neurons. Moreover, our data also suggest that RCP expression in DRG and spinal cord can be modulated during CGRP receptor blockade, inflammation or neuropathic pain and this CGRP receptor-associated protein is dynamically regulated.

Meta-analysis of epidural analgesia versus peripheral nerve blockade after total knee joint replacement.

PubMed

Gerrard, Adam Daniel; Brooks, Ben; Asaad, Peter; Hajibandeh, Shahab; Hajibandeh, Shahin

2017-01-01

Postoperative pain after major knee surgery can be severe. Our aim was to compare the outcomes of epidural analgesia and peripheral nerve blockade (PNB) in patients undergoing total knee joint replacement (TKR). Moreover, we aimed to compare outcomes of adductor canal block (ACB) with those of femoral nerve block (FNB) after TKR. We conducted a systematic search of electronic information sources, including MEDLINE; EMBASE; CINAHL; and the Cochrane Central Register of Controlled Trials (CENTRAL). We applied a combination of free text and controlled vocabulary search adapted to thesaurus headings, search operators, and limits in each of the above databases. Pain intensity assessed on visual analogue scale (VAS), nausea and vomiting, systolic hypotension, and urinary retention was the reported outcome parameters. We identified 12 randomised controlled trials (RCTs) comparing outcomes of epidural analgesia and PNB reporting a total of 670 patients. There was no significant difference between two groups in VAS scores at 0-12 h (MD -0.48; 95 % CI -1.07-0.11, P = 0.11), 12-24 h (MD 0.04; 95 % CI -0.81-0.88, P = 0.93), and 24-48 h (MD 0.16; 95 % CI -0.08-0.40, P = 0.19). However, epidural analgesia was associated with significantly higher risk of postoperative nausea and vomiting (RR 1.65; 95 % CI, 1.20-2.28, P = 0.002), hypotension (RR 1.76; 95 % CI, 1.26-2.45, P = 0.0009), and urinary retention (RR 4.51; 95 % CI, 2.27-8.96, P < 0.0001) compared to PNB. Moreover, pooled analysis of data from 6 RCTs demonstrated no significant difference in VAS score between ACB and FNB at 24 h (MD -0.00; 95 % CI, -0.56-0.56, P = 0.99) and 48 h (MD -0.06; 95 % CI, -0.14-0.03, P = 0.23). PNB is as effective as epidural analgesia for postoperative pain management in patients undergoing TKR. Moreover, it is associated with significantly lower postoperative complications. ACB appears to be an effective PNB with similar analgesic effect to FNB after TKR. Future RCTs may provide better evidence regarding knee range of motion, length of hospital stay, and neurological complications.

Regenerative peripheral nerve interface viability and signal transduction with an implanted electrode.

PubMed

Kung, Theodore A; Langhals, Nicholas B; Martin, David C; Johnson, Philip J; Cederna, Paul S; Urbanchek, Melanie G

2014-06-01

The regenerative peripheral nerve interface is an internal interface for signal transduction with external electronics of prosthetic limbs; it consists of an electrode and a unit of free muscle that is neurotized by a transected residual peripheral nerve. Adding a conductive polymer coating on electrodes improves electrode conductivity. This study examines regenerative peripheral nerve interface tissue viability and signal fidelity in the presence of an implanted electrode coated or uncoated with a conductive polymer. In a rat model, the extensor digitorum longus muscle was moved as a nonvascularized free tissue transfer and neurotized by the divided peroneal nerve. Either a stainless steel pad electrode (n = 8) or a pad electrode coated with poly(3,4-ethylenedioxythiophene) conductive polymer (PEDOT) (n = 8) was implanted on the muscle transfer and secured with an encircling acellular extracellular matrix. The contralateral muscle served as the control. The free muscle transfers were successfully revascularized and over time reinnervated as evidenced by serial insertional needle electromyography. Compound muscle action potentials were successfully transduced through the regenerative peripheral nerve interface. The conductive polymer coating on the implanted electrode resulted in increased recorded signal amplitude that was observed throughout the course of the study. Histologic examination confirmed axonal sprouting, elongation, and synaptogenesis within regenerative peripheral nerve interface regardless of electrode type. The regenerative peripheral nerve interface remains viable over seven months in the presence of an implanted electrode. Electrodes with and without conductive polymer reliably transduced signals from the regenerative peripheral nerve interface. Electrodes with a conductive polymer coating resulted in recording more of the regenerative peripheral nerve interface signal.

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

DTIC Science & Technology

2017-07-01

AWARD NUMBER: W81XWH-15-2-0026 TITLE: Clinical Evaluation of Decellularized Nerve Allograft with Autologous Bone Marrow Stem Cells to Improve...of Decellularized Nerve Allograft with 5a. CONTRACT NUMBER Autologous Bone Marrow Stem Cells to Improve Peripheral Nerve 5b. GRANT NUMBER W81XWH...commercially available decellularized processed peripheral nerve allograft scaffold (Avance® Nerve Graft, AxoGen, Alachua FL) with autologous bone marrow

Estimation of ultrasound reference values for the lower limb peripheral nerves in adults: A cross-sectional study.

PubMed

Bedewi, Mohamed Abdelmohsen; Abodonya, Ahmed; Kotb, Mamdouh; Kamal, Sanaa; Mahmoud, Gehan; Aldossari, Khaled; Alqabbani, Abdullah; Swify, Sherine

2018-03-01

The objective of this study is to estimate the reference values for the lower limb peripheral nerves in adults.The demographics and physical characteristics of 69 adult healthy volunteers were evaluated and recorded. The estimated reference values and their correlations with the age, weight, height, body mass index (BMI) were evaluated.The cross sectional area reference values were obtained at 5 predetermined sites for 3 important lower limb peripheral nerves. Our CSA values correlated significantly with age, weight, and BMI. The normal reference values for each nerve were as follows: Tibial nerve at the popliteal fossa 19 mm ± 6.9, tibial nerve at the level of the medial malleolus 12.7 mm ± 4.5, common peroneal nerve at the popliteal fossa 9.5 mm ± 4, common peroneal nerve fibular head 8.9 mm ± 3.2, sural nerve 3.5 mm ± 1.4.The reference values for the lower limb peripheral nerves were identified. These values could be used for future management of peripheral nerve disorders.

α-Adrenoceptor blockade modifies neurally induced atrial arrhythmias

PubMed Central

Richer, Louis-Philippe; Vinet, Alain; Kus, Teresa; Cardinal, René; Ardell, Jeffrey L.; Armour, John Andrew

2008-01-01

Our objective was to determine whether neuronally induced atrial arrhythmias can be modified by α-adrenergic receptor blockade. In 30 anesthetized dogs, trains of five electrical stimuli (1 mA; 1 ms) were delivered immediately after the P wave of the ECG to mediastinal nerves associated with the superior vena cava. Regional atrial electrical events were monitored with 191 atrial unipolar electrodes. Mediastinal nerve sites were identified that reproducibly initiated atrial arrhythmias. These sites were then restimulated following 1 h (time control, n = 6), or the intravenous administration of naftopidil (α1-adrenergic blocker: 0.2 mg/kg, n = 6), yohimbine (α2-adrenergic blocker: 1 mg/kg, n = 6) or both (n = 8). A ganglionic blocker (hexamethonium: 1 mg/kg) was tested in four dogs. Stimulation of mediastinal nerves sites consistently elicited atrial tachyarrhythmias. Repeat stimulation after 1 h in the time-control group exerted a 19% decrease of the sites still able to induce atrial tachyarrhythmias. Hexamethonium inactivated 78% of the previously active sites. Combined α-adrenoceptor blockade inactivated 72% of the previously active sites. Bradycardia responses induced by mediastinal nerve stimulation were blunted by hexamethonium, but not by α1,2-adrenergic blockade. Naftopidil or yohimbine alone eliminated atrial arrhythmia induction from 31% and 34% of the sites (similar to time control). We conclude that heterogeneous activation of the intrinsic cardiac nervous system results in atrial arrhythmias that involve intrinsic cardiac neuronal α-adrenoceptors. In contrast to the global suppression exerted by hexamethonium, we conclude that α-adrenoceptor blockade targets intrinsic cardiac local circuit neurons involved in arrhythmia formation and not the flow-through efferent projections of the cardiac nervous system. PMID:18716036

Alpha-adrenoceptor blockade modifies neurally induced atrial arrhythmias.

PubMed

Richer, Louis-Philippe; Vinet, Alain; Kus, Teresa; Cardinal, René; Ardell, Jeffrey L; Armour, John Andrew

2008-10-01

Our objective was to determine whether neuronally induced atrial arrhythmias can be modified by alpha-adrenergic receptor blockade. In 30 anesthetized dogs, trains of five electrical stimuli (1 mA; 1 ms) were delivered immediately after the P wave of the ECG to mediastinal nerves associated with the superior vena cava. Regional atrial electrical events were monitored with 191 atrial unipolar electrodes. Mediastinal nerve sites were identified that reproducibly initiated atrial arrhythmias. These sites were then restimulated following 1 h (time control, n = 6), or the intravenous administration of naftopidil (alpha(1)-adrenergic blocker: 0.2 mg/kg, n = 6), yohimbine (alpha(2)-adrenergic blocker: 1 mg/kg, n = 6) or both (n = 8). A ganglionic blocker (hexamethonium: 1 mg/kg) was tested in four dogs. Stimulation of mediastinal nerves sites consistently elicited atrial tachyarrhythmias. Repeat stimulation after 1 h in the time-control group exerted a 19% decrease of the sites still able to induce atrial tachyarrhythmias. Hexamethonium inactivated 78% of the previously active sites. Combined alpha-adrenoceptor blockade inactivated 72% of the previously active sites. Bradycardia responses induced by mediastinal nerve stimulation were blunted by hexamethonium, but not by alpha(1,2)-adrenergic blockade. Naftopidil or yohimbine alone eliminated atrial arrhythmia induction from 31% and 34% of the sites (similar to time control). We conclude that heterogeneous activation of the intrinsic cardiac nervous system results in atrial arrhythmias that involve intrinsic cardiac neuronal alpha-adrenoceptors. In contrast to the global suppression exerted by hexamethonium, we conclude that alpha-adrenoceptor blockade targets intrinsic cardiac local circuit neurons involved in arrhythmia formation and not the flow-through efferent projections of the cardiac nervous system.

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

PubMed

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

2016-02-01

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

Peripheral Neuropathy and Nerve Compression Syndromes in Burns.

PubMed

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

2017-10-01

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

Label-free photoacoustic microscopy of peripheral nerves

NASA Astrophysics Data System (ADS)

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

2014-01-01

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

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

PubMed

Singh, Kunwarpal; Gupta, Kamlesh; Kaur, Sukhdeep

2017-12-01

High-resolution ultrasonography of the tibial nerve is a fast and non invasive tool for diagnosis of diabetic peripheral neuropathy. Our study was aimed at finding out the correlation of the cross sectional area and maximum thickness of nerve fascicles of the tibial nerve with the presence and severity of diabetic peripheral neuropathy. 75 patients with type 2 diabetes mellitus clinically diagnosed with diabetic peripheral neuropathy were analysed, and the severity of neuropathy was determined using the Toronto Clinical Neuropathy Score. 58 diabetic patients with no clinical suspicion of diabetic peripheral neuropathy and 75 healthy non-diabetic subjects were taken as controls. The cross sectional area and maximum thickness of nerve fascicles of the tibial nerves were calculated 3 cm cranial to the medial malleolus in both lower limbs. The mean cross sectional area (22.63 +/- 2.66 mm 2 ) and maximum thickness of nerve fascicles (0.70 mm) of the tibial nerves in patients with diabetic peripheral neuropathy compared with both control groups was significantly larger, and statistically significant correlation was found with the Toronto Clinical Neuropathy Score ( p < 0.001). The diabetic patients with no signs of peripheral neuropathy had a larger mean cross sectional area (14.40 +/- 1.72 mm 2 ) and maximum thickness of nerve fascicles of the tibial nerve (0.40 mm) than healthy non-diabetic subjects (12.42 +/- 1.01 mm 2 and 0.30 mm respectively). The cross sectional area and maximum thickness of nerve fascicles of the tibial nerve is larger in diabetic patients with or without peripheral neuropathy than in healthy control subjects, and ultrasonography can be used as a good screening tool in these patients.

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

PubMed

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

2017-12-01

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

Inhibition of N-type Ca2+ channels ameliorates an imbalance in cardiac autonomic nerve activity and prevents lethal arrhythmias in mice with heart failure.

PubMed

Yamada, Yuko; Kinoshita, Hideyuki; Kuwahara, Koichiro; Nakagawa, Yasuaki; Kuwabara, Yoshihiro; Minami, Takeya; Yamada, Chinatsu; Shibata, Junko; Nakao, Kazuhiro; Cho, Kosai; Arai, Yuji; Yasuno, Shinji; Nishikimi, Toshio; Ueshima, Kenji; Kamakura, Shiro; Nishida, Motohiro; Kiyonaka, Shigeki; Mori, Yasuo; Kimura, Takeshi; Kangawa, Kenji; Nakao, Kazuwa

2014-10-01

Dysregulation of autonomic nervous system activity can trigger ventricular arrhythmias and sudden death in patients with heart failure. N-type Ca(2+) channels (NCCs) play an important role in sympathetic nervous system activation by regulating the calcium entry that triggers release of neurotransmitters from peripheral sympathetic nerve terminals. We have investigated the ability of NCC blockade to prevent lethal arrhythmias associated with heart failure. We compared the effects of cilnidipine, a dual N- and L-type Ca(2+) channel blocker, with those of nitrendipine, a selective L-type Ca(2+) channel blocker, in transgenic mice expressing a cardiac-specific, dominant-negative form of neuron-restrictive silencer factor (dnNRSF-Tg). In this mouse model of dilated cardiomyopathy leading to sudden arrhythmic death, cardiac structure and function did not significantly differ among the control, cilnidipine, and nitrendipine groups. However, cilnidipine dramatically reduced arrhythmias in dnNRSF-Tg mice, significantly improving their survival rate and correcting the imbalance between cardiac sympathetic and parasympathetic nervous system activity. A β-blocker, bisoprolol, showed similar effects in these mice. Genetic titration of NCCs, achieved by crossing dnNRSF-Tg mice with mice lacking CACNA1B, which encodes the α1 subunit of NCCs, improved the survival rate. With restoration of cardiac autonomic balance, dnNRSF-Tg;CACNA1B(+/-) mice showed fewer malignant arrhythmias than dnNRSF-Tg;CACNA1B(+/+) mice. Both pharmacological blockade of NCCs and their genetic titration improved cardiac autonomic balance and prevented lethal arrhythmias in a mouse model of dilated cardiomyopathy and sudden arrhythmic death. Our findings suggest that NCC blockade is a potentially useful approach to preventing sudden death in patients with heart failure. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

The blocking action of choline 2:6-xylyl ether bromide on adrenergic nerves

PubMed Central

Exley, K. A.

1957-01-01

Choline 2:6-xylyl ether bromide (TM 10), given systemically to cats in doses of 5 to 15 mg./kg., abolishes the effects of adrenergic nerve stimulation whilst leaving the reactions of the effector organs to adrenaline unimpaired. The effects of a single dose may take up to one hour to become fully established and last for more than twenty-four hours. Apart from transitory ganglionic blockade, cholinergic autonomic nerves are unaffected even by large doses of TM 10. Doses of TM 10 which produce effective blockade do not impair conduction along adrenergic nerve trunks; the drug must, therefore, act at, or close to, the nerve terminals. TM 10 prevents the output of noradrenaline from the spleen on stimulating the splenic nerves; but, in acute experiments, it does not influence the liberation of pressor amines from the stimulated suprarenals. Examination of some ethers related to TM 10 revealed no correlation between TM 10-like adrenergic blocking activity and local anaesthetic activity. The action of TM 10 on adrenergic nerves does not, therefore, seem to be accounted for by axonal block. ImagesFIG. 8 PMID:13460234

Tarsal tunnel syndrome

MedlinePlus

Tibial nerve dysfunction; Neuropathy - posterior tibial nerve; Peripheral neuropathy - tibial nerve; Tibial nerve entrapment ... Tarsal tunnel syndrome is an unusual form of peripheral neuropathy . It occurs when there is damage to the ...

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

PubMed

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

2017-05-01

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

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

Novel technique for repair of severed peripheral nerves in rats using polyurea crosslinked silica aerogel scaffold.

PubMed

Sabri, Firouzeh; Gerth, David; Tamula, George-Rudolph M; Phung, Thien-Chuong N; Lynch, Kyle J; Boughter, John D

2014-10-01

To design, synthesize, and test in vivo an aerogel-based top-open peripheral nerve scaffold to simultaneously support and guide multiple completely severed peripheral nerves in a rat model. Also, to explore options for immobilizing severed nerves on the aerogel material without the use of sutures resulting in reduced surgical time. A novel material and approach was developed for the reattachment of severed peripheral nerves. Nerve confinement and alignment in this case relies on the surface properties of a lightweight, highly porous, polyurea crosslinked silica aerogel scaffold. The distal and proximal ends of completely transected nerve terminals were positioned inside prefabricated "top-open" corrugated channels that cradled approximately two thirds of the circumference of the nerve trunk and connectivity of the severed nerves was evaluated using sciatic function index (SFI) technique for five months post-surgery on 10 female Sprague-Dawley rats then compared with the gold standard for peripheral nerve repair. The interaction of nerves with the surface of the scaffold was investigated also. Multichannel aerogel-based nerve support scaffold showed similar SFI recovery trend as the case suture repair technique. Usage of an adhesion-promoting coating reduced the friction between the nerve and the scaffold leading to slippage and lack of attachment between nerve and surface. The aerogel scaffold used in this study did not collapse under pressure during the incubation period and allowed for a rapid and non-invasive peripheral nerve repair approach without the demands of microsurgery on both time and surgical expertise. This technique may allow for simultaneous repair and reconnection of multiple severed nerves particularly relevant to nerve branching sites.

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

PubMed

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

2018-05-29

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

Use of nerve conduits for peripheral nerve injury repair: A Web of Science-based literature analysis.

PubMed

Nan, Jinniang; Hu, Xuguang; Li, Hongxiu; Zhang, Xiaonong; Piao, Renjing

2012-12-15

To identify global research trends in the use of nerve conduits for peripheral nerve injury repair. Numerous basic and clinical studies on nerve conduits for peripheral nerve injury repair were performed between 2002-2011. We performed a bibliometric analysis of the institutions, authors, and hot topics in the field, from the Web of Science, using the key words peripheral nerve and conduit or tube. peer-reviewed published articles on nerve conduits for peripheral nerve injury repair, indexed in the Web of Science; original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial material, and news items. articles requiring manual searching or telephone access; documents not published in the public domain; and several corrected papers. (a) Annual publication output; (b) publication type; (c) publication by research field; (d) publication by journal; (e) publication by funding agency; (f) publication by author; (g) publication by country and institution; (h) publications by institution in China; (i) most-cited papers. A total of 793 publications on the use of nerve conduits for peripheral nerve injury repair were retrieved from the Web of Science between 2002-2011. The number of publications gradually increased over the 10-year study period. Articles constituted the main type of publication. The most prolific journals were Biomaterials, Microsurgery, and Journal of Biomedical Materials Research Part A. The National Natural Science Foundation of China supported 27 papers, more than any other funding agency. Of the 793 publications, almost half came from American and Chinese authors and institutions. Nerve conduits have been studied extensively for peripheral nerve regeneration; however, many problems remain in this field, which are difficult for researchers to reach a consensus.

Side Effects: Nerve Problems (Peripheral Neuropathy)

Cancer.gov

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

Motor Cortex Stimulation Regenerative Effects in Peripheral Nerve Injury: An Experimental Rat Model.

PubMed

Nicolas, Nicolas; Kobaiter-Maarrawi, Sandra; Georges, Samuel; Abadjian, Gerard; Maarrawi, Joseph

2018-06-01

Immediate microsurgical nerve suture remains the gold standard after peripheral nerve injuries. However, functional recovery is delayed, and it is satisfactory in only 2/3 of cases. Peripheral electrical nerve stimulation proximal to the lesion enhances nerve regeneration and muscle reinnervation. This study aims to evaluate the effects of the motor cortex electrical stimulation on peripheral nerve regeneration after injury. Eighty rats underwent right sciatic nerve section, followed by immediate microsurgical epineural sutures. Rats were divided into 4 groups: Group 1 (control, n = 20): no electrical stimulation; group 2 (n = 20): immediate stimulation of the sciatic nerve just proximal to the lesion; Group 3 (n = 20): motor cortex stimulation (MCS) for 15 minutes after nerve section and suture (MCSa); group 4 (n = 20): MCS performed over the course of two weeks after nerve suture (MCSc). Assessment included electrophysiology and motor functional score at day 0 (baseline value before nerve section), and at weeks 4, 8, and 12. Rats were euthanized for histological study at week 12. Our results showed that MCS enhances functional recovery, nerve regeneration, and muscle reinnervation starting week 4 compared with the control group (P < 0.05). The MCS induces higher reinnervation rates even compared with peripheral stimulation, with better results in the MCSa group (P < 0.05), especially in terms of functional recovery. MCS seems to have a beneficial effect after peripheral nerve injury and repair in terms of nerve regeneration and muscle reinnervation, especially when acute mode is used. Copyright © 2018 Elsevier Inc. All rights reserved.

Revision of loop colostomy under regional anaesthesia and sedation.

PubMed

Ng, Oriana; Thong, Sze Ying; Chia, Claramae Shulyn; Teo, Melissa Ching Ching

2015-05-01

Patients presenting for emergency abdominal procedures often have medical issues that cause both general anaesthesia and central neuraxial blockade to pose significant risks. Regional anaesthetic techniques are often used adjunctively for abdominal procedures under general anaesthesia, but there is limited published data on procedures done under peripheral nerve or plexus blocks. We herein report the case of a patient with recent pulmonary embolism and supraventricular tachycardia who required colostomy refashioning. Ultrasonography-guided regional anaesthesia was administered using a combination of ilioinguinal-iliohypogastric, rectus sheath and transversus abdominis plane blocks. This was supplemented with propofol and dexmedetomidine sedation as well as intermittent fentanyl and ketamine boluses to cover for visceral stimulation. We discuss the anatomical rationale for the choice of blocks and compare the anaesthetic conduct with similar cases that were previously reported.

Innovations in interventional pain management of chronic spinal pain.

PubMed

Manchikanti, Laxmaiah; Boswell, Mark V; Hirsch, Joshua A

2016-09-01

Interventional pain management dates back to 1901, with significant innovations, which include the definition, literature synthesis, pathophysiology, and technical interventions. Interventional pain management and interventional techniques include neural blockade, neural ablative procedures, spinal cord and peripheral nerve stimulation, intrathecal drug delivery systems, minimally invasive lumbar decompression (MILD®), percutaneous endoscopic spinal decompression, and regenerative medicine. In addition, advances are also related to the evidence synthesis of comparative effectiveness research. Expert commentary: Multiple innovations in interventional pain management and potential innovations may reduce costs and improve care and outcomes with proper evidence synthesis and application of principles of evidence-based medicine. Innovations in interventional pain management in managing chronic spinal pain depend on extensive research and appropriate evidence synthesis. Innovations should be developed in conjunction with health care policy based on principles of evidence-based medicine.

Primary sensory neuron-specific interference of TRPV1 signaling by adeno-associated virus-encoded TRPV1 peptide aptamer attenuates neuropathic pain

PubMed Central

Xiang, Hongfei; Liu, Zhen; Wang, Fei; Xu, Hao; Roberts, Christopher; Fischer, Gregory; Stucky, Cheryl L; Dean, Caron; Pan, Bin; Hogan, Quinn H; Yu, Hongwei

2017-01-01

Background TRPV1 (transient receptor potential vanilloid subfamily member 1) is a pain signaling channel highly expressed in primary sensory neurons. Attempts for analgesia by systemic TRPV1 blockade produce undesirable side effects, such as hyperthermia and impaired heat pain sensation. One approach for TRPV1 analgesia is to target TRPV1 along the peripheral sensory pathway. Results For functional blockade of TRPV1 signaling, we constructed an adeno-associated virus (AAV) vector expressing a recombinant TRPV1 interfering peptide aptamer, derived from a 38mer tetrameric assembly domain (TAD), encompassing residues 735 to 772 of rat TRPV1, fused to the C-terminus of enhanced green fluorescent protein (EGFP). AAV-targeted sensory neurons expressing EGFP-TAD after vector injection into the dorsal root ganglia (DRG) revealed decreased inward calcium current and diminished intracellular calcium accumulation in response to capsaicin, compared to neurons of naïve or expressing EGFP alone. To examine the potential for treating neuropathic pain, AAV-EGFP-TAD was injected into fourth and fifth lumbar (L) DRGs of rats subjected to neuropathic pain by tibial nerve injury (TNI). Results showed that AAV-directed selective expression of EGFP-TAD in L4/L5 DRG neuron somata, and their peripheral and central axonal projections can limit TNI-induced neuropathic pain behavior, including hypersensitivity to heat and, to a less extent, mechanical stimulation. Conclusion Selective inhibition of TRPV1 activity in primary sensory neurons by DRG delivery of AAV-encoded analgesic interfering peptide aptamers is efficacious in attenuation of neuropathic pain. With further improvements of vector constructs and in vivo application, this approach might have the potential to develop as an alternative gene therapy strategy to treat chronic pain, especially heat hypersensitivity, without complications due to systemic TRPV1 blockade. PMID:28604222

A 63-year-old man with peripheral facial nerve paralysis and a pulmonary lesion.

PubMed

Yserbyt, J; Wilms, G; Lievens, Y; Nackaerts, K

2009-01-01

Occasionally, malignant neoplasms may cause peripheral facial nerve paralysis as a presenting symptom. A 63-year-old man was referred to the Emergency Department because of a peripheral facial nerve paralysis, lasting for 10 days. Initial diagnostic examinations revealed no apparent cause for this facial nerve paralysis. Chest X-ray, however, showed a suspicious tumoural mass, located in the right hilar region, as confirmed by CAT scan. The diagnosis of an advanced stage lung adenocarcinoma was finally confirmed by bronchial biopsy. MRI scanning showed diffuse brain metastases and revealed a pontine lesion as the most probable underlying cause of this case of peripheral facial nerve paralysis. Platin-based palliative chemotherapy was given, after an initial pancranial irradiation. According to the MRI findings, the pontine lesion was responsible for the peripheral facial nerve paralysis, as an initial presenting symptom in this case of lung adenocarcinoma. This clinical case of a peripheral facial nerve paralysis was caused by a pontine brain metastasis and illustrates a rather rare presenting symptom of metastatic lung cancer.

[Interest of ultrasonographic guidance in paediatric regional anaesthesia].

PubMed

Dadure, C; Raux, O; Rochette, A; Capdevila, X

2009-10-01

The use of ultrasonographic guidance for regional anaesthesia has known recently a big interest in children in recent years. The linear ultrasound probes with a 25 mm active surface area (or probes with 38 mm active surface area in older children), with high sound frequencies in the range 8-14 MHz, allow a good compromise between excellent resolution for superficial structure and good penetration depths. In children, the easiest ultrasound guided blocks are axillar blocks, femoral blocks, fascia iliaca compartment blocks, ilio-inguinal blocks and para-umbilical blocks, caudal blocks. They permit a safe and easy learning curve of these techniques. The main advantage of ultrasound guided regional anaesthesia is the visualization of different anatomical structures and the approximate localization of the tip of needle. The other advantages for ultrasound guided peripheral nerve blocks in children are: faster onset time of sensory and motor block, longer duration of sensory blockade, increase of blockade quality and reduction of local anesthetic injection. The use of ultrasonographic guidance for central block allows to visualize different structures as well as spine and his content. Spinous process, ligament flavum, dura mater, conus medullaris and cerebrospinal fluid are identifiable, and give some information on spine, epidural space and the depth between epidural space and skin. At last, in caudal block, ultrasounds permit to evaluate the anatomy of caudal epidural space, especially the relation of the sacral hiatus to the dural sac and the search of occult spinal dysraphism. Benefit of this technique is the visualization of targeted nerves or spaces and the spread of injected local anaesthetic.

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

PubMed

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

2016-07-01

Adrenal tumors with more than one cellular component are uncommon. Furthermore, an adrenal tumor composed of a pheochromocytoma and a malignant peripheral nerve sheath tumor is extremely rare. A composite pheochromocytoma with malignant peripheral nerve sheath tumor in a 42-year-old man is reported here. After adequate preoperative control, left adrenalectomy was performed simultaneously with resection of the ipsilateral kidney for spontaneous rupture of the left adrenal tumor. Pathological findings demonstrated pheochromocytoma and malignant peripheral nerve sheath tumor in a ruptured adrenal tumor. To date, there have been only four reported cases of composite pheochromocytoma with malignant peripheral nerve sheath tumor, so the present case is only the fifth case in the world. Despite the very poor prognosis of patients with pheochromocytoma and malignant peripheral nerve sheath tumors reported in the literature, the patient remains well without evidence of recurrence or new metastatic lesions at 36 months postoperatively. Copyright © 2012. Published by Elsevier Taiwan.

MRI abnormalities of peripheral nerve and muscle are common in amyotrophic lateral sclerosis and share features with multifocal motor neuropathy

PubMed Central

Staff, Nathan P.; Amrami, Kimberly K.; Howe, Benjamin M.

2015-01-01

Introduction MRI of peripheral nerve and muscle in patients with ALS may be performed to investigate alternative diagnoses including multifocal motor neuropathy (MMN). MRI findings of peripheral nerve and muscle are not well described in these conditions, making interpretation of results difficult. Methods We examined systematically the peripheral nerve and muscle MRI findings in patients with ALS (n=60) and MMN (n=8). Results In patients with ALS and MMN, abnormal MRIs were common (85% and 75%, respectively) but did not correlate with disease severity. Peripheral nerve MRI abnormalities were similar in frequency (ALS: 58% vs. MMN: 63%) with most changes being of mild-to-moderate severity. Muscle MRI changes were more common in ALS (57% vs. 33%), and no muscle atrophy was seen in patients with MMN. Discussion MRI abnormalities of peripheral nerve and muscle in ALS and MMN are common and share some features. PMID:25736373

Nicotine Prevents and Reverses Paclitaxel-Induced Mechanical Allodynia in a Mouse Model of CIPN.

PubMed

Kyte, S Lauren; Toma, Wisam; Bagdas, Deniz; Meade, Julie A; Schurman, Lesley D; Lichtman, Aron H; Chen, Zhi-Jian; Del Fabbro, Egidio; Fang, Xianjun; Bigbee, John W; Damaj, M Imad; Gewirtz, David A

2018-01-01

Chemotherapy-induced peripheral neuropathy (CIPN), a consequence of peripheral nerve fiber dysfunction or degeneration, continues to be a dose-limiting and debilitating side effect during and/or after cancer chemotherapy. Paclitaxel, a taxane commonly used to treat breast, lung, and ovarian cancers, causes CIPN in 59-78% of cancer patients. Novel interventions are needed due to the current lack of effective CIPN treatments. Our studies were designed to investigate whether nicotine can prevent and/or reverse paclitaxel-induced peripheral neuropathy in a mouse model of CIPN, while ensuring that nicotine will not stimulate lung tumor cell proliferation or interfere with the antitumor properties of paclitaxel. Male C57BL/6J mice received paclitaxel every other day for a total of four injections (8 mg/kg, i.p.). Acute (0.3-0.9 mg/kg, i.p.) and chronic (24 mg/kg per day, s.c.) administration of nicotine respectively reversed and prevented paclitaxel-induced mechanical allodynia. Blockade of the antinociceptive effect of nicotine with mecamylamine and methyllycaconitine suggests that the reversal of paclitaxel-induced mechanical allodynia is primarily mediated by the α 7 nicotinic acetylcholine receptor subtype. Chronic nicotine treatment also prevented paclitaxel-induced intraepidermal nerve fiber loss. Notably, nicotine neither promoted proliferation of A549 and H460 non-small cell lung cancer cells nor interfered with paclitaxel-induced antitumor effects, including apoptosis. Most importantly, chronic nicotine administration did not enhance Lewis lung carcinoma tumor growth in C57BL/6J mice. These data suggest that the nicotinic acetylcholine receptor-mediated pathways may be promising drug targets for the prevention and treatment of CIPN. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Drug Distribution into Peripheral Nerve.

PubMed

Liu, Houfu; Chen, Yan; Huang, Liang; Sun, Xueying; Fu, Tingting; Wu, Shengqian; Zhu, Xiaoyan; Zhen, Wei; Liu, Jihong; Lu, Gang; Cai, Wei; Yang, Ting; Zhang, Wandong; Yu, Xiaohong; Wan, Zehong; Wang, Jianfei; Summerfield, Scott G; Dong, Kelly; Terstappen, Georg C

2018-05-01

Little is known about the impact of the blood-nerve barrier (BNB) on drug distribution into peripheral nerves. In this study, we examined the peripheral nerve penetration in rats of 11 small-molecule drugs possessing diverse physicochemical and transport properties and ProTx-II, a tarantula venom peptide with molecular mass of 3826 Daltons. Each drug was administered as constant rate intravenous infusion for 6 hours (small molecules) or 24 hours (ProTx-II). Blood and tissues including brain, spinal cord, sciatic nerve, and dorsal root ganglion (DRG) were collected for drug concentration measurements. Unbound fractions of a set of compounds were determined by equilibrium dialysis method in rat blood, brains, spinal cords, sciatic nerves, and DRG. We also investigated the influence of N -[4-[2-(6,7-dimethoxy-3,4-dihydro-1 H -isoquinolin-2-yl)ethyl]phenyl]-5-methoxy-9-oxo-10 H -acridine-4-carboxamide (GF120918), a P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) inhibitor, on the peripheral nerve and central nervous system (CNS) tissue penetration of imatinib. We found that: 1) the unbound fraction in brain tissue homogenate highly correlates with that in the spinal cord, sciatic nerve, and DRG for a set of compounds and thus provides a good surrogate for spinal cord and peripheral nerve tissues, 2) small-molecule drugs investigated can penetrate the DRG and sciatic nerve, 3) P-gp and BCRP have a limited impact on the distribution of small-molecule drugs into peripheral nerves, and 4) DRG is permeable to ProTx-II, but its distribution into sciatic nerve and CNS tissues is restricted. These results demonstrate that small-molecule drugs investigated can penetrate peripheral nerve tissues, and P-gp/BCRP may not be a limiting factor at the BNB. Biologics as large as ProTx-II can access the DRG but not sciatic nerve and CNS tissues. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

External Nasal Neuralgia: A Neuropathic Pain Within the Territory of the External Nasal Nerve.

PubMed

García-Moreno, Héctor; Aledo-Serrano, Ángel; Gimeno-Hernández, Jesús; Cuadrado, María-Luz

2015-10-01

Nasal pain is a challenging diagnosis and very little has been reported in the neurological literature. The nose is a sophisticated structure regarding its innervation, which is supplied by the first and second divisions of the trigeminal nerve. Painful cranial neuropathies are an important group in the differential diagnosis, although they have been described only scarcely. Here, we report a case that can conform a non-traumatic external nasal nerve neuralgia. A 76-year-old woman was referred to our office due to pain in her left nose. She was suffering from daily excruciating attacks, which were strictly limited to the territory supplied by her left external nasal nerve (left ala nasi and apex nasi). She denied previous traumatisms and the ancillary tests did not yield any underlying pathology. An anesthetic blockade of her left external nasal nerve achieved a marked reduction of the number of episodes as well as their intensity. External nasal neuralgia seems a specific neuralgia causing nasal pain. Anesthetic blockades of the external nasal nerve may be a valid treatment for this condition. © 2015 American Headache Society.

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.

A continuous quality improvement approach to improving clinical practice in the areas of sedation, analgesia, and neuromuscular blockade.

PubMed

Arbour, Richard

2003-01-01

Practice concerns associated with the medical prescription and nurses' administration and monitoring of sedatives, analgesics, and neuromuscular blocking agents were identified by the clinical nurse specialist within a surgical intensive care unit of a large, tertiary-care referral center. These concerns were identified using a variety of needs assessment strategies. Results of the needs assessment were used to develop a program of care, including a teaching initiative, specific to these practice areas. The teaching initiative incorporated principles of andragogy, the theory of adult learning. Educational techniques included inservice education, bedside instruction using "teaching moments," competency-based education modules, and integration of instruction into critical care orientation. Content and approach were based on the background and level of experience of participants. Educational program outcomes included increased consistency in monitoring neuromuscular blockade by clinical assessment and peripheral nerve stimulation. A second outcome was more accurate patient assessment leading to the provision of drug therapy specific to the patients' clinical states, including anxiety or pain. The continuous quality improvement approach offers a model for improving patient care using individualized needs assessment, focused educational interventions, and program evaluation strategies.

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

Necrotizing Fasciitis as a Complication of a Continuous Sciatic Nerve Catheter Using the Lateral Popliteal Approach.

PubMed

Dott, Daltry; Canlas, Christopher; Sobey, Christopher; Obremskey, William; Thomson, Andrew Brian

Necrotizing fasciitis is an infection of the soft tissue that is characterized by rapidly spreading inflammation and subsequent necrosis. It is a rare complication of peripheral nerve blocks. We report a rare case of necrotizing fasciitis after placement of a peripheral nerve catheter. A 58-year-old woman presented for an elective right second metatarsal resection and received a sciatic nerve catheter for postoperative pain control. On postoperative day 7, clinical examination and imaging supported the diagnosis of necrotizing fasciitis. Multiple reports have been published of necrotizing fasciitis after single-shot peripheral nerve block injections, neuraxial anesthesia, and intramuscular injections. This case highlights the potential for the rare complication of necrotizing fasciitis after peripheral nerve catheter placement.

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

Blockade of the mental nerve for lower lip surgery as a safe alternative to general anesthesia in two very old patients.

PubMed

Tan, Ferdinand Frederik Som Ling; Schiere, Sjouke; Reidinga, Auke C; Wit, Fennie; Veldman, Peter Hjm

2015-01-01

Regional anesthesia is gaining popularity with anesthesiologists as it offers superb postoperative analgesia. However, as the sole anesthetic technique in high-risk patients in whom general anesthesia is not preferred, some regional anesthetic possibilities may be easily overlooked. By presenting two cases of very old patients with considerable comorbidities, we would like to bring the mental nerve field block under renewed attention as a safe alternative to general anesthesia and to achieve broader application of this simple nerve block. Two very old male patients (84 and 91 years) both presented with an ulcerative lesion at the lower lip for which surgical removal was scheduled. Because of their considerable comorbidities and increased frailty, bilateral blockade of the mental nerve was considered superior to general anesthesia. As an additional advantage for the 84-year-old patient, who had a pneumonectomy in his medical history, the procedure could be safely performed in a beach-chair position to prevent atelectasis and optimize the ventilation/perfusion ratio of the single lung. The mental nerve blockades were performed intraorally in a blind fashion, after eversion of the lip and identifying the lower canine. A 5 mL syringe with a 23-gauge needle attached was passed into the buccal mucosa until it approximated the mental foramen, where 2 mL of lidocaine 2% with adrenaline 1:100.000 was injected. The other side was anesthetized in a similar fashion. Both patients underwent the surgical procedure uneventfully under a bilateral mental nerve block and were discharged from the hospital on the same day. A mental nerve block is an easy-to-perform regional anesthetic technique for lower lip surgery. This technique might be especially advantageous in the very old, frail patient.

Suppression of Peripheral Sympathetic Activity Underlies Protease-Activated Receptor 2-Mediated Hypotension

PubMed Central

Kim, Young-Hwan; Ahn, Duck-Sun; Joeng, Ji-Hyun

2014-01-01

Protease-activated receptor (PAR)-2 is expressed in endothelial cells and vascular smooth muscle cells. It plays a crucial role in regulating blood pressure via the modulation of peripheral vascular tone. Although some reports have suggested involvement of a neurogenic mechanism in PAR-2-induced hypotension, the accurate mechanism remains to be elucidated. To examine this possibility, we investigated the effect of PAR-2 activation on smooth muscle contraction evoked by electrical field stimulation (EFS) in the superior mesenteric artery. In the present study, PAR-2 agonists suppressed neurogenic contractions evoked by EFS in endothelium-denuded superior mesenteric arterial strips but did not affect contraction elicited by the external application of noradrenaline (NA). However, thrombin, a potent PAR-1 agonist, had no effect on EFS-evoked contraction. Additionally, ω-conotoxin GVIA (CgTx), a selective N-type Ca2+ channel (ICa-N) blocker, significantly inhibited EFS-evoked contraction, and this blockade almost completely occluded the suppression of EFS-evoked contraction by PAR-2 agonists. Finally, PAR-2 agonists suppressed the EFS-evoked overflow of NA in endothelium-denuded rat superior mesenteric arterial strips and this suppression was nearly completely occluded by ω-CgTx. These results suggest that activation of PAR-2 may suppress peripheral sympathetic outflow by modulating activity of ICa-N which are located in peripheral sympathetic nerve terminals, which results in PAR-2-induced hypotension. PMID:25598663

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 nerve...

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 nerve...

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

PubMed

Thapa, Lekhjung; Rana, P V S

2016-01-01

Objective. Nondiabetic obese individuals have subclinical involvement of peripheral nerves. We report the factors predicting peripheral nerve function in overweight and obese nondiabetic Nepalese individuals. Methodology. In this cross-sectional study, we included 50 adult overweight and obese nondiabetic volunteers without features of peripheral neuropathy and 50 healthy volunteers to determine the normative nerve conduction data. In cases of abnormal function, the study population was classified on the basis of the number of nerves involved, namely, "<2" or "≥2." Multivariable logistic regression analysis was carried out to predict outcomes. Results. Fasting blood glucose (FBG) was the significant predictor of motor nerve dysfunction (P = 0.039, 95% confidence interval (CI) = 1.003-1.127). Homeostatic model assessment of insulin resistance (HOMA-IR) was the significant predictor (P = 0.019, 96% CI = 1.420-49.322) of sensory nerve dysfunction. Body mass index (BMI) was the significant predictor (P = 0.034, 95% CI = 1.018-1.577) in case of ≥2 mixed nerves' involvement. Conclusion. FBG, HOMA-IR, and BMI were significant predictors of peripheral nerve dysfunction in overweight and obese Nepalese individuals.

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

Peripheral substance P and neurokinin-1 receptors have a role in inflammatory and neuropathic orofacial pain models.

PubMed

Teodoro, Fernanda C; Tronco Júnior, Marcos F; Zampronio, Aleksander R; Martini, Alessandra C; Rae, Giles A; Chichorro, Juliana G

2013-06-01

There is accumulating evidence that substance P released from peripheral sensory neurons participates in inflammatory and neuropathic pain. In this study it was investigated the ability of substance P to induce orofacial nociception and thermal and mechanical hyperalgesia, as well as the role of NK1 receptors on models of orofacial inflammatory and neuropathic pain. Substance P injected into the upper lip at 1, 10 and 100 μg/50 μL failed to induce nociceptive behavior. Also, substance P (0.1-10 μg/50 μL) injected into the upper lip did not evoke orofacial cold hyperalgesia and when injected at 1 μg/50 μL did not induce mechanical hyperalgesia. However, substance P at this latter dose induced orofacial heat hyperalgesia, which was reduced by the pre-treatment of rats with a non-peptide NK1 receptor antagonist (SR140333B, 3mg/kg). Systemic treatment with SR140333B (3 mg/kg) also reduced carrageenan-induced heat hyperalgesia, but did not exert any influence on carrageenan-induced cold hyperalgesia. Blockade of NK1 receptors with SR140333B also reduced by about 50% both phases of the formalin response evaluated in the orofacial region. Moreover, heat, but not cold or mechanical, hyperalgesia induced by constriction of the infraorbital nerve, a model of trigeminal neuropathic pain, was abolished by pretreatment with SR140333B. Considering that substance P was peripherally injected (i.e. upper lip) and the NK1 antagonist used lacks the ability to cross the blood-brain-barrier, our results demonstrate that the peripheral SP/NK1 system participates in the heat hyperalgesia associated with inflammation or nerve injury and in the persistent pain evoked by formalin in the orofacial region. Copyright © 2012 Elsevier Ltd. All rights reserved.

Convection-Enhanced Delivery (CED) in an Animal Model of Malignant Peripheral Nerve Sheath (MPNST) Tumors and Plexiform Neurofibromas (PN)

DTIC Science & Technology

2012-09-01

TITLE: Convection-Enhanced Delivery ( CED ) in an Animal Model of Malignant Peripheral Nerve Sheath ( MPNST ) Tumors and Plexiform Neurofibromas (PN...within the sciatic nerve. 15. SUBJECT TERMS Convection-Enhanced Delivery ( CED ), Malignant Peripheral Nerve Sheath ( MPNST ), Plexiform Neurofibromas...determine the distribution of macromolecules delivered to intraneural PNs and MPNST via CED . Design: Orthotopic xenograft models of sciatic intraneural

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

PubMed Central

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

2015-01-01

Schwann cells (SCs) are the principal glia of the peripheral nervous system. The end point of SC development is the formation of myelinating and nonmyelinating cells which ensheath large and small diameter axons, respectively. They play an important role in axon regeneration after injury, including cavernous nerve injury that leads to erectile dysfunction (ED). Despite improvement in radical prostatectomy surgical techniques, many patients still suffer from ED postoperatively as surgical trauma causes traction injuries and local inflammatory changes in the neuronal microenvironment of the autonomic fibers innervating the penis resulting in pathophysiological alterations in the end organ. The aim of this review is to summarize contemporary evidence regarding: (1) the origin and development of SCs in the peripheral and penile nerve system; (2) Wallerian degeneration and SC plastic change following peripheral and penile nerve injury; (3) how SCs promote peripheral and penile nerve regeneration by secreting neurotrophic factors; (4) and strategies targeting SCs to accelerate peripheral nerve regeneration. We searched PubMed for articles related to these topics in both animal models and human research and found numerous studies suggesting that SCs could be a novel target for treatment of nerve injury-induced ED. PMID:25999359

Resident Exposure to Peripheral Nerve Surgical Procedures During Residency Training

PubMed Central

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

2016-01-01

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

Blockade of hyperpolarization-activated channels modifies the effect of beta-adrenoceptor stimulation.

PubMed

Zefirov, T L; Ziyatdinova, N I; Gainullin, A A; Zefirov, A L

2002-05-01

Experiments on rats showed that blockade of hyperpolarization-activated currents moderates tachycardia induced by beta-adrenoceptor agonist isoproterenol and potentiates the increase in stroke volume produced by this agonist. Electrical stimulation of the vagus nerve against the background of isoproterenol treatment augmented bradycardia and increased stroke volume. Blockade of hyperpolarization-activated currents followed by application of isoproterenol moderated vagus-induced bradycardia and had no effect on the dynamics of stroke volume.

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...

Optical cuff for optogenetic control of the peripheral nervous system.

PubMed

Michoud, Frédéric; Sottas, Loïc; Browne, Liam E; Asboth, Léonie; Latremoliere, Alban; Sakuma, Miyuki; Courtine, Grégoire; Woolf, Clifford J; Lacour, Stéphanie P

2018-02-01

Nerves in the peripheral nervous system (PNS) contain axons with specific motor, somatosensory and autonomic functions. Optogenetics offers an efficient approach to selectively activate axons within the nerve. However, the heterogeneous nature of nerves and their tortuous route through the body create a challenging environment to reliably implant a light delivery interface. Here, we propose an optical peripheral nerve interface-an optocuff-, so that optogenetic modulation of peripheral nerves become possible in freely behaving mice. Using this optocuff, we demonstrate orderly recruitment of motor units with epineural optical stimulation of genetically targeted sciatic nerve axons, both in anaesthetized and in awake, freely behaving animals. Behavioural experiments and histology show the optocuff does not damage the nerve thus is suitable for long-term experiments. These results suggest that the soft optocuff might be a straightforward and efficient tool to support more extensive study of the PNS using optogenetics.

Optical cuff for optogenetic control of the peripheral nervous system

NASA Astrophysics Data System (ADS)

Michoud, Frédéric; Sottas, Loïc; Browne, Liam E.; Asboth, Léonie; Latremoliere, Alban; Sakuma, Miyuki; Courtine, Grégoire; Woolf, Clifford J.; Lacour, Stéphanie P.

2018-02-01

Objective. Nerves in the peripheral nervous system (PNS) contain axons with specific motor, somatosensory and autonomic functions. Optogenetics offers an efficient approach to selectively activate axons within the nerve. However, the heterogeneous nature of nerves and their tortuous route through the body create a challenging environment to reliably implant a light delivery interface. Approach. Here, we propose an optical peripheral nerve interface—an optocuff—, so that optogenetic modulation of peripheral nerves become possible in freely behaving mice. Main results. Using this optocuff, we demonstrate orderly recruitment of motor units with epineural optical stimulation of genetically targeted sciatic nerve axons, both in anaesthetized and in awake, freely behaving animals. Behavioural experiments and histology show the optocuff does not damage the nerve thus is suitable for long-term experiments. Significance. These results suggest that the soft optocuff might be a straightforward and efficient tool to support more extensive study of the PNS using optogenetics.

[Comparative assessment of prolonged femoral nerve blockade and epidural analgesia for postoperative pain in total knee joint arthroplasty].

PubMed

Churadze, B T; Sevalkin, S A; Zadorozhnyĭ, M V; Volkov, P A; Gur'ianov, V A

2013-01-01

The study deals with two mostly discussed techniques of postoperative analgesia for total knee joint arthroplasty. Surgeries were performed under subarachnoid anaesthesia with intravenous sedation. 9 patients of first group in received prolonged femoral nerve blockade as a component of multimodal analgesia. 8 patients of second group received epidural infusion of naropine. If basic technique of analgesia was not effective patients received trimeperidine 20 mg intramuscular. Patients of second group had less pain syndrome (in order to visual analogue scale) and did not need additional administration of opioids.

Ultrasound-guided peripheral nerve interventions for common pain disorders

PubMed Central

Krishna Prasad, B P; Joy, Binu; Raghavendra, Vijayakumar A; Toms, Ajith; George, Danny; Ray, Brijesh

2018-01-01

There are a number of common pain disorders that can be managed effectively by injections around or ablation of peripheral nerves. Ultrasound is a universally available imaging tool, is safe, cost-effective, and is excellent in imaging many peripheral nerves and guiding needles to the site of the nerves. This article aims to present an overview of indications and techniques of such procedures that can be effectively performed by a radiologist. PMID:29692534

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

PubMed Central

Chuang, David Chwei-Chin

2016-01-01

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

Involvement of peripheral III nerve in multiple sclerosis patient: Report of a new case and discussion of the underlying mechanism.

PubMed

Shor, Natalia; Amador, Maria Del Mar; Dormont, Didier; Lubetzki, Catherine; Bertrand, Anne

2017-04-01

Multiple sclerosis (MS) is a chronic disorder that affects the central nervous system myelin. However, a few radiological cases have documented an involvement of peripheral cranial nerves, within the subarachnoid space, in MS patients. We report the case of a 36-year-old female with a history of relapsing-remitting (RR) MS who consulted for a subacute complete paralysis of the right III nerve. Magnetic resonance imaging (MRI) examination showed enhancement and thickening of the cisternal right III nerve, in continuity with a linear, mesencephalic, acute demyelinating lesion. Radiological involvement of the cisternal part of III nerve has been reported only once in MS patients. Radiological involvement of the cisternal part of V nerve occurs more frequently, in almost 3% of MS patients. In both situations, the presence of a central demyelinating lesion, in continuity with the enhancement of the peripheral nerve, suggests that peripheral nerve damage is a secondary process, rather than a primary target of demyelination.

Emerging nanotechnology approaches in tissue engineering for peripheral nerve regeneration.

PubMed

Cunha, Carla; Panseri, Silvia; Antonini, Stefania

2011-02-01

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

X-ray irradiation has positive effects for the recovery of peripheral nerve injury maybe through the vascular smooth muscle contraction signaling pathway.

PubMed

Jiang, Bo; Zhang, Yong; She, Chang; Zhao, Jiaju; Zhou, Kailong; Zuo, Zhicheng; Zhou, Xiaozhong; Wang, Peiji; Dong, Qirong

2017-09-01

It is well known that moderate to high doses of ionizing radiation have a toxic effect on the organism. However, there are few experimental studies on the mechanisms of LDR ionizing radiation on nerve regeneration after peripheral nerve injury. We established the rats' peripheral nerve injury model via repaired Peripheral nerve injury nerve, vascular endothelial growth factor a and Growth associated protein-43 were detected from different treatment groups. We performed transcriptome sequencing focusing on investigating the differentially expressed genes and gene functions between the control group and 1Gy group. Sequencing was done by using high-throughput RNA-sequencing (RNA-seq) technologies. The results showed the 1Gy group to be the most effective promoting repair. RNA-sequencing identified 619 differently expressed genes between control and treated groups. A Gene Ontology analysis of the differentially expressed genes revealed enrichment in the functional pathways. Among them, candidate genes associated with nerve repair were identified. Pathways involved in cell-substrate adhesion, vascular smooth muscle contraction and cell adhesion molecule signaling may be involved in recovery from peripheral nerve injury. Copyright © 2017. Published by Elsevier B.V.

In vivo targeted peripheral nerve imaging with a nerve-specific nanoscale magnetic resonance probe.

PubMed

Zheng, Linfeng; Li, Kangan; Han, Yuedong; Wei, Wei; Zheng, Sujuan; Zhang, Guixiang

2014-11-01

Neuroimaging plays a pivotal role in clinical practice. Currently, computed tomography (CT), magnetic resonance imaging (MRI), ultrasonography, and positron emission tomography (PET) are applied in the clinical setting as neuroimaging modalities. There is no optimal imaging modality for clinical peripheral nerve imaging even though fluorescence/bioluminescence imaging has been used for preclinical studies on the nervous system. Some studies have shown that molecular and cellular MRI (MCMRI) can be used to visualize and image the cellular and molecular level of the nervous system. Other studies revealed that there are different pathological/molecular changes in the proximal and distal sites after peripheral nerve injury (PNI). Therefore, we hypothesized that in vivo peripheral nerve targets can be imaged using MCMRI with specific MRI probes. Specific probes should have higher penetrability for the blood-nerve barrier (BNB) in vivo. Here, a functional nanometre MRI probe that is based on nerve-specific proteins as targets, specifically, using a molecular antibody (mAb) fragment conjugated to iron nanoparticles as an MRI probe, was constructed for further study. The MRI probe allows for imaging the peripheral nerve targets in vivo. Copyright © 2014 Elsevier Ltd. All rights reserved.

Synovial sarcoma of nerve.

PubMed

Scheithauer, Bernd W; Amrami, Kimberly K; Folpe, Andrew L; Silva, Ana I; Edgar, Mark A; Woodruff, James M; Levi, Allan D; Spinner, Robert J

2011-04-01

Tumors of peripheral nerve are largely neuroectodermal in nature and derived from 2 elements of nerve, Schwann or perineurial cells. In contrast, mesenchymal tumors affecting peripheral nerve are rare and are derived mainly from epineurial connective tissue. The spectrum of the latter is broad and includes lipoma, vascular neoplasms, hematopoietic tumors, and even meningioma. Of malignant peripheral nerve neoplasms, the vast majority are primary peripheral nerve sheath tumors. Malignancies of mesenchymal type are much less common. To date, only 12 cases of synovial sarcoma of nerve have been described. Whereas in the past, parallels were drawn between synovial sarcoma and malignant glandular schwannoma, an uncommon form of malignant peripheral nerve sheath tumor, molecular genetics have since clarified the distinction. Herein, we report 10 additional examples of molecularly confirmed synovial sarcoma, all arising within minor or major nerves. Affecting 7 female and 3 male patients, 4 tumors occurred in pediatric patients. Clinically and radiologically, most lesions were initially thought to be benign nerve sheath tumors. On reinterpretation of imaging, they were considered indeterminate in nature with some features suspicious for malignancy. Synovial sarcoma of nerve, albeit rare, seems to behave in a manner similar to its more common, soft tissue counterpart. Those affecting nerve have a variable prognosis. Definitive recommendations regarding surgery and adjuvant therapies await additional reports and long-term follow-up. The literature is reviewed and a meta-analysis is performed with respect to clinicopathologic features versus outcome. Copyright © 2011. Published by Elsevier Inc.

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

PubMed

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

2015-01-01

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

[Blood-nerve barrier and peripheral nerve regeneration].

PubMed

Kanda, Takashi

2013-01-01

Blood-nerve barrier (BNB) restricts the movement of soluble mediators and leukocytes from the blood contents to the peripheral nervous system (PNS) parenchyma and thus maintains the endoneurial homeostasis. However, it interferes the supply of various neurotrophic factors from the blood constituents and stops the drainage of toxic substances out of the PNS parenchyma, resulting in the inhibition of peripheral nerve regeneration. If the manipulation of BNB function is possible, regeneration of peripheral nerve may be facilitated via the alteration of peripheral nerve microenvironment and ample supply of neurotrophic substances. A possible method to manipulate the BNB for therapeutic purposes is to modify the endothelial function using siRNAs, oligonucleotides and virus vectors. Another possible method is to modify BNB pericytes: small hydrophobic substances that can reach the pericyte membrane through the endothelial monolayer and strengthen the pericytic activity, including the release of various cytokines/chemokines that influence endothelial function, may also be useful as drug candidates to control the BNB function.

A silk sericin/silicone nerve guidance conduit promotes regeneration of a transected sciatic nerve.

PubMed

Xie, Hongjian; Yang, Wen; Chen, Jianghai; Zhang, Jinxiang; Lu, Xiaochen; Zhao, Xiaobo; Huang, Kun; Li, Huili; Chang, Panpan; Wang, Zheng; Wang, Lin

2015-10-28

Peripheral nerve gap defects lead to significant loss of sensory or motor function. Tissue engineering has become an important alternative to nerve repair. Sericin, a major component of silk, is a natural protein whose value in tissue engineering has just begun to be explored. Here, the first time use of sericin in vivo is reported as a long-term implant for peripheral nerve regeneration. A sericin nerve guidance conduit is designed and fabricated. This conduit is highly porous with mechanical strength matching peripheral nerve tissue. It supports Schwann cell proliferation and is capable of up-regulating the transcription of glial cell derived neurotrophic factor and nerve growth factor in Schwann cells. The sericin conduit wrapped with a silicone conduit (sericin/silicone double conduits) is used for bridging repair of a 5 mm gap in a rat sciatic nerve transection model. The sericin/silicone double conduits achieve functional recovery comparable to that of autologous nerve grafting as evidenced by drastically improved nerve function and morphology. Importantly, this improvement is mainly attributed to the sericin conduit as the silicone conduit alone only produces marginal functional recovery. This sericin/silicone-double-conduit strategy offers an efficient and valuable alternative to autologous nerve grafting for repairing damaged peripheral nerve. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Axillary nerve dysfunction

MedlinePlus

... Causes Axillary nerve dysfunction is a form of peripheral neuropathy . It occurs when there is damage to the ... and the A.D.A.M. Editorial team. Peripheral Nerve Disorders Read more NIH MedlinePlus Magazine Read more Health ...

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

PubMed Central

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

2017-01-01

Abstract Schwann cells (SCs) play pivotal roles in the maintenance and regeneration of the peripheral nervous system. Although transplantation of SCs enhances repair of experimentally damaged peripheral and central nerve tissues, it is difficult to prepare a sufficient number of functional SCs for transplantation therapy without causing adverse events for the donor. Here, we generated functional SCs by somatic cell reprogramming procedures and demonstrated their capability to promote peripheral nerve regeneration. Normal human fibroblasts were phenotypically converted into SCs by transducing SOX10 and Krox20 genes followed by culturing for 10 days resulting in approximately 43% directly converted Schwann cells (dSCs). The dSCs expressed SC‐specific proteins, secreted neurotrophic factors, and induced neuronal cells to extend neurites. The dSCs also displayed myelin‐forming capability both in vitro and in vivo. Moreover, transplantation of the dSCs into the transected sciatic nerve in mice resulted in significantly accelerated regeneration of the nerve and in improved motor function at a level comparable to that with transplantation of the SCs obtained from a peripheral nerve. The dSCs induced by our procedure may be applicable for novel regeneration therapy for not only peripheral nerve injury but also for central nerve damage and for neurodegenerative disorders related to SC dysfunction. Stem Cells Translational Medicine 2017;6:1207–1216 PMID:28186702

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

PubMed

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

2015-11-15

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

Stimulating effect of thyroid hormones in peripheral nerve regeneration: research history and future direction toward clinical therapy

PubMed Central

Barakat-Walter, I.; Kraftsik, R.

2018-01-01

Injury to peripheral nerves is often observed in the clinic and severe injuries may cause loss of motor and sensory functions. Despite extensive investigation, testing various surgical repair techniques and neurotrophic molecules, at present, a satisfactory method to ensuring successful recovery does not exist. For successful molecular therapy in nerve regeneration, it is essential to improve the intrinsic ability of neurons to survive and to increase the speed of axonal outgrowth. Also to induce Schwann cell phenotypical changes to prepare the local environment favorable for axonal regeneration and myelination. Therefore, any molecule that regulates gene expression of both neurons and Schwann cells could play a crucial role in peripheral nerve regeneration. Clinical and experimental studies have reported that thyroid hormones are essential for the normal development and function of the nervous system, so they could be candidates for nervous system regeneration. This review provides an overview of studies devoted to testing the effect of thyroid hormones on peripheral nerve regeneration. Also it emphasizes the importance of combining biodegradable tubes with local administration of triiodothyronine for future clinical therapy of human severe injured nerves. We highlight that the local and single administration of triiodothyronine within biodegradable nerve guide improves significantly the regeneration of severed peripheral nerves, and accelerates functional recovering. This technique provides a serious step towards future clinical application of triiodothyronine in human severe injured nerves. The possible regulatory mechanism by which triiodothyronine stimulates peripheral nerve regeneration is a rapid action on both axotomized neurons and Schwann cells. PMID:29722302

Nervous system (image)

MedlinePlus

Peripheral Neuropathy is not a distinct disease, but the manifestation of many conditions that damage the peripheral nerves ( ... abnormal. Damaged motor nerves impair movement or function. Peripheral neuropathy may be caused by direct or indirect injury, ...

Feedforward neural control of toe walking in humans.

PubMed

Lorentzen, Jakob; Willerslev-Olsen, Maria; Hüche Larsen, Helle; Svane, Christian; Forman, Christian; Frisk, Rasmus; Farmer, Simon Francis; Kersting, Uwe; Nielsen, Jens Bo

2018-03-23

Activation of ankle muscles at ground contact during toe walking is unaltered when sensory feedback is blocked or the ground is suddenly dropped. Responses in the soleus muscle to transcranial magnetic stimulation, but not peripheral nerve stimulation, are facilitated at ground contact during toe walking. We argue that toe walking is supported by feedforward control at ground contact. Toe walking requires careful control of the ankle muscles in order to absorb the impact of ground contact and maintain a stable position of the joint. The present study aimed to clarify the peripheral and central neural mechanisms involved. Fifteen healthy adults walked on a treadmill (3.0 km h -1 ). Tibialis anterior (TA) and soleus (Sol) EMG, knee and ankle joint angles, and gastrocnemius-soleus muscle fascicle lengths were recorded. Peripheral and central contributions to the EMG activity were assessed by afferent blockade, H-reflex testing, transcranial magnetic brain stimulation (TMS) and sudden unloading of the planter flexor muscle-tendon complex. Sol EMG activity started prior to ground contact and remained high throughout stance. TA EMG activity, which is normally seen around ground contact during heel strike walking, was absent. Although stretch of the Achilles tendon-muscle complex was observed after ground contact, this was not associated with lengthening of the ankle plantar flexor muscle fascicles. Sol EMG around ground contact was not affected by ischaemic blockade of large-diameter sensory afferents, or the sudden removal of ground support shortly after toe contact. Soleus motor-evoked potentials elicited by TMS were facilitated immediately after ground contact, whereas Sol H-reflexes were not. These findings indicate that at the crucial time of ankle stabilization following ground contact, toe walking is governed by centrally mediated motor drive rather than sensory driven reflex mechanisms. These findings have implications for our understanding of the control of human gait during voluntary toe walking. © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.

Benign Peripheral Nerve Sheath Tumor in a Wild Toco Toucan ( Ramphastos toco ).

PubMed

Carvalho, Marcelo P N; Fernandes, Natalia C C A; Nemer, Viviane C; Neto, Ramiro N Dias; Teixeira, Rodrigo H F; Miranda, Bruna S; Mamprim, Maria J; Catão-Dias, José L; Réssio, Rodrigo A

2016-09-01

Peripheral nerve sheath tumors are a heterogeneous group of neoplasms that comprise neurofibromas, schwannomas, neurilemmomas, and perineuromas. In animals, peripheral nerve sheath neoplasms are most commonly diagnosed in dogs and cattle, followed by horses, goats, and cats, but their occurrence is uncommon in birds. An adult, free-living, male toco (common) toucan ( Ramphastos toco ) was admitted to the zoo animal clinic with weight loss, dehydration, and presence of a soft nodule adhered to the medial portion of the left pectoral muscle. Clinical, cytologic, and computed tomography scan results were indicative of a neoplasm. The toucan died during surgical resection of the mass. Necropsy, histopathologic, and immunohistochemical findings confirmed the diagnosis of benign peripheral nerve sheath tumor. To our knowledge, benign peripheral nerve sheath tumor has not previously been reported in a toucan or any other species in the order Piciformes.

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. © The Author(s) 2014.

Stem cell and peripheral nerve injury and repair.

PubMed

Dong, Ming-min; Yi, Tian-hua

2010-10-01

Peripheral motor nerve injuries are a significant source of morbidity. Neural stem cells (NSCs), a group of relatively primitive cells, possess self-renewal ability and multidifferentiation potential. NSCs may be successfully separated from the human embryo and central nervous system (CNS) and differentiated into mature neurons and gliacytes by in vitro induction or transplantation into the body and may be differentiated into Schwann-like cells under specific conditions. It has been demonstrated that the ability of peripheral nerves to regenerate is mainly attributable to Schwann cells. NSC transplantation can promote peripheral nerve regeneration and provide a new means for treatment of peripheral nerve injury. In recent years, the study of NSCs has become a focus of many laboratories, but the biological characteristics and differentiation regulation mechanisms are not fully clear. In this article, we provide a brief review of NSC characteristics, cultivation, oriented differentiation, and clinical application. © Thieme Medical Publishers.

The role of β-adrenergic blockers in Parkinson's disease: possible genetic and cell-signaling mechanisms.

PubMed

Luong, Khanh vinh quoc; Nguyen, Lan Thi Hoàng

2013-06-01

Genetic studies have identified numerous factors linking β-adrenergic blockade to Parkinson's disease (PD), including human leukocyte antigen genes, the renin-angiotensin system, poly(adenosine diphosphate-ribose) polymerase 1, nerve growth factor, vascular endothelial growth factor, and the reduced form of nicotinamide adenine dinucleotide phosphate. β-Adrenergic blockade has also been implicated in PD via its effects on matrix metalloproteinases, mitogen-activated protein kinase pathways, prostaglandins, cyclooxygenase 2, and nitric oxide synthase. β-Adrenergic blockade may have a significant role in PD; therefore, the characterization of β-adrenergic blockade in patients with PD is needed.

Distal median nerve dysfunction

MedlinePlus

... Distal median nerve dysfunction is a form of peripheral neuropathy that affects the movement of or sensation in ... and the A.D.A.M. Editorial team. Peripheral Nerve Disorders Read more NIH MedlinePlus Magazine Read more Health ...

Nanofiber Nerve Guide for Peripheral Nerve Repair and Regeneration

DTIC Science & Technology

2016-04-01

faster regeneration and functional recovery. Peripheral nerve injury is a common complication of complex tissue trauma and often results in significant...having poor regeneration overall, the areas of regenerating nerve tissue could often be found in sections of the nerve guide where luminal spaces of...conducted in this Aim also provided important insight into the NGC design parameters necessary to allow for maximum nerve tissue ingrowth and regeneration

BLOCKADE OF NERVE GROWTH FACTOR (NGF) RECEPTOR TRKA ATTENUATES DIESEL EXHAUST PARTICULATE MATTER (DEP) ENHANCEMENT OF ALLERGIC INFLAMMATION

EPA Science Inventory

Recent studies have shown that asthmatics have increased levels of the neurotrophin, NGF, in their lungs. In addition, antibody blockade of NGF in mice attenuates airway resistance associated with allergic airway responses. DEP has been linked to asthma exacerbation in many c...

Intercostal nerve blockade with a mixture of bupivacaine and phenol enhance the efficacy of intravenous patient-controlled analgesia in the control of post-cholecystectomy pain.

PubMed

Maidatsi, P; Gorgias, N; Zaralidou, A; Ourailoglou, V; Giala, M

1998-09-01

Prolonged nerve conduction blockade has been proposed to result from the summed effects of charged and neutral local anaesthetics. Thirty-seven patients were randomly allocated to receive intravenous patient-controlled analgesia alone or combined with intercostal blockade (T7-T11) with a mixture of 0.45% bupivacaine and 0.6% phenol for post-cholecystectomy analgesia. Adequacy of pain relief was measured by patient scores on a 10-cm visual analogue scale and by dose-demand ratio, amounts of loading dose and total consumption of morphine and also the duration of patient-controlled analgesia in each group. No differences were found between groups in post-operative scores, dose-demand ratios and loading doses of morphine. However, in the combined treatment group, a significantly lower total consumption of morphine (P < 0.05), associated with a shorter duration of patient-controlled analgesia (P < 0.02) and a decreased mean number of unsuccessful demands (P < 0.001) were recorded. Intercostal blockade with bupivacaine-phenol supplements intravenous patient-controlled analgesia for post-cholecystectomy pain relief.

Quantitative magnetic resonance (MR) neurography for evaluation of peripheral nerves and plexus injuries

PubMed Central

Barousse, Rafael; Socolovsky, Mariano; Luna, Antonio

2017-01-01

Traumatic conditions of peripheral nerves and plexus have been classically evaluated by morphological imaging techniques and electrophysiological tests. New magnetic resonance imaging (MRI) studies based on 3D fat-suppressed techniques are providing high accuracy for peripheral nerve injury evaluation from a qualitative point of view. However, these techniques do not provide quantitative information. Diffusion weighted imaging (DWI) and diffusion tensor imaging (DTI) are functional MRI techniques that are able to evaluate and quantify the movement of water molecules within different biological structures. These techniques have been successfully applied in other anatomical areas, especially in the assessment of central nervous system, and now are being imported, with promising results for peripheral nerve and plexus evaluation. DWI and DTI allow performing a qualitative and quantitative peripheral nerve analysis, providing valuable pathophysiological information about functional integrity of these structures. In the field of trauma and peripheral nerve or plexus injury, several derived parameters from DWI and DTI studies such as apparent diffusion coefficient (ADC) or fractional anisotropy (FA) among others, can be used as potential biomarkers of neural damage providing information about fiber organization, axonal flow or myelin integrity. A proper knowledge of physical basis of these techniques and their limitations is important for an optimal interpretation of the imaging findings and derived data. In this paper, a comprehensive review of the potential applications of DWI and DTI neurographic studies is performed with a focus on traumatic conditions, including main nerve entrapment syndromes in both peripheral nerves and brachial or lumbar plexus. PMID:28932698

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

PubMed Central

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

2015-01-01

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

Morphological abnormalities of embryonic cranial nerves after in utero exposure to valproic acid: implications for the pathogenesis of autism with multiple developmental anomalies.

PubMed

Tashiro, Yasura; Oyabu, Akiko; Imura, Yoshio; Uchida, Atsuko; Narita, Naoko; Narita, Masaaki

2011-06-01

Autism is often associated with multiple developmental anomalies including asymmetric facial palsy. In order to establish the etiology of autism with facial palsy, research into developmental abnormalities of the peripheral facial nerves is necessary. In the present study, to investigate the development of peripheral cranial nerves for use in an animal model of autism, rat embryos were treated with valproic acid (VPA) in utero and their cranial nerves were visualized by immunostaining. Treatment with VPA after embryonic day 9 had a significant effect on the peripheral fibers of several cranial nerves. Following VPA treatment, immunoreactivity within the trigeminal, facial, glossopharyngeal and vagus nerves was significantly reduced. Additionally, abnormal axonal pathways were observed in the peripheral facial nerves. Thus, the morphology of several cranial nerves, including the facial nerve, can be affected by prenatal VPA exposure as early as E13. Our findings indicate that disruption of early facial nerve development is involved in the etiology of asymmetric facial palsy, and may suggest a link to the etiology of autism. Copyright © 2011 ISDN. Published by Elsevier Ltd. All rights reserved.

The first radiographic image of a peripheral nerve disorder? Lipomatous macrodactyly (unrecognized lipomatosis of nerve).

PubMed

Mahan, Mark A; Prasad, Nikhil; Spinner, Robert J

2015-06-01

Lipomatosis of nerves (LN) involves benign fibro-fatty infiltration and is often associated with territorial overgrowth of soft tissue and bone; this distinctive disease pattern can be visualized on plain radiographs. We recently discovered a case (presented by Sir Robert Jones in 1898 to the Pathological Society of London) that indirectly represents a historical landmark in the imaging of peripheral nerves. The clinical findings and image, with obvious soft tissue and bone overgrowth, are pathognomonic for LN, making this one of the earliest radiological observations of a peripheral nerve lesion.

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.

Preoperative transcutaneous electrical nerve stimulation for localizing superficial nerve paths.

PubMed

Natori, Yuhei; Yoshizawa, Hidekazu; Mizuno, Hiroshi; Hayashi, Ayato

2015-12-01

During surgery, peripheral nerves are often seen to follow unpredictable paths because of previous surgeries and/or compression caused by a tumor. Iatrogenic nerve injury is a serious complication that must be avoided, and preoperative evaluation of nerve paths is important for preventing it. In this study, transcutaneous electrical nerve stimulation (TENS) was used for an in-depth analysis of peripheral nerve paths. This study included 27 patients who underwent the TENS procedure to evaluate the peripheral nerve path (17 males and 10 females; mean age: 59.9 years, range: 18-83 years) of each patient preoperatively. An electrode pen coupled to an electrical nerve stimulator was used for superficial nerve mapping. The TENS procedure was performed on patients' major peripheral nerves that passed close to the surgical field of tumor resection or trauma surgery, and intraoperative damage to those nerves was apprehensive. The paths of the target nerve were detected in most patients preoperatively. The nerve paths of 26 patients were precisely under the markings drawn preoperatively. The nerve path of one patient substantially differed from the preoperative markings with numbness at the surgical region. During surgery, the nerve paths could be accurately mapped preoperatively using the TENS procedure as confirmed by direct visualization of the nerve. This stimulation device is easy to use and offers highly accurate mapping of nerves for surgical planning without major complications. The authors conclude that TENS is a useful tool for noninvasive nerve localization and makes tumor resection a safe and smooth procedure. Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

A 3D-engineered porous conduit for peripheral nerve repair

PubMed Central

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

2017-01-01

End-to-end neurorrhaphy is the most commonly used method for treating peripheral nerve injury. However, only 50% of patients can regain useful function after treating with neurorrhaphy. Here, we constructed a 3D-engineered porous conduit to promote the function recovery of the transected peripheral nerve after neurorrhaphy. The conduit that consisted of a gelatin cryogel was prepared by molding with 3D-printed moulds. Due to its porous structure and excellent mechanical properties, this conduit could be collapsed by the mechanical force and resumed its original shape after absorption of normal saline. This shape-memory property allowed a simply surgery process for installing the conduits. Moreover, the biodegradable conduit could prevent the infiltration of fibroblasts and reduce the risk of scar tissue, which could provide an advantageous environment for nerve regeneration. The efficiency of the conduits in assisting peripheral nerve regeneration after neurorrhaphy was evaluated in a rat sciatic nerve transected model. Results indicated that conduits significantly benefitted the recovery of the transected peripheral nerve after end-to-end neurorrhaphy on the static sciatic index (SSI), electrophysiological results and the re-innervation of the gastrocnemius muscle. This work demonstrates a biodegradable nerve conduit that has potentially clinical application in promoting the neurorrhaphy. PMID:28401914

Ergonomic task analysis of ultrasound-guided femoral nerve block: a pilot study.

PubMed

Ajmal, Muhammad; Power, Susan; Smith, Tim; Shorten, George D

2011-02-01

To apply ergonomic task analysis to the performance of ultrasound-guided (US-guided) femoral nerve block (FNB) in an acute hospital setting. Pilot prospective observational study. Orthopedic operating room of a regional trauma hospital. 15 anesthesiologists of various levels of experience in US-guided FNB (estimated minimum experience < 10 procedures; maximum about 50 procedures, and from basic trainees to consultants); and 15 patients (5 men and 10 women), aged 77 ± 15 (mean ± SD yrs) years. MEASUREMENTS/OBSERVATIONS: A data capture "tool", which was modified from one previously developed for ergonomic study of spinal anesthesia, was studied. Patient, operator, and heterogeneous environmental factors related to ergonomic performance of US-guided FNB were identified. The observation period started immediately before commencement of positioning the patient and ended on completion of perineural injection. Data were acquired using direct observations, photography, and application of a questionnaire. The quality of ergonomic performance was generally suboptimal and varied greatly among operators. Eight (experience < 10 procedures) of 15 operators excessively rotated their head, neck, and/or back to visualize the image on the ultrasound machine. Eight operators (experience < 10 procedures) performed the procedure with excessive thoracolumbar flexion. Performance of US-guided FNB presents ergonomic challenges and was suboptimal during most of the procedures observed. Formal training in US-guided peripheral nerve blockade should include reference to ergonomic factors. Copyright © 2011 Elsevier Inc. All rights reserved.

Autologous transplantation with fewer fibers repairs large peripheral nerve defects

PubMed Central

Deng, Jiu-xu; Zhang, Dian-yin; Li, Ming; Weng, Jian; Kou, Yu-hui; Zhang, Pei-xun; Han, Na; Chen, Bo; Yin, Xiao-feng; Jiang, Bao-guo

2017-01-01

Peripheral nerve injury is a serious disease and its repair is challenging. A cable-style autologous graft is the gold standard for repairing long peripheral nerve defects; however, ensuring that the minimum number of transplanted nerve attains maximum therapeutic effect remains poorly understood. In this study, a rat model of common peroneal nerve defect was established by resecting a 10-mm long right common peroneal nerve. Rats receiving transplantation of the common peroneal nerve in situ were designated as the in situ graft group. Ipsilateral sural nerves (10–30 mm long) were resected to establish the one sural nerve graft group, two sural nerves cable-style nerve graft group and three sural nerves cable-style nerve graft group. Each bundle of the peroneal nerve was 10 mm long. To reduce the barrier effect due to invasion by surrounding tissue and connective-tissue overgrowth between neural stumps, small gap sleeve suture was used in both proximal and distal terminals to allow repair of the injured common peroneal nerve. At three months postoperatively, recovery of nerve function and morphology was observed using osmium tetroxide staining and functional detection. The results showed that the number of regenerated nerve fibers, common peroneal nerve function index, motor nerve conduction velocity, recovery of myodynamia, and wet weight ratios of tibialis anterior muscle were not significantly different among the one sural nerve graft group, two sural nerves cable-style nerve graft group, and three sural nerves cable-style nerve graft group. These data suggest that the repair effect achieved using one sural nerve graft with a lower number of nerve fibers is the same as that achieved using the two sural nerves cable-style nerve graft and three sural nerves cable-style nerve graft. This indicates that according to the ‘multiple amplification’ phenomenon, one small nerve graft can provide a good therapeutic effect for a large peripheral nerve defect. PMID:29323049

Near-infrared signals associated with electrical stimulation of peripheral nerves

NASA Astrophysics Data System (ADS)

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

2009-02-01

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

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

PubMed

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

2018-06-01

Recently in peripheral nerve regeneration, preclinical studies have shown that the use of nerve guidance conduits (NGCs) with multiple longitudinally channels and intra-luminal topography enhance the functional outcomes when bridging a nerve gap caused by traumatic injury. These features not only provide guidance cues for regenerating nerve, but also become the essential approaches for developing a novel NGC. In this study, a novel spiral NGC with aligned nanofibers and wrapped with an outer nanofibrous tube was first developed and investigated. Using the common rat sciatic 10-mm nerve defect model, the in vivo study showed that a novel spiral NGC (with and without inner nanofibers) increased the successful rate of nerve regeneration after 6 weeks recovery. Substantial improvements in nerve regeneration were achieved by combining the spiral NGC with inner nanofibers and outer nanofibrous tube, based on the results of walking track analysis, electrophysiology, nerve histological assessment, and gastrocnemius muscle measurement. This demonstrated that the novel spiral NGC with inner aligned nanofibers and wrapped with an outer nanofibrous tube provided a better environment for peripheral nerve regeneration than standard tubular NGCs. Results from this study will benefit for future NGC design to optimize tissue-engineering strategies for peripheral nerve regeneration. We developed a novel spiral nerve guidance conduit (NGC) with coated aligned nanofibers. The spiral structure increases surface area by 4.5 fold relative to a tubular NGC. Furthermore, the aligned nanofibers was coated on the spiral walls, providing cues for guiding neurite extension. Finally, the outside of spiral NGC was wrapped with randomly nanofibers to enhance mechanical strength that can stabilize the spiral NGC. Our nerve histological data have shown that the spiral NGC had 50% more myelinated axons than a tubular structure for nerve regeneration across a 10 mm gap in a rat sciatic nerve. Results from this study can help further optimize tissue engineering strategies for peripheral nerve repair. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Use of Nerve Conduction Velocity to Assess Peripheral Nerve Health in Aging Mice

PubMed Central

Walsh, Michael E.; Sloane, Lauren B.; Fischer, Kathleen E.; Austad, Steven N.; Richardson, Arlan

2015-01-01

Nerve conduction velocity (NCV), the speed at which electrical signals propagate along peripheral nerves, is used in the clinic to evaluate nerve function in humans. A decline in peripheral nerve function is associated with a number of age-related pathologies. While several studies have shown that NCV declines with age in humans, there is little information on the effect of age on NCV in peripheral nerves in mice. In this study, we evaluated NCV in male and female C57Bl/6 mice ranging from 4 to 32 months of age. We observed a decline in NCV in both male and female mice after 20 months of age. Sex differences were detected in sensory NCV as well as the rate of decline during aging in motor nerves; female mice had slower sensory NCV and a slower age-related decline in motor nerves compared with male mice. We also tested the effect of dietary restriction on NCV in 30-month-old female mice. Dietary restriction prevented the age-related decline in sciatic NCV but not other nerves. Because NCV is clinically relevant to the assessment of nerve function, we recommend that NCV be used to evaluate healthspan in assessing genetic and pharmacological interventions that increase the life span of mice. PMID:25477428

Sensory and motor peripheral nerve function and lower-extremity quadriceps strength: the health, aging and body composition study.

PubMed

Strotmeyer, Elsa S; de Rekeneire, Nathalie; Schwartz, Ann V; Resnick, Helaine E; Goodpaster, Bret H; Faulkner, Kimberly A; Shorr, Ronald I; Vinik, Aaron I; Harris, Tamara B; Newman, Anne B

2009-11-01

To determine whether sensory and motor nerve function is associated cross-sectionally with quadriceps or ankle dorsiflexion strength in an older community-based population. Cross-sectional analyses within a longitudinal cohort study. Two U.S. clinical sites. Two thousand fifty-nine Health, Aging and Body Composition Study (Health ABC) participants (49.5% male, 36.7% black, aged 73-82) in 2000/01. Quadriceps and ankle strength were measured using an isokinetic dynamometer. Sensory and motor peripheral nerve function in the legs and feet was assessed using 10-g and 1.4-g monofilaments, vibration threshold, and peroneal motor nerve conduction amplitude and velocity. Monofilament insensitivity, poorest vibration threshold quartile (>60 mu), and poorest motor nerve conduction amplitude quartile (<1.7 mV) were associated with 11%, 7%, and 8% lower quadriceps strength (all P<.01), respectively, than in the best peripheral nerve function categories in adjusted linear regression models. Monofilament insensitivity and lowest amplitude quartile were both associated with 17% lower ankle strength (P<.01). Multivariate analyses were adjusted for demographic characteristics, diabetes mellitus, body composition, lifestyle factors, and chronic health conditions and included all peripheral nerve measures in the same model. Monofilament insensitivity (beta=-7.19), vibration threshold (beta=-0.097), and motor nerve conduction amplitude (beta=2.01) each contributed independently to lower quadriceps strength (all P<.01). Monofilament insensitivity (beta=-5.29) and amplitude (beta=1.17) each contributed independently to lower ankle strength (all P<.01). Neither diabetes mellitus status nor lean mass explained the associations between peripheral nerve function and strength. Reduced sensory and motor peripheral nerve function is related to poorer lower extremity strength in older adults, suggesting a mechanism for the relationship with lower extremity disability.

Peripheral nerve injuries secondary to missiles.

PubMed

Katzman, B M; Bozentka, D J

1999-05-01

Peripheral nerve injuries secondary to missiles can present some of the most challenging problems faced by hand surgeons. This article reviews the pertinent neural anatomy, injury classifications, and repair techniques. Options in the management of nerve gaps are presented including the use of vascularized nerve grafts. The results are discussed and a treatment algorithm is presented.

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

DTIC Science & Technology

2016-09-01

AWARD NUMBER: W81XWH-13-1-0309 TITLE: Acceleration of Regeneration of Large-Gap Peripheral Nerve Injuries Using Acellular Nerve Allografts...plus amniotic Fluid Derived Stem Cells (AFS). PRINCIPAL INVESTIGATOR: Thomas L. Smith, PhD RECIPIENT: Wake Forest University Health Sciences

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

PubMed Central

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

2017-01-01

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

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

PubMed

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

2017-04-01

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

Nerve 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…

Neurophysiological mechanism of possibly confounding peripheral activation of the facial nerve during corticobulbar tract monitoring.

PubMed

Téllez, Maria J; Ulkatan, Sedat; Urriza, Javier; Arranz-Arranz, Beatriz; Deletis, Vedran

2016-02-01

To improve the recognition and possibly prevent confounding peripheral activation of the facial nerve caused by leaking transcranial electrical stimulation (TES) current during corticobulbar tract monitoring. We applied a single stimulus and a short train of electrical stimuli directly to the extracranial portion of the facial nerve. We compared the peripherally elicited compound muscle action potential (CMAP) of the facial nerve with the responses elicited by TES during intraoperative monitoring of the corticobulbar tract. A single stimulus applied directly to the facial nerve at subthreshold intensities did not evoke a CMAP, whereas short trains of subthreshold stimuli repeatedly evoked CMAPs. This is due to the phenomenon of sub- or near-threshold super excitability of the cranial nerve. Therefore, the facial responses evoked by short trains TES, when the leaked current reaches the facial nerve at sub- or near-threshold intensity, could lead to false interpretation. Our results revealed a potential pitfall in the current methodology for facial corticobulbar tract monitoring that is due to the activation of the facial nerve by subthreshold trains of stimuli. This study proposes a new criterion to exclude peripheral activation during corticobulbar tract monitoring. The failure to recognize and avoid facial nerve activation due to leaking current in the peripheral portion of the facial nerve during TES decreases the reliability of corticobulbar tract monitoring by increasing the possibility of false interpretation. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Combining Gene and Stem Cell Therapy for Peripheral Nerve Tissue Engineering.

PubMed

Busuttil, Francesca; Rahim, Ahad A; Phillips, James B

2017-02-15

Despite a substantially increased understanding of neuropathophysiology, insufficient functional recovery after peripheral nerve injury remains a significant clinical challenge. Nerve regeneration following injury is dependent on Schwann cells, the supporting cells in the peripheral nervous system. Following nerve injury, Schwann cells adopt a proregenerative phenotype, which supports and guides regenerating nerves. However, this phenotype may not persist long enough to ensure functional recovery. Tissue-engineered nerve repair devices containing therapeutic cells that maintain the appropriate phenotype may help enhance nerve regeneration. The combination of gene and cell therapy is an emerging experimental strategy that seeks to provide the optimal environment for axonal regeneration and reestablishment of functional circuits. This review aims to summarize current preclinical evidence with potential for future translation from bench to bedside.

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.

A magnetically responsive nanocomposite scaffold combined with Schwann cells promotes sciatic nerve regeneration upon exposure to magnetic field

PubMed Central

Huang, Liangliang; Sun, Zhen; Zeng, Wen; Huang, Jinghui; Luo, Zhuojing

2017-01-01

Peripheral nerve repair is still challenging for surgeons. Autologous nerve transplantation is the acknowledged therapy; however, its application is limited by the scarcity of available donor nerves, donor area morbidity, and neuroma formation. Biomaterials for engineering artificial nerves, particularly materials combined with supportive cells, display remarkable promising prospects. Schwann cells (SCs) are the absorbing seeding cells in peripheral nerve engineering repair; however, the attenuated biologic activity restricts their application. In this study, a magnetic nanocomposite scaffold fabricated from magnetic nanoparticles and a biodegradable chitosan–glycerophosphate polymer was made. Its structure was evaluated and characterized. The combined effects of magnetic scaffold (MG) with an applied magnetic field (MF) on the viability of SCs and peripheral nerve injury repair were investigated. The magnetic nanocomposite scaffold showed tunable magnetization and degradation rate. The MGs synergized with the applied MF to enhance the viability of SCs after transplantation. Furthermore, nerve regeneration and functional recovery were promoted by the synergism of SCs-loaded MGs and MF. Based on the current findings, the combined application of MGs and SCs with applied MF is a promising therapy for the engineering of peripheral nerve regeneration. PMID:29123395

Spinal microglia are required for long-term maintenance of neuropathic pain.

PubMed

Echeverry, Stefania; Shi, Xiang Qun; Yang, Mu; Huang, Hao; Wu, YiChen; Lorenzo, Louis-Etienne; Perez-Sanchez, Jimena; Bonin, Robert P; De Koninck, Yves; Zhang, Ji

2017-09-01

While spinal microglia play a role in early stages of neuropathic pain etiology, whether they are useful targets to reverse chronic pain at late stages remains unknown. Here, we show that microglia activation in the spinal cord persists for >3 months following nerve injury in rodents, beyond involvement of proinflammatory cytokine and chemokine signalling. In this chronic phase, selective depletion of spinal microglia in male rats with the targeted immunotoxin Mac1-saporin and blockade of brain-derived neurotrophic factor-TrkB signalling with intrathecal TrkB Fc chimera, but not cytokine inhibition, almost completely reversed pain hypersensitivity. By contrast, local spinal administration of Mac1-saporin did not affect nociceptive withdrawal threshold in control animals nor did it affect the strength of afferent-evoked synaptic activity in the spinal dorsal horn in normal conditions. These findings show that the long-term, chronic phase of nerve injury-induced pain hypersensitivity is maintained by microglia-neuron interactions. The findings also effectively separate the central signalling pathways underlying the maintenance phase of the pathology from the early and peripheral inflammatory reactions to injury, pointing to different targets for the treatment of acute vs chronic injury-induced pain.

Pharmacological pain management in chronic pancreatitis

PubMed Central

Olesen, Søren S; Juel, Jacob; Graversen, Carina; Kolesnikov, Yuri; Wilder-Smith, Oliver HG; Drewes, Asbjørn M

2013-01-01

Intense abdominal pain is a prominent feature of chronic pancreatitis and its treatment remains a major clinical challenge. Basic studies of pancreatic nerves and experimental human pain research have provided evidence that pain processing is abnormal in these patients and in many cases resembles that seen in neuropathic and chronic pain disorders. An important ultimate outcome of such aberrant pain processing is that once the disease has advanced and the pathophysiological processes are firmly established, the generation of pain can become self-perpetuating and independent of the initial peripheral nociceptive drive. Consequently, the management of pain by traditional methods based on nociceptive deafferentation (e.g., surgery and visceral nerve blockade) becomes difficult and often ineffective. This novel and improved understanding of pain aetiology requires a paradigm shift in pain management of chronic pancreatitis. Modern mechanism based pain treatments taking into account altered pain processing are likely to increasingly replace invasive therapies targeting the nociceptive source, which should be reserved for special and carefully selected cases. In this review, we offer an overview of the current available pharmacological options for pain management in chronic pancreatitis. In addition, future options for pain management are discussed with special emphasis on personalized pain medicine and multidisciplinarity. PMID:24259960

The pattern of peripheral nerve injuries among Pakistani soldiers in the war against terror.

PubMed

Razaq, Sarah; Yasmeen, Rehana; Butt, Aamir Waheed; Akhtar, Noreen; Mansoor, Sahibzada Nasir

2015-05-01

To determine the pattern of peripheral nerve injuries in Pakistani soldiers in the War against terror. Case series. Department of Electrodiagnosis at Armed Forces Institute of Rehabilitation Medicine (AFIRM), Rawalpindi, Pakistan, from June 2008 to June 2011. All new cases of war wounded soldiers with peripheral nerve injuries were consecutively enrolled. Physical examination and electrodiagnostic study was carried out by experienced physiatrists. Data was entered in pretested especially designed questionnaire which was analysed using SPSS version 17.0. Seddon's classification system was used to assess the severity of injury. There were 418 cases of peripheral nerve injuries with 504 different nerve segments. Mean age was 29.41 ±8 years. Blast was the main cause of nerve injury in 244 (48.5%) cases followed by gunshot in 215 (42.7%) and 45 (8.9%) cases had nerve injuries secondary to fall, burial under debris and motor vehicle accidents. Eighty six (17%) cases had multiple nerve injuries. Most commonly injured nerve was ulnar (20.6%) followed by sciatic (16.7%), median (16.5%), radial (16.3%), peroneal (8.7%), brachial plexus (8.5%), axillary (4.8%), tibial (2%), femoral (1.8%), long thoracic (0.4%) and others (3.8%). Axonotmesis was seen in 459 (91.1%) cases, 44 (8.7%) cases revealed neurotmesis and 1 (0.2%) case had neuropraxia. Peripheral nerve injuries are a major component of war related injuries mainly involving the upper limbs. Electrodiagnostic studies help in assessing severity and determining prognosis. Precise documentation of severity of nerve injuries is important to estimate the burden on our resources and to extend rehabilitation services.

The Relationship of Reduced Peripheral Nerve Function and Diabetes With Physical Performance in Older White and Black Adults

PubMed Central

Strotmeyer, Elsa S.; de Rekeneire, Nathalie; Schwartz, Ann V.; Faulkner, Kimberly A.; Resnick, Helaine E.; Goodpaster, Bret H.; Shorr, Ronald I.; Vinik, Aaron I.; Harris, Tamara B.; Newman, Anne B.

2008-01-01

OBJECTIVE—Poor peripheral nerve function is prevalent in diabetes and older populations, and it has great potential to contribute to poor physical performance. RESEARCH DESIGN AND METHODS—Cross-sectional analyses were done for the Health, Aging, and Body Composition (Health ABC) Study participants (n = 2,364; 48% men; 38% black; aged 73–82 years). Sensory and motor peripheral nerve function in legs/feet was assessed by 10- and 1.4-g monofilament perception, vibration detection, and peroneal motor nerve conduction amplitude and velocity. The Health ABC lower-extremity performance battery was a supplemented version of the Established Populations for the Epidemiologic Studies of the Elderly battery (chair stands, standing balance, and 6-m walk), adding increased stand duration, single foot stand, and narrow walk. RESULTS—Diabetic participants had fewer chair stands (0.34 vs. 0.36 stands/s), shorter standing balance time (0.69 vs. 0.75 ratio), slower usual walking speed (1.11 vs. 1.14 m/s), slower narrow walking speed (0.80 vs. 0.90 m/s), and lower performance battery score (6.43 vs. 6.93) (all P < 0.05). Peripheral nerve function was associated with each physical performance measure independently. After addition of peripheral nerve function in fully adjusted models, diabetes remained significantly related to a lower performance battery score and slower narrow walking speed but not to chair stands, standing balance, or usual walking speed. CONCLUSIONS—Poor peripheral nerve function accounts for a portion of worse physical performance in diabetes and may be directly associated with physical performance in older diabetic and nondiabetic adults. The impact of peripheral nerve function on incident disability should be evaluated in older adults. PMID:18535192

Endocannabinoids in Liver Disease

PubMed Central

Tam, Joseph; Liu, Jie; Mukhopadhyay, Bani; Cinar, Resat; Godlewski, Grzegorz; Kunos, George

2010-01-01

Endocannabinoids are lipid mediators of the same cannabinoid (CB) receptors that mediate the effects of marijuana. The endocannabinoid system (ECS) consists of CB receptors, endocannabinoids, and the enzymes involved in their biosynthesis and degradation, and is present both in brain and peripheral tissues, including the liver. The hepatic ECS is activated in various liver diseases, which contributes to the underlying pathologies. In cirrhosis of various etiologies, activation of vascular and cardiac CB1 receptors by macrophage- and platelet-derived endocannabinoids contribute to the vasodilated state and cardiomyopathy, which can be reversed by CB1 blockade. In mouse models of liver fibrosis, activation of CB1 receptors on hepatic stellate cells is fibrogenic, and CB1 blockade slows the progression of fibrosis. Fatty liver induced by high-fat diets or chronic alcohol feeding depend on activation of peripheral, including hepatic CB1 receptors, which also contribute to insulin resistance and dyslipidemias. Although the documented therapeutic potential of CB1 blockade is limited by neuropsychiatric side effects, these may be mitigated by using novel, peripherally restricted CB1 antagonists. PMID:21254182

Fate of combat nerve injury.

PubMed

Beltran, Michael J; Burns, Travis C; Eckel, Tobin T; Potter, Benjamin K; Wenke, Joseph C; Hsu, Joseph R

2012-11-01

Assess a cohort of combat-related type III open tibia fractures with peripheral nerve injury to determine the injury mechanism and likelihood for recovery or improvement in nerve function. Retrospective study. Three military medical centers. Out of a study cohort of 213 type III open tibia fractures, 32 fractures (in 32 patients) with a total of 43 peripheral nerve injuries (peroneal or tibial) distal to the popliteal fossa met inclusion criteria and were available for follow-up at an average of 20 months (range, 2-48 months). Clinical assessment of motor and sensory nerve improvement. There was a 22% incidence of peripheral nerve injury in the study cohort. At an average follow-up of 20 months (range, 2-48 months), 89% of injured motor nerves were functional, whereas the injured sensory nerves had function in 93%. Fifty percent and 27% of motor and sensory injuries demonstrated improvement, respectively (P = 0.043). With the numbers available, there was no difference in motor or sensory improvement based on mechanism of injury, fracture severity or location, soft tissue injury, or specific nerve injured. In the subset of patients with an initially impaired sensory examination, full improvement was related to fracture location (P = 0.0164). Type III open tibia fractures sustained in combat are associated with a 22% incidence of peripheral nerve injury, and the majority are due to multiple projectile penetrating injury. Despite the severe nature of these injuries, the vast majority of patients had a functional nerve status by an average of 2-year follow-up. Based on these findings, discussions regarding limb salvage and amputation should not be overly influenced by the patient's peripheral nerve status. Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

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

PubMed

Koehler, Peter J; Lanska, Douglas J

2004-12-01

Describe the influence of S. Weir Mitchell's (1829-1914) work, and in particular his ideas on causalgia, on European physicians who treated peripheral nerve injuries during World War I (WWI). During the American Civil War (1861-1865), Mitchell studied peripheral nerve injuries with colleagues George Read Morehouse and William Williams Keen. Three monographs resulted from this work. All were important landmarks in the evolution of knowledge of peripheral nerve injuries. A subsequent occasion to improve knowledge came in WWI. The most important European monographs or series on peripheral nerve injuries from WWI were studied with special interest in references to causalgia and Mitchell's works on peripheral nerve injuries. We included works by Tinel, Athanassio-Benisty, Purves-Stewart & Evans and Carter, Foerster and Oppenheim. Tinel and Athanassio-Benisty provided the most detailed information on peripheral nerve injuries and causalgia and often referred to Mitchell. Both mentioned a possible sympathetic origin. Athanassio-Benisty described tremor and other movement disorders in relation to causalgia. Purves-Stewart and Evans mentioned Mitchell and causalgia in the second edition of their book. They advocated the term "thermalgia." Carter, who had access to data of many cases, concentrated his work on causalgia, referring to Mitchell. Foerster provided data of a great number of peripheral nerve injuries, but did not refer to Mitchell. However, he described the symptoms of causalgia cursorily, applying the term Reflexschmerz (reflexpain). Oppenheim was particularly interested in muscle innervation and referred to Mitchell with respect to hypertrichosis and glossy skin. Oppenheim did not use the term causalgia, although he described the syndrome in some of his patients. It wasn't until around 1920 that German physicians devoted significant attention to causalgia and began using the term. Knowledge of peripheral nerve injuries was greatly advanced during and after WWI. Mitchell's influence was mainly found in the French medical literature, where his findings provided the basis for further research on the origin of causalgia. In England, Mitchell and causalgia were also well-known. We found evidence to suggest that some of the English knowledge came from French physicians. German physicians described the symptoms of causalgia, but did not use the term, nor did they refer to Mitchell. This variation in Mitchell's influence by country probably reflects the fact that Mitchell's Injuries of nerves and their consequences was translated into French but not German.

Diabetes and nerve damage

MedlinePlus

Diabetic neuropathy; Diabetes - neuropathy; Diabetes - peripheral neuropathy ... pubmed/27979897 . Boulton AJM, Malik RA. Diabetes mellitus: ... of peripheral nerves. In: Daroff RB, Jankovic J, Mazziotta JC, ...

Using Arrays of Microelectrodes Implanted in Residual Peripheral Nerves to Provide Dextrous Control of, and Modulated Sensory Feedback from, a Hand Prosthesis

DTIC Science & Technology

2015-10-01

Modulated Sensory Feedback from, a Hand Prosthesis PRINCIPAL INVESTIGATOR: Bradley Greger, PhD CONTRACTING ORGANIZATION: Arizona State University...Residual Peripheral Nerves to Provide Dextrous Control of, and Modulated Sensory Feedback from, a Hand Prosthesis 5a. CONTRACT NUMBER 5b. GRANT...Peripheral Nerve Interface, Prosthetic Hand, Neural Prosthesis , Sensory Feedback, Micro-stimulation, Electrophysiology, Action Potentials, Micro

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:23102114

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. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

DTIC Science & Technology

2016-07-01

AWARD NUMBER: W81XWH-15-2-0026 TITLE: Clinical Evaluation of Decellularized Nerve Allograft With Autologous Bone Marrow Stem Cells To Improve...5b. GRANT NUMBER W81XWH-15-2-0026 CClinical Evaluation of Decellularized Nerve Allograft With Autologous Bone Marrow Stem Cells To Improve...co- treatments of a commercially available decellularized processed peripheral nerve allograft scaffold (Avance® Nerve Graft, AxoGen, Alachua FL) with

Current Concept in Adult Peripheral Nerve and Brachial Plexus Surgery.

PubMed

Rasulic, Lukas

2017-01-01

Peripheral nerve injuries and brachial plexus injuries are relatively frequent. Significance of these injuries lies in the fact that the majority of patients with these types of injuries constitute working population. Since these injuries may create disability, they present substantial socioeconomic problem nowadays. This article will present current state-of-the-art achievements of minimal invasive brachial plexus and peripheral nerve surgery. It is considered that the age of the patient, the mechanism of the injury, and the associated vascular and soft-tissue injuries are factors that primarily influence the extent of recovery of the injured nerve. The majority of patients are treated using classical open surgical approach. However, new minimally invasive open and endoscopic approaches are being developed in recent years-endoscopic carpal and cubital tunnel release, targeted minimally invasive approaches in brachial plexus surgery, endoscopic single-incision sural nerve harvesting, and there were even attempts to perform endoscopic brachial plexus surgery. The use of the commercially available nerve conduits for bridging short nerve gap has shown promising results. Multidisciplinary approach individually designed for every patient is of the utmost importance for the successful treatment of these injuries. In the future, integration of biology and nanotechnology may fabricate a new generation of nerve conduits that will allow nerve regeneration over longer nerve gaps and start new chapter in peripheral nerve surgery.

Fibronectin connecting segment-1 peptide inhibits pathogenic leukocyte trafficking and inflammatory demyelination in experimental models of chronic inflammatory demyelinating polyradiculoneuropathy.

PubMed

Dong, Chaoling; Greathouse, Kelsey M; Beacham, Rebecca L; Palladino, Steven P; Helton, E Scott; Ubogu, Eroboghene E

2017-06-01

The molecular determinants of pathogenic leukocyte migration across the blood-nerve barrier (BNB) in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) are unknown. Specific disease modifying therapies for CIDP are also lacking. Fibronectin connecting segment-1 (FNCS1), an alternatively spliced fibronectin variant expressed by microvascular endothelial cells at sites of inflammation in vitro and in situ, is a counterligand for leukocyte α 4 integrin (also known as CD49d) implicated in pathogenic leukocyte trafficking in multiple sclerosis and inflammatory bowel disease. We sought to determine the role of FNCS1 in CIDP patient leukocyte trafficking across the BNB in vitro and in severe chronic demyelinating neuritis in vivo using a representative spontaneous murine CIDP model. Peripheral blood mononuclear leukocytes from 7 untreated CIDP patients were independently infused into a cytokine-treated, flow-dependent in vitro BNB model system. Time-lapse digital video microscopy was performed to visualize and quantify leukocyte trafficking, comparing FNCS1 peptide blockade to relevant controls. Fifty 24-week old female B7-2 deficient non-obese diabetic mice with spontaneous autoimmune peripheral polyneuropathy (SAPP) were treated daily with 2mg/kg FNCS1 peptide for 5days via intraperitoneal injection with appropriate controls. Neurobehavioral measures of disease severity, motor nerve electrophysiology assessments and histopathological quantification of inflammation and morphometric assessment of demyelination were performed to determine in vivo efficacy. The biological relevance of FNCS1 and CD49d in CIDP was evaluated by immunohistochemical detection in affected patient sural nerve biopsies. 25μM FNCS1 peptide maximally inhibited CIDP leukocyte trafficking at the human BNB in vitro. FNCS1 peptide treatment resulted in significant improvements in disease severity, motor electrophysiological parameters of demyelination and histological measures of inflammatory demyelination. Microvessels demonstrating FNCS1 expression and CD49d+ leukocytes were seen within the endoneurium of patient nerve biopsies. Taken together, these results imply a role for FNCS1 in pathogenic leukocyte trafficking in CIDP, providing a potential target for therapeutic modulation. Copyright © 2017 Elsevier Inc. All rights reserved.

Y1R control of sciatic nerve blood flow in the Wistar Kyoto rat.

PubMed

Twynstra, Jasna; Medeiros, Philip J; Lacefield, James C; Jackson, Dwayne N; Shoemaker, J Kevin

2012-09-01

We hypothesized that neuropeptide Y (NPY) exerts vasoconstrictor properties in sciatic nerve blood supply by a Y1 receptor (Y1R) mechanism. Using Doppler ultrasound (40MHz), we measured blood flow velocity through a sciatic nerve supply artery during infusions of NPY and/or Y1R blockade with BIBP3226 in Wistar Kyoto rats before, and following, ganglionic blockade with Hexamethonium (Hex). Following Hex infusion, mean arterial pressure (baseline: 83±18, Hex: 57±3 mm Hg) was reduced. After 30 min, the index of conductance at the sciatic nerve (velocity/MAP expressed as % baseline) started to increase from 103±35 to 127±39% baseline in the following 30 min (p<0.05). Infusion of NPY (Y1 agonist) minimized this dilatory response (Hex baseline: 99±15, NPY: 104±11% baseline; NS). This NPY-induced attenuation was, in turn, minimized by BIBP3226 (Hex baseline: 73±12, NPY+BIBP3226: 89±14% baseline). Neither NPY nor BIBP3226 infusions without Hex affected the sciatic nerve arterial conductance. We conclude that the late dilation following Hex which is reversed by Y1R activation suggests some level of sympathetic control over sciatic nerve blood flow. Copyright © 2012 Elsevier Inc. All rights reserved.

MiR-7 inhibited peripheral nerve injury repair by affecting neural stem cells migration and proliferation through cdc42.

PubMed

Zhou, Nan; Hao, Shuang; Huang, Zongqiang; Wang, Weiwei; Yan, Penghui; Zhou, Wei; Zhu, Qihang; Liu, Xiaokang

2018-01-01

Objective Neural stem cells play an important role in the recovery and regeneration of peripheral nerve injury, and the microRNA-7 (miR-7) regulates differentiation of neural stem cells. This study aimed to explore the role of miR-7 in neural stem cells homing and proliferation and its influence on peripheral nerve injury repair. Methods The mice model of peripheral nerve injury was created by segmental sciatic nerve defect (sciatic nerve injury), and neural stem cells treatment was performed with a gelatin hydrogel conduit containing neural stem cells inserted into the sciatic nerve injury mice. The Sciatic Function Index was used to quantify sciatic nerve functional recovery in the mice. The messenger RNA and protein expression were detected by reverse transcription polymerase chain reaction and Western blot, respectively. Luciferase reporter assay was used to confirm the binding between miR-7 and the 3'UTR of cell division cycle protein 42 (cdc42). The neural stem cells migration and proliferation were analyzed by transwell assay and a Cell-LightTM EdU DNA Cell Proliferation kit, respectively. Results Neural stem cells treatment significantly promoted nerve repair in sciatic nerve injury mice. MiR-7 expression was decreased in sciatic nerve injury mice with neural stem cells treatment, and miR-7 mimic transfected into neural stem cells suppressed migration and proliferation, while miR-7 inhibitor promoted migration and proliferation. The expression level and effect of cdc42 on neural stem cells migration and proliferation were opposite to miR-7, and the luciferase reporter assay proved that cdc42 was a target of miR-7. Using co-transfection into neural stem cells, we found pcDNA3.1-cdc42 and si-cdc42 could reverse respectively the role of miR-7 mimic and miR-7 inhibitor on neural stem cells migration and proliferation. In addition, miR-7 mimic-transfected neural stem cells could abolish the protective role of neural stem cells on peripheral nerve injury. Conclusion MiR-7 inhibited peripheral nerve injury repair by affecting neural stem cells migration and proliferation through cdc42.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cheng, Lei; Liu, Yi; Zhao, Hua

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

A novel approach to 32-channel peripheral nervous system myelin imaging in vivo, with single axon resolution.

PubMed

Grochmal, Joey; Teo, Wulin; Gambhir, Hardeep; Kumar, Ranjan; Stratton, Jo Anne; Dhaliwal, Raveena; Brideau, Craig; Biernaskie, Jeff; Stys, Peter K; Midha, Rajiv

2018-01-19

OBJECTIVE Intravital spectral imaging of the large, deeply situated nerves in the rat peripheral nervous system (PNS) has not been well described. Here, the authors have developed a highly stable platform for performing imaging of the tibial nerve in live rodents, thus allowing the capture of high-resolution, high-magnification spectral images requiring long acquisition times. By further exploiting the qualities of the topically applied myelin dye Nile red, this technique is capable of visualizing the detailed microenvironment of peripheral nerve demyelination injury and recovery, while allowing us to obtain images of exogenous Schwann cell myelination in a living animal. METHODS The authors caused doxorubicin-induced focal demyelination in the tibial nerves of 25 Thy-1 GFP rats, of which 2 subsets (n = 10 each) received either BFP-labeled SKP-SCs or SCs to the zone of injury. Prior to acquiring images of myelin recovery in these nerves, a tibial nerve window was constructed using a silicone hemitube, a fast drying silicone polymer, and a small coverslip. This construct was then affixed to a 3D-printed nerve stage, which in turn was affixed to an external fixation/microscope stage device. Myelin visualization was facilitated by the topical application of Nile red. RESULTS The authors reliably demonstrated intravital peripheral nerve myelin imaging with micron-level resolution and magnification, and minimal movement artifact. The detailed microenvironment of nerve remyelination can be vividly observed, while exogenously applied Schwann cells and skin-derived precursor Schwann cells can be seen myelinating axons. CONCLUSIONS Topically applied Nile red enables intravital study of myelin in the living rat PNS. Furthermore, the use of a tibial nerve window facilitates stable intravital peripheral nerve imaging, making possible high-definition spectral imaging with long acquisition times.

Paeoniae alba Radix Promotes Peripheral Nerve Regeneration

PubMed Central

Huang, Kun-Shan; Lin, Jaung-Geng; Lee, Han-Chung; Tsai, Fuu-Jen; Bau, Da-Tian; Huang, Chih-Yang; Yao, Chun-Hsu; Chen, Yueh-Sheng

2011-01-01

The present study provides in vitro and in vivo evaluation of Paeoniae alba Radix (PR) on peripheral nerve regeneration. In the in vitro study, we found the PR caused a marked enhancement of the nerve growth factor-mediated neurite outgrowth from PC12 cells as well as their expression of growth associated protein 43 and synapsin I. In the in vivo study, silicone rubber chambers filled with the PR water extract were used to bridge a 10-mm sciatic nerve defect in rats. At the conclusion of 8 weeks, regenerated nerves in the PR groups, especially at 1.25 mg ml−1 had a higher rate of successful regeneration across the wide gap, relatively larger mean values of total nerve area, myelinated axon count and blood vessel number, and a significantly larger nerve conductive velocity compared to the control group (P  <  .05). These results suggest that the PR extract can be a potential nerve growth-promoting factor, being salutary in aiding the growth of injured peripheral nerve. PMID:19687191

European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of multifocal motor neuropathy. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society--first revision.

PubMed

2010-12-01

A European Federation of Neurological Societies/Peripheral Nerve Society consensus guideline on the definition, investigation, and treatment of multifocal motor neuropathy (MMN) was published in 2006. The aim is to revise this guideline. Disease experts considered references retrieved from MEDLINE and Cochrane Systematic Reviews published between August 2004 and July 2009 and prepared statements that were agreed to in an iterative fashion. The Task Force agreed on Good Practice Points to define clinical and electrophysiological diagnostic criteria for MMN, investigations to be considered, and principal recommendations for treatment. © 2010 Peripheral Nerve Society.

Exploration of a Novel Persistent Reversal of Pathological Pain: Mechanisms and Mediators

DTIC Science & Technology

2015-04-01

ability of a single IT ATL313 dose to reverse neuropathic pain from traumatic peripheral neuropathy . Milestone 2 is complete. We determined that 1 pmol...cord injury; to prevent and reverse neuropathic pain from inflammatory peripheral neuropathy following either IT or peri-sciatic nerve ( peripheral ...ATL313 can reverse neuropathic pain from inflammatory peripheral neuropathy following either IT or peri-sciatic nerve ( peripheral ) injections. We also

Cross sectional study to evaluate the effect of duration of type 2 diabetes mellitus on the nerve conduction velocity in diabetic peripheral neuropathy.

PubMed

Hussain, Gauhar; Rizvi, S Aijaz Abbas; Singhal, Sangeeta; Zubair, Mohammad; Ahmad, Jamal

2014-01-01

To study the nerve conduction velocity in clinically undetectable and detectable peripheral neuropathy in type 2 diabetes mellitus with variable duration. This cross sectional study was conducted in diagnosed type 2 diabetes mellitus patients. They were divided in groups: Group I (n=37) with clinically detectable diabetic peripheral neuropathy of shorter duration and Group II (n=27) with clinically detectable diabetic peripheral neuropathy of longer duration. They were compared with T2DM patients (n=22) without clinical neuropathy. Clinical diagnosis was based on neuropathy symptom score (NSS) and neuropathy disability score (NDS) for signs. Nerve conduction velocity was measured in both upper and lower limbs. Median, ulnar, common peroneal and posterior tibial nerves were selected for motor nerve conduction study and median and sural nerves were selected for sensory nerve conduction study. The comparisons were done between nerve conduction velocities of motor and sensory nerves in patients of clinically detectable neuropathy and patients without neuropathy in type 2 diabetes mellitus population. This study showed significant electrophysiological changes with duration of disease. Nerve conduction velocities in lower limbs were significantly reduced even in patients of shorter duration with normal upper limb nerve conduction velocities. Diabetic neuropathy symptom score (NSS) and neuropathy disability score (NDS) can help in evaluation of diabetic sensorimotor polyneuropathy though nerve conduction study is more powerful test and can help in diagnosing cases of neuropathy. Copyright © 2013 Diabetes India. Published by Elsevier Ltd. All rights reserved.

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

USDA-ARS?s Scientific Manuscript database

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...

Lipid-lowering drugs (statins) and peripheral neuropathy.

PubMed

Emad, Mohammadreza; Arjmand, Hosein; Farpour, Hamid Reza; Kardeh, Bahareh

2018-03-01

Peripheral neuropathy is a disorder with often unknown causes. Some drugs, including statins, are proposed to be among the causes of peripheral neuropathy. This study aimed at evaluating this condition by electrodiagnostic study among patients who had received statins. This case-control study was conducted in Shiraz, Iran in 2015, and included 39 patients aged 35-55 who had received statins for at least 6 months, and 39 healthy matched controls. Using electrodiagnosis, the sensory and motor wave features (amplitude, latency and nerve conduction velocity) of the peripheral nerves (Median, Ulnar, Tibial, Sural, and Peroneal) were evaluated among the subjects. Data were analyzed using SPSS software and p<0.05 was considered statistically significant. Regarding the occurrence of neuropathy, there were no significant differences in any of the definitions presented for peripheral neuropathy. However, the difference was close to significance for one definition [2 abnormalities in 2 nerves (p=0.055)]. Regarding mean values of the features, significant differences were observed in two features: amplitude of the peroneal motor nerve (p=0.048) and amplitude of the sural sensory nerve (p=0.036). Since statins are widely used, awareness regarding their side-effects would lead to better treatment. Even though no significant differences were found between the groups regarding the occurrence of peripheral neuropathy, there were significant differences in amplitudes of the sural sensory response and the peroneal motor response. This indicates the involvement of peripheral nerves. Therefore, we recommend that patients and physicians should be informed about the possible symptoms of this condition.

Reflex effects on components of synchronized renal sympathetic nerve activity.

PubMed

DiBona, G F; Jones, S Y

1998-09-01

The effects of peripheral thermal receptor stimulation (tail in hot water, n = 8, anesthetized) and cardiac baroreceptor stimulation (volume loading, n = 8, conscious) on components of synchronized renal sympathetic nerve activity (RSNA) were examined in rats. The peak height and peak frequency of synchronized RSNA were determined. The renal sympathoexcitatory response to peripheral thermal receptor stimulation was associated with an increase in the peak height. The renal sympathoinhibitory response to cardiac baroreceptor stimulation was associated with a decrease in the peak height. Although heart rate was significantly increased with peripheral thermal receptor stimulation and significantly decreased with cardiac baroreceptor stimulation, peak frequency was unchanged. As peak height reflects the number of active fibers, reflex increases and decreases in synchronized RSNA are mediated by parallel increases and decreases in the number of active renal nerve fibers rather than changes in the centrally based rhythm or peak frequency. The increase in the number of active renal nerve fibers produced by peripheral thermal receptor stimulation reflects the engagement of a unique group of silent renal sympathetic nerve fibers with a characteristic response pattern to stimulation of arterial baroreceptors, peripheral and central chemoreceptors, and peripheral thermal receptors.

Neural control of blood pressure in women: differences according to age

PubMed Central

Peinado, Ana B.; Harvey, Ronee E.; Hart, Emma C.; Charkoudian, Nisha; Curry, Timothy B.; Nicholson, Wayne T.; Wallin, B. Gunnar; Joyner, Michael J.; Barnes, Jill N.

2017-01-01

Purpose The blood pressure “error signal” represents the difference between an individual’s mean diastolic blood pressure and the diastolic blood pressure at which 50% of cardiac cycles are associated with a muscle sympathetic nerve activity burst (the “T50”). In this study we evaluated whether T50 and the error signal related to the extent of change in blood pressure during autonomic blockade in young and older women, to study potential differences in sympathetic neural mechanisms regulating blood pressure before and after menopause. Methods We measured muscle sympathetic nerve activity and blood pressure in 12 premenopausal (25±1 years) and 12 postmenopausal women (61±2 years) before and during complete autonomic blockade with trimethaphan camsylate. Results At baseline, young women had a negative error signal (−8±1 versus 2±1 mmHg, p<0.001; respectively) and lower muscle sympathetic nerve activity (15±1 versus 33±3 bursts/min, p<0.001; respectively) than older women. The change in diastolic blood pressure after autonomic blockade was associated with baseline T50 in older women (r=−0.725, p=0.008) but not in young women (r=−0.337, p=0.29). Women with the most negative error signal had the lowest muscle sympathetic nerve activity in both groups (young: r=0.886, p<0.001; older: r=0.870, p<0.001). Conclusions Our results suggest that there are differences in baroreflex control of muscle sympathetic nerve activity between young and older women, using the T50 and error signal analysis. This approach provides further information on autonomic control of blood pressure in women. PMID:28205011

CHRONIC PERIPHERAL NERVE COMPRESSION DISRUPTS PARANODAL AXOGLIAL JUNCTIONS

PubMed Central

Otani, Yoshinori; Yermakov, Leonid M.; Dupree, Jeffrey L.; Susuki, Keiichiro

2016-01-01

Introduction Peripheral nerves are often exposed to mechanical stress leading to compression neuropathies. The pathophysiology underlying nerve dysfunction by chronic compression is largely unknown. Methods We analyzed molecular organization and fine structures at and near nodes of Ranvier in a compression neuropathy model in which a silastic tube was placed around the mouse sciatic nerve. Results Immunofluorescence study showed that clusters of cell adhesion complex forming paranodal axoglial junctions were dispersed with frequent overlap with juxtaparanodal components. These paranodal changes occurred without internodal myelin damage. The distribution and pattern of paranodal disruption suggests that these changes are the direct result of mechanical stress. Electron microscopy confirmed loss of paranodal axoglial junctions. Discussion Our data show that chronic nerve compression disrupts paranodal junctions and axonal domains required for proper peripheral nerve function. These results provide important clues toward better understanding of the pathophysiology underlying nerve dysfunction in compression neuropathies. PMID:27463510

Electron microscopy of human peripheral nerves of clinical relevance to the practice of nerve blocks. A structural and ultrastructural review based on original experimental and laboratory data.

PubMed

Reina, M A; Arriazu, R; Collier, C B; Sala-Blanch, X; Izquierdo, L; de Andrés, J

2013-12-01

The goal is to describe the ultrastructure of normal human peripheral nerves, and to highlight key aspects that are relevant to the practice of peripheral nerve block anaesthesia. Using samples of sciatic nerve obtained from patients, and dural sac, nerve root cuff and brachial plexus dissected from fresh human cadavers, an analysis of the structure of peripheral nerve axons and distribution of fascicles and topographic composition of the layers that cover the nerve is presented. Myelinated and unmyelinated axons, fascicles, epineurium, perineurium and endoneurium obtained from patients and fresh cadavers were studied by light microscopy using immunohistochemical techniques, and transmission and scanning electron microscopy. Structure of perineurium and intrafascicular capillaries, and its implications in blood-nerve barrier were revised. Each of the anatomical elements is analyzed individually with regard to its relevance to clinical practice to regional anaesthesia. Routine practice of regional anaesthetic techniques and ultrasound identification of nerve structures has led to conceptions, which repercussions may be relevant in future applications of these techniques. In this regard, the ultrastructural and histological perspective accomplished through findings of this study aims at enlightening arising questions within the field of regional anaesthesia. Copyright © 2013 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.

Silicone Molding and Lifetime Testing of Peripheral Nerve Interfaces for Neuroprostheses

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gupte, Kimaya; Tolosa, Vanessa

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

The Triterpenoid Betulin Protects against the Neuromuscular Effects of Bothrops jararacussu Snake Venom In Vivo

PubMed Central

Ferraz, Miriéle Cristina; de Oliveira, Jhones Luiz; de Oliveira Junior, Joel Reis; Cogo, José Carlos; dos Santos, Márcio Galdino; Franco, Luiz Madaleno; Puebla, Pilar; Ferraz, Helena Onishi; Ferraz, Humberto Gomes; da Rocha, Marisa Maria Teixeira; Hyslop, Stephen

2015-01-01

We confirmed the ability of the triterpenoid betulin to protect against neurotoxicity caused by Bothrops jararacussu snake venom in vitro in mouse isolated phrenic nerve-diaphragm (PND) preparations and examined its capability of in vivo protection using the rat external popliteal/sciatic nerve-tibialis anterior (EPSTA) preparation. Venom caused complete, irreversible blockade in PND (40 μg/mL), but only partial blockade (~30%) in EPSTA (3.6 mg/kg, i.m.) after 120 min. In PND, preincubation of venom with commercial bothropic antivenom (CBA) attenuated the venom-induced blockade, and, in EPSTA, CBA given i.v. 15 min after venom also attenuated the blockade (by ~70% in both preparations). Preincubation of venom with betulin (200 μg/mL) markedly attenuated the venom-induced blockade in PND; similarly, a single dose of betulin (20 mg, i.p., 15 min after venom) virtually abolished the venom-induced decrease in contractility. Plasma creatine kinase activity was significantly elevated 120 min after venom injection in the EPSTA but was attenuated by CBA and betulin. These results indicate that betulin given i.p. has a similar efficacy as CBA given i.v. in attenuating the neuromuscular effects of B. jararacussu venom in vivo and could be a useful complementary measure to antivenom therapy for treating snakebite. PMID:26633987

Mechanical Loading for Peripheral Nerve Stabilization and Regeneration

DTIC Science & Technology

2012-10-01

Dahlin, L., Johansson, F., Lindwall, C., and Kanje, M. Chapter 28: Future perspective in peripheral nerve reconstruction . Int Rev Neurobiol 87, 507...Genden, E.M., MacKinnon, S.E., Doolabh, V.B., and Hunter, D.A. Regeneration through long nerve grafts in the swine model. Microsurgery 18, 379, 1998. 12

[Features of maxillary and mandibular nerves imaging during stem regional blockades. From paresthesia to 3D-CT guidance].

PubMed

Zaytsev, A Yu; Nazaryan, D N; Kim, S Yu; Dubrovin, K V; Svetlov, V A; Khovrin, V V

2014-01-01

There are difficulties in procedure of regional block of 2 and 3 brunches of the trigeminal nerve despite availability of many different methods of nerves imaging. The difficulties are connected with complex anatomy structure. Neurostimulation not always effective and as a rule, is accompanied with wrong interpretation of movement response on stimulation. The changing of the tactics on paraesthesia search improves the situation. The use of new methods of nerves imaging (3D-CT) also allows decreasing the frequency of fails during procedure of regional block of the brunches of the trigeminal nerve.

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

DTIC Science & Technology

2016-08-01

peripheral nerve sheath tumor (MPSNT)”, 11/5/2015, SARC-CTOS (Connective Tissue Oncology Society) Symposium, Salt Lake City, Utah b) “PRC2 loss in...of malignant peripheral nerve sheath tumor (MPSNT)”, 11/5/2015, SARC-CTOS (Connective Tissue Oncology Society) Symposium, Salt Lake City, Utah 2...Medical Oncology Service FROM: Roger S Wilson, MD Chairman, Institutional Review Board/Privacy Board-A DATE: 02/11/2016 RE: Protocol # 16-052 Your

Sodium-dependent Vitamin C transporter 2 deficiency impairs myelination and remyelination after injury: Roles of collagen and demethylation.

PubMed

Röhr, Dominik; Halfter, Hartmut; Schulz, Jörg B; Young, Peter; Gess, Burkhard

2017-07-01

Peripheral nerve myelination involves rapid production of tightly bound lipid layers requiring cholesterol biosynthesis and myelin protein expression, but also a collagen-containing extracellular matrix providing mechanical stability. In previous studies, we showed a function of ascorbic acid in peripheral nerve myelination and extracellular matrix formation in adult mice. Here, we sought the mechanism of action of ascorbic acid in peripheral nerve myelination using different paradigms of myelination in vivo and in vitro. We found impaired myelination and reduced collagen expression in Sodium-dependent Vitamin C Transporter 2 heterozygous mice (SVCT2 +/- ) during peripheral nerve development and after peripheral nerve injury. In dorsal root ganglion (DRG) explant cultures, hypo-myelination could be rescued by precoating with different collagen types. The activity of the ascorbic acid-dependent demethylating Ten-eleven-translocation (Tet) enzymes was reduced in ascorbic acid deprived and SVCT2 +/- DRG cultures. Further, in ascorbic acid-deprived DRG cultures, methylation of a CpG island in the collagen alpha1 (IV) and alpha2 (IV) bidirectional promoter region was increased compared to wild-type and ascorbic acid treated controls. Taken together, these results provide further evidence for the function of ascorbic acid in myelination and extracellular matrix formation in peripheral nerves and suggest a putative molecular mechanism of ascorbic acid function in Tet-dependent demethylation of collagen promoters. © 2017 Wiley Periodicals, Inc.

Deficiency of electroneutral K+-Cl- cotransporter 3 causes a disruption in impulse propagation along peripheral nerves.

PubMed

Sun, Yuan-Ting; Lin, Thy-Sheng; Tzeng, Shun-Fen; Delpire, Eric; Shen, Meng-Ru

2010-10-01

Nerve conduction requires the fine tuning of ionic currents through delicate interactions between axons and Schwann cells. The K(+)-Cl(-) cotransporter (KCC) family includes four isoforms (KCC1-4) that play an important role in the maintenance of cellular osmotic homeostasis via the coupled electroneutral movement of K(+) and Cl(-) with concurrent water flux. Mutation in SLC12A6 gene encoding KCC3 results in an autosomal recessive disease, known as agenesis of the corpus callosum associated with peripheral neuropathy. Nevertheless, the role of KCC3 in nerve function remains a puzzle. In this study, the microscopic examination of KCC isoforms expressed in peripheral nerves showed high expression of KCC2-4 in nodal segments of the axons and in the perinucleus and microvilli of Schwann cells. The KCC inhibitor [[(dihydroindenyl)oxy]alkanoic acid] but not the Na(+)-K(+)-2Cl(-)-cotransport inhibitor (bumetanide) dose-dependently suppressed the amplitude and area of compound muscle action potential, indicating the involvement of KCC activity in peripheral nerve conduction. Furthermore, the amplitude and area under the curve were smaller, and the nerve conduction velocity was slower in nerves from KCC3(-/-) mice than in nerves from wild-type mice, while the expression pattern of KCC2 and KCC4 was similar in KCC3 kockout and wild-type strains. KCC3(-/-) mice also manifested a prominent motor deficit in the beam-walking test. This is the first study to demonstrate that the K(+)-Cl(-) cotransporter activity of KCC3 contributes to the propagation of action potentials along peripheral nerves. (c) 2010 Wiley-Liss, Inc.

Lower-extremity peripheral nerve blocks in the perioperative pain management of orthopaedic patients: AAOS exhibit selection.

PubMed

Stein, Benjamin E; Srikumaran, Umasuthan; Tan, Eric W; Freehill, Michael T; Wilckens, John H

2012-11-21

The utilization of peripheral nerve blocks in orthopaedic surgery has paralleled the rise in the number of ambulatory surgical procedures performed. Optimization of pain control in the perioperative orthopaedic patient contributes to improved patient satisfaction, early mobilization, decreased length of hospitalization, and decreased associated hospital and patient costs. Our purpose was to provide a concise, pertinent review of the use of peripheral nerve blocks in various orthopaedic procedures of the lower extremity, with specific focus on procedural anatomy, indications, patient outcome measures, and complications. We reviewed the literature and reference textbooks on commonly performed lower-extremity peripheral nerve block procedures in orthopaedic surgery, focusing on those most commonly used. The use of lower-extremity peripheral nerve blocks is a safe and effective approach to perioperative pain management. Different techniques and timing can have an important impact on patient satisfaction, and each technique has specific indications and complications. For major hip surgery, one of the most commonly used is the lumbar plexus block, which can result in early mobilization, reduced postoperative pain, and decreased opioid-associated adverse events. Associated complications include epidural spread of anesthesia, retroperitoneal hematoma formation, and postoperative falls. For arthroscopic and open knee procedures, the femoral nerve block is frequently used adjunctively. It provides improved early postoperative pain control, early mobilization with therapy, and increased patient satisfaction compared with intra-articular or intravenous opioids alone; it also provides cost savings. However, some studies have shown no significant difference in outcome measures compared with intra-articular opioids alone for arthroscopic anterior cruciate ligament reconstruction. Associated complications include nerve injury, intravascular injection, and postoperative falls. The use of peripheral nerve blocks in lower-extremity surgery is becoming a mainstay of perioperative pain management strategy.

A collagen-based nerve guide conduit for peripheral nerve repair: an electrophysiological study of nerve regeneration in rodents and nonhuman primates.

PubMed

Archibald, S J; Krarup, C; Shefner, J; Li, S T; Madison, R D

1991-04-22

When a peripheral nerve is severed and left untreated, the most likely result is the formation of an endbulb neuroma; this tangled mass of disorganized nerve fibers blocks functional recovery following nerve injury. Although there are several different approaches for promoting nerve repair, which have been greatly refined over recent years, the clinical results of peripheral nerve repair remain very disappointing. In this paper we compare the results of a collagen nerve guide conduit to the more standard clinical procedure of nerve autografting to promote repair of transected peripheral nerves in rats and nonhuman primates. In rats, we tested recovery from sciatic nerve transection and repair by 1) direct microsurgical suture, 2) 4 mm autograft, or 3) entubulation repair with collagen-based nerve guide conduits. Evoked muscle action potentials (MAP) were recorded from the gastrocnemius muscle at 4 and 12 weeks following sciatic nerve transection. At 4 weeks the repair group of direct suture demonstrated a significantly greater MAP, compared to the other surgical repair groups. However, at 12 weeks all four surgical repair groups displayed similar levels of recovery of the motor response. In six adult male Macaca fascicularis monkeys the median nerve was transected 2 cm above the wrist and repaired by either a 4 mm nerve autograft or a collagen-based nerve guide conduit leaving a 4 mm gap between nerve ends. Serial studies of motor and sensory fibers were performed by recording the evoked MAP from the abductor pollicis brevis muscle (APB) and the sensory action potential (SAP) evoked by stimulation of digital nerves (digit II), respectively, up to 760 days following surgery. Evoked muscle responses returned to normal baseline levels in all cases. Statistical analysis of the motor responses, as judged by the slope of the recovery curves, indicated a significantly more rapid rate of recovery for the nerve guide repair group. The final level of recovery of the MAP amplitudes was not significantly different between the groups. In contrast, the SAP amplitude only recovered to the low normal range and there were no statistically significant differences between the two groups in terms of sensory recovery rates. The rodent and primate studies suggest that in terms of recovery of physiological responses from target muscle and sensory nerves, entubulation repair of peripheral nerves with a collagen-based nerve guide conduit over a short nerve gap (4 mm) is as effective as a standard nerve autograft.(ABSTRACT TRUNCATED AT 400 WORDS)

Expression of Nrf2 Promotes Schwann Cell-Mediated Sciatic Nerve Recovery in Diabetic Peripheral Neuropathy.

PubMed

Tang, Wei; Chen, Xiangfang; Liu, Haoqi; Lv, Qian; Zou, Junjie; Shi, Yongquan; Liu, Zhimin

2018-04-26

High glucose-induced oxidative stress and inflammatory responses play an important role in painful diabetic neuropathy by activating the TLR4/NFκB signal pathway. Schwann cells (SCs) are integral to peripheral nerve biology, contributing to saltatory conduction along axons, nerve and axon development, and axonal regeneration. SCs provide a microenvironment favoring vascular regeneration but their low survival ratio in hyperglycemic conditions suppress the function to promote nerve growth. Nuclear factor erythroid 2-related factor 2 (Nrf2) promotes remyelination after peripheral nerve injury. The aim of this study was to identify the role of Nrf2 in SC-mediated functional recovery after sciatic nerve injury. We compared plasma inflammatory factors in diabetic patients (DN) with/without diabetic peripheral neuropathy (DPN) and assessed whether Nrf2 expression in SCs could repair peripheral nerve injury in a rat model. Nrf2, TLR4/NFκB signal pathway and apoptosis relative protein expression were detected by western blot. Apoptosis and angiogenesis were determined by immunofluorescence and tubule formation assay, respectively. Regenerated nerves were determined by transmission electron microscope. Higher levels of inflammatory factors and VEGF expression were found in DPN patients. Cellular experiments indicate that Nrf2 expression inhibits hyperglycemia-induced apoptosis and promotes angiogenesis by regulating the TLR4/NFκB signal pathway. Animal experiments show that nerve conduction velocity, myelin sheath thickness, and sciatic vasa nervorum are restored with transplantation of SCs overexpressing Nrf2. Taken together, the high survival ratio of SCs in a DPN rat model indicates that overexpression of Nrf2 restores nerve injury. © 2018 The Author(s). Published by S. Karger AG, Basel.

Peripheral nerve pathology, including aberrant Schwann cell differentiation, is ameliorated by doxycycline in a laminin-α2-deficient mouse model of congenital muscular dystrophy

PubMed Central

Homma, Sachiko; Beermann, Mary Lou; Miller, Jeffrey Boone

2011-01-01

The most common form of childhood congenital muscular dystrophy, Type 1A (MDC1A), is caused by mutations in the human LAMA2 gene that encodes the laminin-α2 subunit. In addition to skeletal muscle deficits, MDC1A patients typically show a loss of peripheral nerve function. To identify the mechanisms underlying this loss of nerve function, we have examined pathology and cell differentiation in sciatic nerves and ventral roots of the laminin-α2-deficient (Lama2−/−) mice, which are models for MDC1A. We found that, compared with wild-type, sciatic nerves of Lama2−/− mice had a significant increase in both proliferating (Ki67+) cells and premyelinating (Oct6+) Schwann cells, but also had a significant decrease in both immature/non-myelinating [glial fibrillary acidic protein (GFAP)+] and myelinating (Krox20+) Schwann cells. To extend our previous work in which we found that doxycycline, which has multiple effects on mammalian cells, improves motor behavior and more than doubles the median life-span of Lama2−/− mice, we also determined how nerve pathology was affected by doxycycline treatment. We found that myelinating (Krox20+) Schwann cells were significantly increased in doxycycline-treated compared with untreated sciatic nerves. In addition, doxycycline-treated peripheral nerves had significantly less pathology as measured by assays such as amount of unmyelinated or disorganized axons. This study thus identified aberrant proliferation and differentiation of Schwann cells as key components of pathogenesis in peripheral nerves and provided proof-of-concept that pharmaceutical therapy can be of potential benefit for peripheral nerve dysfunction in MDC1A. PMID:21505075

Threshold dose for peripheral neuropathy following intraoperative radiotherapy (IORT) in a large animal model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kinsella, T.J.; DeLuca, A.M.; Barnes, M.

1991-04-01

Radiation injury to peripheral nerve is a dose-limiting toxicity in the clinical application of intraoperative radiotherapy, particularly for pelvic and retroperitoneal tumors. Intraoperative radiotherapy-related peripheral neuropathy in humans receiving doses of 20-25 Gy is manifested as a mixed motor-sensory deficit beginning 6-9 months following treatment. In a previous experimental study of intraoperative radiotherapy-related neuropathy of the lumbro-sacral plexus, an approximate inverse linear relationship was reported between the intraoperative dose (20-75 Gy range) and the time to onset of hind limb paresis (1-12 mos following intraoperative radiotherapy). The principal histological lesion in irradiated nerve was loss of large nerve fibers andmore » perineural fibrosis without significant vascular injury. Similar histological changes in irradiated nerves were found in humans. To assess peripheral nerve injury to lower doses of intraoperative radiotherapy in this same large animal model, groups of four adult American Foxhounds received doses of 10, 15, or 20 Gy to the right lumbro-sacral plexus and sciatic nerve using 9 MeV electrons. The left lumbro-sacral plexus and sciatic nerve were excluded from the intraoperative field to allow each animal to serve as its own control. Following treatment, a complete neurological exam, electromyogram, and nerve conduction studies were performed monthly for 1 year. Monthly neurological exams were performed in years 2 and 3 whereas electromyogram and nerve conduction studies were performed every 3 months during this follow-up period. With follow-up of greater than or equal to 42 months, no dog receiving 10 or 15 Gy IORT shows any clinical or laboratory evidence of peripheral nerve injury. However, all four dogs receiving 20 Gy developed right hind limb paresis at 8, 9, 9, and 12 mos following intraoperative radiotherapy.« less

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

PubMed

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

2018-02-06

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

Artificial sensory organs: latest progress.

PubMed

Nakamura, Tatsuo; Inada, Yuji; Shigeno, Keiji

2018-03-01

This study introduces the latest progress on the study of artificial sensory organs, with a special emphasis on the clinical results of artificial nerves and the concept of in situ tissue engineering. Peripheral nerves have a strong potential for regeneration. An artificial nerve uses this potential to recover a damaged peripheral nerve. The polyglycolic acid collagen tube (PGA-C tube) is a bio-absorbable tube stuffed with collagen of multi-chamber structure that consists of thin collagen films. The clinical application of the PGA-C tube began in 2002 in Japan. The number of PGA-C tubes used is now beyond 300, and satisfactory results have been reported on peripheral nerve repairs. This PGA-C tube is also effective for patients suffering from neuropathic pain.

Motor Nerve Conduction Velocity In Postmenopausal Women with Peripheral Neuropathy.

PubMed

Singh, Akanksha; Asif, Naiyer; Singh, Paras Nath; Hossain, Mohd Mobarak

2016-12-01

The post-menopausal phase is characterized by a decline in the serum oestrogen and progesterone levels. This phase is also associated with higher incidence of peripheral neuropathy. To explore the relationship between the peripheral motor nerve status and serum oestrogen and progesterone levels through assessment of Motor Nerve Conduction Velocity (MNCV) in post-menopausal women with peripheral neuropathy. This cross-sectional study was conducted at Jawaharlal Nehru Medical College during 2011-2013. The study included 30 post-menopausal women with peripheral neuropathy (age: 51.4±7.9) and 30 post-menopausal women without peripheral neuropathy (control) (age: 52.5±4.9). They were compared for MNCV in median, ulnar and common peroneal nerves and serum levels of oestrogen and progesterone estimated through enzyme immunoassays. To study the relationship between hormone levels and MNCV, a stepwise linear regression analysis was done. The post-menopausal women with peripheral neuropathy had significantly lower MNCV and serum oestrogen and progesterone levels as compared to control subjects. Stepwise linear regression analysis showed oestrogen with main effect on MNCV. The findings of the present study suggest that while the post-menopausal age group is at a greater risk of peripheral neuropathy, it is the decline in the serum estrogen levels which is critical in the development of peripheral neuropathy.

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

PubMed Central

Sánchez, Mikel; Garate, Ane; Delgado, Diego; Padilla, Sabino

2017-01-01

Therapies such as direct tension-free microsurgical repair or transplantation of a nerve autograft, are nowadays used to treat traumatic peripheral nerve injuries (PNI), focused on the enhancement of the intrinsic regenerative potential of injured axons. However, these therapies fail to recreate the suitable cellular and molecular microenvironment of peripheral nerve repair and in some cases, the functional recovery of nerve injuries is incomplete. Thus, new biomedical engineering strategies based on tissue engineering approaches through molecular intervention and scaffolding offer promising outcomes on the field. In this sense, evidence is accumulating in both, preclinical and clinical settings, indicating that platelet-rich plasma products, and fibrin scaffold obtained from this technology, hold an important therapeutic potential as a neuroprotective, neurogenic and neuroinflammatory therapeutic modulator system, as well as enhancing the sensory and motor functional nerve muscle unit recovery. PMID:28250739

Non-Invasive Targeted Peripheral Nerve Ablation Using 3D MR Neurography and MRI-Guided High-Intensity Focused Ultrasound (MR-HIFU): Pilot Study in a Swine Model.

PubMed

Huisman, Merel; Staruch, Robert M; Ladouceur-Wodzak, Michelle; van den Bosch, Maurice A; Burns, Dennis K; Chhabra, Avneesh; Chopra, Rajiv

2015-01-01

Ultrasound (US)-guided high intensity focused ultrasound (HIFU) has been proposed for noninvasive treatment of neuropathic pain and has been investigated in in-vivo studies. However, ultrasound has important limitations regarding treatment guidance and temperature monitoring. Magnetic resonance (MR)-imaging guidance may overcome these limitations and MR-guided HIFU (MR-HIFU) has been used successfully for other clinical indications. The primary purpose of this study was to evaluate the feasibility of utilizing 3D MR neurography to identify and guide ablation of peripheral nerves using a clinical MR-HIFU system. Volumetric MR-HIFU was used to induce lesions in the peripheral nerves of the lower limbs in three pigs. Diffusion-prep MR neurography and T1-weighted images were utilized to identify the target, plan treatment and immediate post-treatment evaluation. For each treatment, one 8 or 12 mm diameter treatment cell was used (sonication duration 20 s and 36 s, power 160-300 W). Peripheral nerves were extracted < 3 hours after treatment. Ablation dimensions were calculated from thermal maps, post-contrast MRI and macroscopy. Histological analysis included standard H&E staining, Masson's trichrome and toluidine blue staining. All targeted peripheral nerves were identifiable on MR neurography and T1-weighted images and could be accurately ablated with a single exposure of focused ultrasound, with peak temperatures of 60.3 to 85.7°C. The lesion dimensions as measured on MR neurography were similar to the lesion dimensions as measured on CE-T1, thermal dose maps, and macroscopy. Histology indicated major hyperacute peripheral nerve damage, mostly confined to the location targeted for ablation. Our preliminary results indicate that targeted peripheral nerve ablation is feasible with MR-HIFU. Diffusion-prep 3D MR neurography has potential for guiding therapy procedures where either nerve targeting or avoidance is desired, and may also have potential for post-treatment verification of thermal lesions without contrast injection.

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

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

PubMed Central

Gordon, Tessa; English, Arthur W.

2015-01-01

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

Resistance of the peripheral nervous system to the effects of chronic canine hypothyroidism.

PubMed

Rossmeisl, J H

2010-01-01

Hypothyroidism has been implicated in the development of multiple peripheral mono- and polyneuropathies in dogs. The objectives of this study were to evaluate the clinical and electrophysiologic effects of experimentally induced hypothyroidism on the peripheral nervous system of dogs. Chronic hypothyroidism will induce peripheral nerve sensorimotor dysfunction. Eighteen purpose-bred, female dogs. Prospective, longitudinal study: Hypothyroidism was induced by radioactive iodine administration in 9 dogs, and the remaining 9 served as untreated controls. Neurological examinations were performed monthly. Electrophysiologic testing consisting of electromyography (EMG); motor nerve conduction studies of the sciatic-tibial, radial, ulnar, and recurrent laryngeal nerves; sciatic-tibial and ulnar F-wave studies; sensory nerve conduction studies of the tibial, ulnar, and radial nerves; and evaluation of blink reflex and facial responses were performed before and 6, 12, and 18 months after induction of hypothyroidism and compared with controls. Clinical evidence of peripheral nervous dysfunction did not occur in any dog. At 6 month and subsequent evaluations, all hypothyroid dogs had EMG and histologic evidence of hypothyroid myopathy. Hypothyroid dogs had significant (Por=.1) or sensory nerve conduction velocity (P>or=.24) or nerve roots (P>or=.16) throughout the study period, with values remaining within reference ranges in all dogs. Chronic hypothyroidism induced by thyroid irradiation does not result in clinical or electrophysiologic evidence of peripheral neuropathy, but does cause subclinical myopathy.

Influence of peripheral magnetic stimulation of soleus muscle on H and M waves.

PubMed

Matsuda, Tadamitsu; Kurayama, Taichi; Tagami, Miki; Fujino, Yuji; Manji, Atsushi; Kusumoto, Yasuaki; Amimoto, Kazu

2018-05-01

[Purpose] This study evaluated the effects of repetitive peripheral magnetic stimulation of the soleus muscle on spinal cord and peripheral motor nerve excitability. [Subjects and Methods] Twelve healthy adults (mean age 22 years) who provided written informed consent were administered repetitive peripheral magnetic stimulation for 10 min. Pre-and post-stimulation latencies and amplitudes of H- and M-waves of the soleus muscle were measured using electromyography and compared using paired t-tests. [Results] Pre- and post-stimulation latencies (28.3 ± 3.3 vs. 29.1 ± 1.3 ms, respectively) and amplitudes (35.8 ± 1.3 vs. 35.8 ± 1.1 mV, respectively) of H-waves were similar. Pre-stimulation latencies of M-waves were significantly higher than post-stimulation latencies (6.1 ± 2.2 vs. 5.0 ± 0.9 ms, respectively), although pre- and post-stimulation amplitudes were similar (12.2 ± 1.4 vs. 12.2 ± 1.3 mV, respectively). Motor neuron excitability, based on the excitability of motor nerves and peripheral nerve action, was increased by M-waves following magnetic stimulation. [Conclusion] The lack of effect of magnetic stimulation on the amplitude and latency of the H-reflex suggests that magnetic stimulation did not activate sensory nerve synapses of α motor neurons in the spinal cord. However, because motor nerves were stimulated together with sensory nerves, the increased H-wave amplitude may have reflected changes in peripheral rather than in α motor nerves.

Usefulness of sural nerve biopsy in the genomic era.

PubMed

Kanda, Takashi

2009-08-01

The value of peripheral nerve biopsy is now sometimes questioned due to the high complication rate and the recent development of noninvasive molecular techniques for diagnosis of hereditary neuropathy. However, the disorders that can be diagnosed by genetic analysis are limited and sural nerve biopsy is still a powerful tool for making a correct diagnosis of peripheral neuropathy. Histological evaluation of the sural nerve has long focused on changes of the two major components of peripheral nerves, axons and myelin, as well as on the detection of diagnostic changes such as amyloid deposits, sarcoid tubercles, and vasculitis. In addition to these components, the sural nerve biopsy specimen contains various important cells, including perineurial cells, mast cells, endothelial cells, pericytes, and lymphocytes. Among these cells, the endothelial cells and pericytes form the blood-nerve barrier (BNB) and investigation of these cells can reveal important information, especially in inflammatory neuropathies. To better understand the biological basis of BNB, we established rat and human immortal cell lines from the endothelial cells and pericytes of endoneurial microvessels. Characterization of these cell lines is now underway at our laboratory. These BNB cell lines should provide useful information concerning the pathophysiology of peripheral neuropathy, and we should obtain a new perspective for the investigation of nerve biopsy specimens after understanding the molecular background of the BNB.

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

PubMed

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

2016-01-01

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

[Features of peripheral nerve injuries in workers exposed to vibration: an analysis of 197 cases].

PubMed

Situ, J; Lin, C M; Qin, Z H; Zhu, D X; Lin, H; Zhang, F F; Zhang, J J

2016-12-20

Objective: To investigate the features of peripheral nerve injuries in workers exposed to vibration. Methods: A total of 197 male workers [median age: 34 years (21 - 50 years) ; median working years of vibration exposure: 7.3 years (1 - 20 years) ] engaged in grinding in an enterprise were enrolled. Their clinical data and electromyography results were analyzed to investigate the features of peripheral nerve impairment. Results: Of all workers, 96 (48.73%) had abnormal electromyography results. Of all workers, 88 (44.7%) had simple mild median nerve injury in the wrist, who accounted for 91.7% (88/96) of all workers with abnormal electromy-ography results. Six workers had ulnar nerve injury, superficial radial nerve injury, or/and superficial peroneal nerve injury and accounted for 6.3% of all workers with abnormal electromyography results. Of all workers, 88 had a reduced amplitude of median nerve sensory transduction, and 28 had slowed median nerve sensory transduction. A total of 46 workers were diagnosed with occupational hand-arm vibration disease and hospitalized for treatment. They were followed up for more than 4 months after leaving their jobs, and most of them showed improvements in neural electromyography results and returned to a normal state. Conclusion: Workers exposed to vibration have a high incidence rate of nerve injury in the hand, mainly sensory function impairment at the distal end of the median nerve, and all injuries are mild peripheral nerve injuries. After leaving the vibration job and being treated, most workers can achieve improvements and return to a normal state.

Viral neurotropism, peripheral neuropathy and other morphological abnormalities in bovine ephemeral fever virus-infected downer cattle.

PubMed

Barigye, R; Davis, S; Hunt, R; Hunt, N; Walsh, S; Elliott, N; Burnup, C; Aumann, S; Day, C; Dyrting, K; Weir, R; Melville, L F

2016-10-01

This study assessed the neurotropism of bovine ephemeral fever (BEF) virus (BEFV) and described histomorphological abnormalities of the brain, spinal cord and peripheral nerves that may causally contribute to paresis or paralysis in BEF. Four paralysed and six asymptomatic but virus-infected cattle were monitored, and blood and serum samples screened by qRT-PCR, virus isolation and neutralisation tests. Fresh brain, spinal cord, peripheral nerve and other tissues were qRT-PCR-tested for viral RNA, while formalin-fixed specimens were processed routinely and immunohistochemically evaluated for histomorphological abnormalities and viral antigen distribution, respectively. The neurotropism of BEFV was immunohistochemically confirmed in the brain and peripheral nerves and peripheral neuropathy was demonstrated in three paralysed but not the six aneurological but virus-infected animals. Wallerian degeneration (WD) was present in the ventral funicular white matter of the lumbar spinal cord of a paralysed steer and in cervical and thoracic spinal cord segments of three paralysed animals. Although no spinal cord lesions were seen in the steer euthanased within 7 days of illness, peripheral neuropathy was present and more severe in nerves of the brachial plexuses than in the gluteal or fibular nerves. The only steer with WD in the lumbar spinal cord also showed intrahistiocytic cell viral antigen that was spatially distributed within areas of moderate brain stem encephalitis. The data confirmed neurotropism of BEFV in cattle and documented histomorphological abnormalities in peripheral nerves and brain which, together with spinal cord lesions, may contribute to chronic paralysis in BEFV-infected downer cattle. © 2016 Australian Veterinary Association.

Burning Feet

MedlinePlus

... are most often a sign of nerve damage (peripheral neuropathy). Nerve damage has many different causes, including diabetes, ... if any of the various conditions that cause peripheral neuropathy are to blame. Eleftheriadou I, et al. A ...

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

Whole-Mount Adult Ear Skin Imaging Reveals Defective Neuro-Vascular Branching Morphogenesis in Obese and Type 2 Diabetic Mouse Models.

PubMed

Yamazaki, Tomoko; Li, Wenling; Yang, Ling; Li, Ping; Cao, Haiming; Motegi, Sei-Ichiro; Udey, Mark C; Bernhard, Elise; Nakamura, Takahisa; Mukouyama, Yoh-Suke

2018-01-11

Obesity and type 2 diabetes are frequently associated with peripheral neuropathy. Though there are multiple methods for diagnosis and analysis of morphological changes of peripheral nerves and blood vessels, three-dimensional high-resolution imaging is necessary to appreciate the pathogenesis with an anatomically recognizable branching morphogenesis and patterning. Here we established a novel technique for whole-mount imaging of adult mouse ear skin to visualize branching morphogenesis and patterning of peripheral nerves and blood vessels. Whole-mount immunostaining of adult mouse ear skin showed that peripheral sensory and sympathetic nerves align with large-diameter blood vessels. Diet-induced obesity (DIO) mice exhibit defective vascular smooth muscle cells (VSMCs) coverage, while there is no significant change in the amount of peripheral nerves. The leptin receptor-deficient db/db mice, a severe obese and type 2 diabetic mouse model, exhibit defective VSMC coverage and a large increase in the amount of smaller-diameter nerve bundles with myelin sheath and unmyelinated nerve fibers. Interestingly, an increase in the amount of myeloid immune cells was observed in the DIO but not db/db mouse skin. These data suggest that our whole-mount imaging method enables us to investigate the neuro-vascular and neuro-immune phenotypes in the animal models of obesity and diabetes.

Correlation between serum vitamin B12 level and peripheral neuropathy in atrophic gastritis.

PubMed

Yang, Guo-Tao; Zhao, Hong-Ying; Kong, Yu; Sun, Ning-Ning; Dong, Ai-Qin

2018-03-28

To explore the correlation between serum vitamin B12 level and peripheral neuropathy in patients with chronic atrophic gastritis (CAG). A total of 593 patients diagnosed with chronic gastritis by gastroscopy and pathological examination from September 2013 to September 2016 were selected for this study. The age of these patients ranged within 18- to 75-years-old. Blood pressure, height and weight were measured in each patient, and the body mass index value was calculated. Furthermore, gastric acid, serum gastrin, serum vitamin and serum creatinine tests were performed, and peripheral nerve conduction velocity and Helicobacter pylori ( H. pylori ) were detected. In addition, the type of gastritis was determined by gastroscopy. The above factors were used as independent variables to analyze chronic gastritis with peripheral neuropathy and vitamin B12 deficiency risk factors, and to analyze the relationship between vitamin B12 levels and peripheral nerve conduction velocity. In addition, in the treatment of CAG on the basis of vitamin B12, patients with peripheral neuropathy were observed. Age, H. pylori infection, CAG, vitamin B9 and vitamin B12 were risk factors for the occurrence of peripheral nerve degeneration. Furthermore, CAG and H. pylori infection were risk factors for chronic gastritis associated with vitamin B12 deficiency. Serum vitamin B12 level was positively correlated with sensory nerve conduction velocity in the tibial nerve ( R = 0.463). After vitamin B12 supplementation, patients with peripheral neuropathy improved. Serum vitamin B12 levels in patients with chronic gastritis significantly decreased, and the occurrence of peripheral neuropathy had a certain correlation. CAG and H. pylori infection are risk factors for vitamin B12 deficiency and peripheral neuropathy. When treating CAG, vitamin B12 supplementation can significantly reduce peripheral nervous system lesions. Therefore, the occurrence of peripheral neuropathy associated with vitamin B12 deficiency may be considered in patients with CAG. Furthermore, the timely supplementation of vitamin B12 during the clinical treatment of CAG can reduce or prevent peripheral nervous system lesions.

Foot orgasm syndrome: a case report in a woman.

PubMed

Waldinger, Marcel D; de Lint, Govert J; van Gils, Ad P G; Masir, Farhad; Lakke, Egbert; van Coevorden, Ruben S; Schweitzer, Dave H

2013-08-01

Spontaneous orgasm triggered from inside the foot has so far not been reported in medical literature. The study aims to report orgasmic feelings in the left foot of a woman. A woman presented with complaints of undesired orgasmic sensations originating in her left foot. In-depth interview, physical examination, sensory testing, magnetic resonance imaging (MRI-scan), electromyography (EMG), transcutaneous electrical nerve stimulation (TENS), and blockade of the left S1 dorsal root ganglion were performed. The main outcomes are description of this clinical syndrome, results of TENS application, and S1 dorsal root ganglion blockade. Subtle attenuation of sensory amplitudes of the left suralis, and the left medial and lateral plantar nerve tracts was found at EMG. MRI-scan disclosed no foot abnormalities. TENS at the left metatarso-phalangeal joint-III of the left foot elicited an instant orgasmic sensation that radiated from plantar toward the vagina. TENS applied to the left side of the vagina elicited an orgasm that radiated to the left foot. Diagnostic blockade of the left S1 dorsal root ganglion with 0.8 mL bupivacaine 0.25 mg attenuated the frequency and intensity of orgasmic sensation in the left foot with 50% and 80%, respectively. Additional therapeutic blockade of the same ganglion with 0.8 mL bupivacaine 0.50 mg combined with pulsed radiofrequency treatment resulted in a complete disappearance of the foot-induced orgasmic sensations. Foot orgasm syndrome (FOS) is descibed in a woman. Blockade of the left S1 dorsal root ganglion alleviated FOS. It is hypothesized that FOS, occurring 1.5 years after an intensive care emergency, was caused by partial nerve regeneration (axonotmesis), after which afferent (C-fiber) information from a small reinnervated skin area of the left foot and afferent somatic and autonomous (visceral) information from the vagina on at least S1 spinal level is misinterpreted by the brain as being solely information originating from the vagina. © 2013 International Society for Sexual Medicine.

Chronic inflammatory polyneuropathy

MedlinePlus

... to nerves outside the brain or spinal cord ( peripheral neuropathy ). Polyneuropathy means several nerves are involved. CIDP often ... Philadelphia, PA: Elsevier; 2016:chap 107. Shy ME. Peripheral neuropathies. In: Goldman L, Schafer AI, eds. Goldman's Cecil ...

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

NASA Astrophysics Data System (ADS)

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

2017-02-01

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

The Minimum Effective Dose of Lidocaine Needed to Block Evoked Potentials in the Sciatic Nerve of the Rat

DTIC Science & Technology

1998-10-01

which include the sciatic nerve, will be described. Gilman and Newman (1996) describe the PNS in their book, Manter and Gatz’s Essentials of Clinical ...Neural Blockade in Clinical Anesthesia and Management of Pain. He wrote that sensory and motor messages are transported along a nerve in the form of an...different groups of local anesthetics, the esters (procaine, chloroprocaine, tetracaine) and the amides (lidocaine, mepivacaine, bupivacaine , etidocaine

Peripheral choline acetyltransferase in rat skin demonstrated by immunohistochemistry.

PubMed

Hanada, Keiji; Kishimoto, Saburo; Bellier, Jean-Pierre; Kimura, Hiroshi

2013-03-01

Conventional choline acetyltransferase immunohistochemistry has been used widely for visualizing central cholinergic neurons and fibers but not often for labeling peripheral structures, probably because of their poor staining. The recent identification of the peripheral type of choline acetyltransferase (pChAT) has enabled the clear immunohistochemical detection of many known peripheral cholinergic elements. Here, we report the presence of pChAT-immunoreactive nerve fibers in rat skin. Intensely stained nerve fibers were distributed in association with eccrine sweat glands, blood vessels, hair follicles and portions just beneath the epidermis. These results suggest that pChAT-positive nerves participate in the sympathetic cholinergic innervation of eccrine sweat glands. Moreover, pChAT also appears to play a role in cutaneous sensory nerve endings. These findings are supported by the presence of many pChAT-positive neuronal cells in the sympathetic ganglion and dorsal root ganglion. Thus, pChAT immunohistochemistry should provide a novel and unique tool for studying cholinergic nerves in the skin.

The effect of nerve blockade on forearm and finger skin blood flow during body heating and cooling.

PubMed

Saumet, J L; Degoute, C S; Saumet, M; Abraham, P

1992-08-01

To determine the role of the active cutaneous vasodilatator response in forearm and finger skin, direct assessment of only skin blood flow was performed before and after musculocutaneous and median nerve blockade during whole body heating and cooling. Forearm laser Doppler flow (LDF forearm), forearm heat thermal clearance (HTC forearm), and finger laser Doppler flow (LDF finger) were monitored in the nerve blocked skin and contralateral untreated skin (control). In the pre-blockade period, no significant differences were found between experimental and control arm skin. After nerve block a significant increase occurred only in LDF finger, which rose from 4.3 +/- 0.6 to 6.0 +/- 0.5 volts (p less than 0.05). During whole body heating LDF forearm and HTC forearm increased significantly on both arms. The increase in LDF forearm was greater (p less than 0.05) in control (18.3 +/- 1.2 volts) than in nerve blocked skin (14.6 +/- 1.8 volts) and occurred earlier. The same tendency was observed in HTC forearm between nerve blocked skin (0.522 +/- 0.06 W.m-1.degrees C-1) and control 0.671 +/- 0.037 W.m-1.degrees C-1) (NS). LDF raise up to 6.6 +/- 0.5 and 6.8 +/- 0.5 volts in the blocked finger and in the control respectively. During cooling LDF finger in the control decreased to 1.3 +/- 0.1 volt and was significantly (p less than 0.05) lower than in the resting period, and lower than that in the nerve blocked finger (3.4 +/- 0.8 volts) (p less than 0.05). We conclude that the active vasodilatator system plays an important role as far as the timing and the amplitude of the cutaneous vasodilatator response to whole body heating in the forearm but not in the finger. At thermal neutrality, the vascular vasoconstrictor tone is high to the finger but not to the forearm. The vasoconstrictor response to cooling occurred only in the finger.

Femoral nerve dysfunction

MedlinePlus

... in the groin Diabetes or other causes of peripheral neuropathy Internal bleeding in the pelvis or belly area ( ... Editorial team. Leg Injuries and Disorders Read more Peripheral Nerve Disorders Read more NIH MedlinePlus Magazine Read more A. ...

Ulnar nerve dysfunction

MedlinePlus

... Philadelphia, PA: Elsevier; 2016:chap 107. Shy ME. Peripheral neuropathies. In: Goldman L, Schafer AI, eds. Goldman's Cecil ... Editorial team. Hand Injuries and Disorders Read more Peripheral Nerve Disorders Read more NIH MedlinePlus Magazine Read more A. ...

Radial nerve dysfunction

MedlinePlus

... Philadelphia, PA: Elsevier; 2016:chap 107. Shy ME. Peripheral neuropathies. In: Goldman L, Schafer AI, eds. Goldman's Cecil ... Read more Hand Injuries and Disorders Read more Peripheral Nerve Disorders Read more A.D.A.M., Inc. is ...

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

Peripheral nerve reconstruction with epsilon-caprolactone conduits seeded with vasoactive intestinal peptide gene-transfected mesenchymal stem cells in a rat model

NASA Astrophysics Data System (ADS)

Hernández-Cortés, P.; Toledo-Romero, M. A.; Delgado, M.; Sánchez-González, C. E.; Martin, F.; Galindo-Moreno, P.; O'Valle, F.

2014-08-01

Objective. Attempts have been made to improve nerve conduits in peripheral nerve reconstruction. We investigated the potential therapeutic effect of a vasoactive intestinal peptide (VIP), a neuropeptide with neuroprotective, trophic and developmental regulatory actions, in peripheral nerve regeneration in a severe model of nerve injury that was repaired with nerve conduits. Approach. The sciatic nerve of each male Wistar rat was transected unilaterally at 10 mm and then repaired with Dl-lactic-ɛ-caprolactone conduits. The rats were treated locally with saline, with the VIP, with adipose-derived mesenchymal stem cells (ASCs) or with ASCs that were transduced with the VIP-expressing lentivirus. The rats with the transected nerve, with no repairs, were used as untreated controls. At 12 weeks post-surgery, we assessed their limb function by measuring the ankle stance angle and the percentage of their muscle mass reduction, and we evaluated the histopathology, immunohistochemistry and morphometry of the myelinated fibers. Main results. The rats that received a single injection of VIP-expressing ASCs showed a significant functional recovery in the ankle stance angle (p = 0.049) and a higher number of myelinated fibers in the middle and distal segments of the operated nerve versus the other groups (p = 0.046). Significance. These results suggest that utilization of a cellular substrate, plus a VIP source, is a promising method for enhancing nerve regeneration using Dl-lactic-ɛ-caprolactone conduits and that this method represents a potential useful clinical approach to repairing peripheral nerve damage.

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. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

PubMed

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

2001-01-01

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

Role of Neuroactive Steroids in the Peripheral Nervous System

PubMed Central

Melcangi, Roberto Cosimo; Giatti, Silvia; Pesaresi, Marzia; Calabrese, Donato; Mitro, Nico; Caruso, Donatella; Garcia-Segura, Luis Miguel

2011-01-01

Several reviews have so far pointed out on the relevant physiological and pharmacological role exerted by neuroactive steroids in the central nervous system. In the present review we summarize observations indicating that synthesis and metabolism of neuroactive steroids also occur in the peripheral nerves. Interestingly, peripheral nervous system is also a target of their action. Indeed, as here reported neuroactive steroids are physiological regulators of peripheral nerve functions and they may also represent interesting therapeutic tools for different types of peripheral neuropathy. PMID:22654839

Scaffolds for peripheral nerve repair and reconstruction.

PubMed

Yi, Sheng; Xu, Lai; Gu, Xiaosong

2018-06-02

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

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.

Different effects of astrocytes and Schwann cells on regenerating retinal axons.

PubMed

Campbell, Gregor; Kitching, Juliet; Anderson, Patrick N; Lieberman, A Robert

2003-11-14

Following a crush injury of the optic nerve in adult rats, the axons of retinal ganglion cells, stimulated to regenerate by a lens injury and growing within the optic nerve, are associated predominantly with astrocytes: they remain of small diameter (0.1-0.5 microm) and unmyelinated for > or = 2 months after the operation. In contrast, when the optic nerve is cut and a segment of a peripheral nerve is grafted to the ocular stump of the optic nerve, the regenerating retinal axons are associated predominantly with Schwann cells: they are of larger diameter than in the previous experiment and include unmyelinated axons (0.2-2.5 microm) and myelinated axons (mean diameter 2.3 microm). Thus, the grafted peripheral nerve, and presumably its Schwann cells, stimulate enlargement of the regenerating retinal axons leading to partial myelination, whereas the injured optic nerve itself, and presumably its astrocytes, does not. The result points to a marked difference of peripheral (Schwann cells) and central (astrocytes) glia in their effect on regenerating retinal axons.

Macrophage Depletion Ameliorates Peripheral Neuropathy in Aging Mice.

PubMed

Yuan, Xidi; Klein, Dennis; Kerscher, Susanne; West, Brian L; Weis, Joachim; Katona, Istvan; Martini, Rudolf

2018-05-09

Aging is known as a major risk factor for the structure and function of the nervous system. There is urgent need to overcome such deleterious effects of age-related neurodegeneration. Here we show that peripheral nerves of 24-month-old aging C57BL/6 mice of either sex show similar pathological alterations as nerves from aging human individuals, whereas 12-month-old adult mice lack such alterations. Specifically, nerve fibers showed demyelination, remyelination and axonal lesion. Moreover, in the aging mice, neuromuscular junctions showed features typical for dying-back neuropathies, as revealed by a decline of presynaptic markers, associated with α-bungarotoxin-positive postsynapses. In line with these observations were reduced muscle strengths. These alterations were accompanied by elevated numbers of endoneurial macrophages, partially comprising the features of phagocytosing macrophages. Comparable profiles of macrophages could be identified in peripheral nerve biopsies of aging persons. To determine the pathological impact of macrophages in aging mice, we selectively targeted the cells by applying an orally administered CSF-1R specific kinase (c-FMS) inhibitor. The 6-month-lasting treatment started before development of degenerative changes at 18 months and reduced macrophage numbers in mice by ∼70%, without side effects. Strikingly, nerve structure was ameliorated and muscle strength preserved. We show, for the first time, that age-related degenerative changes in peripheral nerves are driven by macrophages. These findings may pave the way for treating degeneration in the aging peripheral nervous system by targeting macrophages, leading to reduced weakness, improved mobility, and eventually increased quality of life in the elderly. SIGNIFICANCE STATEMENT Aging is a major risk factor for the structure and function of the nervous system. Here we show that peripheral nerves of 24-month-old aging mice show similar degenerative alterations as nerves from aging human individuals. Both in mice and humans, these alterations were accompanied by endoneurial macrophages. To determine the pathological impact of macrophages in aging mice, we selectively targeted the cells by blocking a cytokine receptor, essential for macrophage survival. The treatment strongly reduced macrophage numbers and substantially improved nerve structure and muscle strength. We show, for the first time, that age-related degenerative changes in peripheral nerves are driven by macrophages. These findings may be helpful for treatment weakness and reduced mobility in the elderly. Copyright © 2018 the authors 0270-6474/18/384610-11$15.00/0.

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

PubMed

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

1997-09-29

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

Evaluation of tissue components in the peripheral nervous system using Sirius red staining and immunohistochemistry: a comparative study (human, pig, rat).

PubMed

Kaemmer, D; Bozkurt, A; Otto, J; Junge, K; Klink, C; Weis, J; Sellhaus, B; O'Dey, D M; Pallua, N; Jansen, M; Schumpelick, V; Klinge, U

2010-06-30

Little is known about species differences in the peripheral nerve system and quantitative evaluation of main tissue components has rarely been done. Nevertheless, animal models are used for example in pain research without exact knowledge of degree of fibrosis in pathological states which would determine possible treatment options. It would therefore be of crucial interest to describe the degree of fibrosis and the remaining functional nerve tissue as exact as possible. In the present study we evaluated collagen (stroma) and nerve fiber (parenchyma) composition of peripheral nerves in three species (human, rat, pig) and used digital colour-separation and analysis for collagen type differentiation and quantification of immuno-positive-stained area. We found similar ratios of collagen types I and III in epineurium and similar immuno-positive area for staining of neurofilament and S-100beta. In contrast, we measured significantly different ratios of collagen type I to type III in the endoneurium. This combined analysis of the main tissue components of peripheral nerves could be an easy-to-use tool in evaluating changes during damage caused by scaring, systemic disease or compression syndromes. The calculated collagen type I/III ratio may serve as an objective diagnostic value for the description or as prognostic marker for therapeutic approaches in peripheral nerve pathology. However, in particular studies of collagen accumulation in nerves, species dependant differences have to be considered. Copyright 2010 Elsevier B.V. All rights reserved.

Occipital peripheral nerve stimulation in the management of chronic intractable occipital neuralgia in a patient with neurofibromatosis type 1: a case report.

PubMed

Skaribas, Ioannis; Calvillo, Octavio; Delikanaki-Skaribas, Evangelia

2011-05-10

Occipital peripheral nerve stimulation is an interventional pain management therapy that provides beneficial results in the treatment of refractory chronic occipital neuralgia. Herein we present a first-of-its-kind case study of a patient with neurofibromatosis type 1 and bilateral occipital neuralgia treated with occipital peripheral nerve stimulation. A 42-year-old Caucasian woman presented with bilateral occipital neuralgia refractory to various conventional treatments, and she was referred for possible treatment with occipital peripheral nerve stimulation. She was found to be a suitable candidate for the procedure, and she underwent implantation of two octapolar stimulating leads and a rechargeable, programmable, implantable generator. The intensity, severity, and frequency of her symptoms resolved by more than 80%, but an infection developed at the implantation site two months after the procedure that required explantation and reimplantation of new stimulating leads three months later. To date she continues to experience symptom resolution of more than 60%. These results demonstrate the significance of peripheral nerve stimulation in the management of refractory occipital neuralgias in patients with neurofibromatosis type 1 and the possible role of neurofibromata in the development of occipital neuralgia in these patients.

Peripheral neuropathy

MedlinePlus

... peripheral; Neuritis - peripheral; Nerve disease; Polyneuropathy; Chronic pain - peripheral neuropathy ... Philadelphia, PA: Elsevier; 2016:chap 107. Shy ME. Peripheral neuropathies. In: Goldman L, Schafer AI, eds. Goldman's Cecil ...

Reversal of profound and "deep" residual rocuronium-induced neuromuscular blockade by sugammadex: a neurophysiological study.

PubMed

Pavoni, V; Gianesello, L; De Scisciolo, G; Provvedi, E; Horton, D; Barbagli, R; Conti, P; Conti, R; Giunta, F

2012-05-01

Sugammadex is the first of a new class of selective relaxant binding drugs developed for the rapid and complete reversal of neuromuscular blockade (NMB) induced by the aminosteroid neuromuscular blocking drugs rocuronium and vecuronium. Neuromuscular blocking drugs block the transmission from the peripheral nerve to the muscle units, with reduction and disappearance of the evoked electromyographic activity. Usually, neuromuscular monitoring for the investigational reversal drug is performed by calibrated acceleromyography. The efficacy of sugammadex in reversing profound and "deep" residual rocuronium-induced NMB using myogenic motor evoked potentials (mMEPs) monitoring was evaluated. In this prospective trial, 30 consenting patients undergoing propofol-remifentanil anesthesia for spine surgery were enrolled and divided into two groups: Group 1, reversal of profound NMB (sugammadex 16 mg/Kg, 3 minutes after rocuronium 1.2 mg/Kg) and Group 2, reversal of "deep" residual NMB (sugammadex 4 mg/Kg, 15 minutes after rocuronium 0.6 mg/Kg). Myogenic MEPs registrations of upper and lower limbs and the diaphragm were performed, as well as TOF monitoring. After injection of 4 mg/Kg of sugammadex, the means of recovery time of the basal mMEPs amplitudes (diaphragm, and lower limbs and upper limbs) were 124±9.6, 143±163, 151±207 sec, respectively whereas after 16 mg/Kg of sugammadex the times were 109±13.8, 124±0.6, and 135±14.1 sec. Times to TOF ratio 0.9 were 114±75 and 186±105 sec in Group 1 and 2, respectively. No serious adverse effects related to sugammadex and to electrical stimulation were reported. No reoccurrence of neuromuscular block was observed. Neurophysiological monitoring using mMEPs confirmed that sugammadex provided a complete recovery from profound and "deep" residual rocuronium-induced neuromuscular blockade.

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

PubMed

Graham, James B; Muir, David

2016-01-01

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

Circadian Rhythm Influences the Promoting Role of Pulsed Electromagnetic Fields on Sciatic Nerve Regeneration in Rats

PubMed Central

Zhu, Shu; Ge, Jun; Liu, Zhongyang; Liu, Liang; Jing, Da; Ran, Mingzi; Wang, Meng; Huang, Liangliang; Yang, Yafeng; Huang, Jinghui; Luo, Zhuojing

2017-01-01

Circadian rhythm (CR) plays a critical role in the treatment of several diseases. However, the role of CR in the treatment of peripheral nerve defects has not been studied. It is also known that the pulsed electromagnetic fields (PEMF) can provide a beneficial microenvironment to quicken the process of nerve regeneration and to enhance the quality of reconstruction. In this study, we evaluate the impact of CR on the promoting effect of PEMF on peripheral nerve regeneration in rats. We used the self-made “collagen-chitosan” nerve conduits to bridge the 15-mm nerve gaps in Sprague-Dawley rats. Our results show that PEMF stimulation at daytime (DPEMF) has most effective outcome on nerve regeneration and rats with DPEMF treatment achieve quickly functional recovery after 12 weeks. These findings indicate that CR is an important factor that determines the promoting effect of PEMF on peripheral nerve regeneration. PEMF exposure in the daytime enhances the functional recovery of rats. Our study provides a helpful guideline for the effective use of PEMF mediations experimentally and clinically. PMID:28360885

Limb myokymia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Albers, J.W.; Allen, A.A.; Bastron, J.A.

Thirty-eight patients with myokymic discharges localized to limb muscles on needle electromyography had various neurologic lesions, both acute and chronic. Of the 38 patients, 27 had had previous radiation therapy and the clinical diagnosis of radiation-induced plexopathy, myelopathy, or both. For the remaining 11 patients, the diagnoses included multiple sclerosis, inflammatory polyradiculoneuropathy, ischemic neuropathy, inflammatory myopathy, and chronic disorders of the spinal cord and peripheral nerves. The clinical presentations and results of local ischemia, peripheral nerve block, and percutaneous stimulation suggest that most limb myokymic discharges arise focally at the site of a chronic peripheral nerve lesion.

F wave index: A diagnostic tool for peripheral neuropathy.

PubMed

Sathya, G R; Krishnamurthy, N; Veliath, Susheela; Arulneyam, Jayanthi; Venkatachalam, J

2017-03-01

Each skeletal muscle is usually supplied by two or more nerve roots and if one nerve root is affected and the other is spared, the clinically used F wave minimum latency can still be normal. An F wave index was constructed taking into consideration the other parameters of the F wave such as persistence, chronodispersion, latency, arm-length to determine its usefulness in the diagnosis of peripheral neuropathy. This study was undertaken to construct the F wave index in the upper limb for the median nerve in normal healthy adult males and in patients with peripheral neuropathy and to compare the values obtained in both groups. This hospital-based study was carried out on 40 males who were diagnosed to have peripheral neuropathy and on 40 age matched healthy males who served as the control group. The F wave recording was done using a digitalized nerve conduction/electromyography/EP machine in a quiet and dimly lit room. All recordings were done between 0900 and 1100 h at an ambient temperature of 22°C. The F wave recording was obtained from a fully relaxed muscle by stimulating the median nerve. The median value for F wave index obtained from median nerve (abductor pollicis brevis) in patients with peripheral neuropathy [right arm - 35.85, interquartile range (IQR) - 35.26; left arm - 39.49, IQR - 39.49] was significantly lower (P=0.001) as compared to the control group (right arm - 102.62, IQR - 83.76; left arm - 77.43, IQR - 58.02). Our results showed that F wave index in upper limb was significantly lower in patients with peripheral neuropathy than the healthy controls, and could be used for early detection of peripheral neuropathy.

Basic science of pain.

PubMed

DeLeo, Joyce A

2006-04-01

The origin of the theory that the transmission of pain is through a single channel from the skin to the brain can be traced to the philosopher and scientist René Descartes. This simplified scheme of the reflex was the beginning of the development of the modern doctrine of reflexes. Unfortunately, Descartes' reflex theory directed both the study and treatment of pain for more than 330 years. It is still described in physiology and neuroscience textbooks as fact rather than theory. The gate control theory proposed by Melzack and Wall in 1965 rejuvenated the field of pain study and led to further investigation into the phenomena of spinal sensitization and central nervous system plasticity, which are the potential pathophysiologic correlates of chronic pain. The processing of pain takes place in an integrated matrix throughout the neuroaxis and occurs on at least three levels-at peripheral, spinal, and supraspinal sites. Basic strategies of pain control monopolize on this concept of integration by attenuation or blockade of pain through intervention at the periphery, by activation of inhibitory processes that gate pain at the spinal cord and brain, and by interference with the perception of pain. This article discusses each level of pain modulation and reviews the mechanisms of action of opioids and potential new analgesics. A brief description of animal models frames a discussion about recent advances regarding the role of glial cells and central nervous system neuroimmune activation and innate immunity in the etiology of chronic pain states. Future investigation into the discovery and development of novel, nonopioid drug therapy may provide needed options for the millions of patients who suffer from chronic pain syndromes, including syndromes in which the pain originates from peripheral nerve, nerve root, spinal cord, bone, muscle, and disc.

Ultrasound-guided rectus sheath block in children with umbilical hernia: Case series.

PubMed

Alsaeed, Abdul Hamid; Thallaj, Ahmed; Khalil, Nancy; Almutaq, Nada; Aljazaeri, Ayman

2013-10-01

Umbilical hernia repair, a common day-case surgery procedure in children, is associated with a significant postoperative pain. The most popular peripheral nerve blocks used in umbilical hernia repair are rectus sheath infiltration and caudal block. The rectus sheath block may offer improved pain relief following umbilical hernia repair with no undesired effects such as lower limb motor weakness or urinary retention seen with caudal block which might delay discharge from the hospital. Ultrasound guidance of peripheral nerve blocks has reduced the number of complications and improved the quality of blocks. The aim of this case series is to assess the post rectus sheath block pain relief in pediatric patients coming for umbilical surgery. Twenty two (22) children (age range: 1.5-8 years) scheduled for umbilical hernia repair were included in the study. Following the induction of general anesthesia, the ultrasonographic anatomy of the umbilical region was studied with a 5-16 MHz 50 mm linear probe. An ultrasound-guided posterior rectus sheath block of both rectus abdominis muscles (RMs) was performed (total of 44 punctures). An in-plain technique using Stimuplex A insulated facet tip needle 22G 50mm. Surgical conditions, intraoperative hemodynamic parameters, and postoperative analgesia by means of the modified CHEOPS scale were evaluated. ultrasonograghic visualization of the posterior sheath was possible in all patients. The ultrasound guided rectus sheath blockade provided sufficient analgesia in all children with no need for additional analgesia except for one patient who postoperatively required morphine 0.1 mg/kg intravenously. There were no complications. Ultrasound guidance enables performances of an effective rectus sheath block for umbilical hernia. Use of the Stimuplex A insulated facet tip needle 22G 50mm provides easy, less traumatic skin and rectus muscle penetration and satisfactory needle visualiza.

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.

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

PubMed

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

2017-03-01

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

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

Engineering Bi-Layer Nanofibrous Conduits for Peripheral Nerve Regeneration

PubMed Central

Zhu, Yiqian; Wang, Aijun; Patel, Shyam; Kurpinski, Kyle; Diao, Edward; Bao, Xuan; Kwong, George; Young, William L.

2011-01-01

Trauma injuries often cause peripheral nerve damage and disability. A goal in neural tissue engineering is to develop synthetic nerve conduits for peripheral nerve regeneration having therapeutic efficacy comparable to that of autografts. Nanofibrous conduits with aligned nanofibers have been shown to promote nerve regeneration, but current fabrication methods rely on rolling a fibrous sheet into the shape of a conduit, which results in a graft with inconsistent size and a discontinuous joint or seam. In addition, the long-term effects of nanofibrous nerve conduits, in comparison with autografts, are still unknown. Here we developed a novel one-step electrospinning process and, for the first time, fabricated a seamless bi-layer nanofibrous nerve conduit: the luminal layer having longitudinally aligned nanofibers to promote nerve regeneration, and the outer layer having randomly organized nanofibers for mechanical support. Long-term in vivo studies demonstrated that bi-layer aligned nanofibrous nerve conduits were superior to random nanofibrous conduits and had comparable therapeutic effects to autografts for nerve regeneration. In summary, we showed that the engineered nanostructure had a significant impact on neural tissue regeneration in situ. The results from this study will also lead to the scalable fabrication of engineered nanofibrous nerve conduits with designed nanostructure. This technology platform can be combined with drug delivery and cell therapies for tissue engineering. PMID:21501089

Peripheral Nerve Disorders

MedlinePlus

... outlet syndrome. In some cases, like complex regional pain syndrome and brachial plexus injuries, the problem begins after an injury. Some people are born with peripheral nerve disorders. Symptoms often start gradually, and then ... Burning or tingling Muscle weakness Sensitivity to touch ...

Identification of PN1, a Predominant Voltage-Dependent Sodium Channel Expressed Principally in Peripheral Neurons

NASA Astrophysics Data System (ADS)

Toledo-Aral, Juan J.; Moss, Brenda L.; He, Zhi-Jun; Koszowski, Adam G.; Whisenand, Teri; Levinson, Simon R.; Wolf, John J.; Silos-Santiago, Inmaculada; Halegoua, Simon; Mandel, Gail

1997-02-01

Membrane excitability in different tissues is due, in large part, to the selective expression of distinct genes encoding the voltage-dependent sodium channel. Although the predominant sodium channels in brain, skeletal muscle, and cardiac muscle have been identified, the major sodium channel types responsible for excitability within the peripheral nervous system have remained elusive. We now describe the deduced primary structure of a sodium channel, peripheral nerve type 1 (PN1), which is expressed at high levels throughout the peripheral nervous system and is targeted to nerve terminals of cultured dorsal root ganglion neurons. Studies using cultured PC12 cells indicate that both expression and targeting of PN1 is induced by treatment of the cells with nerve growth factor. The preferential localization suggests that the PN1 sodium channel plays a specific role in nerve excitability.

Motor-commands decoding using peripheral nerve signals: a review

NASA Astrophysics Data System (ADS)

Hong, Keum-Shik; Aziz, Nida; Ghafoor, Usman

2018-06-01

During the last few decades, substantial scientific and technological efforts have been focused on the development of neuroprostheses. The major emphasis has been on techniques for connecting the human nervous system with a robotic prosthesis via natural-feeling interfaces. The peripheral nerves provide access to highly processed and segregated neural command signals from the brain that can in principle be used to determine user intent and control muscles. If these signals could be used, they might allow near-natural and intuitive control of prosthetic limbs with multiple degrees of freedom. This review summarizes the history of neuroprosthetic interfaces and their ability to record from and stimulate peripheral nerves. We also discuss the types of interfaces available and their applications, the kinds of peripheral nerve signals that are used, and the algorithms used to decode them. Finally, we explore the prospects for future development in this area.

Large Extremity Peripheral Nerve Repair

DTIC Science & Technology

2014-10-01

Shahani B. Peripheral-nerve allotransplantation in rats immunosuppressed with transient or long-term FK-506. Journal of reconstructive microsurgery ...multicenter study of utilization and outcomes in sensory, mixed, and motor nerve reconstructions . Microsurgery . 2012 Jan;32(1):1-14. PubMed PMID: 22121093...PTB method can provide fixation strengths 6 approaching that of conventional microsurgery and that the PTB repair is unlikely to be disturbed in

Microsurgical Outcome of Post-traumatic Peripheral Nerve Injuries: An Experience of 23 Cases and Review of Literature.

PubMed

Garg, Kanwaljeet; Sinha, Sumit; Satyarthee, Guru Dutta; Agarwal, Deepak; Gupta, Deepak Kumar; Sharma, Bhawani; Mahapatra, Ashok Kumar

2016-01-01

The present study aimed to evaluate the microsurgical outcome in post-traumatic peripheral nerve injuries and its correlation with time since injury and the type of the operative procedure performed. All the patients admitted to our center with the diagnosis of post-traumatic peripheral nerve injury were included in the study. The data of all patients was retrospectively analysed from the computerized database of our hospital. The time period of the study was from January 2008 to March 2011. A total of 23 patients were included in the study. The interval between injury and surgery was 28.8 weeks (range: 1 day - 70 weeks). The most common mode of injury was road traffic accidents (39%, n=9). The mean follow up was 24.7 ± 11.3 months (range 9-45 months). Six (60%) patients had a good outcome. There was no statistically significant correlation between outcome and time since injury or type of operative procedure performed (p > 0.05). Post-traumatic peripheral nerve injury is a rare form of nerve injury. There is no correlation between the surgical outcome and time since injury. Some of the nerves have a better outcome as compared to others.

A Pilot Study of a Novel Automated Somatosensory Evoked Potential (SSEP) Monitoring Device for Detection and Prevention of Intraoperative Peripheral Nerve Injury in Total Shoulder Arthroplasty Surgery.

PubMed

Chui, Jason; Murkin, John M; Drosdowech, Darren

2018-05-21

Peripheral nerve injury is a potentially devastating complication after total shoulder arthroplasty (TSA) surgery. This pilot study aimed to assess the feasibility of using an automated somatosensory evoked potential (SSEP) device to provide a timely alert/intervention to minimize intraoperative nerve insults during TSA surgery. A prospective, single-arm, observational study was conducted in a single university hospital. The attending anesthesiologist monitored the study participants using the EPAD automated SSEP device and an intervention was made if there was an alert during TSA surgery. The median, radial, and ulnar nerve SSEP on the operative arm, as well as the median nerve SSEP of the nonoperative arm were monitored for each patient. All patients were evaluated for postoperative neurological deficits 6 weeks postoperatively. In total, 21 patients were consented and were successfully monitored. In total, 4 (19%) patients developed intraoperative abnormal SSEP signal changes in the operative arm, in which 3 were reversible and 1 was irreversible till the end of surgery. Median and radial nerves were mostly involved (3/4 patients). The mean cumulative duration of nerve insult (abnormal SSEP) was 21.7±26.2 minutes. Univariate analysis did not identify predictor of intraoperative nerve insults. No patients demonstrated postoperative peripheral neuropathy at 6 weeks. A high incidence (19%) of intraoperative nerve insult was observed in this study demonstrating the feasibility of using an automated SSEP device to provide a timely alert and enable an intervention in order to minimize peripheral nerve injury during TSA. Further randomized studies are warranted.

An in vivo study of tricalcium phosphate and glutaraldehyde crosslinking gelatin conduits in peripheral nerve repair.

PubMed

Chen, Ming-Hong; Chen, Pei-Ru; Chen, Mei-Hsiu; Hsieh, Sung-Tsang; Huang, Jing-Shan; Lin, Feng-Huei

2006-04-01

In order to modulate the mechanical properties of gelatin, we previously developed a biodegradable composite composed by tricalcium phosphate and glutaraldehyde crosslinking gelatin (GTG) feasible for surgical manipulation. In this study, we evaluated the in vivo applications of GTG conduit for peripheral nerve repair. The effect of sciatic nerve reconstruction was compared between resorbable permeable GTG conduits and durable impermeable silicone tubes. Traditional methods of assessing nerve recovery following peripheral nerve repair including histomorphometric and electrophysiologic features were conducted in our study. In addition, autotomy score and sciatic function index (SFI) in walking tract analysis were used as additional parameters for assessing the return of nerve function. Twenty-four weeks after sciatic nerve repair, the GTG conduits were harvested. Microscopically, regeneration of nerves was observed in the cross-section at the mid portion of all implanted GTG conduits. The cross-sectional area of regenerated nerve of the GTG group was significant larger than that of the silicone group. In the compound muscle action potentials (CMAP), the mean recovery index of CMAP amplitude was 0.24 +/- 0.02 for the silicone group, 0.41 +/- 0.07 for the GTG group. The mean SFI increased with time in the GTG group during the evaluation period until 24 weeks. Walking tract analysis showed a higher SFI score in the GTG group at both 12 and 24 weeks. The difference reached a significant level at 24 weeks. Thus, the histomorphometric, electrophysiologic, and functional assessments demonstrate that GTG can be a candidate for peripheral nerve repair.

Neural vasodilator control in the rectum of the cat and its possible mediation by vasoactive intestinal polypeptide.

PubMed Central

Andersson, P O; Bloom, S R; Edwards, A V; Järhult, J; Mellander, S

1983-01-01

Vascular and motor responses in the rectum to pelvic nerve stimulation are described in the anaesthetized cat and compared with corresponding effects observed in the colon. The responses comprise a cholinergic and a non-cholinergic component, and an attempt has been made to elucidate the latter. Pelvic nerve stimulation evoked a pronounced and well maintained vasodilator response in the rectum whereas that in the colon was transient. Maximal vasodilatation occurred at much lower stimulus frequencies in the rectum (2-4 Hz) than it did in the colon (8-16 Hz) and maximal blood flow under these conditions was also greater in the rectum (greater than 200 ml 100 g-1 min-1) than the colon (less than 150 ml 100 g-1 min-1). Muscarinic blockade further curtailed the colonic vasodilator response to pelvic nerve stimulation, whereas the rectal dilatation was only slightly reduced in the presence of atropine. Pelvic nerve stimulation caused a substantial release of vasoactive intestinal polypeptide (VIP) from the rectum, which was related both in magnitude and duration to the vasodilatation. Intra-arterial infusions of VIP, which reproduced this rise in rectal venous VIP concentration, caused a rectal vasodilator response which closely resembled that during pelvic nerve stimulation after cholinergic blockade. The rectal vasculature was estimated to be 50-100 times more sensitive to VIP than the colonic vasculature. VIP therefore seems to be the most likely putative neurotransmitter responsible for non-cholinergic rectal vasodilatation. Stimulation of the pelvic nerves also caused rapid contractile motor responses before, and more gradual motor responses after, muscarinic blockade in both the colon and rectum, in the latter preceded by a non-cholinergic relaxation. These patterns of motor activity largely confirm previous results. Infusions of substance P effectively mimicked the non-cholinergic contractile motor responses but failed to demonstrate significant release of this peptide during pelvic nerve stimulation in the present experiments. However, substance P is rapidly inactivated and might possibly be involved in these responses. Stimulation of the pelvic nerves in bursts at high frequencies (up to 80 Hz), simulating a discharge pattern observed electrophysiologically in vivo, was effective in eliciting all the above responses, with the exception of the colonic contraction. PMID:6197521

Reinforcement in an in Vitro Analog of Appetitive Classical Conditioning of Feeding Behavior in "Aplysia": Blockade by a Dopamine Antagonist

ERIC Educational Resources Information Center

Reyes, Fredy D.; Mozzachiodi, Riccardo; Baxter, Douglas A.; Byrne, John H.

2005-01-01

In a recently developed in vitro analog of appetitive classical conditioning of feeding in "Aplysia," the unconditioned stimulus (US) was electrical stimulation of the esophageal nerve (En). This nerve is rich in dopamine (DA)-containing processes, which suggests that DA mediates reinforcement during appetitive conditioning. To test this…

Effect of Platelet-Rich Fibrin on Peripheral Nerve Regeneration.

PubMed

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

2016-10-01

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

[Peripheral nerve repair: 30 centuries of scientific research].

PubMed

Desouches, C; Alluin, O; Mutaftschiev, N; Dousset, E; Magalon, G; Boucraut, J; Feron, F; Decherchi, P

2005-11-01

Nerve injury compromises sensory and motor functions. Techniques of peripheral nerve repair are based on our knowledge regarding regeneration. Microsurgical techniques introduced in the late 1950s and widely developed for the past 20 years have improved repairs. However, functional recovery following a peripheral mixed nerve injury is still incomplete. Good motor and sensory function after nerve injury depends on the reinnervation of the motor end plates and sensory receptors. Nerve regeneration does not begin if the cell body has not survived the initial injury or if it is unable to initiate regeneration. The regenerated axons must reach and reinnervate the appropriate target end-organs in a timely fashion. Recovery of motor function requires a critical number of motor axons reinnervating the muscle fibers. Sensory recovery is possible if the delay in reinnervation is short. Many additional factors influence the success of nerve repair or reconstruction. The timing of the repair, the level of injury, the extent of the zone of injury, the technical skill of the surgeon, and the method of repair and reconstruction contribute to the functional outcome after nerve injury. This review presents the recent advances in understanding of neural regeneration and their application to the management of primary repairs and nerve gaps.

In vivo predegeneration of peripheral nerves: an effective technique to obtain activated Schwann cells for nerve conduits.

PubMed

Keilhoff, G; Fansa, H; Schneider, W; Wolf, G

1999-07-01

In vivo predegeneration of peripheral nerves is presented as a convenient and effective method to obtain activated Schwann cells and an enhanced cell yield following in vitro cultivation. The experiments conducted in rats were aimed at clinical use in gaining Schwann cell suspensions for filling artificial conduits in order to bridge peripheral nerve gaps. The rat sciatic nerve used as a model was transected distally to the spinal ganglia. Predegeneration in vivo was allowed to take place for 1, 2, 3 and 4 days and up to 1, 2 and 3 weeks. The nerve was then resected and prepared for cell cultivation. Schwann cells cultivated from the contralateral untreated nerve served as control. Immunostaining for S100, nerve growth factor receptor and the adhesion molecules N-cadherin and L1 was used to characterize the general state of the cultures. Viability was assessed by fluorescein fluorescence staining, and the proliferation index was determined by bromodeoxyuridine-DNA incorporation. The Schwann cells from predegenerated nerves revealed an increased proliferation rate compared to the control, whereas fibroblast contamination was decreased. Best results were obtained 1 week after predegeneration.

Functional collagen conduits combined with human mesenchymal stem cells promote regeneration after sciatic nerve transection in dogs.

PubMed

Cui, Yi; Yao, Yao; Zhao, Yannan; Xiao, Zhifeng; Cao, Zongfu; Han, Sufang; Li, Xing; Huan, Yong; Pan, Juli; Dai, Jianwu

2018-05-01

Numerous studies have focused on the development of novel and innovative approaches for the treatment of peripheral nerve injury using artificial nerve guide conduits. In this study, we attempted to bridge 3.5-cm defects of the sciatic nerve with a longitudinally oriented collagen conduit (LOCC) loaded with human umbilical cord mesenchymal stem cells (hUC-MSCs). The LOCC contains a bundle of longitudinally aligned collagenous fibres enclosed in a hollow collagen tube. Our previous studies showed that an LOCC combined with neurotrophic factors enhances peripheral nerve regeneration. However, it remained unknown whether an LOCC seeded with hUC-MSCs could also promote regeneration. In this study, using various histological and electrophysiological analyses, we found that an LOCC provides mechanical support to newly growing nerves and functions as a structural scaffold for cells, thereby stimulating sciatic nerve regeneration. The LOCC and hUC-MSCs synergistically promoted regeneration and improved the functional recovery in a dog model of sciatic nerve injury. Therefore, the combined use of an LOCC and hUC-MSCs might have therapeutic potential for the treatment of peripheral nerve injury. Copyright © 2018 John Wiley & Sons, Ltd.

Deficiency in Monocarboxylate Transporter 1 (MCT1) in Mice Delays Regeneration of Peripheral Nerves following Sciatic Nerve Crush

PubMed Central

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

2014-01-01

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 and MCT1 tdTomato BAC reporter mice. To investigate whether MCT1 is necessary for peripheral nerve regeneration, sciatic nerves in MCT1 heterozygous null mice are crushed and peripheral nerve regeneration 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 through 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

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. Copyright © 2014 Elsevier Inc. All rights reserved.

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

PubMed

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

2018-04-23

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

Preoperative percutaneous cranial nerve mapping in head and neck surgery.

PubMed

Park, Jung I

2003-01-01

To identify and map the course of the peripheral branches of the cranial nerve preoperatively and percutaneously. Prospective study. Preoperative percutaneous nerve mapping performed prior to the operation under deep sedation or general anesthesia without muscle paralysis. Private office surgery suite, freestanding surgery center, and regional medical centers. A total of 142 patients undergoing head and neck surgery and facial plastic surgery between August 1994 and July 1999. Monopolar probe was used for nerve stimulation. Electromyographic reading was done through intramuscular bipolar recording electrodes. The equipment used was a nerve monitor. The mandibular divisions were tested in 142 cases, the frontal division in 60 cases, the accessory nerve in 12 cases, and the hypoglossal nerve in 3 cases. Satisfactory mappings were obtained in 115 cases of the mandibular division, 49 cases of the frontal division, 8 cases of the accessory division, and 1 case of the hypoglossal nerve. Preoperative percutaneous nerve mapping is a new method of identifying the location of the peripheral branches of the cranial nerves. Identifying and mapping the course of peripheral branches of the cranial nerves safely assists the head and neck surgeon in the placement of incisions in a favorable location and in the dissection of the area involving the nerves. Mapping alerts the surgeon to an area containing a nerve and allows the surgeon to avoid just the specific area where a nerve is present, preventing large-scale abandonment of unmapped areas for fear of potential nerve damage.

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

Non-Invasive Targeted Peripheral Nerve Ablation Using 3D MR Neurography and MRI-Guided High-Intensity Focused Ultrasound (MR-HIFU): Pilot Study in a Swine Model

PubMed Central

Huisman, Merel; Staruch, Robert M.; Ladouceur-Wodzak, Michelle; van den Bosch, Maurice A.; Burns, Dennis K.; Chhabra, Avneesh; Chopra, Rajiv

2015-01-01

Purpose Ultrasound (US)-guided high intensity focused ultrasound (HIFU) has been proposed for noninvasive treatment of neuropathic pain and has been investigated in in-vivo studies. However, ultrasound has important limitations regarding treatment guidance and temperature monitoring. Magnetic resonance (MR)-imaging guidance may overcome these limitations and MR-guided HIFU (MR-HIFU) has been used successfully for other clinical indications. The primary purpose of this study was to evaluate the feasibility of utilizing 3D MR neurography to identify and guide ablation of peripheral nerves using a clinical MR-HIFU system. Methods Volumetric MR-HIFU was used to induce lesions in the peripheral nerves of the lower limbs in three pigs. Diffusion-prep MR neurography and T1-weighted images were utilized to identify the target, plan treatment and immediate post-treatment evaluation. For each treatment, one 8 or 12 mm diameter treatment cell was used (sonication duration 20 s and 36 s, power 160–300 W). Peripheral nerves were extracted < 3 hours after treatment. Ablation dimensions were calculated from thermal maps, post-contrast MRI and macroscopy. Histological analysis included standard H&E staining, Masson’s trichrome and toluidine blue staining. Results All targeted peripheral nerves were identifiable on MR neurography and T1-weighted images and could be accurately ablated with a single exposure of focused ultrasound, with peak temperatures of 60.3 to 85.7°C. The lesion dimensions as measured on MR neurography were similar to the lesion dimensions as measured on CE-T1, thermal dose maps, and macroscopy. Histology indicated major hyperacute peripheral nerve damage, mostly confined to the location targeted for ablation. Conclusion Our preliminary results indicate that targeted peripheral nerve ablation is feasible with MR-HIFU. Diffusion-prep 3D MR neurography has potential for guiding therapy procedures where either nerve targeting or avoidance is desired, and may also have potential for post-treatment verification of thermal lesions without contrast injection. PMID:26659073

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

Decreased glycolytic and tricarboxylic acid cycle intermediates coincide with peripheral nervous system oxidative stress in a murine model of type 2 diabetes.

PubMed

Hinder, Lucy M; Vivekanandan-Giri, Anuradha; McLean, Lisa L; Pennathur, Subramaniam; Feldman, Eva L

2013-01-01

Diabetic neuropathy (DN) is the most common complication of diabetes and is characterized by distal-to-proximal loss of peripheral nerve axons. The idea of tissue-specific pathological alterations in energy metabolism in diabetic complications-prone tissues is emerging. Altered nerve metabolism in type 1 diabetes models is observed; however, therapeutic strategies based on these models offer limited efficacy to type 2 diabetic patients with DN. Therefore, understanding how peripheral nerves metabolically adapt to the unique type 2 diabetic environment is critical to develop disease-modifying treatments. In the current study, we utilized targeted liquid chromatography-tandem mass spectrometry (LC/MS/MS) to characterize the glycolytic and tricarboxylic acid (TCA) cycle metabolomes in sural nerve, sciatic nerve, and dorsal root ganglia (DRG) from male type 2 diabetic mice (BKS.Cg-m+/+Lepr(db); db/db) and controls (db/+). We report depletion of glycolytic intermediates in diabetic sural nerve and sciatic nerve (glucose-6-phosphate, fructose-6-phosphate, fructose-1,6-bisphosphate (sural nerve only), 3-phosphoglycerate, 2-phosphoglycerate, phosphoenolpyruvate, and lactate), with no significant changes in DRG. Citrate and isocitrate TCA cycle intermediates were decreased in sural nerve, sciatic nerve, and DRG from diabetic mice. Utilizing LC/electrospray ionization/MS/MS and HPLC methods, we also observed increased protein and lipid oxidation (nitrotyrosine; hydroxyoctadecadienoic acids) in db/db tissue, with a proximal-to-distal increase in oxidative stress, with associated decreased aconitase enzyme activity. We propose a preliminary model, whereby the greater change in metabolomic profile, increase in oxidative stress, and decrease in TCA cycle enzyme activity may cause distal peripheral nerves to rely on truncated TCA cycle metabolism in the type 2 diabetes environment.

Human amniotic fluid mesenchymal stem cells in combination with hyperbaric oxygen augment peripheral nerve regeneration.

PubMed

Pan, Hung-Chuan; Chin, Chun-Shih; Yang, Dar-Yu; Ho, Shu-Peng; Chen, Chung-Jung; Hwang, Shiaw-Min; Chang, Ming-Hong; Cheng, Fu-Chou

2009-07-01

Attenuation of pro-inflammatory cytokines and associated inflammatory cell deposits rescues human amniotic fluid mesenchymal stem cells (AFS) from apoptosis. Hyperbaric oxygen (HBO) suppressed stimulus-induced pro-inflammatory cytokine production in blood-derived monocyte-macrophages. Herein, we evaluate the beneficial effect of hyperbaric oxygen on transplanted AFS in a sciatic nerve injury model. Peripheral nerve injury was produced in Sprague-Dawley rats by crushing the left sciatic nerve using a vessel clamp. The AFS were embedded in fibrin glue and delivered to the injured site. Hyperbaric oxygen (100% oxygen, 2 ATA, 60 min/day) was administered 12 h after operation for seven consecutive days. Transplanted cell apoptosis, oxidative stress, inflammatory cell deposits and associated chemokines, pro-inflammatory cytokines, motor function, and nerve regeneration were evaluated 7 and 28 days after injury. Crush injury induced an inflammatory response, disrupted nerve integrity, and impaired nerve function in the sciatic nerve. However, crush injury-provoked inflammatory cytokines, deposits of inflammatory cytokines, and associated macrophage migration chemokines were attenuated in groups receiving hyperbaric oxygen but not in the AFS-only group. No significant increase in oxidative stress was observed after administration of HBO. In transplanted AFS, marked apoptosis was detected and this event was reduced by HBO treatment. Increased nerve myelination and improved motor function were observed in AFS-transplant, HBO-administrated, and AFS/HBO-combined treatment groups. Significantly, the AFS/HBO combined treatment showed the most beneficial effect. AFS in combination with HBO augment peripheral nerve regeneration, which may involve the suppression of apoptotic death in implanted AFS and the attenuation of an inflammatory response detrimental to peripheral nerve regeneration.

Relationship between sensorimotor peripheral nerve function and indicators of cardiovascular autonomic function in older adults from the Health, Aging and Body Composition Study.

PubMed

Lange-Maia, Brittney S; Newman, Anne B; Jakicic, John M; Cauley, Jane A; Boudreau, Robert M; Schwartz, Ann V; Simonsick, Eleanor M; Satterfield, Suzanne; Vinik, Aaron I; Zivkovic, Sasa; Harris, Tamara B; Strotmeyer, Elsa S

2017-10-01

Age-related peripheral nervous system (PNS) impairments are highly prevalent in older adults. Although sensorimotor and cardiovascular autonomic function have been shown to be related in persons with diabetes, the nature of the relationship in general community-dwelling older adult populations is unknown. Health, Aging and Body Composition participants (n=2399, age=76.5±2.9years, 52% women, 38% black) underwent peripheral nerve testing at the 2000/01 clinic visit. Nerve conduction amplitude and velocity were measured at the peroneal motor nerve. Sensory nerve function was assessed with vibration detection threshold and monofilament (1.4-g/10-g) testing at the big toe. Symptoms of lower-extremity peripheral neuropathy were collected by self-report. Cardiovascular autonomic function indicators included postural hypotension, resting heart rate (HR), as well as HR response to and recovery from submaximal exercise testing (400m walk). Multivariable modeling adjusted for demographic/lifestyle factors, medication use and comorbid conditions. In fully adjusted models, poor motor nerve conduction velocity (<40m/s) was associated with greater odds of postural hypotension, (OR=1.6, 95% CI: 1.0-2.5), while poor motor amplitude (<1mV) was associated with 2.3beats/min (p=0.003) higher resting HR. No associations were observed between sensory nerve function or symptoms of peripheral neuropathy and indicators of cardiovascular autonomic function. Motor nerve function and indicators of cardiovascular autonomic function remained significantly related even after considering many potentially shared risk factors. Future studies should investigate common underlying processes for developing multiple PNS impairments in older adults. Copyright © 2017 Elsevier Inc. All rights reserved.

Identification of a Peripheral Nerve Neurite Growth-Promoting Activity by Development and Use of an in vitro Bioassay

NASA Astrophysics Data System (ADS)

Sandrock, Alfred W.; Matthew, William D.

1987-10-01

The effective regeneration of severed neuronal axons in the peripheral nerves of adult mammals may be explained by the presence of molecules in situ that promote the effective elongation of neurites. The absence of such molecules in the central nervous system of these animals may underlie the relative inability of axons to regenerate in this tissue after injury. In an effort to identify neurite growth-promoting molecules in tissues that support effective axonal regeneration, we have developed an in vitro bioassay that is sensitive to substrate-bound factors of peripheral nerve that influence the growth of neurites. In this assay, neonatal rat superior cervical ganglion explants are placed on longitudinal cryostat sections of fresh-frozen sciatic nerve, and the regrowing axons are visualized by catecholamine histofluorescence. Axons are found to regenerate effectively over sciatic nerve tissue sections. When ganglia are similarly explanted onto cryostat sections of adult rat central nervous system tissue, however, axonal regeneration is virtually absent. We have begun to identify the molecules in peripheral nerve that promote effective axonal regeneration by examining the effect of antibodies that interfere with the activity of previously described neurite growth-promoting factors. Axonal elongation over sciatic nerve tissue was found to be sensitive to the inhibitory effects of INO (for inhibitor of neurite outgrowth), a monoclonal antibody that recognizes and inhibits a neurite growth-promoting activity from PC-12 cell-conditioned medium. The INO antigen appears to be a molecular complex of laminin and heparan sulfate proteoglycan. In contrast, a rabbit antiserum that recognizes laminin purified from mouse Engelbreth-Holm-Swarm (EHS) sarcoma, stains the Schwann cell basal lamina of peripheral nerve, and inhibits neurite growth over purified laminin substrata has no detectable effect on the rate of axonal regeneration in our assay.

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

DTIC Science & Technology

2016-09-01

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

Acceleration of Regeneration of Large-Gap Peripheral Nerve Injuries Using Acellular Nerve Allografts Plus Amniotic Fluid Derived Stem Cells (AFS)

DTIC Science & Technology

2017-09-01

AFS seeded ANA used for nerve repair resulted in an improved functional outcome for the rats compared to ANA alone and were equivalent to those...junction morphology were equivalent between the AFS seeded ANA. Additional studies investigated the use of post-partum acellular materials to promote...techniques for repairing large-gap (6 cm) nerve injuries in non -human primates. This pre-clinical model represents a more translational model of peripheral

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

2016-05-27

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.

Patterns of innervation of neurones in the inferior mesenteric ganglion of the cat.

PubMed Central

Julé, Y; Krier, J; Szurszewski, J H

1983-01-01

The patterns of peripheral and central synaptic input to non-spontaneous, irregular discharging and regular discharging neurones in the inferior mesenteric ganglion of the cat were studied in vitro using intracellular recording techniques. All three types of neurones in rostral and caudal lobes received central synaptic input primarily from L3 and L4 spinal cord segments. Since irregular discharging neurones received synaptic input from intraganglionic regular discharging neurones, some of the central input to irregular discharging neurones may have been relayed through the regular discharging neurones. In the rostral lobes of the ganglion, more than 70% of the non-spontaneous and irregular discharging neurones tested received peripheral synaptic input from the lumbar colonic, intermesenteric and left and right hypogastric nerves. Most of the regular discharging neurones tested received synaptic input from the intermesenteric and lumbar colonic nerves; none of the regular discharging neurones received synaptic input from the hypogastric nerves. Some of the peripheral synaptic input from the lumbar colonic and intermesenteric nerves to irregular discharging neurones may have been relayed through the regular discharging neurones. Axons of non-spontaneous and irregular discharging neurones located in the rostral lobes travelled to the periphery exclusively in the lumbar colonic nerves. Antidromic responses were not observed in regular discharging neurones during stimulation of any of the major peripheral nerve trunks. This suggests these neurones were intraganglionic. In the caudal lobes, irregular discharging neurones received a similar pattern of peripheral synaptic input as did irregular discharging neurones located in the rostral lobes. The majority of irregular discharging neurones in the caudal lobes projected their axons to the periphery through the lumbar colonic nerves. Non-spontaneous neurones in the caudal lobes, in contrast to those located in the rostral lobes, received peripheral synaptic input primarily from the hypogastric nerves. Axons of the majority of non-spontaneous neurones located in the caudal lobes travelled to the periphery through hypogastric nerves. The results suggest that non-spontaneous neurones and irregular discharging neurones in the rostral lobes and the majority of irregular discharging neurones in the caudal lobes transact and integrate neural commands destined for abdominal viscera supplied by the lumbar colonic nerves. Non-spontaneous neurones in the caudal lobes transact and integrate neural commands destined for pelvic viscera supplied by the hypogastric nerves. PMID:6655582

Patterns of innervation of neurones in the inferior mesenteric ganglion of the cat.

PubMed

Julé, Y; Krier, J; Szurszewski, J H

1983-11-01

The patterns of peripheral and central synaptic input to non-spontaneous, irregular discharging and regular discharging neurones in the inferior mesenteric ganglion of the cat were studied in vitro using intracellular recording techniques. All three types of neurones in rostral and caudal lobes received central synaptic input primarily from L3 and L4 spinal cord segments. Since irregular discharging neurones received synaptic input from intraganglionic regular discharging neurones, some of the central input to irregular discharging neurones may have been relayed through the regular discharging neurones. In the rostral lobes of the ganglion, more than 70% of the non-spontaneous and irregular discharging neurones tested received peripheral synaptic input from the lumbar colonic, intermesenteric and left and right hypogastric nerves. Most of the regular discharging neurones tested received synaptic input from the intermesenteric and lumbar colonic nerves; none of the regular discharging neurones received synaptic input from the hypogastric nerves. Some of the peripheral synaptic input from the lumbar colonic and intermesenteric nerves to irregular discharging neurones may have been relayed through the regular discharging neurones. Axons of non-spontaneous and irregular discharging neurones located in the rostral lobes travelled to the periphery exclusively in the lumbar colonic nerves. Antidromic responses were not observed in regular discharging neurones during stimulation of any of the major peripheral nerve trunks. This suggests these neurones were intraganglionic. In the caudal lobes, irregular discharging neurones received a similar pattern of peripheral synaptic input as did irregular discharging neurones located in the rostral lobes. The majority of irregular discharging neurones in the caudal lobes projected their axons to the periphery through the lumbar colonic nerves. Non-spontaneous neurones in the caudal lobes, in contrast to those located in the rostral lobes, received peripheral synaptic input primarily from the hypogastric nerves. Axons of the majority of non-spontaneous neurones located in the caudal lobes travelled to the periphery through hypogastric nerves. The results suggest that non-spontaneous neurones and irregular discharging neurones in the rostral lobes and the majority of irregular discharging neurones in the caudal lobes transact and integrate neural commands destined for abdominal viscera supplied by the lumbar colonic nerves. Non-spontaneous neurones in the caudal lobes transact and integrate neural commands destined for pelvic viscera supplied by the hypogastric nerves.

Microscale Electrode Implantation during Nerve Repair: Effects on Nerve Morphology, Electromyography, and Recovery of Muscle Contractile Function

PubMed Central

Urbanchek, Melanie G; Wei, Benjamin; Egeland, Brent M; Abidian, Mohammad R; Kipke, Daryl R; Cederna, Paul S

2011-01-01

Background Our goal is to develop a peripheral nerve electrode with long-term stability and fidelity for use in nerve-machine interfaces. Microelectromechanical systems (MEMS) use silicon probes that contain multi-channel actuators, sensors, and electronics. We tested the null hypothesis that implantation of MEMS probes do not have a detrimental effect on peripheral nerve function or regeneration. Methods A rat hindlimb, peroneal nerve model was utilized in all experimental groups: a) intact nerve (Control, n= 10); b) nerve division and repair (Repair, n= 9); and c) Nerve division, insertion of MEMS probe, and repair (Repair + Probe, n=9). Nerve morphology, nerve to muscle compound action potential (CMAP) studies, walking tracks, and extensor digitorum longus (EDL) muscle function tests were evaluated following an 80 day recovery. Results Repair and Repair + Probe showed no differences in axon count, axon size, percent non-neural area, CMAP amplitude, latency, muscle mass, muscle force, or walking track scores. Though there was some local fibrosis around each MEMS probe, this did not lead to measurable detrimental effects in any anatomic or functional outcome measurements. Conclusions The lack of a significant difference between Repair and Repair + Probe groups in histology, CMAP, walking tracks, and muscle force suggests that MEMS electrodes are compatible with regenerating axons and show promise for establishing chemical and electrical interfaces with peripheral nerves. PMID:21921739

Defining the neural fulcrum for chronic vagus nerve stimulation: implications for integrated cardiac control.

PubMed

Ardell, Jeffrey L; Nier, Heath; Hammer, Matthew; Southerland, E Marie; Ardell, Christopher L; Beaumont, Eric; KenKnight, Bruce H; Armour, J Andrew

2017-11-15

The evoked cardiac response to bipolar cervical vagus nerve stimulation (VNS) reflects a dynamic interaction between afferent mediated decreases in central parasympathetic drive and suppressive effects evoked by direct stimulation of parasympathetic efferent axons to the heart. The neural fulcrum is defined as the operating point, based on frequency-amplitude-pulse width, where a null heart rate response is reproducibly evoked during the on-phase of VNS. Cardiac control, based on the principal of the neural fulcrum, can be elicited from either vagus. Beta-receptor blockade does not alter the tachycardia phase to low intensity VNS, but can increase the bradycardia to higher intensity VNS. While muscarinic cholinergic blockade prevented the VNS-induced bradycardia, clinically relevant doses of ACE inhibitors, beta-blockade and the funny channel blocker ivabradine did not alter the VNS chronotropic response. While there are qualitative differences in VNS heart control between awake and anaesthetized states, the physiological expression of the neural fulcrum is maintained. Vagus nerve stimulation (VNS) is an emerging therapy for treatment of chronic heart failure and remains a standard of therapy in patients with treatment-resistant epilepsy. The objective of this work was to characterize heart rate (HR) responses (HRRs) during the active phase of chronic VNS over a wide range of stimulation parameters in order to define optimal protocols for bidirectional bioelectronic control of the heart. In normal canines, bipolar electrodes were chronically implanted on the cervical vagosympathetic trunk bilaterally with anode cephalad to cathode (n = 8, 'cardiac' configuration) or with electrode positions reversed (n = 8, 'epilepsy' configuration). In awake state, HRRs were determined for each combination of pulse frequency (2-20 Hz), intensity (0-3.5 mA) and pulse widths (130-750 μs) over 14 months. At low intensities and higher frequency VNS, HR increased during the VNS active phase owing to afferent modulation of parasympathetic central drive. When functional effects of afferent and efferent fibre activation were balanced, a null HRR was evoked (defined as 'neural fulcrum') during which HRR ≈ 0. As intensity increased further, HR was reduced during the active phase of VNS. While qualitatively similar, VNS delivered in the epilepsy configuration resulted in more pronounced HR acceleration and reduced HR deceleration during VNS. At termination, under anaesthesia, transection of the vagi rostral to the stimulation site eliminated the augmenting response to VNS and enhanced the parasympathetic efferent-mediated suppressing effect on electrical and mechanical function of the heart. In conclusion, VNS activates central then peripheral aspects of the cardiac nervous system. VNS control over cardiac function is maintained during chronic therapy. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Peripheral cannabinoid-1 receptor blockade restores hypothalamic leptin signaling.

PubMed

Tam, Joseph; Szanda, Gergő; Drori, Adi; Liu, Ziyi; Cinar, Resat; Kashiwaya, Yoshihiro; Reitman, Marc L; Kunos, George

2017-10-01

In visceral obesity, an overactive endocannabinoid/CB 1 receptor (CB 1 R) system promotes increased caloric intake and decreases energy expenditure, which are mitigated by global or peripheral CB 1 R blockade. In mice with diet-induced obesity (DIO), inhibition of food intake by the peripherally restricted CB 1 R antagonist JD5037 could be attributed to endogenous leptin due to the rapid reversal of hyperleptinemia that maintains leptin resistance, but the signaling pathway engaged by leptin has remained to be determined. We analyzed the hypothalamic circuitry targeted by leptin following chronic treatment of DIO mice with JD5037. Leptin treatment or an increase in endogenous leptin following fasting/refeeding induced STAT3 phosphorylation in neurons in the arcuate nucleus (ARC) in lean and JD5037-treated DIO mice, but not in vehicle-treated DIO animals. Co-localization of pSTAT3 in leptin-treated mice was significantly less common with NPY + than with POMC + ARC neurons. The hypophagic effect of JD5037 was absent in melanocortin-4 receptor (MC4R) deficient obese mice or DIO mice treated with a MC4R antagonist, but was maintained in NPY -/- mice kept on a high-fat diet. Peripheral CB 1 R blockade in DIO restores sensitivity to endogenous leptin, which elicits hypophagia via the re-activation of melanocortin signaling in the ARC. Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.

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

PubMed Central

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

2017-01-01

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

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

PubMed

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

2012-08-01

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

Bridging extra large defects of peripheral nerves: possibilities and limitations of alternative biological grafts from acellular muscle and Schwann cells.

PubMed

Keilhoff, Gerburg; Prätsch, Florian; Wolf, Gerald; Fansa, Hisham

2005-01-01

Defects of peripheral nerves are bridged with autologous nerve grafts. Tissue-engineered nerve grafts offer a laboratory-based alternative to overcome limited donor nerve availability. Our objective was to evaluate whether a graft made from acellular muscle enriched with cultivated Schwann cells can bridge extra large gaps where conventional conduits usually fail. Our well-established rat sciatic nerve model was used with an increased gap length of 50 mm. The conduits consisted of freeze-thawed or chemically extracted homologous acellular rat rectus muscles and implanted Schwann cells. Autologous nerve grafts were used for control purposes. Biocompatibility of the grafts was demonstrated by Schwann cell settlement, revascularization, and macrophage recruitment. After 12 weeks regeneration was assessed clinically, histologically, and morphometrically. The control group showed superior results regarding axon counts, histologic appearance, and functional recovery compared with the muscle grafts. The chemically extracted conduits completely failed to support nerve regeneration. They were not stable enough to bridge longer nerve gaps with an expanded regeneration time. On the basis of morphological parameters freeze-thawed muscle grafts were, however, able to support peripheral nerve regeneration even over the extralong distance of 50 mm, and therefore are of potential benefit for new therapeutic strategies.

Avulsion of the brachial plexus in a great horned owl (Bubo virginaus)

USGS Publications Warehouse

Moore, M.P.; Stauber, E.; Thomas, N.J.

1989-01-01

Avulsion of the brachial plexus was documented in a Great Horned Owl (Bubo virginianus). A fractured scapula was also present. Cause of these injuries was not known but was thought to be due to trauma. Differentiation of musculoskeletal injury from peripheral nerve damage can be difficult in raptors. Use of electromyography and motor nerve conduction velocity was helpful in demonstrating peripheral nerve involvement. A brachial plexus avulsion was suspected on the basis of clinical signs, presence of electromyographic abnormalities in all muscles supplied by the nerves of the brachial plexus and absence of median-ulnar motor nerve conduction velocities.

Correlation between serum vitamin B12 level and peripheral neuropathy in atrophic gastritis

PubMed Central

Yang, Guo-Tao; Zhao, Hong-Ying; Kong, Yu; Sun, Ning-Ning; Dong, Ai-Qin

2018-01-01

AIM To explore the correlation between serum vitamin B12 level and peripheral neuropathy in patients with chronic atrophic gastritis (CAG). METHODS A total of 593 patients diagnosed with chronic gastritis by gastroscopy and pathological examination from September 2013 to September 2016 were selected for this study. The age of these patients ranged within 18- to 75-years-old. Blood pressure, height and weight were measured in each patient, and the body mass index value was calculated. Furthermore, gastric acid, serum gastrin, serum vitamin and serum creatinine tests were performed, and peripheral nerve conduction velocity and Helicobacter pylori (H. pylori) were detected. In addition, the type of gastritis was determined by gastroscopy. The above factors were used as independent variables to analyze chronic gastritis with peripheral neuropathy and vitamin B12 deficiency risk factors, and to analyze the relationship between vitamin B12 levels and peripheral nerve conduction velocity. In addition, in the treatment of CAG on the basis of vitamin B12, patients with peripheral neuropathy were observed. RESULTS Age, H. pylori infection, CAG, vitamin B9 and vitamin B12 were risk factors for the occurrence of peripheral nerve degeneration. Furthermore, CAG and H. pylori infection were risk factors for chronic gastritis associated with vitamin B12 deficiency. Serum vitamin B12 level was positively correlated with sensory nerve conduction velocity in the tibial nerve (R = 0.463). After vitamin B12 supplementation, patients with peripheral neuropathy improved. CONCLUSION Serum vitamin B12 levels in patients with chronic gastritis significantly decreased, and the occurrence of peripheral neuropathy had a certain correlation. CAG and H. pylori infection are risk factors for vitamin B12 deficiency and peripheral neuropathy. When treating CAG, vitamin B12 supplementation can significantly reduce peripheral nervous system lesions. Therefore, the occurrence of peripheral neuropathy associated with vitamin B12 deficiency may be considered in patients with CAG. Furthermore, the timely supplementation of vitamin B12 during the clinical treatment of CAG can reduce or prevent peripheral nervous system lesions. PMID:29599609

[Artificial control of blood-nerve barrier: a novel therapeutic approach to peripheral neuropathies].

PubMed

Kanda, Takashi

2011-11-01

Blood-nerve barrier (BNB) is a "Janus-faced" structure for the peripheral nerve parenchyma. Healthy BNB may contribute to stabilize the internal milleu of peripheral nervous system (PNS) and to stop the entrance of toxic substances and harmful leukocytes into nerve parenchyma. On the other hand, healthy BNB may sometimes be a drawback because the peripheral nerve parenchyma cannot receive enough amount of nutrients and growth factors and cannot excrete toxic substances into systemic circulation because of its presence. Here we present a future therapeutic strategy to control BNB function, based on the basic knowledge acquired from recently developed human immortalized cell lines of BNB origin. If we can artificially regulate the BNB permeability and the expression of adhesion molecules on the surface of BNB-forming endothelial cells, and stop the entrance of toxic substances as well as pathogenic leukocytes into PNS parenchyma, the treatment of inflammatory neuropathies may make great progresses. For hereditary, metabolic and ischemic neuropathies, the promotion of the entrance of growth factors into PNS parenchyma and of the excretion of toxic substances should powerfully encourage the regeneration of axons.

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.

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. Published by Elsevier Inc.

Blockade of dopamine D2 receptors disrupts intrahippocampal connectivity and enhances pain-related working memory deficits in neuropathic pain rats.

PubMed

Cardoso-Cruz, H; Dourado, M; Monteiro, C; Galhardo, V

2018-05-01

Dopamine (DA) is thought to be important to local hippocampal networks integrity during spatial working memory (sWM) processing. Chronic pain may contribute to deficient dopaminergic signalling, which may in turn affect cognition. However, the neural mechanisms that determine this impairment are poorly understood. Here, we evaluated whether the sWM impairment characteristic of animal models of chronic pain is dependent on DA D2 receptor (D2r) activity. To address this issue, we implanted multichannel arrays of electrodes in the dorsal and ventral hippocampal CA1 field (dvCA1) of rats and recorded the neuronal activity during a classical delayed food-reinforced T-maze sWM task. Within-subject behavioural performance and patterns of dorsoventral neural activity were assessed before and after the onset of persistent neuropathic pain using the spared nerve injury (SNI) model. Our results show that the peripheral nerve lesion caused a disruption in sWM and hippocampus spike activity and that disruption was maximized by the systemic administration of the D2r antagonist raclopride. These deficits are strictly correlated with a selective disruption of hippocampal theta-oscillations. Particularly, we found a significant decrease in intrahippocampal CA1 field connectivity level. Together, these results suggest that disruption of the dopaminergic balance in the intrahippocampal networks may be important for the development of cognitive deficits experienced during painful conditions. This study provides new insights into the role of D2r in the manifestation of pain-related sWM deficits. Our findings support that selective blockade of D2r produces a significant decrease in intrahippocampal connectivity mediated by theta-oscillations, and amplifies pain-related sWM deficits. These results suggest that further characterization of intrahippocampal dopaminergic modulation may be clinically relevant for the understanding of cognitive impairments that accompanies nociceptive stressful conditions. © 2018 European Pain Federation - EFIC®.

Nerve regeneration with aid of nanotechnology and cellular engineering.

PubMed

Sedaghati, Tina; Yang, Shi Yu; Mosahebi, Afshin; Alavijeh, Mohammad S; Seifalian, Alexander M

2011-01-01

Repairing nerve defects with large gaps remains one of the most operative challenges for surgeons. Incomplete recovery from peripheral nerve injuries can produce a diversity of negative outcomes, including numbness, impairment of sensory or motor function, possibility of developing chronic pain, and devastating permanent disability. In the last few years, numerous microsurgical techniques, such as coaptation, nerve autograft, and different biological or polymeric nerve conduits, have been developed to reconstruct a long segment of damaged peripheral nerve. A few of these techniques are promising and have become popular among surgeons. Advancements in the field of tissue engineering have led to development of synthetic nerve conduits as an alternative for the nerve autograft technique, which is the current practice to bridge nerve defects with gaps larger than 30 mm. However, to date, despite significant progress in this field, no material has been found to be an ideal alternative to the nerve autograft. This article briefly reviews major up-to-date published studies using different materials as an alternative to the nerve autograft to bridge peripheral nerve gaps in an attempt to assess their ability to support and enhance nerve regeneration and their prospective drawbacks, and also highlights the promising hope for nerve regeneration with the next generation of nerve conduits, which has been significantly enhanced with the tissue engineering approach, especially with the aid of nanotechnology in development of the three-dimensional scaffold. The goal is to determine potential alternatives for nerve regeneration and repair that are simply and directly applicable in clinical conditions. Copyright © 2011 International Union of Biochemistry and Molecular Biology, Inc.

Peripherally injected linalool and bergamot essential oil attenuate mechanical allodynia via inhibiting spinal ERK phosphorylation.

PubMed

Kuwahata, Hikari; Komatsu, Takaaki; Katsuyama, Soh; Corasaniti, Maria Tiziana; Bagetta, Giacinto; Sakurada, Shinobu; Sakurada, Tsukasa; Takahama, Kazuo

2013-02-01

Bergamot essential oil (BEO) is one of the most common essential oil containing linalool and linalyl acetate as major volatile components. This study investigated the effect of intraplantar (i.pl.) bergamot essential oil (BEO) or linalool on neuropathic hypersensitivity induced by partial sciatic nerve ligation (PSNL) in mice. The i.pl. injection of BEO or linalool into the ipsilateral hindpaw to PSNL reduced PSNL-induced mechanical allodynia in a dose-dependent manner. Peripheral (i.pl.) injection of BEO or linalool into the contralateral hindpaw did not yield anti-allodynic effects, suggesting a local anti-mechanical allodynic effect of BEO or linalool in PSNL mice. Anti-mechanical hypersensitivity of morphine was enhanced by the combined injection of BEO or linalool at an ineffective dose when injected alone. We also examined the possible involvement of spinal extracellular signal-regulated protein kinase (ERK) in BEO or linalool-induced anti-mechanical allodynia. In western blotting analysis, i.pl. injection of BEO or linalool resulted in a significant blockade of spinal ERK activation induced by PSNL. These results suggest that i.pl. injection of BEO or linalool may reduce PSNL-induced mechanical allodynia followed by decreasing spinal ERK activation. Copyright © 2012 Elsevier Inc. All rights reserved.

Differential involvement of forearm muscles in ALS does not relate to sonographic structural nerve alterations.

PubMed

Schreiber, Stefanie; Schreiber, Frank; Debska-Vielhaber, Grazyna; Garz, Cornelia; Hensiek, Nathalie; Machts, Judith; Abdulla, Susanne; Dengler, Reinhard; Petri, Susanne; Nestor, Peter J; Vielhaber, Stefan

2018-07-01

We aimed to assess whether differential peripheral nerve involvement parallels dissociated forearm muscle weakness in amyotrophic lateral sclerosis (ALS). The analysis comprised 41 ALS patients and 18 age-, sex-, height- and weight-matched healthy controls. Strength of finger-extension and -flexion was measured using the Medical Research Council (MRC) scale. Radial, median and ulnar nerve sonographic cross-sectional area (CSA) and echogenicity, expressed by the hypoechoic fraction (HF), were determined. In ALS, finger extensors were significantly weaker than finger flexors. Sonographic evaluation revealed peripheral nerve atrophy, affecting various nerve segments in ALS. HF was unaltered. This systematic study confirmed a long-observed physical examination finding in ALS - weakness in finger-extension out of proportion to finger-flexion. This phenomenon was not related to any particular sonographic pattern of upper limb peripheral nerve alteration. In ALS, dissociated forearm muscle weakness could aid in the disease's diagnosis. Nerve ultrasound did not provide additional information on the differential involvement of finger-extension and finger-flexion strength. Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Non-invasive peripheral nerve stimulation via focused ultrasound in vivo

NASA Astrophysics Data System (ADS)

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

2018-02-01

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

Recovery of C-fiber-induced extravasation following peripheral nerve injury in the rat.

PubMed

Bester, H; Allchorne, A J; Woolf, C J

1998-12-01

Peripheral nerve injury leads to substantial alterations in injured sensory neurons. These include cell death, phenotypic modifications, and regeneration. Primary sensory neurons have recently been shown not to die until a time beyond 4 months following a nerve crush or ligation and this loss is, moreover, limited to cells with unmyelinated axons, the C-fibers. The late loss of C-fibers may be due to a lack of target reinnervation during the regenerative phase. In order to investigate this, we have used a particular peripheral function, unique to C-fibers, as a measure of peripheral reinnervation: an increase in capillary permeability on antidromic activation of C-fibers, i.e., neurogenic extravasation. This was investigated in rats that had received a nerve crush injury 1 to 50 weeks earlier. Some recovery of the capacity of C-fibers to generate extravasation was detected at 8-10 weeks, which increased further at 12-14 weeks, and then plateaued at this level with no further recovery at 30 or 50 weeks. In intact and damaged sciatic nerves, A beta-fibers never induced extravasation. These findings are compatible with the hypothesis that those C-fibers which make it back to their peripheral targets do not subsequently die and those that do not, may die. Copyright 1998 Academic Press.

“Can't Walk Nor Raise Arms to Head”

PubMed Central

Pendleton, Courtney; Dorsi, Michael J.; Belzberg, Allan J.; Cohen-Gadol, Aaron A.; Quiñones-Hinojosa, Alfredo

2015-01-01

Study Design This study was a retrospective chart review for patients undergoing operative treatment by Dr. Harvey Cushing at the Johns Hopkins Hospital between 1896 and 1912. Objective To illustrate the early use of peripheral nerve anastomoses for the treatment of postpoliomyelitis paralysis. Summary of Background Data At the turn of the 20th century, poliomyelitis was recognized as a disease of neurons; neurological surgeons sought to find a surgical cure for the paralysis occurring after the disease onset. Peripheral nerve anastomoses were an attractive option employed during this time. Methods Following IRB approval, and through the courtesy of the Alan Mason Chesney Archives, the surgical records of the Johns Hopkins Hospital from 1896 to 1912 were reviewed. A single case of peripheral nerve anastomosis for the treatment of postpoliomyelitis paralysis was selected for further analysis. Results Cushing performed a multiple peripheral nerve anastomoses in a 3-year-old girl. Although the patient experienced no postoperative complications, there was no improvement in her function at the time of discharge from the hospital, and no long-term follow-up was available. Conclusion While unsuccessful, Cushing's use of peripheral nerve anastomoses to restore motor function in the pediatric patient described here demonstrates his commitment to pushing the boundaries of neurological surgery at the turn of the 20th century. PMID:21301395

"Can't walk nor raise arms to head": Harvey Cushing's surgical treatment of poliomyelitis.

PubMed

Pendleton, Courtney; Dorsi, Michael J; Belzberg, Allan J; Cohen-Gadol, Aaron A; Quiñones-Hinojosa, Alfredo

2012-02-15

This study was a retrospective chart review for patients undergoing operative treatment by Dr. Harvey Cushing at the Johns Hopkins Hospital between 1896 and 1912. To illustrate the early use of peripheral nerve anastomoses for the treatment of postpoliomyelitis paralysis. At the turn of the 20th century, poliomyelitis was recognized as a disease of neurons; neurological surgeons sought to find a surgical cure for the paralysis occurring after the disease onset. Peripheral nerve anastomoses were an attractive option employed during this time. Following IRB approval, and through the courtesy of the Alan Mason Chesney Archives, the surgical records of the Johns Hopkins Hospital from 1896 to 1912 were reviewed. A single case of peripheral nerve anastomosis for the treatment of postpoliomyelitis paralysis was selected for further analysis. Cushing performed a multiple peripheral nerve anastomoses in a 3-year-old girl. Although the patient experienced no postoperative complications, there was no improvement in her function at the time of discharge from the hospital, and no long-term follow-up was available. While unsuccessful, Cushing's use of peripheral nerve anastomoses to restore motor function in the pediatric patient described here demonstrates his commitment to pushing the boundaries of neurological surgery at the turn of the 20th century.

Occipital peripheral nerve stimulation in the management of chronic intractable occipital neuralgia in a patient with neurofibromatosis type 1: a case report

PubMed Central

2011-01-01

Introduction Occipital peripheral nerve stimulation is an interventional pain management therapy that provides beneficial results in the treatment of refractory chronic occipital neuralgia. Herein we present a first-of-its-kind case study of a patient with neurofibromatosis type 1 and bilateral occipital neuralgia treated with occipital peripheral nerve stimulation. Case presentation A 42-year-old Caucasian woman presented with bilateral occipital neuralgia refractory to various conventional treatments, and she was referred for possible treatment with occipital peripheral nerve stimulation. She was found to be a suitable candidate for the procedure, and she underwent implantation of two octapolar stimulating leads and a rechargeable, programmable, implantable generator. The intensity, severity, and frequency of her symptoms resolved by more than 80%, but an infection developed at the implantation site two months after the procedure that required explantation and reimplantation of new stimulating leads three months later. To date she continues to experience symptom resolution of more than 60%. Conclusion These results demonstrate the significance of peripheral nerve stimulation in the management of refractory occipital neuralgias in patients with neurofibromatosis type 1 and the possible role of neurofibromata in the development of occipital neuralgia in these patients. PMID:21569290

Clindamycin enhances a nondepolarizing neuromuscular blockade.

PubMed

Becker, L D; Miller, R D

1976-07-01

Neuromuscular blockades induced by clindamycin alone and with d-tubocurarine or pancuronium were examined in the in-vitro guinea pig lumbrical muscle-nerve preparation. Clindamycin, 80-240 mug/ml, initially increased twitch tension. With higher concentrations (180-240 mug/ml) twitch tension subsequently decreased. With 15 to 20 per cent depression of twitch tension by clindamycin, neostigmine (5-20 ng/ml) or calcium (81 mug/ml) slightly but not completely antagonized the blockade. Clindamycin, 40 mug/ml, a dose that did not depress twitch tension, potentiated d-tubocurarine- or pancuronium-induced neuromuscular bloackade. Plasma concentrations of clindamycin of 10-40 mug/ml were recommended for treating serious infections. The authors conclude that the administration of clindamycin may augment nondepolarizing blockade in man, and antagonism by neostigmine and calcium may be incomplete.

Functional role of peripheral opioid receptors in the regulation of cardiac spinal afferent nerve activity during myocardial ischemia

PubMed Central

Longhurst, John C.

2013-01-01

Thinly myelinated Aδ-fiber and unmyelinated C-fiber cardiac sympathetic (spinal) sensory nerve fibers are activated during myocardial ischemia to transmit the sensation of angina pectoris. Although recent observations showed that myocardial ischemia increases the concentrations of opioid peptides and that the stimulation of peripheral opioid receptors inhibits chemically induced visceral and somatic nociception, the role of opioids in cardiac spinal afferent signaling during myocardial ischemia has not been studied. The present study tested the hypothesis that peripheral opioid receptors modulate cardiac spinal afferent nerve activity during myocardial ischemia by suppressing the responses of cardiac afferent nerve to ischemic mediators like bradykinin and extracellular ATP. The nerve activity of single unit cardiac afferents was recorded from the left sympathetic chain (T2–T5) in anesthetized cats. Forty-three ischemically sensitive afferent nerves (conduction velocity: 0.32–3.90 m/s) with receptive fields in the left and right ventricles were identified. The responses of these afferent nerves to repeat ischemia or ischemic mediators were further studied in the following protocols. First, epicardial administration of naloxone (8 μmol), a nonselective opioid receptor antagonist, enhanced the responses of eight cardiac afferent nerves to recurrent myocardial ischemia by 62%, whereas epicardial application of vehicle (PBS) did not alter the responses of seven other cardiac afferent nerves to ischemia. Second, naloxone applied to the epicardial surface facilitated the responses of seven cardiac afferent nerves to epicardial ATP by 76%. Third, administration of naloxone enhanced the responses of seven other afferent nerves to bradykinin by 85%. In contrast, in the absence of naloxone, cardiac afferent nerves consistently responded to repeated application of ATP (n = 7) or bradykinin (n = 7). These data suggest that peripheral opioid peptides suppress the responses of cardiac sympathetic afferent nerves to myocardial ischemia and ischemic mediators like ATP and bradykinin. PMID:23645463

A voltage-controlled capacitive discharge method for electrical activation of peripheral nerves.

PubMed

Rosellini, Will M; Yoo, Paul B; Engineer, Navzer; Armstrong, Scott; Weiner, Richard L; Burress, Chester; Cauller, Larry

2011-01-01

A voltage-controlled capacitive discharge (VCCD) method was investigated as an alternative to rectangular stimulus pulses currently used in peripheral nerve stimulation therapies.  In two anesthetized Gottingen mini pigs, the threshold (total charge per phase) for evoking a compound nerve action potential (CNAP) was compared between constant current (CC) and VCCD methods. Electrical pulses were applied to the tibial and posterior cutaneous femoralis nerves using standard and modified versions of the Medtronic 3778 Octad.  In contrast to CC stimulation, the combined application of VCCD pulses with a modified Octad resulted in a marked decrease (-73 ± 7.4%) in the stimulation threshold for evoking a CNAP. This was consistent for different myelinated fiber types and locations of stimulation.  The VCCD method provides a highly charge-efficient means of activating myelinated fibers that could potentially be used within a wireless peripheral nerve stimulator system. © 2011 International Neuromodulation Society.

Peripheral neuromodulation: a review.

PubMed

Goroszeniuk, Teodor; Pang, David

2014-05-01

Peripheral nerve stimulation (PNS) is likely the most diverse and rapidly expanding area of neuromodulation. Its expansion has become possible due to both technological and clinical advances in pain medicine. The first implantable systems were surgically placed. However, it is currently commonplace to use percutaneous leads, as this approach has become instrumental in its expansion. The first percutaneous peripheral nerve stimulators were reported in 1999. Cylindrical leads were implanted to stimulate the greater occipital nerve to manage intractable headache. It has been expanded into other individual nerves or nerve plexuses to treat neuropathic, visceral, cardiac, abdominal, low back and facial pain. The use of PNS in modulating organ function in treatment of syndromes such as epilepsy, incontinence and obesity with vagal, tibial and gastric stimulation is under extensive investigation. New technologies that allow easier and safer electrode placement are expected to further expand the uses of PNS. A noninvasive stimulation will open this treatment modality to more clinicians of varying backgrounds.

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

PubMed

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

2011-01-01

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

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

PubMed Central

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

2011-01-01

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

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

PubMed

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

2009-10-01

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

Sciatic Nerve Intrafascicular Lidocaine Injection-induced Peripheral Neuropathic Pain: Alleviation by Systemic Minocycline Administration.

PubMed

Cheng, Kuang-I; Wang, Hung-Chen; Wu, Yi-Chia; Tseng, Kuang-Yi; Chuang, Yi-Ta; Chou, Chao-Wen; Chen, Ping-Luen; Chang, Lin-Li; Lai, Chung-Sheng

2016-06-01

Peripheral nerve block guidance with a nerve stimulator or echo may not prevent intrafascicular injury. This study investigated whether intrafascicular lidocaine induces peripheral neuropathic pain and whether this pain can be alleviated by minocycline administration. A total of 168 male Sprague-Dawley rats were included. In experiment 1, 2% lidocaine (0.1 mL) was injected into the left sciatic nerve. Hindpaw responses to thermal and mechanical stimuli, and sodium channel and activating transcription factor (ATF-3) expression in dorsal root ganglion (DRG) and glial cells in the spinal dorsal horn (SDH), were measured on days 4, 7, 14, 21, and 28. On the basis of the results in experiment 1, rats in experiment 2 were divided into sham, extraneural, intrafascicular, peri-injury minocycline, and postinjury minocycline groups. Behavioral responses, macrophage recruitment, expression changes of myelin basic protein and Schwann cells in the sciatic nerve, dysregulated expression of ATF-3 in the DRG, and activated glial cells in L5 SDH were assessed on days 7 and 14. Intrafascicular lidocaine induced mechanical allodynia, downregulated Nav1.8, increased ATF-3 expression in the DRG, and activated glial cells in the SDH. Increased expression of macrophages, Schwann cells, and myelin basic protein was found in the sciatic nerve. Minocycline attenuated intrafascicular lidocaine-induced neuropathic pain and nerve damage significantly. Peri-injury minocycline was better than postinjury minocycline administration in alleviating mechanical behaviors, mitigating macrophage recruitment into the sciatic nerve, and suppressing activated microglial cells in the spinal cord. Systemic minocycline administration alleviates intrafascicular lidocaine injection-induced peripheral nerve damage.

Electrophysiological measurements of diabetic peripheral neuropathy: A systematic review.

PubMed

Shabeeb, Dheyauldeen; Najafi, Masoud; Hasanzadeh, Gholamreza; Hadian, Mohammed Reza; Musa, Ahmed Eleojio; Shirazi, Alireza

2018-03-28

Peripheral neuropathy is one of the main complications of diabetes mellitus. One of the features of diabetic nerve damage is abnormality of sensory and motor nerve conduction study. An electrophysiological examination can be reproduced and is also a non-invasive approach in the assessment of peripheral nerve function. Population-based and clinical studies have been conducted to validate the sensitivity of these methods. When the diagnosis was based on clinical electrophysiological examination, abnormalities were observed in all patients. In this research, using a review design, we reviewed the issue of clinical electrophysiological examination of diabetic peripheral neuropathy in articles from 2008 to 2017. For this purpose, PubMed, Scopus and Embase databases of journals were used for searching articles. The researchers indicated that diabetes (both types) is a very disturbing health issue in the modern world and should be given serious attention. Based on conducted studies, it was demonstrated that there are different procedures for prevention and treatment of diabetes-related health problems such as diabetic polyneuropathy (DPN). The first objective quantitative indication of the peripheral neuropathy is abnormality of sensory and motor nerve conduction tests. Electrophysiology is accurate, reliable and sensitive. It can be reproduced and also is a noninvasive approach in the assessment of peripheral nerve function. The methodological review has found that the best method for quantitative indication of the peripheral neuropathy compared with all other methods is clinical electrophysiological examination. For best results, standard protocols such as temperature control and equipment calibration are recommended. Copyright © 2018. Published by Elsevier Ltd.

Peripheral Neuropathy in Spinocerebellar Ataxia Type 1, 2, 3, and 6.

PubMed

Linnemann, Christoph; Tezenas du Montcel, Sophie; Rakowicz, Maryla; Schmitz-Hübsch, Tanja; Szymanski, Sandra; Berciano, Jose; van de Warrenburg, Bart P; Pedersen, Karine; Depondt, Chantal; Rola, Rafal; Klockgether, Thomas; García, Antonio; Mutlu, Gurkan; Schöls, Ludger

2016-04-01

Spinocerebellar ataxias (SCAs) are characterized by autosomal dominantly inherited progressive ataxia but are clinically heterogeneous due to variable involvement of non-cerebellar parts of the nervous system. Non-cerebellar symptoms contribute significantly to the burden of SCAs, may guide the clinician to the underlying genetic subtype, and might be useful markers to monitor disease. Peripheral neuropathy is frequently observed in SCA, but subtype-specific features and subclinical manifestations have rarely been evaluated. We performed a multicenter nerve conduction study with 162 patients with genetically confirmed SCA1, SCA2, SCA3, and SCA6. The study proved peripheral nerves to be involved in the neurodegenerative process in 82 % of SCA1, 63 % of SCA2, 55 % of SCA3, and 22 % of SCA6 patients. Most patients of all subtypes revealed affection of both sensory and motor fibers. Neuropathy was most frequently of mixed type with axonal and demyelinating characteristics in all SCA subtypes. However, nerve conduction velocities of SCA1 patients were slower compared to other genotypes. SCA6 patients revealed less axonal damage than patients with other subtypes. No influence of CAG repeat length or biometric determinants on peripheral neuropathy could be identified in SCA1, SCA3, and SCA6. In SCA2, earlier onset and more severe ataxia were associated with peripheral neuropathy. We proved peripheral neuropathy to be a frequent site of the neurodegenerative process in all common SCA subtypes. Since damage to peripheral nerves is readily assessable by electrophysiological means, nerve conduction studies should be performed in a longitudinal approach to assess these parameters as potential progression markers.

Connexin32 expression in central and peripheral nervous systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deschenes, S.M.; Scherer, S.S.; Fischbeck, K.H.

1994-09-01

Mutations have been identified in the gap junction gene, connexin32 (Cx32), in patients affected with the X-linked form of the demyelinating neuropathy, Charcot-Marie-Tooth disease (CMTX). Gap junctions composed of Cx32 are present and developmentally regulated in a wide variety of tissues. In peripheral nerve, our immunohistochemical analysis localized Cx32 to the noncompacted myelin of the paranodal regions and the Schmidt-Lantermann incisures, where previous studies describe gap junctions. In contrast to the location of Cx32 in peripheral nerve and the usual restriction of clinical manifestations to the peripheral nervous system (PNS) (abstract by Paulson describes an exception), preliminary studies show thatmore » Cx32 is present in the compacted myelin of the central nervous system (CNS), as demonstrated by radial staining through the myelin sheath of oligodendrocytes in rat spinal cord. Analysis of Cx32 expression in various regions of rat CNS during development shows that the amount of Cx32 mRNA and protein increases as myelination increases, a pattern observed for other myelin genes. Studies in the PNS provide additional evidence that Cx32 and myelin genes are coordinately regulated at the transcriptional level; Cx32 and peripheral myelin gene PMP-22 mRNAs are expressed in parallel following transient or permanent nerve injury. Differences in post-translational regulation of Cx32 in the CNS and PNS may be indicated by the presence of a faster migrating form of Cs32 in cerebrum versus peripheral nerve. Studies are currently underway to determine the unique role of Cx32 in peripheral nerve.« less

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

NASA Astrophysics Data System (ADS)

Vasudevan, Srikanth; Patel, Kunal; Welle, Cristin

2017-02-01

Objective. In the US alone, there are approximately 185 000 cases of limb amputation annually, which can reduce the quality of life for those individuals. Current prosthesis technology could be improved by access to signals from the nervous system for intuitive prosthesis control. After amputation, residual peripheral nerves continue to convey motor signals and electrical stimulation of these nerves can elicit sensory percepts. However, current technology for extracting information directly from peripheral nerves has limited chronic reliability, and novel approaches must be vetted to ensure safe long-term use. The present study aims to optimize methods to establish a test platform using rodent model to assess the long term safety and performance of electrode interfaces implanted in the peripheral nerves. Approach. Floating Microelectrode Arrays (FMA, Microprobes for Life Sciences) were implanted into the rodent sciatic nerve. Weekly in vivo recordings and impedance measurements were performed in animals to assess performance and physical integrity of electrodes. Motor (walking track analysis) and sensory (Von Frey) function tests were used to assess change in nerve function due to the implant. Following the terminal recording session, the nerve was explanted and the health of axons, myelin and surrounding tissues were assessed using immunohistochemistry (IHC). The explanted electrodes were visualized under high magnification using scanning electrode microscopy (SEM) to observe any physical damage. Main results. Recordings of axonal action potentials demonstrated notable session-to-session variability. Impedance of the electrodes increased upon implantation and displayed relative stability until electrode failure. Initial deficits in motor function recovered by 2 weeks, while sensory deficits persisted through 6 weeks of assessment. The primary cause of failure was identified as lead wire breakage in all of animals. IHC indicated myelinated and unmyelinated axons near the implanted electrode shanks, along with dense cellular accumulations near the implant site. Scanning electron microscopy (SEM) showed alterations of the electrode insulation and deformation of electrode shanks. Significance. We describe a comprehensive testing platform with applicability to electrodes that record from the peripheral nerves. This study assesses the long term safety and performance of electrodes in the peripheral nerves using a rodent model. Under this animal test platform, FMA electrodes record single unit action potentials but have limited chronic reliability due to structural weaknesses. Future work will apply these methods to other commercially-available and novel peripheral electrode technologies. This research was carried out in the Division of Biomedical Physics, Office of Science and Engineering Laboratory, Center for Devices and Radiological Health, US Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA.

Quantifying Demyelination in NK venom treated nerve using its electric circuit model

NASA Astrophysics Data System (ADS)

Das, H. K.; Das, D.; Doley, R.; Sahu, P. P.

2016-03-01

Reduction of myelin in peripheral nerve causes critical demyelinating diseases such as chronic inflammatory demyelinating polyneuropathy, Guillain-Barre syndrome, etc. Clinical monitoring of these diseases requires rapid and non-invasive quantification of demyelination. Here we have developed formulation of nerve conduction velocity (NCV) in terms of demyelination considering electric circuit model of a nerve having bundle of axons for its quantification from NCV measurements. This approach has been validated and demonstrated with toad nerve model treated with crude Naja kaouthia (NK) venom and also shows the effect of Phospholipase A2 and three finger neurotoxin from NK-venom on peripheral nerve. This opens future scope for non-invasive clinical measurement of demyelination.

Quantifying Demyelination in NK venom treated nerve using its electric circuit model

PubMed Central

Das, H. K.; Das, D.; Doley, R.; Sahu, P. P.

2016-01-01

Reduction of myelin in peripheral nerve causes critical demyelinating diseases such as chronic inflammatory demyelinating polyneuropathy, Guillain-Barre syndrome, etc. Clinical monitoring of these diseases requires rapid and non-invasive quantification of demyelination. Here we have developed formulation of nerve conduction velocity (NCV) in terms of demyelination considering electric circuit model of a nerve having bundle of axons for its quantification from NCV measurements. This approach has been validated and demonstrated with toad nerve model treated with crude Naja kaouthia (NK) venom and also shows the effect of Phospholipase A2 and three finger neurotoxin from NK-venom on peripheral nerve. This opens future scope for non-invasive clinical measurement of demyelination. PMID:26932543

Quantifying Demyelination in NK venom treated nerve using its electric circuit model.

PubMed

Das, H K; Das, D; Doley, R; Sahu, P P

2016-03-02

Reduction of myelin in peripheral nerve causes critical demyelinating diseases such as chronic inflammatory demyelinating polyneuropathy, Guillain-Barre syndrome, etc. Clinical monitoring of these diseases requires rapid and non-invasive quantification of demyelination. Here we have developed formulation of nerve conduction velocity (NCV) in terms of demyelination considering electric circuit model of a nerve having bundle of axons for its quantification from NCV measurements. This approach has been validated and demonstrated with toad nerve model treated with crude Naja kaouthia (NK) venom and also shows the effect of Phospholipase A2 and three finger neurotoxin from NK-venom on peripheral nerve. This opens future scope for non-invasive clinical measurement of demyelination.

Dexamethasone as Adjuvant to Bupivacaine Prolongs the Duration of Thermal Antinociception and Prevents Bupivacaine-Induced Rebound Hyperalgesia via Regional Mechanism in a Mouse Sciatic Nerve Block Model

PubMed Central

An, Ke; Elkassabany, Nabil M.; Liu, Jiabin

2015-01-01

Background Dexamethasone has been studied as an effective adjuvant to prolong the analgesia duration of local anesthetics in peripheral nerve block. However, the route of action for dexamethasone and its potential neurotoxicity are still unclear. Methods A mouse sciatic nerve block model was used. The sciatic nerve was injected with 60ul of combinations of various medications, including dexamethasone and/or bupivacaine. Neurobehavioral changes were observed for 2 days prior to injection, and then continuously for up to 7 days after injection. In addition, the sciatic nerves were harvested at either 2 days or 7 days after injection. Toluidine blue dyeing and immunohistochemistry test were performed to study the short-term and long-term histopathological changes of the sciatic nerves. There were six study groups: normal saline control, bupivacaine (10mg/kg) only, dexamethasone (0.5mg/kg) only, bupivacaine (10mg/kg) combined with low-dose (0.14mg/kg) dexamethasone, bupivacaine (10mg/kg) combined with high-dose (0.5mg/kg) dexamethasone, and bupivacaine (10mg/kg) combined with intramuscular dexamethasone (0.5mg/kg). Results High-dose perineural dexamethasone, but not systemic dexamethasone, combined with bupivacaine prolonged the duration of both sensory and motor block of mouse sciatic nerve. There was no significant difference on the onset time of the sciatic nerve block. There was “rebound hyperalgesia” to thermal stimulus after the resolution of plain bupivacaine sciatic nerve block. Interestingly, both low and high dose perineural dexamethasone prevented bupivacaine-induced hyperalgesia. There was an early phase of axon degeneration and Schwann cell response as represented by S-100 expression as well as the percentage of demyelinated axon and nucleus in the plain bupivacaine group compared with the bupivacaine plus dexamethasone groups on post-injection day 2, which resolved on post-injection day 7. Furthermore, we demonstrated that perineural dexamethasone, but not systemic dexamethasone, could prevent axon degeneration and demyelination. There was no significant caspase-dependent apoptosis process in the mouse sciatic nerve among all study groups during our study period. Conclusions Perineural, not systemic, dexamethasone added to a clinical concentration of bupivacaine may not only prolong the duration of sensory and motor blockade of sciatic nerve, but also prevent the bupivacaine-induced reversible neurotoxicity and short-term “rebound hyperalgesia” after the resolution of nerve block. PMID:25856078

Inhibition of KLF7-Targeting MicroRNA 146b Promotes Sciatic Nerve Regeneration.

PubMed

Li, Wen-Yuan; Zhang, Wei-Ting; Cheng, Yong-Xia; Liu, Yan-Cui; Zhai, Feng-Guo; Sun, Ping; Li, Hui-Ting; Deng, Ling-Xiao; Zhu, Xiao-Feng; Wang, Ying

2018-06-01

A previous study has indicated that Krüppel-like factor 7 (KLF7), a transcription factor that stimulates Schwann cell (SC) proliferation and axonal regeneration after peripheral nerve injury, is a promising therapeutic transcription factor in nerve injury. We aimed to identify whether inhibition of microRNA-146b (miR-146b) affected SC proliferation, migration, and myelinated axon regeneration following sciatic nerve injury by regulating its direct target KLF7. SCs were transfected with miRNA lentivirus, miRNA inhibitor lentivirus, or KLF7 siRNA lentivirus in vitro. The expression of miR146b and KLF7, as well as SC proliferation and migration, were subsequently evaluated. In vivo, an acellular nerve allograft (ANA) followed by injection of GFP control vector or a lentiviral vector encoding an miR-146b inhibitor was used to assess the repair potential in a model of sciatic nerve gap. miR-146b directly targeted KLF7 by binding to the 3'-UTR, suppressing KLF7. Up-regulation of miR-146b and KLF7 knockdown significantly reduced the proliferation and migration of SCs, whereas silencing miR-146b resulted in increased proliferation and migration. KLF7 protein was localized in SCs in which miR-146b was expressed in vivo. Similarly, 4 weeks after the ANA, anti-miR-146b increased KLF7 and its target gene nerve growth factor cascade, promoting axonal outgrowth. Closer analysis revealed improved nerve conduction and sciatic function index score, and enhanced expression of neurofilaments, P0 (anti-peripheral myelin), and myelinated axon regeneration. Our findings provide new insight into the regulation of KLF7 by miR-146b during peripheral nerve regeneration and suggest a potential therapeutic strategy for peripheral nerve injury.

Peripheral nerve regeneration using a microporous polylactic acid asymmetric conduit in a rabbit long-gap sciatic nerve transection model.

PubMed

Hsu, Shan-Hui; Chan, Shan-Ho; Chiang, Chih-Ming; Chen, Clayton Chi-Chang; Jiang, Ching-Fen

2011-05-01

The performance of an asymmetric conduit made of microporous polylactic acid (PLA) in promoting the long-term peripheral nerve regeneration across a 20-mm-long sciatic nerve gap was evaluated by a rabbit sciatic nerve transection model. Magnetic resonance imaging (MRI) was employed to monitor the nerve regeneration process. The extents of nerve regeneration and conduit degradation were quantified by image analysis. Functional and histological analyses were followed to assess nerve reinnervation. MR images showed that the transected nerve was connected at about 4 months. The diameter of the regenerated nerve continued to increase while the conduit was gradually degraded. The conduit was completely degraded in 18 months. The degradation kinetics in vivo was estimated based on MR images. The functional recovery after 18 months was ∼82% based on electrophysiology. The extension range of the operated limb was slowly recuperated to ∼81% at 18 months. Histology showed that nerve bundles were self-assembled after 16-18 months, but the morphologies were still different from those of normal sciatic nerve. This was the first work on the long-term evaluation of peripheral nerve regeneration in a rabbit model, and the first to report the use of MRI to obtain the real-time images of regenerated nerve in a biomaterial conduit as well as to define the degradation rate of the conduit in vivo. The platform established in this study serves to evaluate the regeneration of larger-diameter (>3-mm) nerve across a long-gap bridged by a conduit. Copyright © 2011 Elsevier Ltd. All rights reserved.

The course of the greater occipital nerve in the suboccipital region: a proposal for setting landmarks for local anesthesia in patients with occipital neuralgia.

PubMed

Natsis, K; Baraliakos, X; Appell, H J; Tsikaras, P; Gigis, I; Koebke, J

2006-05-01

The anatomical relationships of the greater occipital nerve (GON) to the semispinalis capitis muscle (SCM) and the trapezius muscle aponeurosis (TMA) were examined to identify topographic landmarks for use in anesthetic blockade of the GON in occipital neuralgia. The course and the diameter of the GON were studied in 40 cadavers (29 females, 11 males), and the points where it pierced the SCM and the TMA were identified. The course of the GON did not differ between males and females. A left-right difference was detected in the site of the GON in the TMA region but not in the SCM region. The nerve became wider towards the periphery. This may be relevant to entrapment of the nerve in the development of occipital neuralgia. In three cases, the GON split into two branches before piercing the TMA and reunited after having passed the TMA, and it pierced the obliquus capitis inferior muscle in another three cases. The GON and the lesser occipital nerve reunited at the level of the occiput in 80% of the specimens. The occiput and the nuchal midline are useful topographic landmarks to guide anesthetic blockade of the GON for diagnosis and therapy of occipital neuralgia. The infiltration is probably best aimed at the site where the SCM is pierced by the GON.

Sapanisertib or Pazopanib Hydrochloride in Treating Patients With Locally Advanced or Metastatic Sarcoma

ClinicalTrials.gov

2018-06-20

High Grade Sarcoma; Metastatic Leiomyosarcoma; Metastatic Malignant Peripheral Nerve Sheath Tumor; Metastatic Synovial Sarcoma; Metastatic Undifferentiated Pleomorphic Sarcoma; Myxofibrosarcoma; Recurrent Leiomyosarcoma; Recurrent Malignant Peripheral Nerve Sheath Tumor; Recurrent Synovial Sarcoma; Recurrent Undifferentiated Pleomorphic Sarcoma; Uterine Corpus Leiomyosarcoma

Optimal conditions for peripheral nerve storage in green tea polyphenol: an experimental study in animals.

PubMed

Matsumoto, Taiichi; Kakinoki, Ryosuke; Ikeguchi, Ryosuke; Hyon, Suong-Hyu; Nakamura, Takashi

2005-06-30

Our previous study demonstrated successful peripheral nerve storage for 1 month using polyphenol solution. We here report two studies to solve residual problems in using polyphenols as a storage solution for peripheral nerves. Study 1 was designed to determine the optimal concentration of the polyphenol solution and the optimal immersion period for nerve storage. Rat sciatic nerve segments were immersed in polyphenol solution at three different concentrations (2.5, 1.0, and 0.5 mg/ml) for three different periods (1, 7, and 26 days). Electrophysiological and morphological studies demonstrated that nerve regeneration from nerve segments that had been immersed in 1mg/ml polyphenol solution for 1 week and in Dulbecco's modified Eagle's medium (DMEM) for the subsequent 3 weeks was superior to the regeneration in other treatment groups. In study 2, the permeability of nerve tissue to polyphenol solution was investigated using canine sciatic nerve segments stored in 1.0mg/ml polyphenol solution for 1 week and in DMEM for the subsequent 3 weeks. Electron microscopy revealed that the Schwann cell structure within 500-700 microm of the perineurium was preserved, but cells deeper than 500-700 microm were badly damaged or had disappeared. The infiltration limit for polyphenol solution into neural tissue is inferred to be 500-700 microm.

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

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. © 2011 Peripheral Nerve Society.

Review: peripheral nerve regeneration using non-tubular alginate gel crosslinked with covalent bonds.

PubMed

Hashimoto, Tadashi; Suzuki, Yoshihisa; Suzuki, Kyoko; Nakashima, Toshihide; Tanihara, Masao; Ide, Chizuka

2005-06-01

We have developed a nerve regeneration material consisting of alginate gel crosslinked with covalent bonds. in the first part of this study, we attempted to analyze nerve regeneration through alginate gel in the early stages within 2 weeks. in the second part, we tried to regenerate cat peripheral nerve by using alginate tubular or non-tubular nerve regeneration devices, and compared their efficacies. Four days after surgery, regenerating axons grew without Schwann cell investment through the partially degraded alginate gel, being in direct contact with the alginate without a basal lamina covering. One to 2 weeks after surgery, regenerating axons were surrounded by common Schwann cells, forming small bundles, with some axons at the periphery being partly in direct contact with alginate. At the distal stump, numerous Schwann cells had migrated into the alginate 8-14 days after surgery. Remarkable restorations of the 50-mm gap in cat sciatic nerve were obtained after a long term by using tubular or non-tubular nerve regeneration material consisting mainly of alginate gel. However, there was no significant difference between both groups at electrophysiological and morphological evaluation. Although, nowadays, nerve regeneration materials being marketed mostly have a tubular structure, our results suggest that the tubular structure is not indispensable for peripheral nerve regeneration.

Malignant nerve sheath tumor involving glossopharyngeal, vagus and spinal nerve with intracranial-extracranial extension and systemic metastases in a patient with type 1 neurofibromatosis: A case report.

PubMed

Guerra-Mora, José Raúl; Del Castillo-Calcáneo, Juan D; Córdoba-Mosqueda, María Elena; Yáñez-Castro, Jorge; García-González, Ulises; Soriano-Navarro, Eduardo; Llamas-Ceras, Leticia; Vicuña-González, Rosa María

2016-01-01

Intracranial malignant peripheral nerve sheath tumors are an extremely rare pathology with a high morbidity and mortality. Epidemiological, clinical and prognostic data are scarce and with little certainty in the literature. The aim of this paper is to report for first time in English literature, the case of a patient with type 1 neurofibromatosis, who presented a malignant peripheral nerve sheath tumor that involved the left glossopharyngeal, vagus and spinal nerves with intracranial and extracranial extension through jugular foramen and systemic metastases. A 37 years-old female patient with malnutrition and Villaret́s syndrome. It was confirmed by brain magnetic resonance imaging and PET-CT the presence of a neoplasic lesion which was radiologically compatible with malignant peripheral nerve sheath tumor with systemic metastases. Partial surgical resection was performed; the patient postoperative course was without significant clinical improvement but with added peripheral facial palsy. The patient did not accept adjuvant management because of personal reasons. Behavior therapy is unclear due to the low frequency of the disease and the lack of case series, representing a challenge for the physician in its approach and a poor prognosis for the patient. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Role of Netrin-1 Signaling in Nerve Regeneration

PubMed Central

Dun, Xin-Peng; Parkinson, David B.

2017-01-01

Netrin-1 was the first axon guidance molecule to be discovered in vertebrates and has a strong chemotropic function for axonal guidance, cell migration, morphogenesis and angiogenesis. It is a secreted axon guidance cue that can trigger attraction by binding to its canonical receptors Deleted in Colorectal Cancer (DCC) and Neogenin or repulsion through binding the DCC/Uncoordinated (Unc5) A–D receptor complex. The crystal structures of Netrin-1/receptor complexes have recently been revealed. These studies have provided a structure based explanation of Netrin-1 bi-functionality. Netrin-1 and its receptor are continuously expressed in the adult nervous system and are differentially regulated after nerve injury. In the adult spinal cord and optic nerve, Netrin-1 has been considered as an inhibitor that contributes to axon regeneration failure after injury. In the peripheral nervous system, Netrin-1 receptors are expressed in Schwann cells, the cell bodies of sensory neurons and the axons of both motor and sensory neurons. Netrin-1 is expressed in Schwann cells and its expression is up-regulated after peripheral nerve transection injury. Recent studies indicated that Netrin-1 plays a positive role in promoting peripheral nerve regeneration, Schwann cell proliferation and migration. Targeting of the Netrin-1 signaling pathway could develop novel therapeutic strategies to promote peripheral nerve regeneration and functional recovery. PMID:28245592

Lycium barbarum polysaccharide encapsulated Poly lactic-co-glycolic acid Nanofibers: cost effective herbal medicine for potential application in peripheral nerve tissue engineering.

PubMed

Wang, Jing; Tian, Lingling; He, Liumin; Chen, Nuan; Ramakrishna, Seeram; So, Kwok-Fai; Mo, Xiumei

2018-06-06

Nerve regeneration is a serious clinical challenge following peripheral nerve injury. Lycium barbarum polysaccharide (LBP) is the major component of wolfberry extract, which has been shown to be neuroprotective and promising in nerve recovery in many studies. Electrospun nanofibers, especially core-shell structured nanofibers being capable of serving as both drug delivery system and tissue engineering scaffolds, are well known to be suitable scaffolds for regeneration of peripheral nerve applications. In this study, LBP was incorporated into core-shell structured nanofibrous scaffolds via coaxial electrospinning. Alamar blue assays were performed to investigate the proliferation of both PC12 and Schwann cells cultured on the scaffolds. The neuronal differentiation of PC12 cells was evaluated by NF200 expression with immunostaining and morphology changes observed by SEM. The results indicated that the released LBP dramatically enhanced both proliferation and neuronal differentiation of PC12 cells induced by NGF. Additionally, the promotion of Schwann cells myelination and neurite outgrowth of DRG neurons were also observed on LBP loaded scaffolds by LSCM with immunostaining. In summary, LBP, as a drug with neuroprotection, encapsulated into electrospun nanofibers could be a potential candidate as tissue engineered scaffold for peripheral nerve regeneration.

Sandwich technique, peripheral nerve stimulation, peripheral field stimulation and hybrid stimulation for inguinal region and genital pain.

PubMed

Shaw, Andrew; Sharma, Mayur; Zibly, Zion; Ikeda, Daniel; Deogaonkar, Milind

2016-12-01

Ilioinguinal neuralgia (IG) and genitofemoral (GF) neuralgia following inguinal hernia repair is a chronic and debilitating neuropathic condition. Recently, peripheral nerve stimulation has become an effective and minimally invasive option for the treatment of refractory pain. Here we present a retrospective case series of six patients who underwent placement of peripheral nerve stimulation electrodes using various techniques for treatment of refractory post-intervention inguinal region pain. Six patients with post-intervention inguinal, femoral or GF neuropathic pain were evaluated for surgery. Either octopolar percutaneous electrodes or combination of paddle and percutaneous electrodes were implanted in the area of their pain. Pain visual analog scores (VAS), surgical complication rate, preoperative symptom duration, degree of pain relief, preoperative and postoperative work status, postoperative changes in medication usage, and overall degree of satisfaction with this therapy was assessed. All six patients had an average improvement of 62% in the immediate post-operative follow-up. Four patients underwent stimulation for IG, one for femoral neuralgia, and another for GF neuralgia. Peripheral nerve stimulation provided at least 50% pain relief in all the six patients with post-intervention inguinal region pain. 85% of patients indicated they were completely satisfied with the therapy overall. There was one treatment failure with an acceptable complication rate. Peripheral nerve or field stimulation for post-intervention inguinal region pain is a safe and effective treatment for this refractory and complex problem for patients who have exhausted other management options.

Premature aging-related peripheral neuropathy in a mouse model of progeria.

PubMed

Goss, James R; Stolz, Donna Beer; Robinson, Andria Rasile; Zhang, Mingdi; Arbujas, Norma; Robbins, Paul D; Glorioso, Joseph C; Niedernhofer, Laura J

2011-08-01

Peripheral neuropathy is a common aging-related degenerative disorder that interferes with daily activities and leads to increased risk of falls and injury in the elderly. The etiology of most aging-related peripheral neuropathy is unknown. Inherited defects in several genome maintenance mechanisms cause tissue-specific accelerated aging, including neurodegeneration. We tested the hypothesis that a murine model of XFE progeroid syndrome, caused by reduced expression of ERCC1-XPF DNA repair endonuclease, develops peripheral neuropathy. Nerve conduction studies revealed normal nerve function in young adult (8 week) Ercc1(-/Δ) mice, but significant abnormalities in 20 week-old animals. Morphologic and ultrastructural analysis of the sciatic nerve from mutant mice revealed significant alterations at 20 but not 8 weeks of age. We conclude that Ercc1(-/Δ) mice have accelerated spontaneous peripheral neurodegeneration that mimics aging-related disease. This provides strong evidence that DNA damage can drive peripheral neuropathy and offers a rapid and novel model to test therapies. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

PAR(2) and temporomandibular joint inflammation in the rat.

PubMed

Denadai-Souza, A; Cenac, N; Casatti, C A; Câmara, P R de Souza; Yshii, L M; Costa, S K P; Vergnolle, N; Muscará, M N

2010-10-01

The proteinase-activated receptor 2 (PAR(2)) is a putative therapeutic target for arthritis. We hypothesized that the early pro-inflammatory effects secondary to its activation in the temporomandibular joint (TMJ) are mediated by neurogenic mechanisms. Immunofluorescence analysis revealed a high degree of neurons expressing PAR(2) in retrogradely labeled trigeminal ganglion neurons. Furthermore, PAR(2) immunoreactivity was observed in the lining layer of the TMJ, co-localizing with the neuronal marker PGP9.5 and substance-P-containing peripheral sensory nerve fibers. The intra-articular injection of PAR(2) agonists into the TMJ triggered a dose-dependent increase in plasma extravasation, neutrophil influx, and induction of mechanical allodynia. The pharmacological blockade of natural killer 1 (NK(1)) receptors abolished PAR(2)-induced plasma extravasation and inhibited neutrophil influx and mechanical allodynia. We conclude that PAR(2) activation is pro-inflammatory in the TMJ, through a neurogenic mechanism involving NK(1) receptors. This suggests that PAR(2) is an important component of innate neuro-immune response in the rat TMJ.

Local Anesthetic Systemic Toxicity: A Review of Recent Case Reports and Registries.

PubMed

Gitman, Marina; Barrington, Michael J

2018-02-01

This review summarizes presenting features, management, and outcomes of local anesthetic systemic toxicity (LAST) from published cases and those submitted to online registries capturing use of intravenous lipid emulsion (ILE) therapy. The results of single-center and multicenter registries and epidemiologic studies complement this information. Between March 2014 and November 2016, 47 separate cases of LAST were described in 35 peer-reviewed articles. Local anesthetic systemic toxicity events occurred as a result of penile blocks (23%), local infiltration (17%), and upper/lower extremity, torso, and neuraxial blockade. Twenty-two patients (47%) were treated with ILE, and 2 patients (4.3%) died. During the same time period, 11 cases submitted to lipidrescue.org were treated with ILE and survived. The incidence of LAST reported in registries is 0.03% or 0.27 (95% confidence interval, 0.21-0.35) per 1000 peripheral nerve blocks (denominator of 251,325). Seizure (53% and 61% from case reports and registries, respectively) was the most common presenting feature.

In vitro and ex vivo screening of candidate therapeutics to restore neurotransmission in nerve terminals intoxicated by botulinum neurotoxin serotype A1.

PubMed

Beske, Phillip H; Bradford, Aaron B; Hoffman, Katie M; Mason, Sydney J; McNutt, Patrick M

2018-06-01

Botulinum neurotoxins (BoNTs) are exceedingly potent neurological poisons that block cholinergic release in the peripheral nervous system and cause death by asphyxiation. While post-exposure prophylaxis can effectively eliminate toxin in the bloodstream, there are no clinically effective treatments to prevent or reverse disease once BoNT has entered the neuron. To address the need for post-symptomatic countermeasures, we designed and developed an in vitro assay based on whole-cell, patch-clamp electrophysiological monitoring of miniature excitatory post-synaptic currents in synaptically active murine embryonic stem cell-derived neurons. This synaptic function-based assay was used to assess the efficacy of rationally selected drugs to restore neurotransmission in neurons comprehensively intoxicated by BoNT/A. Based on clinical reports suggesting that elevated Ca 2+ signaling promotes symptomatic relief from botulism, we identified seven candidate drugs that modulate presynaptic Ca 2+ signaling and assessed their ability to reverse BoNT/A-induced synaptic blockade. The most effective drugs from the screen were found to phasically agonize voltage-gated calcium channel (VGCC) activity. Lead candidates were then applied to ex vivo studies in BoNT/A-paralyzing mouse phrenic nerve-hemidiaphragm (PND) preparations. Treatment of PNDs with VGCC agonists after paralytic onset transiently potentiated nerve-elicited muscle contraction and delayed progression to neuromuscular failure. Collectively, this study suggests that Ca 2+ -modulating drugs represent a novel symptomatic treatment for neuromuscular paralysis following BoNT/A poisoning. Published by Elsevier Ltd.

Tissue engineering and peripheral nerve reconstruction: an overview.

PubMed

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

2013-01-01

Nerve repair is no more regarded as merely a matter of microsurgical reconstruction. To define this evolving reconstructive/regenerative approach, the term tissue engineering is being increasingly used since it reflects the search for interdisciplinary and integrated treatment strategies. However, the drawback of this new approach is its intrinsic complexity, which is the result of the variety of scientific disciplines involved. This chapter presents a synthetic overview of the state of the art in peripheral nerve tissue engineering with a look forward at the most promising innovations emerging from basic science investigation. This review is intended to set the stage for the collection of papers in the thematic issue of the International Review of Neurobiology that is focused on the various interdisciplinary approaches in peripheral nerve tissue engineering. © 2013 Elsevier Inc. All rights reserved.

The gut-brain axis rewired: adding a functional vagal nicotinic "sensory synapse".

PubMed

Perez-Burgos, Azucena; Mao, Yu-Kang; Bienenstock, John; Kunze, Wolfgang A

2014-07-01

It is generally accepted that intestinal sensory vagal fibers are primary afferent, responding nonsynaptically to luminal stimuli. The gut also contains intrinsic primary afferent neurons (IPANs) that respond to luminal stimuli. A psychoactive Lactobacillus rhamnosus (JB-1) that affects brain function excites both vagal fibers and IPANs. We wondered whether, contrary to its primary afferent designation, the sensory vagus response to JB-1 might depend on IPAN to vagal fiber synaptic transmission. We recorded ex vivo single- and multiunit afferent action potentials from mesenteric nerves supplying mouse jejunal segments. Intramural synaptic blockade with Ca(2+) channel blockers reduced constitutive or JB-1-evoked vagal sensory discharge. Firing of 60% of spontaneously active units was reduced by synaptic blockade. Synaptic or nicotinic receptor blockade reduced firing in 60% of vagal sensory units that were stimulated by luminal JB-1. In control experiments, increasing or decreasing IPAN excitability, respectively increased or decreased nerve firing that was abolished by synaptic blockade or vagotomy. We conclude that >50% of vagal afferents function as interneurons for stimulation by JB-1, receiving input from an intramural functional "sensory synapse." This was supported by myenteric plexus nicotinic receptor immunohistochemistry. These data offer a novel therapeutic target to modify pathological gut-brain axis activity.-Perez-Burgos, A., Mao, Y.-K., Bienenstock, J., Kunze, W. A. The gut-brain axis rewired: adding a functional vagal nicotinic "sensory synapse." © FASEB.

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

PubMed

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

2014-09-01

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

Arterial and venous plasma levels of bupivacaine following peripheral nerve blocks.

PubMed

Moore, D C; Mather, L E; Bridenbaugh, L D; Balfour, R I; Lysons, D F; Horton, W G

1976-01-01

Mean arterial plasma (MAP) and peripheral mean venous plasma (MVP) levels of bupivacaine were ascertained in 3 groups of 10 patients each for: (1) intercostal nerve block, 400 mg; (2) block of the sciatic, femoral, and lateral femoral cutaneous nerves, with or without block of the obturator nerve, 400 mg; and (3) supraclavicular brachial plexus block, 300 mg. MAP levels were consistently higher than simultaneously sampled MVP levels, the highest levels occurring from bilateral intercostal nerve block. No evidence of systemic toxicity was observed. The results suggest that bupivacaine has a much wider margin of safety in humans than is now stated.

Occipital neuralgia.

PubMed

Dougherty, Carrie

2014-05-01

Occipital pain is a common complaint amongst patients with headache, and the differential can include many primary headache disorders such as cervicogenic headache or migraine. Occipital neuralgia is an uncommon cause of occipital pain characterized by paroxysmal lancinating pain in the distribution of the greater, lesser or third occipital nerves. Greater occipital nerve blockade with anesthetics and/or corticosteroids can aid in confirming the diagnosis and providing pain relief. However, nerve blocks are also effective in migraine headache and misdiagnosis can result in a false positive. Physical therapy and preventive medication with antiepileptics and tricyclic antidepressants are often effective treatments for occipital neuralgia. Refractory cases may require intervention with pulsed radiofrequency or occipital nerve stimulation.

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

PubMed

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

2018-06-01

Decellularized matrix hydrogels derived from tissues or organs have been used for tissue repair due to their biocompatibility, tunability, and tissue-specific extracellular matrix (ECM) components. However, the preparation of decellularized peripheral nerve matrix hydrogels and their use to repair nerve defects have not been reported. Here, we developed a hydrogel from porcine decellularized nerve matrix (pDNM-G), which was confirmed to have minimal DNA content and retain collagen and glycosaminoglycans content, thereby allowing gelatinization. The pDNM-G exhibited a nanofibrous structure similar to that of natural ECM, and a ∼280-Pa storage modulus at 10 mg/mL similar to that of native neural tissues. Western blot and liquid chromatography tandem mass spectrometry analysis revealed that the pDNM-G consisted mostly of ECM proteins and contained primary ECM-related proteins, including fibronectin and collagen I and IV). In vitro experiments showed that pDNM-G supported Schwann cell proliferation and preserved cell morphology. Additionally, in a 15-mm rat sciatic nerve defect model, pDNM-G was combined with electrospun poly(lactic-acid)-co-poly(trimethylene-carbonate)conduits to bridge the defect, which did not elicit an adverse immune response and promoted the activation of M2 macrophages associated with a constructive remodeling response. Morphological analyses and electrophysiological and functional examinations revealed that the regenerative outcomes achieved by pDNM-G were superior to those by empty conduits and closed to those using rat decellularized nerve matrix allograft scaffolds. These findings indicated that pDNM-G, with its preserved ECM composition and nanofibrous structure, represents a promising biomaterial for peripheral nerve regeneration. Decellularized nerve allografts have been widely used to treat peripheral nerve injury. However, given their limited availability and lack of bioactive factors, efforts have been made to improve the efficacy of decellularized nerve allograft for nerve regeneration, with limited success. Xenogeneic decellularized tissue matrices or hydrogels have been widely used for surgical applications owing to their ease of harvesting and low immunogenicity. Moreover, decellularized tissue matrix hydrogels show good biocompatibility and are highly tunable. In this study, we prepared a porcine decellularized nerve matrix (pDNM-G) and evaluated its potential for promoting nerve regeneration. Our results demonstrate that pDNM-G can support Schwann cell proliferation and peripheral nerve regeneration by means of residual primary extracellular matrix components and nano-fibrous structure features. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Remodeling of peripheral nerve ensheathment during the larval-to-adult transition in Drosophila.

PubMed

Subramanian, Aswati; Siefert, Matthew; Banerjee, Soumya; Vishal, Kumar; Bergmann, Kayla A; Curts, Clay C M; Dorr, Meredith; Molina, Camillo; Fernandes, Joyce

2017-10-01

Over the course of a 4-day period of metamorphosis, the Drosophila larval nervous system is remodeled to prepare for adult-specific behaviors. One example is the reorganization of peripheral nerves in the abdomen, where five pairs of abdominal nerves (A4-A8) fuse to form the terminal nerve trunk. This reorganization is associated with selective remodeling of four layers that ensheath each peripheral nerve. The neural lamella (NL), is the first to dismantle; its breakdown is initiated by 6 hours after puparium formation, and is completely removed by the end of the first day. This layer begins to re-appear on the third day of metamorphosis. Perineurial glial (PG) cells situated just underneath the NL, undergo significant proliferation on the first day of metamorphosis, and at that stage contribute to 95% of the glial cell population. Cells of the two inner layers, Sub-Perineurial Glia (SPG) and Wrapping Glia (WG) increase in number on the second half of metamorphosis. Induction of cell death in perineurial glia via the cell death gene reaper and the Diptheria toxin (DT-1) gene, results in abnormal bundling of the peripheral nerves, suggesting that perineurial glial cells play a role in the process. A significant number of animals fail to eclose in both reaper and DT-1 targeted animals, suggesting that disruption of PG also impacts eclosion behavior. The studies will help to establish the groundwork for further work on cellular and molecular processes that underlie the co-ordinated remodeling of glia and the peripheral nerves they ensheath. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1144-1160, 2017. © 2017 Wiley Periodicals, Inc.

Regenerative effects of human embryonic stem cell-derived neural crest cells for treatment of peripheral nerve injury.

PubMed

Jones, Iwan; Novikova, Liudmila N; Novikov, Lev N; Renardy, Monika; Ullrich, Andreas; Wiberg, Mikael; Carlsson, Leif; Kingham, Paul J

2018-04-01

Surgical intervention is the current gold standard treatment following peripheral nerve injury. However, this approach has limitations, and full recovery of both motor and sensory modalities often remains incomplete. The development of artificial nerve grafts that either complement or replace current surgical procedures is therefore of paramount importance. An essential component of artificial grafts is biodegradable conduits and transplanted cells that provide trophic support during the regenerative process. Neural crest cells are promising support cell candidates because they are the parent population to many peripheral nervous system lineages. In this study, neural crest cells were differentiated from human embryonic stem cells. The differentiated cells exhibited typical stellate morphology and protein expression signatures that were comparable with native neural crest. Conditioned media harvested from the differentiated cells contained a range of biologically active trophic factors and was able to stimulate in vitro neurite outgrowth. Differentiated neural crest cells were seeded into a biodegradable nerve conduit, and their regeneration potential was assessed in a rat sciatic nerve injury model. A robust regeneration front was observed across the entire width of the conduit seeded with the differentiated neural crest cells. Moreover, the up-regulation of several regeneration-related genes was observed within the dorsal root ganglion and spinal cord segments harvested from transplanted animals. Our results demonstrate that the differentiated neural crest cells are biologically active and provide trophic support to stimulate peripheral nerve regeneration. Differentiated neural crest cells are therefore promising supporting cell candidates to aid in peripheral nerve repair. © 2018 The Authors. Journal of Tissue Engineering and Regenerative Medicine published by John Wiley & Sons, Ltd.

Six cases of sporadic schwannomatosis: Topographic distribution and outcomes of peripheral nerve tumors.

PubMed

Chick, G; Victor, J; Hollevoet, N

2017-10-01

The diagnosis of schwannomatosis is often overestimated and is based on the existence of multiple peripheral nerve tumors composed exclusively of schwannomas, in the absence of clinical signs of neurofibromatosis type 2 (NF2). Sporadic forms are much more frequent than familial forms. The objective of this study was to describe the distribution of peripheral nerve tumors and investigate the outcomes of schwannomas in the context of sporadic schwannomatosis. We conducted a retrospective study of patients who fulfilled clinical diagnostic criteria for sporadic schwannomatosis. Six patients were reviewed with a mean follow-up of 38.5months (27-60months). Patients' demographic, clinical, radiographic, and pathologic data were extracted. All patients underwent slit-lamp examination, enhanced brain magnetic resonance imaging (MRI) and a spinal MRI. Enucleation that preserved nerve continuity was performed in symptomatic patients. On average, patients were 36years of age at the time of diagnosis with no sex predominance. The topographic distribution of the peripheral nerve tumors was always unilateral and most frequently targeted the upper limb. In four cases, the tumors involved the same peripheral nerve exclusively. The average number of nerve tumors observed per patient was 4.7 (2-8). The outcome after enucleation was marked by the systematic appearance of new tumors. After enucleation, no recurrence or malignant transformation was observed at the final follow-up. There was no transition to a NF2 configuration. The absence of neurofibroma and NF2 criteria makes schwannomatosis a diagnosis of exclusion. While a good prognosis can be expected following enucleation, two risks related to neurofibromatosis type 3 (NF3) are worth monitoring: the transition to NF2, particularly in young patients, and the appearance of new tumors. Copyright © 2017 SFCM. Published by Elsevier Masson SAS. All rights reserved.

POEMS Syndrome Diagnosed 10 Years after Disabling Peripheral Neuropathy.

PubMed

Nguyen, Viet H

2011-01-01

Peripheral neuropathy is characterized as a generalized, relatively homogeneous process affecting many peripheral nerves and predominantly affecting distal nerves. The epidemiology of peripheral neuropathy is limited since the disease presents with varying etiology, pathology, and severity. Toxic, inflammatory, hereditary, and infectious factors can cause damage to the peripheral nerves resulting in peripheral neuropathy. Peripheral neuropathy is most commonly caused by diabetes, alcohol, HIV infection, and malignancy. We report a case of a 42-year-old female with 10-year history of progressively worsening peripheral neuropathy, hypothyroidism, and skin changes who presents with dyspnea secondary to recurrent pleural and pericardial effusions. Prior to her arrival, her peripheral neuropathy was believed to be secondary to chronic demyelinating inflammatory polyneuropathy (CDIP) given elevated protein in the cerebral spinal fluid (CSF) which was treated with intravenous immunoglobulin (IVIG) and corticosteroids. Unfortunately, her peripheral neuropathy did not have any improvement. Incidentally, patient was found to have splenomegaly and papilledema on physical exam. Serum protein electrophoresis showed a monoclonal pattern of IgA lambda. Patient met the diagnostic criteria for POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes) syndrome. An underlying diagnosis of POEMS syndrome should be considered in patients with chronic debilitating neuropathy and an elevated protein in the CSF.

POEMS Syndrome Diagnosed 10 Years after Disabling Peripheral Neuropathy

PubMed Central

Nguyen, Viet H.

2011-01-01

Peripheral neuropathy is characterized as a generalized, relatively homogeneous process affecting many peripheral nerves and predominantly affecting distal nerves. The epidemiology of peripheral neuropathy is limited since the disease presents with varying etiology, pathology, and severity. Toxic, inflammatory, hereditary, and infectious factors can cause damage to the peripheral nerves resulting in peripheral neuropathy. Peripheral neuropathy is most commonly caused by diabetes, alcohol, HIV infection, and malignancy. We report a case of a 42-year-old female with 10-year history of progressively worsening peripheral neuropathy, hypothyroidism, and skin changes who presents with dyspnea secondary to recurrent pleural and pericardial effusions. Prior to her arrival, her peripheral neuropathy was believed to be secondary to chronic demyelinating inflammatory polyneuropathy (CDIP) given elevated protein in the cerebral spinal fluid (CSF) which was treated with intravenous immunoglobulin (IVIG) and corticosteroids. Unfortunately, her peripheral neuropathy did not have any improvement. Incidentally, patient was found to have splenomegaly and papilledema on physical exam. Serum protein electrophoresis showed a monoclonal pattern of IgA lambda. Patient met the diagnostic criteria for POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes) syndrome. An underlying diagnosis of POEMS syndrome should be considered in patients with chronic debilitating neuropathy and an elevated protein in the CSF. PMID:22013451

New synthetic prosthesis for peripheral nerve injuries: an experimental pilot study.

PubMed

Uranüs, Selman; Bretthauer, Georg; Nagele-Moser, Doris; Saliba, Sarah; Tomasch, Gordana; Rafolt, Dietmar; Justich, Ivo; Waldert, Jörg; Berghold, Andrea; Kleinert, Reinhold; Becker, Heinz; Voges, Udo; Wiederstein-Grasser, Iris; Koch, Horst

2013-04-01

Even the most modern technology has failed to induce satisfactory functional regeneration of traumatically severed peripheral nerves. Delayed neural regeneration and in consequence, slower neural conduction seriously limit muscle function in the area supplied by the injured nerve. This study aimed to compare a new nerve coaptation system involving an innovative prosthesis with the classical clinical method of sutured nerve coaptation. Besides the time and degree of nerve regeneration, the influence of electrostimulation was also tested. The sciatic nerve was severed in 14 female Göttingen minipigs with an average weight of 40.4 kg. The animals were randomized into 2 groups: One group received the new prosthesis and the other underwent microsurgical coaptation. In each group, according to the randomization a part of the animals received postoperative electrostimulation. Postoperative monitoring and the stimulation schedule covered a period of 9 months, during which axonal budding was evaluated monthly. The data from the pilot study indicate that results with the nerve prosthesis were comparable with those of conventional coaptation. The results indicate that implantation of the nerve prosthesis allows for good and effective neural regeneration. This new and simple treatment option for peripheral nerve injuries can be performed in any hospital with surgical facilities as it does not involve the demanding microsurgical suture technique that can only be performed in specialized centers.

P02.05 Peripheral Nerve Sheath Tumor Epidemiology in the South Central Hospital of High Specialty from PEMEX in Mexico

PubMed Central

Guerra Mora, J.; Cordoba Mosqueda, M.; Hernandez Resendiz, R.; Loya Aguilar, I.; Vicuña Gonzalez, R.; Garcia Gonzalez, U.

2016-01-01

Abstract Introduction: The peripheral sheath tumors are part of a large group of neoplasms that range from biologically benign with minimal disorders in life quality to highly malign with life quality deterioration and high mortality. There are subtypes with high prevalence like Schwannomas and some much rarer like the intracranial peripheral nerve sheath tumor which happen to have very bad prognosis. The aim of this study is to describe the epidemiologic and clinical characteristics of patients with peripheral nerve sheat tumors in a hospital of high specialty. Method and materials: Observational study with patients from March 1999 to March 2016 with confirmed diagnosis of peripheral nerve sheath tumor in the electronic files of the South Central Hospital of High Specialty PEMEX. A statistical analysis is made through the SPSS Statistics of the disease in this Institution program. Results: There were 84 patients with the diagnosis of peripheral nerve sheath tumor with a median age of 48.04 years, 65.5% were males, the most common histological type found was the Schwannoma with a 72.6%, followed by senescent Schwannoma 13.1%, neurofibroma 8.3%, and malign peripheral nerve sheath tumor 2.4%. The most frequent location was at the site of cranial nerves, followed by cervical level 27.4%, lumbar 16.7% and thoracic 9.5%. The most common initial symptom was pain in 23.8% of the patients, and the time of the onset of symptoms to the diagnosis was 31.6 months. From the total of patients 8.3% had neurofibromatosis type 1, 6.0% neurofibromatosis type 2. Conclusions: We realized in our series of reported cases that the frequency is similar to those reported in worldwide population; nevertheless the time between the onset of symptoms and the diagnosis is much higher in our cases as well as the population of patients with neurofibromatosis. This study justifies the need of attention quality improvement and the knowledge of this information the medical doctor of first contact so that the right diagnosis can be made and the treatment given in the shortest time possible.

Relevance of nerve conduction velocity in the assessment of balance performance in older adults with diabetes mellitus.

PubMed

Wang, Ting-Yun; Chen, Shih-Ching; Peng, Chih-Wei; Kang, Chun-Wei; Chen, Yu-Luen; Chen, Chun-Lung; Chou, Yi-Lin; Lai, Chien-Hung

2017-03-01

Purpose This study investigated the relationship between peripheral nerve conduction velocity (NCV) and balance performance in older adults with diabetes. Methods Twenty older adults with diabetes were recruited to evaluate the NCV of their lower limbs and balance performance. The balance assessments comprised the timed up and go (TUG) test, Berg balance scale (BBS), unipedal stance test (UST), multidirectional reach test (MDRT), maximum step length (MSL) test and quiet standing with eyes open and closed. The relationship between NCV and balance performance was evaluated by Pearson's correlation coefficients, and the balance performances of the diabetic patients with and without peripheral neuropathy were compared by using Mann-Whitney U tests. Results The NCV in the lower limbs exhibited a moderate to strong correlation with most of the balance tests including the TUG (r = -0.435 to -0.520, p < 0.05), BBS (r = 0.406-0.554, p < 0.05), UST (r = 0.409-0.647, p < 0.05) and MSL (r = 0.399-0.585, P < 0.05). In addition, patients with diabetic peripheral neuropathy had a poorer TUG (p < 0.05), BBS (p < 0.01), UST (p < 0.05) and MSL performance (p < 0.05) compared with those without peripheral neuropathy (p < 0.05). Conclusion Our findings revealed that a decline in peripheral nerve conduction in the lower limb is not only an indication of nerve dysfunction, but may also be related to the impairment of balance performance in patients with diabetes. Implications for Rehabilitation Nerve conduction velocity in the lower limbs of diabetic older adults showed moderate to strong correlations with most of the results of balance tests, which are commonly used in clinics. Decline in nerve conduction velocity of the lower limbs may be related to the impairment of balance control in patients with diabetes. Diabetic older adults with peripheral neuropathy exhibited greater postural instability than those without peripheral neuropathy.

Peripheral Nerve Blocks for the Treatment of Headache in Older Adults: A Retrospective Study.

PubMed

Hascalovici, Jacob R; Robbins, Matthew S

2017-01-01

The objective of this study is to provide demographical and clinical descriptions of patients age 65 years old and older who were treated with peripheral nerve blocks (PNBs) at our institution and evaluate the safety and efficacy of this treatment. Headache disorders are common, disabling chronic neurological diseases that often persist with advancing age. Geriatric headache management poses unique therapeutic challenges because of considerations of comorbidity, drug interactions, and adverse effects. Peripheral nerve blocks are commonly used for acute and short-term prophylactic treatment for headache disorders and may be a safer alternative to standard pharmacotherapy in this demographic. We performed a single center, retrospective chart review of patients at least 65 years of age who received peripheral nerve blocks for headache management over a 6 year period. Sixty-four patients were mostly female (78%) with an average age of 71 years (range 65-94). Representative headache diagnoses were chronic migraine 50%, episodic migraine 12.5%, trigeminal autonomic cephalalgia 9.4%, and occipital neuralgia 7.8%. Average number of headache days/month was 23. Common comorbidities were hypertension 48%, hyperlipidemia 42%, arthritis 27%, depression 47%, and anxiety 33%. Eighty-nine percent were prescribed at least 1 medication fulfilling the Beers criteria. The average number of peripheral nerve blocks per patient was 4. Peripheral nerve blocks were felt to be effective in 73% for all headaches, 81% for chronic migraine, 75% for episodic migraine, 67% for chronic tension type headache, 67% for new daily persistent headache, and 60% for occipital neuralgia. There were no adverse events related to PNBs reported. PNBs might be a safe and effective alternative headache management strategy for older adults. Medical and psychiatric comorbidities, medication overuse, and Beers list medication rates were extraordinarily high, giving credence to the use of peripherally administered therapies in the geriatric population that may be better tolerated and safer. © 2016 American Headache Society.

A Clinical and Electrophysiological Study of Peripheral Neuropathies in Predialysis Chronic Kidney Disease Patients and Relation of Severity of Peripheral Neuropathy with Degree of Renal Failure.

PubMed

Jasti, Dushyanth Babu; Mallipeddi, Sarat; Apparao, A; Vengamma, B; Sivakumar, V; Kolli, Satyarao

2017-01-01

To study the prevalence, clinical features, electrophysiological features, and severity of peripheral neuropathy in predialysis chronic kidney disease (CKD) patients with respect to severity of renal failure and presence of diabetes mellitus. Between May 2015 and December 2016, 200 predialysis CKD patients were assessed prospectively. The prevalence of peripheral neuropathy in predialysis CKD patients in the present study was 45% based on clinical symptoms and 90% electrophysiologically. Mean age of 200 predialysis CKD patients who participated in the study was 53.2 ± 13.2 years. One hundred and thirty-six (68%) patients were male and 64 (32%) patients were female. Mean duration of disease was 2.2 ± 1.6 years. Nearly 45% patients of patients had asymptomatic peripheral neuropathy in the present study, which was more common in mild-to-moderate renal failure group. One hundred twenty-six patients (63%) had definite damage and 54 patients (27%) had early damage. In mild-to-moderate renal failure ( n = 100) and severe renal failure patients ( n = 100), 88% and 92% had significant peripheral neuropathy, respectively. Most common nerves involved were sural nerve, median sensory nerve, and ulnar sensory nerve. Diabetic patients (97%) showed more severe and high prevalence of peripheral neuropathy when compared to nondiabetic patients (83%). Most common patterns were pure axonal sensorimotor neuropathy and mixed sensorimotor neuropathy. Peripheral neuropathy is common in predialysis patients, prevalence and severity of which increases as renal failure worsens. Predialysis patients with diabetes show higher prevalence and severity of peripheral neuropathy when compared with nondiabetics.

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. Copyright © 2015 Elsevier B.V. All rights reserved.

Structural parameters of collagen nerve grafts influence peripheral nerve regeneration.

PubMed

Stang, Felix; Fansa, Hisham; Wolf, Gerald; Reppin, Michael; Keilhoff, Gerburg

2005-06-01

Large nerve defects require nerve grafts to allow regeneration. To avoid donor nerve problems the concept of tissue engineering was introduced into nerve surgery. However, non-neuronal grafts support axonal regeneration only to a certain extent. They lack viable Schwann cells which provide neurotrophic and neurotopic factors and guide the sprouting nerve. This experimental study used the rat sciatic nerve to bridge 2 cm nerve gaps with collagen (type I/III) tubes. The tubes were different in their physical structure (hollow versus inner collagen skeleton, different inner diameters). To improve regeneration Schwann cells were implanted. After 8 weeks the regeneration process was monitored clinically, histologically and morphometrically. Autologous nerve grafts and collagen tubes without Schwann cells served as control. In all parameters autologous nerve grafts showed best regeneration. Nerve regeneration in a noteworthy quality was also seen with hollow collagen tubes and tubes with reduced lumen, both filled with Schwann cells. The inner skeleton, however, impaired nerve regeneration independent of whether Schwann cells were added or not. This indicates that not only viable Schwann cells are an imperative prerequisite but also structural parameters determine peripheral nerve regeneration.

Observations on the responses of muscle to mechanical and electrical stimuli

PubMed Central

Meadows, J. C.

1971-01-01

Responses to mechanical and electrical stimuli have been studied in vastus medialis in four young adults. Percussion causes an immediate, brief contraction in those muscle fibres passing beneath the site of the blow. This is accompanied by EMG activity which is propagated along the muscle fibres at a normal velocity of around 4 m/sec. The EMG activity lasts much longer than that produced by a single electrical stimulus to muscle fibres because repetitive firing occurs in some of the muscle fibres activated mechanically. This response to percussion is unaffected by nerve blockade with 2% xylocaine. Percussion close to the motor point may cause delayed fasciculation due to activation of intramuscular motor nerve fibres. This, too, is unaffected by nerve blockade. Some observations on EMG insertional activity provoked by needle movement are reported. It is concluded that muscle has a basic tendency to discharge repetitively when stimulated by mechanical means and that EMG insertional activity and the EMG response to percussion reported in this paper are both manifestations of this same tendency, which is increased in the myotonias. Images PMID:4251668

Rehabilitation of brachial plexus and peripheral nerve disorders.

PubMed

Scott, Kevin R; Ahmed, Aiesha; Scott, Linda; Kothari, Milind J

2013-01-01

Peripheral nerve lesions are common and can present in a variety of ways. Peripheral nerve injury can result from a broad spectrum of causes. For the majority of patients, rehabilitation is generally indicated regardless of etiology. Evaluation and treatment by a multidisciplinary team including neurologists, psychiatrists, surgeons, occupational and physical therapists, and therapists with specialized training in orthotics maximizes the potential for recovery. This chapter will focus on those upper and lower extremity neuropathies that are most commonly seen in clinical practice. In addition, we discuss various rehabilitative strategies designed to improve function and quality of life. Copyright © 2013 Elsevier B.V. All rights reserved.

Axonal regeneration through acellular muscle grafts

PubMed Central

HALL, SUSAN

1997-01-01

The management of peripheral nerve injury remains a major clinical problem. Progress in this field will almost certainly depend upon manipulating the pathophysiological processes which are triggered by traumatic injuries. One of the most important determinants of functional outcome after the reconstruction of a transected peripheral nerve is the length of the gap between proximal and distal nerve stumps. Long defects (> 2 cm) must be bridged by a suitable conduit in order to support axonal regrowth. This review examines the cellular and acellular elements which facilitate axonal regrowth and the use of acellular muscle grafts in the repair of injuries in the peripheral nervous system. PMID:9034882

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Luo, Lihua; Center of Molecular Medicine, School of Medicine, Hubei University of Arts and Sciences, Xiangyang 441053; Gan, Li

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 appliedmore » 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 conduits in the field of nerve tissue engineering. - Highlights: • A novel nerve conduit was constructed and applied to repair nerve defect in rats. • Transparent hollow cellulose/soy protein isolate tube was used as conduit matrix. • Pyrroloquinoline quinine was adsorbed into the hollow tube as nerve growth factor. • Schwann cells were cultured into the hollow tube as seed cells. • The new nerve conduit could repair and reconstruct the peripheral nerve defects.« less

Convection-Enhanced Delivery (CED) in an Animal Model of Malignant Peripheral Nerve Sheath Tumors and Plexiform Neurofibromas

DTIC Science & Technology

2013-02-01

successfully establish the xenograft within the sciatic nerve. Convection-Enhanced Delivery ( CED ), Malignant Peripheral Nerve Sheath ( MPNST ), Plexiform...intraneural PNs and MPNST via CED . Design: Orthotopic xenograft models of sciatic intraneural NF1 MPNST and PNs in scid mice as described by Perrin et...using convection-enhanced delivery ( CED ). Relative Growth of MPNST cells in vivo treated with rapamycin, imatinib or erlotinib: Elotinib

Alterations in the Local Axonal Environment Influence Target Reinnervation and Neuronal Survival After PostnataI Axotomy

DTIC Science & Technology

2000-06-21

2000 Dissertation directed by: Rosemary C. Borke, Ph.D. Professor Department of Anatomy and Cell Biology Following peripheral nerve injury in adult...augmented at the injury site and the neuromuscular junction (NMJ) following sciatic nerve axotomy. The current work determined that SC apoptosis occurs in...related and location-specific response to peripheral nerve injury . Apoptotic SC were found in two strategic locations for guiding axonal outgrowth during

Bell palsy in lyme disease-endemic regions of canada: a cautionary case of occult bilateral peripheral facial nerve palsy due to Lyme disease.

PubMed

Ho, Karen; Melanson, Michel; Desai, Jamsheed A

2012-09-01

Lyme disease caused by the spirochete Borrelia burgdorferi is a multisystem disorder characterized by three clinical stages: dermatologic, neurologic, and rheumatologic. The number of known Lyme disease-endemic areas in Canada is increasing as the range of the vector Ixodes scapularis expands into the eastern and central provinces. Southern Ontario, Nova Scotia, southern Manitoba, New Brunswick, and southern Quebec are now considered Lyme disease-endemic regions in Canada. The use of field surveillance to map risk and endemic regions suggests that these geographic areas are growing, in part due to the effects of climate warming. Peripheral facial nerve palsy is the most common neurologic abnormality in the second stage of Lyme borreliosis, with up to 25% of Bell palsy (idiopathic peripheral facial nerve palsy) occurring due to Lyme disease. Here we present a case of occult bilateral facial nerve palsy due to Lyme disease initially diagnosed as Bell palsy. In Lyme disease-endemic regions of Canada, patients presenting with unilateral or bilateral peripheral facial nerve palsy should be evaluated for Lyme disease with serologic testing to avoid misdiagnosis. Serologic testing should not delay initiation of appropriate treatment for presumed Bell palsy.

Receptor Tyrosine Kinases as Targets for Treatment of Peripheral Nerve Sheath Tumors in NF 1 Patients

DTIC Science & Technology

2007-03-01

EGFR patterns by interphase cytogenetics (FISH) in malignant peripheral nerve sheath tumor (MPNST) and morphologically similar spindle cell neoplasms ...Armstrong,F., Delsol,G., Dastugue,N. and Brousset,P. (2003) Chronic myeloproliferative disorders with rearrangement of the platelet-derived growth

NMDA Receptors Regulate Genes Responsible for Major Immune Functions of Mononuclears in Human Peripheral Blood.

PubMed

Kuzmina, U Sh; Zainullina, L F; Sadovnikov, S V; Vakhitov, V A; Vakhitova, Yu V

2018-06-19

To determine the role of NMDA receptors in the functional regulation of immunocompetent cells, comparative assay was carried out for genes expressed in the mononuclears in peripheral blood of healthy persons under normal conditions and after blockade of these receptors. The genes, whose expression changed in response to blockade of NMDA receptors in mononuclears, encode the products involved in regulation of the major functions of immune cells, such as proliferation (IL4, VCAM1, and CDKN2A), apoptosis (BAX, MYC, CDKN2A, HSPB1, and CADD45A), activation (IL4R, IL4, VCAM1, and CDKN2A), and differentiation (IL4, VCAM1, and BAX).

HCV RNA Genomic sequences and HCV-E2 glycoprotein in sural nerve biopsies from HCV-infected patients with peripheral neuropathy.

PubMed

Russi, S; Sansonno, D; Monaco, S; Mariotto, S; Ferrari, S; Pavone, F; Lauletta, G; Dammacco, F

2018-06-01

Peripheral neuropathy (PN), the major neurological complication of chronic HCV infection, is frequently associated with mixed cryoglobulinaemia (MC) and small-vessel systemic vasculitis. While humoral and cell-mediated immune mechanisms are suspected to act together in an aberrant immune response that results in peripheral nerve damage, the role of HCV remains largely speculative. The possible demonstration of HCV in peripheral nerve tissue would obviously assume important pathogenic implications. We studied sural nerve biopsies from 11 HCV-positive patients with neuropathic symptoms: five with and six without MC. In situ hybridization (ISH) and immunofluorescence studies were carried out to detect genomic and antigenomic HCV RNA sequences and HCV-encoded E2-glycoprotein, respectively. Epineurial vascular deposits of E2-glycoprotein were found in four (80%) MC and in two (33.3%) non-MC patients, respectively. These findings were enhanced by the perivascular deposition of positive-, though not negative-strand replicative RNA, as also found in the nerve extracts of all patients. Mild inflammatory cell infiltrates with no deposits of immunoglobulins and/or complement proteins were revealed around small vessels, without distinct vasculitis changes between MC and non-MC patients. These results indicate that nerve vascular HCV RNA/E2 deposits associated to perivascular inflammatory infiltrates were similar in chronically HCV-infected patients, regardless of cryoglobulin occurrence. Given the failure to demonstrate HCV productive infection in the examined sural nerve biopsies, nerve damage is likely to result from virus-triggered immune-mediated mechanisms. © 2017 British Neuropathological Society.

Novel drug delivering conduit for peripheral nerve regeneration

NASA Astrophysics Data System (ADS)

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

2017-12-01

Objective. This paper describes the design of a novel drug delivery apparatus integrated with a poly lactic-co-glycolic acid (PLGA) based nerve guide conduit for controlled local delivery of nerve growth factor (NGF) and application in peripheral nerve gap injury. Approach. An NGF dosage curve was acquired to determine the minimum in vitro concentration for optimal neurite outgrowth of dorsal root ganglion (DRG) cells; PLGA based drug delivery devices were then designed and tested in vitro and in vivo across 15 mm rat sciatic nerve gap injury model. Main results. The drug delivery nerve guide was able to release NGF for 28 d at concentrations (0.1-10 ng ml-1) that were shown to enhance DRG neurite growth. Furthermore, the released NGF was bioactive and able to enhance DRG neurite growth. Following these tests, optimized NGF-releasing nerve conduits were implanted across 15 mm sciatic nerve gaps in a rat model, where they demonstrated significant myelination and muscle innervation in vivo as compared to empty nerve conduits (p  <  0.05). This drug delivery nerve guide can release NGF for extended periods of time and enhance axon growth in vitro and in vivo and has the potential to improve nerve regeneration following a peripheral nerve injury. Significance. This integrated drug delivering nerve guide simplifies the design process and provides increased versatility for releasing a variety of different growth factors. This innovative device has the potential for broad applicability and allows for easier customization to change the type of drugs and dosage of individual drugs without devising a completely new biomaterial-drug conjugate each time.

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

PubMed

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

2018-05-01

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

The role of precisely matching fascicles in the quick recovery of nerve function in long peripheral nerve defects

PubMed Central

Yan, Liwei; Yao, Zhi; Lin, Tao; Zhu, Qingtang; Qi, Jian; Gu, Liqiang; Fang, Jintao; Zhou, Xiang

2017-01-01

Peripheral nerve injury therapy in the clinic remains less than satisfactory. The gold standard of treatment for long peripheral nerve defects is autologous nerve grafts; however, numerous clinical complications are associated with this treatment. As tissue engineering has developed, tissue-engineered nerve grafts (TENGs) have shown potential applications as alternatives to autologous nerve grafts. To verify the important role of the biomimetic pathway of fascicle design in TENGs, we designed an animal model to study the role of the precise matching of fascicles in the effectiveness of nerve function recovery. 24 Sprague-Dawley rats were divided randomly into three groups (eight/group) that corresponded to 100% fascicle matching (100%FM), 50%FM and 0%FM. We selected Sprague–Dawley rat long-gap (15 mm) sciatic nerve defects. In the 6 weeks after surgery, we found that the 100%FM group showed the most effective functional recovery among the three groups. The 100%FM group showed better functional recovery on the basis of the sciatic functional index than the 50%FM and 0%FM groups. According to histological evaluation, the 100%FM group showed more regenerating nerve fibres. Moreover, in terms of the prevention of muscle atrophy, the 100%FM group showed excellent physiological outcomes. The 100%FM as tissue-engineered scaffolds can enhance nerve regeneration and effective functional recovery after the repair of large nerve defects. The results of this study provide a theoretical basis for future TENG designs including biomimetic fascicle pathways for repairing long nerve defects. PMID:28914740

Rapid and accurate peripheral nerve detection using multipoint Raman imaging (Conference Presentation)

NASA Astrophysics Data System (ADS)

Kumamoto, Yasuaki; Minamikawa, Takeo; Kawamura, Akinori; Matsumura, Junichi; Tsuda, Yuichiro; Ukon, Juichiro; Harada, Yoshinori; Tanaka, Hideo; Takamatsu, Tetsuro

2017-02-01

Nerve-sparing surgery is essential to avoid functional deficits of the limbs and organs. Raman scattering, a label-free, minimally invasive, and accurate modality, is one of the best candidate technologies to detect nerves for nerve-sparing surgery. However, Raman scattering imaging is too time-consuming to be employed in surgery. Here we present a rapid and accurate nerve visualization method using a multipoint Raman imaging technique that has enabled simultaneous spectra measurement from different locations (n=32) of a sample. Five sec is sufficient for measuring n=32 spectra with good S/N from a given tissue. Principal component regression discriminant analysis discriminated spectra obtained from peripheral nerves (n=863 from n=161 myelinated nerves) and connective tissue (n=828 from n=121 tendons) with sensitivity and specificity of 88.3% and 94.8%, respectively. To compensate the spatial information of a multipoint-Raman-derived tissue discrimination image that is too sparse to visualize nerve arrangement, we used morphological information obtained from a bright-field image. When merged with the sparse tissue discrimination image, a morphological image of a sample shows what portion of Raman measurement points in arbitrary structure is determined as nerve. Setting a nerve detection criterion on the portion of "nerve" points in the structure as 40% or more, myelinated nerves (n=161) and tendons (n=121) were discriminated with sensitivity and specificity of 97.5%. The presented technique utilizing a sparse multipoint Raman image and a bright-field image has enabled rapid, safe, and accurate detection of peripheral nerves.

Myokymia and neuromyotonia in veterinary medicine: a comparison with peripheral nerve hyperexcitability syndrome in humans.

PubMed

Vanhaesebrouck, An E; Bhatti, Sofie F M; Franklin, Robin J M; Van Ham, Luc

2013-08-01

Involuntary muscle hyperactivity can result from muscle or peripheral nerve hyperexcitability or central nervous system dysfunction. In humans, diseases causing hyperexcitability of peripheral nerves are grouped together under the term 'peripheral nerve hyperexcitability' (PNH). Hyperexcitability of the peripheral motor nerve can result into five different phenotypic main variants, i.e. fasciculations, myokymia, neuromyotonia, cramps and tetany, each with their own clinical and electromyographic characteristics. This review focuses on the most commonly described expressions of PNH in veterinary medicine, i.e. myokymia and neuromyotonia, in particular in young Jack Russell terriers. Data from 58 veterinary cases with generalized myokymia and neuromyotonia were analyzed, including unpublished treatment and follow-up data on eight Jack Russell terriers from a previous study and seven additional Jack Russell terriers. A dysfunction of the potassium channel or its associated proteins has been found in many human syndromes characterized by PNH, in particular in generalized myokymia and neuromyotonia, and is suspected to occur in veterinary medicine. Potential pathomechanisms of potassium channel dysfunction leading to signs of PNH are broad and include genetic mutations, antibody-mediated attack or ion channel maldistribution due to axonal degeneration or demyelination. A more accurate classification of the different PNH syndromes will facilitate a more rapid diagnosis and guide further research into natural occurring PNH in animals. Copyright © 2013 Elsevier Ltd. All rights reserved.

Importance of electromyography and the electrophysiological severity scale in forensic reports.

PubMed

Bilgin, Nursel Gamsiz; Ozge, Aynur; Mert, Ertan; Yalçinkaya, Deniz E; Kar, Hakan

2007-05-01

Forensic reports on traumatic peripheral nerve injuries include dysfunction degrees of extremities, which are arranged according to the Turkish Penalty Code. The aim of this study is to discuss the role and importance of electromyography while preparing forensic reports in the cases of traumatic peripheral nerve injuries and the usefulness of scoring systems. A modified global scale, recommended by Mondelli et al., was used to assess the electrophysiological impairment of each peripheral nerve. Forensic reports of 106 patients, reported between 2002 and 2004, were evaluated. Thirty-four percent of the cases were reported as "total loss of function," 41.5% were reported as "functional disability," and there were no dysfunctions in the other cases in forensic reports that were prepared based on Council of Social Insurance Regulations of Health Processes and Guide prepared by the Council of Forensic Medicine and profession associations of forensic medicine. When we rearranged these forensic reports based on the electrophysiological severity scale (ESS), it was clearly found that all of the score 2 cases and 86.7% of the score 3 cases corresponded to "functional disability" and 91.4% of the score 4 cases correspond to "total loss of function." We found a significant correlation between the ESS and functional evaluation in peripheral nerve injury cases. Evaluation of functional disabilities in peripheral nerve injuries with the ESS represents a standardized and objective method used for forensic reports.

Echogenicity and ultrasound visibility of peripheral nerves of the upper extremity.

PubMed

Stolz, Lori A; Acuna, Josie Galarza; Gaskin, Kevin; Murphy, Amanda M; Friedman, Lucas; Stears-Ellis, Summer; Javedani, Parisa; Stolz, Uwe; Adhikari, Srikar

2018-05-02

Regional anesthesia with ultrasound-guidance is an excellent option for pain control if nerves are adequately visualized. Gender, body mass index (BMI), history of diabetes, neck and forearm circumference may affect echotexture and visualization. This study evaluates patient characteristics for their ability to predict the echogenicity or visibility of upper extremity peripheral nerves. This is a prospective observational study. A convenience sample of adult emergency department patients were enrolled. Gender, BMI, history of diabetes, neck circumference and arm circumference were recorded. Sonographic images of the brachial plexus at interscalene and supraclavicular levels, the median, the radial and ulnar nerves were recorded. Three reviewers independently graded the echogenicity and visibility using subjective scales. 395 peripheral nerves were included. Nerves of the forearm (median, ulnar, radial nerves) were found to be more echogenic (OR=9.3; 95% CI: 5.7, 15.3) and visible (OR=10.0; 6.3, 16.0) than more proximal nerves (brachial plexus at interscalene and supraclavicular levels). Gender, BMI, and history of diabetes mellitus were not significantly related to nerve visibility (p=0.9, 0.2, 0.2, respectively) or echogenicity (p=0.3, 0.8, 0.3). Neck circumference was not related to visibility or echogenicity of proximal nerves. Increased forearm circumference improved echogenicity (OR=1.25; 1.09, 1.43) but not visibility of forearm nerves. Gender, BMI and presence of diabetes were not related to echogenicity or visibility of upper extremity nerves. Increasing forearm circumference was associated with increased echogenicity of the adjacent nerves, but not visibility. Neck circumference was not associated with either nerve visibility or echogenicity of brachial plexus nerve bundles.

Sustained Local Release of NGF from a Chitosan-Sericin Composite Scaffold for Treating Chronic Nerve Compression.

PubMed

Zhang, Lei; Yang, Wen; Tao, Kaixiong; Song, Yu; Xie, Hongjian; Wang, Jian; Li, Xiaolin; Shuai, Xiaoming; Gao, Jinbo; Chang, Panpan; Wang, Guobin; Wang, Zheng; Wang, Lin

2017-02-01

Chronic nerve compression (CNC), a common form of peripheral nerve injury, always leads to chronic peripheral nerve pain and dysfunction. Current available treatments for CNC are ineffective as they usually aim to alleviate symptoms at the acute phase with limited capability toward restoring injured nerve function. New approaches for effective recovery of CNC injury are highly desired. Here we report for the first time a tissue-engineered approach for the repair of CNC. A genipin cross-linked chitosan-sericin 3D scaffold for delivering nerve growth factor (NGF) was designed and fabricated. This scaffold combines the advantages of both chitosan and sericin, such as high porosity, adjustable mechanical properties and swelling ratios, the ability of supporting Schwann cells growth, and improving nerve regeneration. The degradation products of the composite scaffold upregulate the mRNA levels of the genes important for facilitating nerve function recovery, including glial-derived neurotrophic factor (GDNF), early growth response 2 (EGR2), and neural cell adhesion molecule (NCAM) in Schwann cells, while down-regulating two inflammatory genes' mRNA levels in macrophages, tumor necrosis factor alpha (TNF-α), and interleukin-1 beta (IL-1β). Importantly, our tissue-engineered strategy achieves significant nerve functional recovery in a preclinical CNC animal model by decreasing neuralgia, improving nerve conduction velocity (NCV), accelerating microstructure restoration, and attenuating gastrocnemius muscles dystrophy. Together, this work suggests a promising clinical alternative for treating chronic peripheral nerve compression injury.

Effect of diet induced obesity or type 1 or type 2 diabetes on corneal nerves and peripheral neuropathy in C57Bl/6J mice

PubMed Central

Yorek, Matthew S.; Obrosov, Alexander; Shevalye, Hanna; Holmes, Amey; Harper, Matthew M.; Kardon, Randy H.; Yorek, Mark A.

2015-01-01

We determined the impact diet induced obesity (DIO) and types 1 and 2 diabetes has on peripheral neuropathy with emphasis on corneal nerve structural changes in C57Bl/6J mice. Endpoints examined included nerve conduction velocity, response to thermal and mechanical stimuli and innervation of the skin and cornea. DIO mice and to a greater extent type 2 diabetic mice were insulin resistant. DIO and both types 1 and 2 diabetic mice developed motor and sensory nerve conduction deficits. In the cornea of DIO and type 2 diabetic mice there was a decrease in sub-epithelial corneal nerves, innervation of the corneal epithelium and corneal sensitivity. Type 1 diabetic mice did not present with any significant changes in corneal nerve structure until after 20 weeks of hyperglycemia. DIO and type 2 diabetic mice developed corneal structural damage more rapidly than type 1 diabetic mice even though hemoglobin A1C values were significantly higher in type 1 diabetic mice. This suggests that DIO with or without hyperglycemia contributes to development and progression of peripheral neuropathy and nerve structural damage in the cornea. PMID:25858759

What is the Best Strategy on Detection of Cornea Neuropathy in People with Diabetes? Recent Advances in Potential Measurements.

PubMed

Lv, Ying; Zhao, Shaozhen

2018-03-26

There are well-acknowledged clinical or pre-clinical measurements concerning diabetic peripheral neuropathy(DPN). The current gold standard for diagnosis of diabetic peripheral neuropathy is nerve conduction suitable for detecting large nerve fiber function[1] and intraepidermal nerve fiber density assessment for small fiber damage evaluation[2]. The lack of a sensitive, non-invasive, and repeatable endpoint to measure changes in small nerve fibers is a major factor holding back clinical trials for the treatment of diabetic peripheral neuropathy. As cornea is the most densely innerved tissue, assessing corneal nerves' structure and function will be promising to predict and assess the degree of DPN [3]. In the diabetic micro-environment, damaged corneal nerves lead to decreased corneal sensitivity, both of which resulting in abnormal tear function. According to this theory, the measurements of nerve structure, corneal sensitivity, tear secretion and tear components, to some extent, can reveal and assess the state of corneal neuropathy. This review focuses on summarizing the knowledge of the latest detective methods of diabetic corneal neuropathy, popular in use or possible to further in study and be applied into clinical practice. Copyright © 2018 Elsevier B.V. All rights reserved.

Sonographic evaluation of peripheral nerves in subtypes of Guillain-Barré syndrome.

PubMed

Mori, Atsuko; Nodera, Hiroyuki; Takamatsu, Naoko; Maruyama-Saladini, Keiko; Osaki, Yusuke; Shimatani, Yoshimitsu; Kaji, Ryuji

2016-05-15

Sonography of peripheral nerves can depict alteration of nerve sizes that could reflect inflammation and edema in inflammatory and demyelinating neuropathies. Guillain-Barré syndrome (GBS). Information on sonographic comparison of an axonal subtype (acute motor [and sensory] axonal neuropathy [AMAN and AMSAN]) and a demyelinating subtype (acute inflammatory demyelinating polyneuropathy [AIDP]) has been sparse. Sonography of peripheral nerves and cervical nerve roots were prospectively recorded in patients with GBS who were within three weeks of disease onset. Five patients with AIDP and nine with AMAN (n=6)/AMSAN (n=3) were enrolled. The patients with AIDP showed evidence of greater degrees of demyelination (e.g., slower conduction velocities and increased distal latencies) than those with AMAN/AMSAN. The patients with AIDP tended to show enlarged nerves in the proximal segments and in the cervical roots, whereas the patients with AMAN/AMSAN had greater enlargement in the distal neve segment, especially in the median nerve (P = 0.03; Wrist-axilla cross-sectional ratio). In this small study, two subtypes of GBS showed different patterns of involvement that might reflect different pathomechanisms. Copyright © 2016 Elsevier B.V. All rights reserved.

[Diagnosis and treatment of peripheral neuropathy induced by ANCA-associated vasculitis].

PubMed

Hattori, Naoki

2014-07-01

ANCA-associated vasculitis is induced by necrotizing angiitis of small vessels supplying the peripheral nervous system. Ischemic processes induce neuronal damage and axonal degeneration in the peripheral nerve. Motor dysfunction as well as sensory disturbance and allodynia caused by neuropathic symptoms may influence an individual's activities of daily living and quality of life. Notably, the peripheral nerve is predominantly affected in ANCA-associated vasculitis. We suggest that early diagnosis and appropriate treatment are important to improve survival in and functional prognosis of ANCA-associated vasculitis.

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

NASA Astrophysics Data System (ADS)

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

2016-12-01

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

Evaluation of central and peripheral neuropathy in patients with chronic obstructive pulmonary disease.

PubMed

Aras, Yeşim Güzey; Aydemir, Yusuf; Güngen, Belma Doğan; Güngen, Adil Can

2018-01-01

The aim of the study was to investigate the frequency and characteristics of peripheral nervous system (PNS) and central nervous system (CNS) involvement in COPD. The study included 41 COPD patients and 41 healthy volunteers. Electrophysiological studies were carried out: electromyography (EMG) and visual evoked potentials (VEPs). The median nerve, ulnar nerve, common peroneal nerve, and tibial nerve were evaluated for latency, amplitude, and conduction velocity. The mean age of patients with COPD was 61.8 years and disease duration 10.3 years. There was no difference between patient and control groups in terms of age, BMI, smoking status, or biochemical parameters. Upon VEP examination, latencies were significantly prolonged and amplitudes shortened in the patient group compared to the control group. In EMG measurements, conduction velocity and amplitudes in all nerves were low in the patient group. Similarly, latencies in all nerves were higher in patients with COPD. Central and peripheral nervous system involvement could develop in patients with moderate-severe COPD, and these patients should be monitored for neuropathic changes in combination with neurological examination.

Early changes in muscle atrophy and muscle fiber type conversion after spinal cord transection and peripheral nerve transection in rats.

PubMed

Higashino, Kosaku; Matsuura, Tetsuya; Suganuma, Katsuyoshi; Yukata, Kiminori; Nishisho, Toshihiko; Yasui, Natsuo

2013-05-20

Spinal cord transection and peripheral nerve transection cause muscle atrophy and muscle fiber type conversion. It is still unknown how spinal cord transection and peripheral nerve transection each affect the differentiation of muscle fiber type conversion mechanism and muscle atrophy. The aim of our study was to evaluate the difference of muscle weight change, muscle fiber type conversion, and Peroxisome proliferator-activated receptor-γ coactivatior-1α (PGC-1α) expression brought about by spinal cord transection and by peripheral nerve transection. Twenty-four Wistar rats underwent surgery, the control rats underwent a laminectomy; the spinal cord injury group underwent a spinal cord transection; the denervation group underwent a sciatic nerve transection. The rats were harvested of the soleus muscle and the TA muscle at 0 week, 1 week and 2 weeks after surgery. Histological examination was assessed using hematoxylin and eosin (H&E) staining and immunofluorescent staing. Western blot was performed with 3 groups. Both sciatic nerve transection and spinal cord transection caused muscle atrophy with the effect being more severe after sciatic nerve transection. Spinal cord transection caused a reduction in the expression of both sMHC protein and PGC-1α protein in the soleus muscle. On the other hand, sciatic nerve transection produced an increase in expression of sMHC protein and PGC-1α protein in the soleus muscle. The results of the expression of PGC-1α were expected in other words muscle atrophy after sciatic nerve transection is less than after spinal cord transection, however muscle atrophy after sciatic nerve transection was more severe than after spinal cord transection. In the conclusion, spinal cord transection diminished the expression of sMHC protein and PGC-1α protein in the soleus muscle. On the other hand, sciatic nerve transection enhanced the expression of sMHC protein and PGC-1α protein in the soleus muscle.

Multifunctional Silk Nerve Guides for Axon Outgrowth

NASA Astrophysics Data System (ADS)

Tupaj, Marie C.

Peripheral nerve regeneration is a critical issue as 2.8% of trauma patients present with this type of injury, estimating a total of 200,000 nerve repair procedures yearly in the United States. While the peripheral nervous system exhibits slow regeneration, at a rate of 0.5 mm -- 9 mm/day following trauma, this regenerative ability is only possible under certain conditions. Clinical repairs have changed slightly in the last 30 years and standard methods of treatment include suturing damaged nerve ends, allografting, and autografting, with the autograft the gold standard of these approaches. Unfortunately, the use of autografts requires a second surgery and there is a shortage of nerves available for grafting. Allografts are a second option however allografts have lower success rates and are accompanied by the need of immunosuppressant drugs. Recently there has been a focus on developing nerve guides as an "off the shelf" approach. Although some natural and synthetic guidance channels have been approved by the FDA, these nerve guides are unfunctionalized and repair only short gaps, less than 3 cm in length. The goal of this project was to identify strategies for functionalizing peripheral nerve conduits for the outgrowth of neuron axons in vitro . To accomplish this, two strategies (bioelectrical and biophysical) were indentified for increasing axon outgrowth and promoting axon guidance. Bioelectrical strategies exploited electrical stimulation for increasing neurite outgrowth. Biophysical strategies tested a range of surface topographies for axon guidance. Novel methods were developed for integrating electrical and biophysical strategies into silk films in 2D. Finally, a functionalized nerve conduit system was developed that integrated all strategies for the purpose of attaching, elongating, and guiding nervous tissue in vitro. Future directions of this work include silk conduit translation into a rat sciatic nerve model in vivo for the purpose of repairing long (> 3 cm) peripheral nerve gaps.

Effects of nerve cells and adhesion molecules on nerve conduit for peripheral nerve regeneration

PubMed Central

Fiorellini, Joseph P.

2017-01-01

Background For peripheral nerve regeneration, recent attentions have been paid to the nerve conduits made by tissue-engineering technique. Three major elements of tissue-engineering are cells, molecules, and scaffolds. Methods In this study, the attachments of nerve cells, including Schwann cells, on the nerve conduit and the effects of both growth factor and adhesion molecule on these attachments were investigated. Results The attachment of rapidly-proliferating cells, C6 cells and HS683 cells, on nerve conduit was better than that of slowly-proliferating cells, PC12 cells and Schwann cells, however, the treatment of nerve growth factor improved the attachment of slowly-proliferating cells. In addition, the attachment of Schwann cells on nerve conduit coated with fibronectin was as good as that of Schwann cells treated with glial cell line-derived neurotrophic factor (GDNF). Conclusions Growth factor changes nerve cell morphology and affects cell cycle time. And nerve growth factor or fibronectin treatment is indispensable for Schwann cell to be used for implantation in artificial nerve conduits. PMID:29090249

Biomechanical and functional variation in rat sciatic nerve following cuff electrode implantation

PubMed Central

2014-01-01

Background Nerve cuff electrodes are commonly and successfully used for stimulating peripheral nerves. On the other hand, they occasionally induce functional and morphological changes following chronic implantation, for reasons not always clear. We hypothesize that restriction of nerve mobility due to cuff implantation may alter nerve conduction. Methods We quantified acute changes in nerve-muscle electrophysiology, using electromyography, and nerve kinematics in anesthetized Sprague Dawley rat sciatic nerves during controlled hindlimb joint movement. We compared electrophysiological and biomechanical response in uncuffed nerves and those secured within a cuff electrode using analysis of variance (ANOVA) and regression analysis. Results Tethering resulting from cuff implantation resulted in altered nerve strain and a complex biomechanical environment during joint movement. Coincident with biomechanical changes, electromyography revealed significantly increased variability in the response of conduction latency and amplitude in cuffed, but not free, nerves following joint movement. Conclusion Our findings emphasize the importance of the mechanical interface between peripheral nerves and their devices on neurophysiological performance. This work has implications for nerve device design, implantation, and prediction of long-term efficacy. PMID:24758405

Are there any functional differences of the enteric nervous system between the right-sided diverticular colon and the left-sided diverticular colon? An in vitro study.

PubMed

Tomita, Ryouichi

2014-05-01

To evaluate functional differences of the enteric nervous system (ENS) in patients between right-side colonic diverticula (RCD) and left-sided colonic diverticula (LCD), the author compared the ENS responses between RCD and LCD. Ten specimens were obtained from 10 patients with RCD, and 16 specimens were taken from 16 LCD. As a control, twenty-two specimens of right-sided normal colon (RNC) were obtained from 22 colonic cancers. Twenty-four specimens of left sided normal colon (LNC) were obtained from 24 colonic cancers. A mechanography was used to evaluate in vitro muscle responses to electrical field stimulation (EFS) before and after treatment with various autonomic nerve blockers. Before blockade of the adrenergic and cholinergic nerves, the incidences of contraction via cholinergic nerve in the colons with diverticula were significantly greater than those in the normal colons (right-sided colon; p = 0.0022, left-sided colon; p < 0.0001). There were no significant differences between RNC and LNC (p = 0.3606), and between RCD and LCD (p = 0.7684). After the blockade of adrenergic and cholinergic nerves, the incidence of relaxation via non-adrenergic non-cholinergic inhibitory (NANC) nerve in the normal colons was significantly greater than that in the diverticular colons (right-sided colon; p = 0.0435, left-sided colon; p = 0.0034). There were no significant differences between RNC and LNC (p = 0.2909) and between RCD and LCD (p = 0.9464). Cholinergic nerves were dominant in bilateral diverticular colon compared with bilateral normal colon. NANC inhibitory nerves were dominant in bilateral normal colon compared with bilateral diverticular colon. There were also no functional differences of the ENS between RCD and LCD.

Perineurial Glial Plasticity and the Role of TGF-β in the Development of the Blood-Nerve Barrier.

PubMed

Morris, Angela D; Lewis, Gwendolyn M; Kucenas, Sarah

2017-05-03

Precisely orchestrated interactions between spinal motor axons and their ensheathing glia are vital for forming and maintaining functional spinal motor nerves. Following perturbations to peripheral myelinating glial cells, centrally derived oligodendrocyte progenitor cells (OPCs) ectopically exit the spinal cord and myelinate peripheral nerves in myelin with CNS characteristics. However, whether remaining peripheral ensheathing glia, such as perineurial glia, properly encase the motor nerve despite this change in glial cell and myelin composition, remains unknown. Using zebrafish mutants in which OPCs migrate out of the spinal cord and myelinate peripheral motor axons, we assayed perineurial glial development, maturation, and response to injury. Surprisingly, in the presence of OPCs, perineurial glia exited the CNS normally. However, aspects of their development, response to injury, and function were altered compared with wildtype larvae. In an effort to better understand the plasticity of perineurial glia in response to myelin perturbations, we identified transforming growth factor-β1 as a partial mediator of perineurial glial development. Together, these results demonstrate the incredible plasticity of perineurial glia in the presence of myelin perturbations. SIGNIFICANCE STATEMENT Peripheral neuropathies can result from damage or dysregulation of the insulating myelin sheath surrounding spinal motor axons, causing pain, inefficient nerve conduction, and the ectopic migration of oligodendrocyte progenitor cells (OPCs), the resident myelinating glial cell of the CNS, into the periphery. How perineurial glia, the ensheathing cells that form the protective blood-nerve barrier, are impacted by this myelin composition change is unknown. Here, we report that certain aspects of perineurial glial development and injury responses are mostly unaffected in the presence of ectopic OPCs. However, perineurial glial function is disrupted along nerves containing centrally derived myelin, demonstrating that, although perineurial glial cells display plasticity despite myelin perturbations, the blood-nerve barrier is compromised in the presence of ectopic OPCs. Copyright © 2017 the authors 0270-6474/17/374790-18$15.00/0.

The neurotrophic effects of different human dental mesenchymal stem cells.

PubMed

Kolar, Mallappa K; Itte, Vinay N; Kingham, Paul J; Novikov, Lev N; Wiberg, Mikael; Kelk, Peyman

2017-10-03

The current gold standard treatment for peripheral nerve injury is nerve grafting but this has disadvantages such as donor site morbidity. New techniques focus on replacing these grafts with nerve conduits enhanced with growth factors and/or various cell types such as mesenchymal stem cells (MSCs). Dental-MSCs (D-MSCs) including stem cells obtained from apical papilla (SCAP), dental pulp stem cells (DPSC), and periodontal ligament stem cells (PDLSC) are potential sources of MSCs for nerve repair. Here we present the characterization of various D-MSCs from the same human donors for peripheral nerve regeneration. SCAP, DPSC and PDLSC expressed BDNF, GDNF, NGF, NTF3, ANGPT1 and VEGFA growth factor transcripts. Conditioned media from D-MSCs enhanced neurite outgrowth in an in vitro assay. Application of neutralizing antibodies showed that brain derived neurotrophic factor plays an important mechanistic role by which the D-MSCs stimulate neurite outgrowth. SCAP, DPSC and PDLSC were used to treat a 10 mm nerve gap defect in a rat sciatic nerve injury model. All the stem cell types significantly enhanced axon regeneration after two weeks and showed neuroprotective effects on the dorsal root ganglia neurons. Overall the results suggested SCAP to be the optimal dental stem cell type for peripheral nerve repair.

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

PubMed

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

2018-04-01

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

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

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

PubMed

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

2016-10-01

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

Oleo gum resin of Ferula assa-foetida L. ameliorates peripheral neuropathy in mice.

PubMed

Homayouni Moghadam, Farshad; Dehghan, Maryam; Zarepur, Ehsan; Dehlavi, Reyhaneh; Ghaseminia, Fatemeh; Ehsani, Shima; Mohammadzadeh, Golnaz; Barzegar, Kazem

2014-05-28

According to the Chinese, European, Iranian and Indian traditional medicines, oleo gum resin of Ferula assa-foetida (asafoetida) has therapeutic effects on different kinds of diseases. Some of these effects are related to the diseases of nervous system such as hysteresis and convulsion. In recent studies, some anti-epileptic and neuroprotective roles were also considered for it and we examined its possible role on treatment of peripheral neuropathy. in vitro studies were carried out to identify the response of isolated sciatic nerves to different concentrations of oleo gum resin of asafoetida solved in Lock׳s solution. Then, in vivo studies were conducted to evaluate its effect on amelioration of peripheral neuropathy in mice. Peripheral neuropathy was induced by intraperiotoneal injection of high doses of pyridoxine in adult Balb/c male mice. Tail flick tests were performed to identify the incidence of neuropathy in animals. After 10 days treatment with asafoetida, the efficiency of treatment was assessed by behavioral, electrophysiological and histological studies. in vitro experiments confirmed that incubating the nerves in aqueous extract of oleo gum rein of asafoetida increased the amplitude and decreased the latent period of nerve compound action potential (CAP). Nerve conduction velocity (NCV) and amplitude of CAP also improved in asafoetida treated animals. Histological and behavioral studies showed that asafoetida was able to facilitate the healing process in peripheral nerves. in vitro experiments showed that asafoetida is a nerve stimulant and its administration in neuropathic mice exerted neuroprotecting effects through stimulating axonal regeneration and remyelination and decrement of lymphocyte infiltration. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Biophysical characterization of interactions between the C-termini of peripheral nerve claudins and the PDZ₁ domain of zonula occludens.

PubMed

Wu, Jiawen; Peng, Dungeng; Zhang, Yang; Lu, Zhenwei; Voehler, Markus; Sanders, Charles R; Li, Jun

2015-03-27

Our recent study has shown that cellular junctions in myelin and in the epi-/perineruium that encase nerve fibers regulate the permeability of the peripheral nerves. This permeability may affect propagation of the action potential. Direct interactions between the PDZ₁ domain of zonula occludens (ZO₁ or ZO₂) and the C-termini of claudins are known to be crucial for the formation of tight junctions. Using the purified PDZ₁ domain of ZO₂ and a variety of C-terminal mutants of peripheral nerve claudins (claudin-1, claudin-2, claudin-3, claudin-5 in epi-/perineurium; claudin-19 in myelin), we have utilized NMR spectroscopy to determine specific roles of the 3 C-terminal claudin residues (position -2, -1, 0) for their interactions with PDZ₁ of ZO₂. In contrast to the canonical model that emphasizes the importance of residues at the -2 and 0 positions, our results demonstrate that, for peripheral nerve claudins, the residue at position -1 plays a critical role in association with PDZ₁, while the side-chain of residue 0 plays a significant but lesser role. Surprisingly, claudin-19, the most abundant claudin in myelin, exhibited no binding to ZO₂. These findings reveal that the binding mechanism of claudin/ZO in epi-/perineurium is distinct from the canonical interactions between non-ZO PDZ-containing proteins with their ligands. This observation provides the molecular basis for a strategy to develop drugs that target tight junctions in the epi-/perineurium of peripheral nerves. Published by Elsevier Inc.

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

NASA Astrophysics Data System (ADS)

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

2017-05-01

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

Nerve Entrapment in Ankle and Foot: Ultrasound Imaging.

PubMed

Chari, Basavaraj; McNally, Eugene

2018-07-01

Peripheral nerve entrapment of the ankle and foot is relatively uncommon and often underdiagnosed because electrophysiologic studies may not contribute to the diagnosis. Anatomy of the peripheral nerves is variable and complex, and along with a comprehensive physical examination, a thorough understanding of the applied anatomy is essential. Several studies have helped identify specific areas in which nerves are commonly compressed. Identified secondary causes of nerve compression include previous trauma, osteophytes, ganglion cysts, edema, accessory muscles, tenosynovitis, vascular lesions, and a primary nerve tumor. Imaging plays a key role in identifying primary and secondary causes of nerve entrapment, specifically ultrasound (US) and magnetic resonance imaging. US is a dynamic imaging modality that is cost effective and offers excellent resolution. Symptoms of nerve entrapment may mimic other common foot and ankle conditions such as plantar fasciitis. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Challenges for Nerve Repair Using Chitosan-Siloxane Hybrid Porous Scaffolds

PubMed Central

Shirosaki, Yuki; Hayakawa, Satoshi; Osaka, Akiyoshi; Lopes, Maria A.; Santos, José D.; Geuna, Stefano; Mauricio, Ana C.

2014-01-01

The treatment of peripheral nerve injuries remains one of the greatest challenges of neurosurgery, as functional recover is rarely satisfactory in these patients. Recently, biodegradable nerve guides have shown great potential for enhancing nerve regeneration. A major advantage of these nerve guides is that no foreign material remains after the device has fulfilled its task, which spares a second surgical intervention. Recently, we studied peripheral nerve regeneration using chitosan-γ-glycidoxypropyltrimethoxysilane (chitosan-GPTMS) porous hybrid membranes. In our studies, these porous membranes significantly improved nerve fiber regeneration and functional recovery in rat models of axonotmetic and neurotmetic sciatic nerve injuries. In particular, the number of regenerated myelinated nerve fibers and myelin thickness were significantly higher in rat treated with chitosan porous hybrid membranes, whether or not they were used in combination with mesenchymal stem cells isolated from the Wharton's jelly of the umbilical cord. In this review, we describe our findings on the use of chitosan-GPTMS hybrids for nerve regeneration. PMID:25054129

Peripheral nerve regeneration with conduits: use of vein tubes

PubMed Central

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

2015-01-01

Treatment of peripheral nerve injuries remains a challenge to modern medicine due to the complexity of the neurobiological nerve regenerating process. There is a greater challenge when the transected nerve ends are not amenable to primary end-to-end tensionless neurorraphy. When facing a segmental nerve defect, great effort has been made to develop an alternative to the autologous nerve graft in order to circumvent morbidity at donor site, such as neuroma formation, scarring and permanent loss of function. Tubolization techniques have been developed to bridge nerve gaps and have been extensively studied in numerous experimental and clinical trials. The use of a conduit intends to act as a vehicle for moderation and modulation of the cellular and molecular ambience for nerve regeneration. Among several conduits, vein tubes were validated for clinical application with improving outcomes over the years. This article aims to address the investigation and treatment of segmental nerve injury and draw the current panorama on the use of vein tubes as an autogenous nerve conduit. PMID:26170802

Peripheral nerve regeneration with conduits: use of vein tubes.

PubMed

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

2015-04-01

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

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

PubMed

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

2018-05-01

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

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)

Supratrochlear Neuralgia: A Prospective Case Series of 15 Patients.

PubMed

Pareja, Juan A; López-Ruiz, Pedro; Mayo, Diego; Villar-Quiles, Rocío-Nur; Cárcamo, Alba; Gutiérrez-Viedma, Álvaro; Lastarria, Carlo P; Romeral, María; Yangüela, Julio; Cuadrado, María-Luz

2017-10-01

The aim of this study was to describe clinical features unique to supratrochlear neuralgia. The supratrochlear nerve supplies the medial aspect of the forehead. Due to the intricate relationship between supraorbital and supratrochlear nerves, neuralgic pain in this region has been traditionally attributed to supraorbital neuralgia. No cases of supratrochlear neuralgia have been reported so far. From 2009 through 2016, we prospectively recruited patients with pain confined to the territory of the supratrochlear nerve. Fifteen patients (13 women, 2 men; mean age 51.4 years, standard deviation 14.9) presented with pain in the lower paramedian forehead, extending to the eyebrow in two patients and to the internal angle of the orbit in another. Pain was unilateral in 11 patients (six on the right, five on the left), and bilateral in four. Six patients had continuous pain and nine described intermittent pain. Palpation of the supratrochlear nerve at the medial third of the supraorbital rim resulted in hypersensitivity in all cases. All but one patient exhibited sensory disturbances within the painful area. Fourteen patients underwent anesthetic blockades of the supratrochlear nerve, with immediate relief in all cases and long-term remission in three. Six of them had received unsuccessful anesthetic blocks of the supraorbital nerve. Five patients were treated successfully with oral drugs and one patient was treated with radiofrequency. Supratrochlear neuralgia is an uncommon disorder causing pain in the medial region of the forehead. It may be differentiated from supraorbital neuralgia and other similar headaches and neuralgias based on the topography of the pain and the response to anesthetic blockade. © 2017 American Headache Society.

Peripheral neurostimulation for control of intractable occipital neuralgia.

PubMed

Weiner, R L; Reed, K L

1999-07-01

Objective. To present a novel approach for treatment of intractable occipital neuralgia using percutaneous peripheral nerve electrostimulation techniques. Methods. Thirteen patients underwent 17 implant procedures for medically refractory occipital neuralgia. A subcutaneous electrode placed transversely at the level of C1 across the base of the occipital nerve trunk produced paresthesias and pain relief covering the regions of occipital nerve pain Results. With follow-up ranging from 1-½ to 6 years, 12 patients continue to report good to excellent response with greater than 50% pain control and requiring little or no additional medications. The 13th patient (first in the series) was subsequently explanted following symptom resolution. Conclusions. In patients with medically intractable occipital neuralgia, peripheral nerve electrostimulation subcutaneously at the level of C1 appears to be a reasonable alternative to more invasive surgical procedures following failure of more conservative therapies.

Transdermal optogenetic peripheral nerve stimulation

NASA Astrophysics Data System (ADS)

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

2017-06-01

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

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

PubMed

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

2017-09-01

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

3D-engineering of Cellularized Conduits for Peripheral Nerve Regeneration

NASA Astrophysics Data System (ADS)

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

2016-08-01

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.

Iodine and freeze-drying enhanced high-resolution MicroCT imaging for reconstructing 3D intraneural topography of human peripheral nerve fascicles.

PubMed

Yan, Liwei; Guo, Yongze; Qi, Jian; Zhu, Qingtang; Gu, Liqiang; Zheng, Canbin; Lin, Tao; Lu, Yutong; Zeng, Zitao; Yu, Sha; Zhu, Shuang; Zhou, Xiang; Zhang, Xi; Du, Yunfei; Yao, Zhi; Lu, Yao; Liu, Xiaolin

2017-08-01

The precise annotation and accurate identification of the topography of fascicles to the end organs are prerequisites for studying human peripheral nerves. In this study, we present a feasible imaging method that acquires 3D high-resolution (HR) topography of peripheral nerve fascicles using an iodine and freeze-drying (IFD) micro-computed tomography (microCT) method to greatly increase the contrast of fascicle images. The enhanced microCT imaging method can facilitate the reconstruction of high-contrast HR fascicle images, fascicle segmentation and extraction, feature analysis, and the tracing of fascicle topography to end organs, which define fascicle functions. The complex intraneural aggregation and distribution of fascicles is typically assessed using histological techniques or MR imaging to acquire coarse axial three-dimensional (3D) maps. However, the disadvantages of histological techniques (static, axial manual registration, and data instability) and MR imaging (low-resolution) limit these applications in reconstructing the topography of nerve fascicles. Thus, enhanced microCT is a new technique for acquiring 3D intraneural topography of the human peripheral nerve fascicles both to improve our understanding of neurobiological principles and to guide accurate repair in the clinic. Additionally, 3D microstructure data can be used as a biofabrication model, which in turn can be used to fabricate scaffolds to repair long nerve gaps. Copyright © 2017 Elsevier B.V. All rights reserved.

Peripheral axotomy of the rat mandibular trigeminal nerve leads to an increase in VIP and decrease of other primary afferent neuropeptides in the spinal trigeminal nucleus.

PubMed

Atkinson, M E; Shehab, S A

1986-12-01

In the vasoactive intestinal polypeptide (VIP)-rich lumbosacral spinal cord, VIP increases at the expense of other neuropeptides after primary sensory nerve axotomy. This study was undertaken to ascertain whether similar changes occur in peripherally axotomised cranial sensory nerves. VIP immunoreactivity increased in the terminal region of the mandibular nerve in the trigeminal nucleus caudalis following unilateral section of the sensory root of the mandibular trigeminal nerve at the foramen orale. Other primary afferent neuropeptides (substance P, cholecystokinin and somatostatin) were depleted and fluoride-resistant acid phosphatase activity was abolished in the same circumscribed areas of the nucleus caudalis. The rise in VIP and depletion of other markers began 4 days postoperatively and was maximal by 10 days, these levels remaining unchanged up to 1 year postoperatively. VIP-immunoreactive cell bodies were absent from trigeminal ganglia from the unoperated side but small and medium cells stained intensely in the ganglia of the operated side after axotomy. These observations indicate that increase of VIP in sensory nerve terminals is a general phenomenon occurring in both cranial and spinal sensory terminal areas. The intense VIP immunoreactivity in axotomised trigeminal ganglia suggests that the increased levels of VIP in the nucleus caudalis are of peripheral origin, indicating a change in expression of neuropeptides within primary afferent neurons following peripheral axotomy.

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

PubMed

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

2017-07-18

Delayed reconstruction of transection or laceration injuries of peripheral nerves is inflicted by a reduced regeneration capacity. Diabetic conditions, more frequently encountered in clinical practice, are known to further impair regeneration in peripheral nerves. Chitosan nerve guides (CNGs) have recently been introduced as a new generation of medical devices for immediate peripheral nerve reconstruction. Here, CNGs were used for 45 days delayed reconstruction of critical length 15 mm rat sciatic nerve defects in either healthy Wistar rats or diabetic Goto-Kakizaki rats; the latter resembling type 2 diabetes. In short and long-term investigations, we comprehensively analyzed the performance of one-chambered hollow CNGs (hCNGs) and two-chambered CNGs (CFeCNGs) in which a chitosan film has been longitudinally introduced. Additionally, we investigated in vitro the immunomodulatory effect provided by the chitosan film. Both types of nerve guides, i.e. hCNGs and CFeCNGs, enabled moderate morphological and functional nerve regeneration after reconstruction that was delayed for 45 days. These positive findings were detectable in generally healthy as well as in diabetic Goto-Kakizaki rats (for the latter only in short-term studies). The regenerative outcome did not reach the degree as recently demonstrated after immediate reconstruction using hCNGs and CFeCNGs. CFeCNG-treatment, however, enabled tissue regrowth in all animals (hCNGs: only in 80% of animals). CFeCNGs did further support with an increased vascularization of the regenerated tissue and an enhanced regrowth of motor axons. One mechanism by which the CFeCNGs potentially support successful regeneration is an immunomodulatory effect induced by the chitosan film itself. Our in vitro results suggest that the pro-regenerative effect of chitosan is related to the differentiation of chitosan-adherent monocytes into pro-healing M2 macrophages. No considerable differences appear for the delayed nerve regeneration process related to healthy and diabetic conditions. Currently available chitosan nerve grafts do not support delayed nerve regeneration to the same extent as they do after immediate nerve reconstruction. The immunomodulatory characteristics of the biomaterial may, however, be crucial for their regeneration supportive effects.

New perspectives concerning feedback influences on cardiorespiratory control during rhythmic exercise and on exercise performance.

PubMed

Dempsey, Jerome A

2012-09-01

The cardioaccelerator and ventilatory responses to rhythmic exercise in the human are commonly viewed as being mediated predominantly via feedforward 'central command' mechanisms, with contributions from locomotor muscle afferents to the sympathetically mediated pressor response. We have assessed the relative contributions of three types of feedback afferents on the cardiorespiratory response to voluntary, rhythmic exercise by inhibiting their normal 'tonic' activity in healthy animals and humans and in chronic heart failure. Transient inhibition of the carotid chemoreceptors during moderate intensity exercise reduced muscle sympathetic nerve activity (MSNA) and increased limb vascular conductance and blood flow; and reducing the normal level of respiratory muscle work during heavier intensity exercise increased limb vascular conductance and blood flow. These cardiorespiratory effects were prevented via ganglionic blockade and were enhanced in chronic heart failure and in hypoxia. Blockade of μ opioid sensitive locomotor muscle afferents, with preservation of central motor output via intrathecal fentanyl: (a) reduced the mean arterial blood pressure (MAP), heart rate and ventilatory responses to all steady state exercise intensities; and (b) during sustained high intensity exercise, reduced O(2) transport, increased central motor output and end-exercise muscle fatigue and reduced endurance performance. We propose that these three afferent reflexes - probably acting in concert with feedforward central command - contribute significantly to preserving O(2) transport to locomotor and to respiratory muscles during exercise. Locomotor muscle afferents also appear to provide feedback concerning the metabolic state of the muscle to influence central motor output, thereby limiting peripheral fatigue development.

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

PubMed

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

2017-03-01

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

A Clinical and Electrophysiological Study of Peripheral Neuropathies in Predialysis Chronic Kidney Disease Patients and Relation of Severity of Peripheral Neuropathy with Degree of Renal Failure

PubMed Central

Jasti, Dushyanth Babu; Mallipeddi, Sarat; Apparao, A.; Vengamma, B.; Sivakumar, V.; Kolli, Satyarao

2017-01-01

Objective: To study the prevalence, clinical features, electrophysiological features, and severity of peripheral neuropathy in predialysis chronic kidney disease (CKD) patients with respect to severity of renal failure and presence of diabetes mellitus. Materials and Methods: Between May 2015 and December 2016, 200 predialysis CKD patients were assessed prospectively. Results: The prevalence of peripheral neuropathy in predialysis CKD patients in the present study was 45% based on clinical symptoms and 90% electrophysiologically. Mean age of 200 predialysis CKD patients who participated in the study was 53.2 ± 13.2 years. One hundred and thirty-six (68%) patients were male and 64 (32%) patients were female. Mean duration of disease was 2.2 ± 1.6 years. Nearly 45% patients of patients had asymptomatic peripheral neuropathy in the present study, which was more common in mild-to-moderate renal failure group. One hundred twenty-six patients (63%) had definite damage and 54 patients (27%) had early damage. In mild-to-moderate renal failure (n = 100) and severe renal failure patients (n = 100), 88% and 92% had significant peripheral neuropathy, respectively. Most common nerves involved were sural nerve, median sensory nerve, and ulnar sensory nerve. Diabetic patients (97%) showed more severe and high prevalence of peripheral neuropathy when compared to nondiabetic patients (83%). Most common patterns were pure axonal sensorimotor neuropathy and mixed sensorimotor neuropathy. Conclusion: Peripheral neuropathy is common in predialysis patients, prevalence and severity of which increases as renal failure worsens. Predialysis patients with diabetes show higher prevalence and severity of peripheral neuropathy when compared with nondiabetics. PMID:29204008

Bioengineered nerve regeneration and muscle reinnervation

PubMed Central

Kingham, Paul J; Terenghi, Giorgio

2006-01-01

The peripheral nervous system has the intrinsic capacity to regenerate but the reinnervation of muscles is often suboptimal and results in limited recovery of function. Injuries to nerves that innervate complex organs such as the larynx are particularly difficult to treat. The many functions of the larynx have evolved through the intricate neural regulation of highly specialized laryngeal muscles. In this review, we examine the responses of nerves and muscles to injury, focusing on changes in the expression of neurotrophic factors, and highlight differences between the skeletal limb and laryngeal muscle systems. We also describe how artificial nerve conduits have become a useful tool for delivery of neurotrophic factors as therapeutic agents to promote peripheral nerve repair and might eventually be useful in the treatment of laryngeal nerve injury. PMID:17005023

[Scalp neuralgia and headache elicited by cranial superficial anatomical causes: supraorbital neuralgia, occipital neuralgia, and post-craniotomy headache].

PubMed

Shimizu, Satoru

2014-01-01

Most scalp neuralgias are supraorbital or occipital. Although they have been considered idiopathic, recent studies revealed that some were attributable to mechanical irritation with the peripheral nerve of the scalp by superficial anatomical cranial structures. Supraorbital neuralgia involves entrapment of the supraorbital nerve by the facial muscle, and occipital neuralgia involves entrapment of occipital nerves, mainly the greater occipital nerve, by the semispinalis capitis muscle. Contact between the occipital artery and the greater occipital nerve in the scalp may also be causative. Decompression surgery to address these neuralgias has been reported. As headache after craniotomy is the result of iatrogenic injury to the peripheral nerve of the scalp, post-craniotomy headache should be considered as a differential diagnosis.

Recognizing schwannomatosis and distinguishing it from neurofibromatosis type 1 or 2.

PubMed

Westhout, Franklin D; Mathews, Marlon; Paré, Laura S; Armstrong, William B; Tully, Patricia; Linskey, Mark E

2007-06-01

Schwannomatosis has become a newly recognized classification of neurofibromatosis. Although the genetic loci are on chromosome 22, it lacks the classic bilateral vestibular schwannomas as seen in NF-2. We present the surgical treatment of 4 patients with schwannomatosis, including a brother and sister. Case 1 presented with multiple progressively enlarging peripheral nerve sheath tumors. Case 4 presented with a trigeminal schwannoma and a vagal nerve schwannoma. Three of 4 patients had spinal intradural, extramedullary nerve sheath tumors. Surgery in all was multistaged and consisted of spinal laminectomies, site-specific explorations, and microsurgical tumor dissection and resection, with intraoperative neurophysiologic monitoring (including somatosensory-evoked and motor-evoked potentials, upper extremity electromyography and intraoperative nerve action potential monitoring, as appropriate). Intraoperatively the schwannomas had cystic and solid features and in all surgical cases the tumors arose from discrete fascicles of sensory nerve roots or sensory peripheral nerve branches. None of the patients experienced neurologic worsening as a result of their resections. Pathologic analysis of specimens from all cases demonstrated schwannoma. Not all patients with multiple schwannomas of cranial nerve, spinal nerve root, or peripheral nerve origin have NF-1 or NF-2. In schwannomatosis, these lesions are present in the absence of cutaneous stigmata, neurofibromas, vestibular schwannomas, or parenchymal brain tumors. Schwannomas in schwannomatosis can be large, cystic, and multiple. However, the predominant nerve involvement seems to be sensory and discrete fascicular in origin, facilitating microsurgical resection with minimal deficit.

Epithelioid Malignant Peripheral Nerve Sheath Tumor Arising in a Schwannoma, in a Patient with “Neuroblastoma-like” Schwannomatosis and a Novel Germline SMARCB1 mutation

PubMed Central

Carter, Jodi M.; O'Hara, Carolyn; Dundas, George; Gilchrist, Dawna; Collins, Mark S.; Eaton, Katherine; Judkins, Alexander R.; Biegel, Jaclyn A.; Folpe, Andrew L.

2011-01-01

Epithelioid malignant peripheral nerve sheath tumors arising in pre-existing schwannomas are extremely rare. We report an unusual example occurring in a patient with multiple schwannomas (schwannomatosis), all but one of which showed “neuroblastoma-like” histology. By immunohistochemistry, both the epithelioid malignant peripheral nerve sheath tumor and the schwannomas showed a complete loss of the Smarcb1 protein. Subsequent genetic evaluation revealed the presence of a novel germline mutation in the SMARCB1/INI1 gene in the patient and three of her children, two of whom were diagnosed with atypical teratoid/rhabdoid tumors of the brain. PMID:22082606

[Hypobaric 0.15% bupivacaine versus hyperbaric 0.5% bupivacaine for posterior (dorsal) spinal block in outpatient anorectal surgery.].

PubMed

Imbelloni, Luiz Eduardo; Vieira, Eneida Maria; Gouveia, M A; Netinho, João Gomes; Cordeiro, José Antonio

2006-12-01

The aim of this study was to study low dose hypobaric 0.15% bupivacaine and hyperbaric 0.5% bupivacaine in outpatient anorectal surgical procedures. Two groups of 50 patients, physical status ASA I and II, undergoing anorectal surgical procedures in a jackknife position, received 6 mg of hypobaric 0.15% bupivacaine in the surgical position (Group 1) or 6 mg of hyperbaric 0.5% bupivacaine in the sitting position for 5 minutes, after which they were placed in a jackknife position (Group 2). Sensitive and motor blockade, time of first urination, ambulation, complications, and the need for analgesics were evaluated. Patients were followed until the third postoperative day and questioned whether they experienced post-puncture headache or temporary neurological symptoms, and until the 30th day and questioned about permanent neurological complications. The test t Student, Mood's median, and Fisher Exact test were used for statistical analysis, and a p < 0.05 was considered significant. Every patient in Group 1 presented selective blockade of the posterior sacral nerve roots, while patients in Group 2 experienced blockade of the anterior and posterior nerve roots. Blockade was significantly higher in Group 1. Motor blockade was significantly less severe in Group 1. Forty-nine patients in Group 1 transferred to the stretcher unassisted while only 40 patients in Group 2 were able to do so. Recovery in Group 1 occurred in 105 +/- 25 minutes and in 95 +/- 15 minutes in Group 2, and this difference was not statistically significant. There were no hemodynamic changes, nausea or vomiting, urine retention, or post-puncture headache. Anorectal surgical procedures under spinal block with low dose bupivacaine, hyperbaric or hypobaric, can be safely done.

Targeting the cMET pathway augments radiation response without adverse effect on hearing in NF2 schwannoma models.

PubMed

Zhao, Yingchao; Liu, Pinan; Zhang, Na; Chen, Jie; Landegger, Lukas D; Wu, Limeng; Zhao, Fu; Zhao, Yanxia; Zhang, Yanling; Zhang, Jing; Fujita, Takeshi; Stemmer-Rachamimov, Anat; Ferraro, Gino B; Liu, Hao; Muzikansky, Alona; Plotkin, Scott R; Stankovic, Konstantina M; Jain, Rakesh K; Xu, Lei

2018-02-27

Neurofibromatosis type II (NF2) is a disease that needs new solutions. Vestibular schwannoma (VS) growth causes progressive hearing loss, and the standard treatment, including surgery and radiotherapy, can further damage the nerve. There is an urgent need to identify an adjunct therapy that, by enhancing the efficacy of radiation, can help lower the radiation dose and preserve hearing. The mechanisms underlying deafness in NF2 are still unclear. One of the major limitations in studying tumor-induced hearing loss is the lack of mouse models that allow hearing testing. Here, we developed a cerebellopontine angle (CPA) schwannoma model that faithfully recapitulates the tumor-induced hearing loss. Using this model, we discovered that cMET blockade by crizotinib (CRZ) enhanced schwannoma radiosensitivity by enhancing DNA damage, and CRZ treatment combined with low-dose radiation was as effective as high-dose radiation. CRZ treatment had no adverse effect on hearing; however, it did not affect tumor-induced hearing loss, presumably because cMET blockade did not change tumor hepatocyte growth factor (HGF) levels. This cMET gene knockdown study independently confirmed the role of the cMET pathway in mediating the effect of CRZ. Furthermore, we evaluated the translational potential of cMET blockade in human schwannomas. We found that human NF2-associated and sporadic VSs showed significantly elevated HGF expression and cMET activation compared with normal nerves, which correlated with tumor growth and cyst formation. Using organoid brain slice culture, cMET blockade inhibited the growth of patient-derived schwannomas. Our findings provide the rationale and necessary data for the clinical translation of combined cMET blockade with radiation therapy in patients with NF2.

Unique Phrenic Nerve-Sparing Regional Anesthetic Technique for Pain Management after Shoulder Surgery

PubMed Central

Olsen, David A.; Amundson, Adam W.

2017-01-01

Background Ipsilateral phrenic nerve blockade is a common adverse event after an interscalene brachial plexus block, which can result in respiratory deterioration in patients with preexisting pulmonary conditions. Diaphragm-sparing nerve block techniques are continuing to evolve, with the intention of providing satisfactory postoperative analgesia while minimizing hemidiaphragmatic paralysis after shoulder surgery. Case Report We report the successful application of a combined ultrasound-guided infraclavicular brachial plexus block and suprascapular nerve block in a patient with a complicated pulmonary history undergoing a total shoulder replacement. Conclusion This case report briefly reviews the important innervations to the shoulder joint and examines the utility of the infraclavicular brachial plexus block for postoperative pain management. PMID:29410922

Prevention and Treatment of Neurofibromatosis Type 1-Associated Malignant Peripheral Nerve Sheath Tumors

DTIC Science & Technology

2016-04-01

Page 1 AWARD NUMBER: W81XWH-14-1-0073 TITLE: Prevention and Treatment of Neurofibromatosis Type 1-Associated Malignant Peripheral...COVERED 04/01/2015 to 03/31/2016 4. TITLE AND SUBTITLE Prevention and Treatment of Neurofibromatosis Type 1- 5a. CONTRACT NUMBER W81XWH-14-1-0073...ABSTRACT The most common cause of death in Neurofibromatosis Type 1 (NF1) patients is malignant peripheral nerve sheath tumor (MPNST). MPNSTs are

Genetic predisposition to peripheral nerve neoplasia: Diagnostic criteria and pathogenesis of neurofibromatoses, Carney complex, and related syndromes

PubMed Central

Rodriguez, Fausto J.; Stratakis, Constantine A.; Evans, D Gareth

2013-01-01

Neoplasms of the peripheral nerve sheath represent essential clinical manifestations of the syndromes known as the neurofibromatoses. Although involvement of multiple organ systems, including skin, central nervous system and skeleton, may also be conspicuous, peripheral nerve neoplasia is often the most important and frequent cause of morbidity in these patients. Clinical characteristics of neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2) have been extensively described and studied during the last century, and the identification of mutations in the NF1 and NF2 genes by contemporary molecular techniques have created a separate multidisciplinary field in genetic medicine. In schwannomatosis, the most recent addition to the neurofibromatosis group, peripheral nervous system involvement is the exclusive (or almost exclusive) clinical manifestation. Although the majority of cases of schwannomatosis are sporadic, approximately a third occur in families and a subset of these has recently been associated with germline mutations in the tumor suppressor gene SMARCB1/INI1. Other curious syndromes that involve the peripheral nervous system are associated with predominant endocrine manifestations, and include Carney Complex and MEN2b, secondary to inactivating mutations in the PRKAR1A gene in a subset, and activating mutations in RET respectively. In this review, we provide a concise update on the diagnostic criteria, pathology and molecular pathogenesis of these enigmatic syndromes in relation to peripheral nerve sheath neoplasia. PMID:22210082

Genetic predisposition to peripheral nerve neoplasia: diagnostic criteria and pathogenesis of neurofibromatoses, Carney complex, and related syndromes.

PubMed

Rodriguez, Fausto J; Stratakis, Constantine A; Evans, D Gareth

2012-03-01

Neoplasms of the peripheral nerve sheath represent essential clinical manifestations of the syndromes known as the neurofibromatoses. Although involvement of multiple organ systems, including skin, central nervous system, and skeleton, may also be conspicuous, peripheral nerve neoplasia is often the most important and frequent cause of morbidity in these patients. Clinical characteristics of neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2) have been extensively described and studied during the last century, and the identification of mutations in the NF1 and NF2 genes by contemporary molecular techniques have created a separate multidisciplinary field in genetic medicine. In schwannomatosis, the most recent addition to the neurofibromatosis group, peripheral nervous system involvement is the exclusive (or almost exclusive) clinical manifestation. Although the majority of cases of schwannomatosis are sporadic, approximately one-third occur in families and a subset of these has recently been associated with germline mutations in the tumor suppressor gene SMARCB1/INI1. Other curious syndromes that involve the peripheral nervous system are associated with predominant endocrine manifestations, and include Carney complex and MEN2b, secondary to inactivating mutations in the PRKAR1A gene in a subset, and activating mutations in RET, respectively. In this review, we provide a concise update on the diagnostic criteria, pathology and molecular pathogenesis of these enigmatic syndromes in relation to peripheral nerve sheath neoplasia.

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.

The effects of hemostatic agents on peripheral nerve function: an experimental study.

PubMed

Alkan, Alper; Inal, Samet; Yildirim, Mehmet; Baş, Burcu; Ağar, Erdal

2007-04-01

In the practice of oral and maxillofacial surgery, hemostatic agents are sometimes placed in close proximity to peripheral nerves. In the present study, we evaluated immediate and delayed effects of 4 hemostatic agents (oxidized regenerated cellulose, 5% colloid silver-added gelatine sponge, bovine collagen, bone wax) on peripheral nerve function. A total of 25 rat sciatic nerves were prepared, and the amplitudes were recorded with a physiological data acquisition system. Animals were randomly assigned to 5 groups: control, oxidized regenerated cellulose, gelatine sponge, bone wax, and bovine collagen. The first hour records are defined as immediate effects of these hemostatic agents on nerve function. The animals were then allowed to recover for 4 weeks. At the end of this period, the same surgical and recording procedures were performed. These final records are defined as delayed effects of hemostatic agents on nerve function. According to nerve conduction velocity (NCV) and compound action potential (CAP) values of the experimental groups, early and delayed effects of each hemostatic agent were statistically compared with Bonferroni corrected test (P < .05). Statistically, NCV was significantly reduced, and the CAP was significantly increased 1 hour after surgery (P < .05) in the group of oxidized regenerated cellulose. However, there were no significant differences after 4 weeks compared with the first records. In the gelatine sponge group, CAP was significantly increased 4 weeks after the application. In the bovine collagen and bone wax groups, NCV and CAP values (1 hour and 4 weeks after the application) were not statistically significant compared with initial control records. The present study shows that bovine collagen is the most suitable hemostatic agent applicable for peripheral nerves.

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

PubMed

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

2018-06-01

Peripheral nerve injury (PNI) is a major burden to society with limited therapeutic options, and novel biomaterials have great potential for shifting the current paradigm of treatment. With a rising prevalence of chronic illnesses such as diabetes mellitus (DM), treatment of PNI is further complicated, and only few studies have proposed therapies suitable for peripheral nerve regeneration in DM. To provide a supportive environment to restore structure and/or function of nerves in DM, we developed a novel thermo-sensitive heparin-poloxamer (HP) hydrogel co-delivered with basic fibroblast growth factor (bFGF) and nerve growth factor (NGF) in diabetic rats with sciatic nerve crush injury. The delivery vehicle not only had a good affinity for large amounts of growth factors (GFs), but also controlled their release in a steady fashion, preventing degradation in vitro. In vivo, compared with HP hydrogel alone or direct GFs administration, GFs-HP hydrogel treatment is more effective at facilitating Schwann cell (SC) proliferation, leading to an increased expression of nerve associated structural proteins, enhanced axonal regeneration and remyelination, and improved recovery of motor function (all p < 0.05). Our mechanistic investigation also revealed that these neuroprotective and neuroregenerative effects of the GFs-HP hydrogel may be associated with activations of phosphatidylinositol 3 kinase and protein kinase B (PI3K/Akt), janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3), and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathways. Our work provides a promising therapy option for peripheral nerve regeneration in patients with DM. Copyright © 2018 Elsevier Ltd. All rights reserved.

Evaluation of peripheral microcirculation improvement of foot after tarsal tunnel release in diabetic patients by transcutaneous oximetry.

PubMed

Trignano, Emilio; Fallico, Nefer; Chen, Hung-Chi; Faenza, Mario; Bolognini, Alfonso; Armenti, Andrea; Santanelli Di Pompeo, Fabio; Rubino, Corrado; Campus, Gian Vittorio

2016-01-01

According to recent studies, peripheral nerve decompression in diabetic patients seems to not only improve nerve function, but also to increase microcirculation; thus decreasing the incidence of diabetic foot wounds and amputations. However, while the postoperative improvement of nerve function is demonstrated, the changes in peripheral microcirculation have not been demonstrated yet. The aim of this study is to assess the degree of microcirculation improvement of foot after the tarsal tunnel release in the diabetic patients by using transcutaneous oximetry. Twenty diabetic male patients aged between 43 and 72 years old (mean age 61.2 years old) suffering from diabetic peripheral neuropathy with superimposed nerve compression underwent transcutaneous oximetry (PtcO2) before and after tarsal tunnel release by placing an electrode on the skin at the level of the dorsum of the foot. Eight lower extremities presented diabetic foot wound preoperatively. Thirty-six lower extremities underwent surgical release of the tibialis posterior nerve only, whereas four lower extremities underwent the combined release of common peroneal nerve, anterior tibialis nerve, and posterior tibialis nerve. Preoperative values of transcutaneous oximetry were below the critical threshold, that is, lower than 40 mmHg (29.1 ± 5.4 mmHg). PtcO2 values at one month after surgery (45.8 ± 6.4 mmHg) were significantly higher than the preoperative ones (P = 0.01). The results of postoperative increase in PtcO2 values demonstrate that the release of the tarsal tunnel determines a relevant increase in microcirculation in the feet of diabetic patients. © 2015 Wiley Periodicals, Inc.

Specific paucity of unmyelinated C-fibers in cutaneous peripheral nerves of the African naked-mole rat: comparative analysis using six species of Bathyergidae.

PubMed

St John Smith, Ewan; Purfürst, Bettina; Grigoryan, Tamara; Park, Thomas J; Bennett, Nigel C; Lewin, Gary R

2012-08-15

In mammalian peripheral nerves, unmyelinated C-fibers usually outnumber myelinated A-fibers. By using transmission electron microscopy, we recently showed that the saphenous nerve of the naked mole-rat (Heterocephalus glaber) has a C-fiber deficit manifested as a substantially lower C:A-fiber ratio compared with other mammals. Here we determined the uniqueness of this C-fiber deficit by performing a quantitative anatomical analysis of several peripheral nerves in five further members of the Bathyergidae mole-rat family: silvery (Heliophobius argenteocinereus), giant (Fukomys mechowii), Damaraland (Fukomys damarensis), Mashona (Fukomys darlingi), and Natal (Cryptomys hottentotus natalensis) mole-rats. In the largely cutaneous saphenous and sural nerves, the naked mole-rat had the lowest C:A-fiber ratio (∼1.5:1 compared with ∼3:1), whereas, in nerves innervating both skin and muscle (common peroneal and tibial) or just muscle (lateral/medial gastrocnemius), this pattern was mostly absent. We asked whether lack of hair follicles alone accounts for the C-fiber paucity by using as a model a mouse that loses virtually all its hair as a consequence of conditional deletion of the β-catenin gene in the skin. These β-catenin loss-of function mice (β-cat LOF mice) displayed only a mild decrease in C:A-fiber ratio compared with wild-type mice (4.42 compared with 3.81). We suggest that the selective cutaneous C-fiber deficit in the cutaneous nerves of naked mole-rats is unlikely to be due primarily to lack of skin hair follicles. Possible mechanisms contributing to this unique peripheral nerve anatomy are discussed. Copyright © 2012 Wiley Periodicals, Inc.

Specific Paucity of Unmyelinated C-Fibers in Cutaneous Peripheral Nerves of the African Naked-Mole Rat: Comparative Analysis Using Six Species of Bathyergidae

PubMed Central

Smith, Ewan S; Purfürst, Bettina; Grigoryan, Tamara; Park, Thomas J; Bennett, Nigel C; Lewin, Gary R

2012-01-01

In mammalian peripheral nerves, unmyelinated C-fibers usually outnumber myelinated A-fibers. By using transmission electron microscopy, we recently showed that the saphenous nerve of the naked mole-rat (Heterocephalus glaber) has a C-fiber deficit manifested as a substantially lower C:A-fiber ratio compared with other mammals. Here we determined the uniqueness of this C-fiber deficit by performing a quantitative anatomical analysis of several peripheral nerves in five further members of the Bathyergidae mole-rat family: silvery (Heliophobius argenteocinereus), giant (Fukomys mechowii), Damaraland (Fukomys damarensis), Mashona (Fukomys darlingi), and Natal (Cryptomys hottentotus natalensis) mole-rats. In the largely cutaneous saphenous and sural nerves, the naked mole-rat had the lowest C:A-fiber ratio (∼1.5:1 compared with ∼3:1), whereas, in nerves innervating both skin and muscle (common peroneal and tibial) or just muscle (lateral/medial gastrocnemius), this pattern was mostly absent. We asked whether lack of hair follicles alone accounts for the C-fiber paucity by using as a model a mouse that loses virtually all its hair as a consequence of conditional deletion of the β-catenin gene in the skin. These β-catenin loss-of function mice (β-cat LOF mice) displayed only a mild decrease in C:A-fiber ratio compared with wild-type mice (4.42 compared with 3.81). We suggest that the selective cutaneous C-fiber deficit in the cutaneous nerves of naked mole-rats is unlikely to be due primarily to lack of skin hair follicles. Possible mechanisms contributing to this unique peripheral nerve anatomy are discussed. J. Comp. Neurol. 520:2785–2803, 2012. © 2012 Wiley Periodicals, Inc. PMID:22528859

[Neuromuscular blocking and respiratory depressing actions of sodium ammonium dimethyl-2-(propano-1,3-dithiosulfate) monohydrate].

PubMed

Cao, B J; Chen, Z K; Chi, Z Q

1990-05-01

The neuromuscular blocking and respiratory depressing actions of the new insecticide sodium ammonium dimethyl-2-(propano-1,3-dithiosulfate) monohydrate (SCD) were investigated. In peroneal-tibialis anterior nerve-muscle preparations of urethane anesthetized rabbit, SCD 6.5 mg/kg iv completely depressed the indirectly elicited twitch tension but not the directly elicited one. This compound also caused initial potentiation of the indirectly elicited twitch tension. In the partially paralyzed preparations, potentiation of contractions occurred following a brief period of indirectly tetanic stimulation. Nereistoxin but not SCD blocked the indirectly elicited twitch tension of isolated rat diaphragm. The neuromuscular blockade induced by SCD and nereistoxin was antagonized by neostigmine and 4-aminopyridine. SCD and nereistoxin had little or no effect on arterial blood pressure and phrenic nerve discharge of rabbits. The results indicated that SCD-poisoned rabbits died of respiratory paralysis following the neuromuscular blockade.

Immune deficiency in mouse models for inherited peripheral neuropathies leads to improved myelin maintenance.

PubMed

Schmid, C D; Stienekemeier, M; Oehen, S; Bootz, F; Zielasek, J; Gold, R; Toyka, K V; Schachner, M; Martini, R

2000-01-15

The adhesive cell surface molecule P(0) is the most abundant glycoprotein in peripheral nerve myelin and fulfills pivotal functions during myelin formation and maintenance. Mutations in the corresponding gene cause hereditary demyelinating neuropathies. In mice heterozygously deficient in P(0) (P(0)(+/-) mice), an established animal model for a subtype of hereditary neuropathies, T-lymphocytes are present in the demyelinating nerves. To monitor the possible involvement of the immune system in myelin pathology, we cross-bred P(0)(+/-) mice with null mutants for the recombination activating gene 1 (RAG-1) or with mice deficient in the T-cell receptor alpha-subunit. We found that in P(0)(+/-) mice myelin degeneration and impairment of nerve conduction properties is less severe when the immune system is deficient. Moreover, isolated T-lymphocytes from P(0)(+/-) mice show enhanced reactivity to myelin components of the peripheral nerve, such as P(0), P(2), and myelin basic protein. We hypothesize that autoreactive immune cells can significantly foster the demyelinating phenotype of mice with a primarily genetically based peripheral neuropathy.

The effect of interleukin-2 on canine peripheral nerve sheath tumours after marginal surgical excision: a double-blind randomized study

PubMed Central

2013-01-01

Background The objective of this study was to evaluate the effect on outcomes of intraoperative recombinant human interleukin-2 injection after surgical resection of peripheral nerve sheath tumours. In this double-blind trial, 40 patients due to undergo surgical excision (<5 mm margins) of presumed peripheral nerve sheath tumours were randomized to receive intraoperative injection of interleukin-2 or placebo into the wound bed. Results There were no significant differences in any variable investigated or in median survival between the two groups. The median recurrence free interval was 874 days (range 48–2141 days), The recurrence-free interval and overall survival time were significantly longer in dogs that undergone the primary surgery by a specialist-certified surgeon compared to a referring veterinarian regardless of whether additional adjunct therapy was given. Conclusion Overall, marginal excision of peripheral nerve sheath tumours in dogs resulted in a long survival time, but adjuvant treatment with recombinant human interleukin-2 (rhIL-2) did not provide a survival advantage. PMID:23927575

High Prevalence and Incidence of Diabetic Peripheral Neuropathy in Children and Adolescents With Type 1 Diabetes Mellitus: Results From a Five-Year Prospective Cohort Study.

PubMed

Walter-Höliner, Isabella; Barbarini, Daniela Seick; Lütschg, Jürg; Blassnig-Ezeh, Anya; Zanier, Ulrike; Saely, Christoph H; Simma, Burkhard

2018-03-01

In this prospective cohort study, we investigated the prevalence of diabetic peripheral neuropathy at baseline and after five years of follow-up in children and adolescents with type 1 diabetes mellitus using both measurements of nerve conduction velocity and clinical neurological examination. A total of 38 patients who underwent insulin pump or intensive insulin therapy were included. The subjects averaged 12.6 ± 2.4 years of age and their diabetes duration averaged 5.6 ± 3.2 years. All patients underwent a detailed physical, neurological, and electrophysiological examination, as well as laboratory testing at their annual checkup. At baseline, the prevalence of diabetic peripheral neuropathy diagnosed using neurological examination was 13.2%, whereas nerve conduction velocity testing revealed diabetic peripheral neuropathy in 31.6%, highlighting a high prevalence of subclinical diabetic peripheral neuropathy. During follow-up, there was a strong increase in the prevalence of clinically diagnosed diabetic peripheral neuropathy, which reached 34.2% (P = 0.039) after five years; the proportion of patients with subclinical diabetic peripheral neuropathy even reached 63.2% (P = 0.002). The most significant changes in electrophysiological parameters were observed in the tibial sensory nerve (P = 0.001). The prevalence of diabetic peripheral neuropathy in children and adolescents with type 1 diabetes mellitus was high, and there was a rapid increase in the prevalence of diabetic peripheral neuropathy during a five-year follow-up interval. Importantly, our data show that a mere clinical evaluation is not sensitive enough to diagnose diabetic peripheral neuropathy in these patients. Nerve conduction velocity measurement, which is regarded as the gold standard for the assessment of diabetic peripheral neuropathy, should be applied more broadly. Copyright © 2017 Elsevier Inc. All rights reserved.

Biocompatible Electroactive Tetra(aniline)-Conjugated Peptide Nanofibers for Neural Differentiation.

PubMed

Arioz, Idil; Erol, Ozlem; Bakan, Gokhan; Dikecoglu, F Begum; Topal, Ahmet E; Urel, Mustafa; Dana, Aykutlu; Tekinay, Ayse B; Guler, Mustafa O

2018-01-10

Peripheral nerve injuries cause devastating problems for the quality of patients' lives, and regeneration following damage to the peripheral nervous system is limited depending on the degree of the damage. Use of nanobiomaterials can provide therapeutic approaches for the treatment of peripheral nerve injuries. Electroactive biomaterials, in particular, can provide a promising cure for the regeneration of nerve defects. Here, a supramolecular electroactive nanosystem with tetra(aniline) (TA)-containing peptide nanofibers was developed and utilized for nerve regeneration. Self-assembled TA-conjugated peptide nanofibers demonstrated electroactive behavior. The electroactive self-assembled peptide nanofibers formed a well-defined three-dimensional nanofiber network mimicking the extracellular matrix of the neuronal cells. Neurite outgrowth was improved on the electroactive TA nanofiber gels. The neural differentiation of PC-12 cells was more advanced on electroactive peptide nanofiber gels, and these biomaterials are promising for further use in therapeutic neural regeneration applications.

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.

Nerve and muscle involvement in mitochondrial disorders: an electrophysiological study.

PubMed

Mancuso, Michelangelo; Piazza, Selina; Volpi, Leda; Orsucci, Daniele; Calsolaro, Valeria; Caldarazzo Ienco, Elena; Carlesi, Cecilia; Rocchi, Anna; Petrozzi, Lucia; Calabrese, Rosanna; Siciliano, Gabriele

2012-04-01

Involvement of the peripheral nervous system in mitochondrial disorders (MD) has been previously reported. However, the exact prevalence of peripheral neuropathy and/or myopathy in MD is still unclear. In order to evaluate the prevalence of neuropathy and myopathy in MD, we performed sensory and motor nerve conduction studies (NCS) and concentric needle electromyography (EMG) in 44 unselected MD patients. NCS were abnormal in 36.4% of cases, and were consistent with a sensori-motor axonal multineuropathy (multifocal neuropathy), mainly affecting the lower limbs. EMG evidence of myopathy was present in 54.5% of patients, again mainly affecting the lower limbs. Nerve and muscle involvement was frequently subclinical. Peripheral nerve and muscle involvement is common in MD patients. Our study supports the variability of the clinical expression of MD. Further studies are needed to better understand the molecular basis underlying the phenotypic variability among MD patients.

Transformation of synaptic vesicle phenotype in the intramedullary axonal arbors of cat spinal motoneurons following peripheral nerve injury.

PubMed

Havton, L A; Kellerth, J O

2001-08-01

Permanent transection of a peripheral motor nerve induces a gradual elimination of whole axon collateral systems in the axotomized spinal motoneurons. There is also an initial concurrent decrease in the amount of recurrent inhibition exerted by these arbors in the spinal cord for up to 6 weeks after the injury, whereas the same reflex action returns to normal by the 12-week postoperative state. The aim of the present investigation was to study the fine structure of the intramedullary axonal arbors of axotomized alpha-motoneurons in the adult cat spinal cord following a permanent peripheral motor nerve lesion. For this purpose, single axotomized alpha-motoneurons were labeled intracellularly with horseradish peroxidase at 12 weeks after permanent transection of their peripheral motor nerve. The intramedullary portions of their motor axon and axon collateral arbors were first reconstructed at the light microscopic level and subsequently studied ultrastructurally. This study shows that the synaptic contacts made by the intramedullary axon collateral arbors of axotomized motoneurons have undergone a change in synaptic vesicle ultrastructure from spherical and clear vesicles to spherical and dense-cored vesicles at 12 weeks after the transection of their peripheral axons. We suggest that the present transformation in synaptic vesicle fine structure may also correspond to a change in the contents of these boutons. This may, in turn, be responsible for the strengthening and recovery of the recurrent inhibitory reflex action exerted by the axotomized spinal motoneurons following a prolonged permanent motor nerve injury.

A forgotten facial nerve tumour: granular cell tumour of the parotid and its implications for treatment.

PubMed

Lerut, B; Vosbeck, J; Linder, T E

2011-04-01

We present a rare case of a facial nerve granular cell tumour in the right parotid gland, in a 10-year-old boy. A parotid or neurogenic tumour was suspected, based on magnetic resonance imaging. Intra-operatively, strong adhesions to surrounding structures were found, and a midfacial nerve branch had to be sacrificed for complete tumour removal. Recent reports verify that granular cell tumours arise from Schwann cells of peripheral nerve branches. The rarity of this tumour within the parotid gland, its origin from peripheral nerves, its sometimes misleading imaging characteristics, and its rare presentation with facial weakness and pain all have considerable implications on the surgical strategy and pre-operative counselling. Fine needle aspiration cytology may confirm the neurogenic origin of this lesion. When resecting the tumour, the surgeon must anticipate strong adherence to the facial nerve and be prepared to graft, or sacrifice, certain branches of this nerve.

A pediatric case with peripheral facial nerve palsy caused by a granulomatous lesion associated with cat scratch disease.

PubMed

Nakamura, Chizuko; Inaba, Yuji; Tsukahara, Keiko; Mochizuki, Mie; Sawanobori, Emi; Nakazawa, Yozo; Aoyama, Kouki

2018-02-01

Cat scratch disease is a common infectious disorder caused by Bartonella henselae that is transmitted primarily by kittens. It typically exhibits a benign and self-limiting course of subacute regional lymphadenopathy and fever lasting two to eight weeks. The most severe complication of cat scratch disease is involvement of the nervous system, such as encephalitis, meningitis, and polyneuritis. Peripheral facial nerve palsy associated with Bartonella infection is rare; few reported pediatric and adult cases exist and the precise pathogenesis is unknown. A previously healthy 7-year-old boy presented with fever, cervical lymphadenopathy, and peripheral facial nerve palsy associated with serologically confirmed cat scratch disease. The stapedius muscle reflex was absent on the left side and brain magnetic resonance imaging revealed a mass lesion at the left internal auditory meatus. The patient's symptoms and imaging findings were gradually resolved after the antibiotics and corticosteroids treatment. The suspected granulomatous lesion was considered to have resulted from the host's immune reaction to Bartonella infection and impaired the facial nerve. This is the first case report providing direct evidence of peripheral facial nerve palsy caused by a suspected granulomatous lesion associated with cat scratch disease and its treatment course. Copyright © 2017. Published by Elsevier B.V.

Electrically stimulated signals from a long-term Regenerative Peripheral Nerve Interface.

PubMed

Langhals, Nicholas B; Woo, Shoshana L; Moon, Jana D; Larson, John V; Leach, Michelle K; Cederna, Paul S; Urbanchek, Melanie G

2014-01-01

Despite modern technological advances, the most widely available prostheses provide little functional recovery beyond basic grasping. Although sophisticated upper extremity prostheses are available, optimal prosthetic interfaces which give patients high-fidelity control of these artificial limbs are limited. We have developed a novel Regenerative Peripheral Nerve Interface (RPNI), which consists of a unit of free muscle that has been neurotized by a transected peripheral nerve. In conjunction with a biocompatible electrode on the muscle surface, the RPNI facilitates signal transduction from a residual peripheral nerve to a neuroprosthetic limb. The purpose of this study was to explore signal quality and reliability in an RPNI following an extended period of implantation. Following a 14-month maturation period, electromyographic signal generation was evaluated via electrical stimulation of the innervating nerve. The long-term RPNI was viable and healthy, as demonstrated by evoked compound muscle action potentials as well as histological tissue analysis. Signals exceeding 4 mV were successfully acquired and amplitudes were consistent across multiple repetitions of applied stimuli. There were no evident signs of muscle denervation, significant scar tissue, or muscle necrosis. This study provides further evidence that after a maturation period exceeding 1 year, reliable and consistent signals can still be acquired from an RPNI.

Social impact of peripheral nerve injuries.

PubMed

Wojtkiewicz, Danielle M; Saunders, James; Domeshek, Leahthan; Novak, Christine B; Kaskutas, Vicki; Mackinnon, Susan E

2015-06-01

Disorders involving the peripheral nervous system can have devastating impacts on patients' daily functions and routines. There is a lack of consideration of the impact of injury on social/emotional well-being and function. We performed a retrospective database and chart review of adult patients presenting between 2010 and 2012 with peripheral nerve compression, brachial plexus injury, thoracic outlet syndrome (TOS), or neuromas. At the initial assessment, patients completed a questionnaire used to obtain demographic and psychosocial variable data including the (1) average level of pain over the last month, (2) self-perceived depression, (3) how much pain impacts quality of life (QoL), (4) current level of stress, and (5) ability to cope with stress. Statistical analyses were used to assess the differences between the dependent variables and diagnostic and demographic groups. This study included 490 patients (mean age 50 ± 15 years); the most common diagnosis was single nerve compression (n = 171). Impact on QoL was significantly greater in patients with TOS, cutaneous peroneal compressions, and neuroma versus single site nerve compressions. Average pain, impact on QoL, and stress at home were significantly higher in females versus males. Impact on QoL was correlated with average pain, depression, stress at home, and ability to cope with stress at home. Our study demonstrates that patients with single site nerve compression neuropathies experience fewer negative psychosocial effects compared to patients with more proximal upper extremity peripheral nerve disorders and neuromas. The impact on QoL was strongly correlated with pain and depression, where patients with neuromas and painful peroneal nerve entrapments reported greater detriments to QoL.

Sensorimotor Peripheral Nerve Function and the Longitudinal Relationship with Endurance Walking in the Health, Aging and Body Composition Study

PubMed Central

Lange-Maia, Brittney S.; Newman, Anne B.; Cauley, Jane A.; Boudreau, Robert M.; Jakicic, John M.; Caserotti, Paolo; Glynn, Nancy W.; Harris, Tamara B.; Kritchevsky, Stephen B.; Schwartz, Ann V.; Satterfield, Suzanne; Simonsick, Eleanor M.; Vinik, Aaron I.; Zivkovic, Sasa; Strotmeyer, Elsa S.

2015-01-01

Objectives To determine whether lower extremity sensorimotor peripheral nerve deficits are associated with reduced walking endurance in older adults. Design Prospective cohort study with six years of follow-up. Setting Two U.S. clinical sites in (Pittsburgh, PA and Memphis, TN). Participants Community-dwelling older adults enrolled in Health, Aging and Body Composition study from the 2000/01 annual clinical examination (n=2393; age 76.5 ± 2.9 years; 48.2% male; 38.2% black) and subset with longitudinal data (n=1,178). Interventions Not applicable Main Outcome Measures Participants underwent peripheral nerve function examination in 2000/01, including peroneal motor nerve conduction amplitude and velocity, vibration perception threshold, and monofilament testing. Symptoms of lower-extremity peripheral neuropathy included numbness or tingling and sudden stabbing, burning, pain, or aches in the feet or legs. The long distance corridor walk (LDCW; 400m) was administered in 2000/01 and every two years afterwards for 6 years to assess endurance walking performance over time. Results In separate fully adjusted linear mixed models poor vibration threshold (>130 microns), 10-g and 1.4-g monofilament insensitivity were each associated with slower LDCW completion time (16.0, 14.1, and 6.7, seconds slower, respectively, P<.05 for each). Poor motor amplitude (<1mV), poor vibration perception threshold, and 10-g monofilament insensitivity were related to greater slowing/year (4.7, 4.3, and 4.3 additional seconds/year, respectively, P<.05), though poor motor amplitude was not associated with initial completion time. Conclusions Poorer sensorimotor peripheral nerve function is related to slower endurance walking and greater slowing longitudinally. Interventions to reduce the burden of sensorimotor peripheral nerve function impairments should be considered in order to help older adults to maintain walking endurance—a critical component for remaining independent in the community. PMID:26343170

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Areti, Aparna; Komirishetty, Prashanth; Kumar, Ash

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

Peripheral changes in endometriosis-associated pain

PubMed Central

Morotti, Matteo; Vincent, Katy; Brawn, Jennifer; Zondervan, Krina T.; Becker, Christian M.

2014-01-01

BACKGROUND Pain remains the cardinal symptom of endometriosis. However, to date, the underlying mechanisms are still only poorly understood. Increasing evidence points towards a close interaction between peripheral nerves, the peritoneal environment and the central nervous system in pain generation and processing. Recently, studies demonstrating nerve fibres and neurotrophic and angiogenic factors in endometriotic lesions and their vicinity have led to increased interest in peripheral changes in endometriosis-associated pain. This review focuses on the origin and function of these nerves and factors as well as possible peripheral mechanisms that may contribute to the generation and modulation of pain in women with endometriosis. METHODS We conducted a systematic search using several databases (PubMed, MEDLINE, EMBASE and CINAHL) of publications from January 1977 to October 2013 to evaluate the possible roles of the peripheral nervous system in endometriosis pathophysiology and how it can contribute to endometriosis-associated pain. RESULTS Endometriotic lesions and peritoneal fluid from women with endometriosis had pronounced neuroangiogenic properties with increased expression of new nerve fibres, a shift in the distribution of sensory and autonomic fibres in some locations, and up-regulation of several neurotrophins. In women suffering from deep infiltrating endometriosis and bowel endometriosis, in which the anatomical distribution of lesions is generally more closely related to pelvic pain symptoms, endometriotic lesions and surrounding tissues present higher nerve fibre densities compared to peritoneal lesions and endometriomas. More data are needed to fully confirm a direct correlation between fibre density in these locations and the amount of perceived pain. A better correlation between the presence of nerve fibres and pain symptoms seems to exist for eutopic endometrium. However, this appears not to be exclusive to endometriosis. No correlation between elevated neurotrophin levels and pain severity seems to exist, suggesting the involvement of other mediators in the modulation of pain. CONCLUSIONS The increased expression of neuotrophic factors and nerve fibres in endometriotic lesions, eutopic endometrium and the peritoneum imply a role of such peripheral changes in the pathogenesis of endometriosis-associated pain. However, a clear link between these findings and pain in patients with endometriosis has so far not been demonstrated. PMID:24859987

Nerve growth factor loaded heparin/chitosan scaffolds for accelerating peripheral nerve regeneration.

PubMed

Li, Guicai; Xiao, Qinzhi; Zhang, Luzhong; Zhao, Yahong; Yang, Yumin

2017-09-01

Artificial chitosan scaffolds have been widely investigated for peripheral nerve regeneration. However, the effect was not as good as that of autologous grafts and therefore could not meet the clinical requirement. In the present study, the nerve growth factor (NGF) loaded heparin/chitosan scaffolds were fabricated via electrostatic interaction for further improving nerve regeneration. The physicochemical properties including morphology, wettability and composition were measured. The heparin immobilization, NGF loading and release were quantitatively and qualitatively characterized, respectively. The effect of NGF loaded heparin/chitosan scaffolds on nerve regeneration was evaluated by Schwann cells culture for different periods. The results showed that the heparin immobilization and NGF loading did not cause the change of bulk properties of chitosan scaffolds except for morphology and wettability. The pre-immobilization of heparin in chitosan scaffolds could enhance the stability of subsequently loaded NGF. The NGF loaded heparin/chitosan scaffolds could obviously improve the attachment and proliferation of Schwann cells in vitro. More importantly, the NGF loaded heparin/chitosan scaffolds could effectively promote the morphology development of Schwann cells. The study may provide a useful experimental basis to design and develop artificial implants for peripheral nerve regeneration and other tissue regeneration. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Expanded Bead Size of Corneal C-Nerve Fibers Visualized by Corneal Confocal Microscopy Is Associated with Slow Conduction Velocity of the Peripheral Nerves in Patients with Type 2 Diabetes Mellitus.

PubMed

Ishibashi, Fukashi; Kojima, Rie; Taniguchi, Miki; Kosaka, Aiko; Uetake, Harumi; Tavakoli, Mitra

2016-01-01

This study aims to establish the corneal nerve fiber (CNF) morphological alterations in a large cohort of type 2 diabetic patients and to investigate the association between the bead size, a novel parameter representing composite of accumulated mitochondria, glycogen particles, and vesicles in CNF, and the neurophysiological dysfunctions of the peripheral nerves. 162 type 2 diabetic patients and 45 healthy control subjects were studied in detail with a battery of clinical and neurological examinations and corneal confocal microscopy. Compared with controls, patients had abnormal CNF parameters. In particular the patients had reduced density and length of CNF and beading frequency and increased bead size. Alterations in CNF parameters were significant even in patients without neuropathy. The HbA1c levels were tightly associated with the bead size, which was inversely related to the motor and sensory nerve conduction velocity (NCV) and to the distal latency period of the median nerve positively. The CNF density and length positively correlated with the NCV and amplitude. The hyperglycemia-induced expansion of beads in CNF might be a predictor of slow NCV in peripheral nerves in type 2 diabetic patients.

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

PubMed

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

2017-06-01

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

Motor neuron activation in peripheral nerves using infrared neural stimulation

NASA Astrophysics Data System (ADS)

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

2014-02-01

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

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

PubMed

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

2013-03-01

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

Sequential involvement of the nervous system in subacute combined degeneration.

PubMed

Minn, Yang-Ki; Kim, Seung-Min; Kim, Se-Hoon; Kwon, Ki-Han; Sunwoo, Il-Nam

2012-03-01

Subacute combined degeneration (SCD) involves progressive degeneration of the spinal cord, optic nerve, and peripheral nerves. Vitamin B12 (VB12) is a co-factor in myelin synthesis. Because each cell that constitutes the myelin component in the central nervous system and peripheral nervous system is different, it is improbable that these cells undergo simultaneous degeneration. However, the sequence of degeneration in SCD has not been established. In this study, we analysed medical records and electrophysiological data of patients who showed neurological symptoms and whose serum VB12 levels were lower than 200 pg/mL. We enrolled 49 patients in this study. Their mean VB12 level was 68.3 pg/mL. Somatosensory evoked potential (SEP) study showed abnormal findings in 38 patients. Of the 40 patients who underwent visual evoked potential (VEP) study, 14 showed abnormal responses. Eighteen patients showed abnormal findings on a nerve conduction study (NCS). In this study, abnormal posterior tibial nerve SEPs only were seen in 16 patients, median nerve SEPs only were seen in 3 patients, abnormal VEPs only in two, and abnormal NCS responses in one patient. No patient complained of cognitive symptoms. In SCD, degeneration appears to progress in the following order: lower spinal cord, cervical spinal cord, peripheral nerve/optic nerve, and finally, the brain.

Motor Neuron Activation in Peripheral Nerves Using Infrared Neural Stimulation

PubMed Central

Peterson, EJ; Tyler, DJ

2014-01-01

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

[Evaluating the risk of sciatic nerve damage in the rabbit by administration of low and intermediate energy extracorporeal shock waves].

PubMed

Rompe, J D; Bohl, J; Riehle, H M; Schwitalle, M; Krischek, O

1998-01-01

The aim of the study was to evaluate the likeliness for peripheral nerve lesions following extracorporeal shock wave application. 82 rabbit sciatic nerves were randomized to undergo low-energetic (0.08 mJ/mm2), middle-energetic (0.28 mJ/mm2) or no (controls) shock wave therapy. After 1 to 28 days an independent neuropathologist checked the specimen for signs of neural lesions. Only after 14 and 28 days vacuolic swelling of the axons was noted, somewhat pronounced in the middle-energetic group. In no case was there any disruption of the nerve's continuity. We did not observe any neurapraxia. Shock wave application does not threaten peripheral nerve integrity in an animal model.

Sciatic nerve regeneration in rats subjected to ketogenic diet.

PubMed

Liśkiewicz, Arkadiusz; Właszczuk, Adam; Gendosz, Daria; Larysz-Brysz, Magdalena; Kapustka, Bartosz; Łączyński, Mariusz; Lewin-Kowalik, Joanna; Jędrzejowska-Szypułka, Halina

2016-01-01

Ketogenic diet (KD) is a high-fat-content diet with insufficiency of carbohydrates that induces ketogenesis. Besides its anticonvulsant properties, many studies have shown its neuroprotective effect in central nervous system, but its influence on peripheral nervous system has not been studied yet. We examined the influence of KD on regeneration of peripheral nerves in adult rats. Fifty one rats were divided into three experimental (n = 15) and one control (n = 6) groups. Right sciatic nerve was crushed and animals were kept on standard (ST group) or ketogenic diet, the latter was introduced 3 weeks before (KDB group) or on the day of surgery (KDA group). Functional (CatWalk) tests were performed once a week, and morphometric (fiber density, axon diameter, and myelin thickness) analysis of the nerves was made after 6 weeks. Body weight and blood ketone bodies level were estimated at the beginning and the end of experiment. Functional analysis showed no differences between groups. Morphometric evaluation showed most similarities to the healthy (uncrushed) nerves in KDB group. Nerves in ST group differed mostly from all other groups. Ketone bodies were elevated in both KD groups, while post-surgery animals' body weight was lower as compared to ST group. Regeneration of sciatic nerves was improved in KD - preconditioned rats. These results suggest a neuroprotective effect of KD on peripheral nerves.

Bidirectional peripheral nerve interface and applications.

PubMed

Thakor, Nitish V; Qihong Wang; Greenwald, Elliot

2016-08-01

Peripheral nerves, due to their small size and complex innervation to organs and complex physiology, pose particularly significant challenges towards interfacing electrodes and electronics to enable neuromodulation. Here, we present a review of the technology for building such interface, including recording and stimulating electrodes and low power electronics, as well as powering. Of particular advantage to building a miniature implanted device is a "bidirectional" system that both senses from the nerves or surrogate organs and stimulates the nerves to affect the organ function. This review and presentation will cover a range of electrodes, electronics, wireless power and data schemes and system integration, and will end with some examples and applications.

Comparative Evaluation of Chitosan Nerve Guides with Regular or Increased Bendability for Acute and Delayed Peripheral Nerve Repair: A Comprehensive Comparison with Autologous Nerve Grafts and Muscle-in-Vein Grafts.

PubMed

Stößel, Maria; Wildhagen, Vivien M; Helmecke, Olaf; Metzen, Jennifer; Pfund, Charlotte B; Freier, Thomas; Haastert-Talini, Kirsten

2018-05-08

Reconstruction of joint-crossing digital nerves requires the application of nerve guides with a much higher flexibility than used for peripheral nerve repair along larger bones. Nevertheless, collapse-resistance should be preserved to avoid secondary damage to the regrowing nerve tissue. In recent years, we presented chitosan nerve guides (CNGs) to be highly supportive for the regeneration of critical gap length peripheral nerve defects in the rat. Now, we evidently increased the bendability of regular CNGs (regCNGs) by developing a wavy wall structure, that is, corrugated CNGs (corrCNGs). In a comprehensive in vivo study, we compared both types of CNGs with clinical gold standard autologous nerve grafts (ANGs) and muscle-in-vein grafts (MVGs) that have recently been highlighted in the literature as a suitable alternative to ANGs. We reconstructed rat sciatic nerves over a critical gap length of 15 mm either immediately upon transection or after a delay period of 45 days. Electrodiagnostic measurements were applied to monitor functional motor recovery at 60, 90, 120, and 150 (only delayed repair) days postreconstruction. Upon explanation, tube properties were analyzed. Furthermore, distal nerve ends were evaluated using histomorphometry, while connective tissue specimens were subjected to immunohistological stainings. After 120 days (acute repair) or 150 days (delayed repair), respectively, compression-stability of regCNGs was slightly increased while it remained stable in corrCNGs. In both substudies, regCNGs and corrCNGs supported functional recovery of distal plantar muscles in a similar way and to a greater extent when compared with MVGs, while ANGs demonstrated the best support of regeneration. Anat Rec, 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

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

PubMed

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

2018-07-01

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

Tissue resident macrophages are sufficient for demyelination during peripheral nerve myelin induced experimental autoimmune neuritis?

PubMed

Taylor, Jude Matthew

2017-12-15

The contribution of resident endoneurial tissue macrophages versus recruited monocyte derived macrophages to demyelination and disease during Experimental Autoimmune Neuritis (EAN) was investigated using passive transfer of peripheral nerve myelin (PNM) specific serum antibodies or adoptive co-transfer of PNM specific T and B cells from EAN donors to leukopenic and normal hosts. Passive transfer of PNM specific serum antibodies or adoptive co-transfer of myelin specific T and B cells into leukopenic recipients resulted in a moderate reduction in nerve conduction block or in the disease severity compared to the normal recipients. This was despite at least a 95% decrease in the number of circulating mononuclear cells during the development of nerve conduction block and disease and a 50% reduction in the number of infiltrating endoneurial macrophages in the nerve lesions of the leukopenic recipients. These observations suggest that during EAN in Lewis rats actively induced by immunization with peripheral nerve myelin, phagocytic macrophages originating from the resident endoneurial population may be sufficient to engage in demyelination initiated by anti-myelin antibodies in this model. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

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

[Preliminary investigation of treatment of ulnar nerve defect by end-to-side neurorrhaphy].

PubMed

Luo, Y; Wang, T; Fang, H

1997-11-01

In the repair of the defect of peripheral nerve, it was necessary to find an operative method with excellent therapeutic effect but simple technique. Based on the experimental study, one case of old injury of the ulnar nerve was treated by end-to-side neurorraphy with the intact median nerve. In this case the nerve defect was over 3 cm and unable to be sutured directly. The patient was followed up for fourteen months after the operation. The recovery of the sensation and the myodynamia was evaluated. The results showed that: the sensation and the motor function innervated by ulnar nerve were recovered. The function of the hand was almost recovered to be normal. It was proved that the end-to-side neurorraphy between the distal stump with the intact median nerve to repair the defect of the ulnar nerve was a new operative procedure for nerve repair. Clinically it had good effect with little operative difficulty. This would give a bright prospect to repair of peripheral nerve defect in the future.

Schwann cell glycogen selectively supports myelinated axon function.

PubMed

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

2012-09-01

Interruption of energy supply to peripheral axons is a cause of axon loss. We determined whether glycogen was present in mammalian peripheral nerve, and whether it supported axon conduction during aglycemia. We used biochemical assay and electron microscopy to determine the presence of glycogen, and electrophysiology to monitor axon function. Glycogen was present in sciatic nerve, its concentration varying directly with ambient glucose. Electron microscopy detected glycogen granules primarily in myelinating Schwann cell cytoplasm, and these diminished after exposure to aglycemia. During aglycemia, conduction failure in large myelinated axons (A fibers) mirrored the time course of glycogen loss. Latency to compound action potential (CAP) failure was directly related to nerve glycogen content at aglycemia onset. Glycogen did not benefit the function of slow-conducting, small-diameter unmyelinated axons (C fibers) during aglycemia. Blocking glycogen breakdown pharmacologically accelerated CAP failure during aglycemia in A fibers, but not in C fibers. Lactate was as effective as glucose in supporting sciatic nerve function, and was continuously released into the extracellular space in the presence of glucose and fell rapidly during aglycemia. Our findings indicated that glycogen is present in peripheral nerve, primarily in myelinating Schwann cells, and exclusively supports large-diameter, myelinated axon conduction during aglycemia. Available evidence suggests that peripheral nerve glycogen breaks down during aglycemia and is passed, probably as lactate, to myelinated axons to support function. Unmyelinated axons are not protected by glycogen and are more vulnerable to dysfunction during periods of hypoglycemia. . Copyright © 2012 American Neurological Association.

Age-Dependent Schwann Cell Phenotype Regulation Following Peripheral Nerve Injury.

PubMed

Chen, Wayne A; Luo, T David; Barnwell, Jonathan C; Smith, Thomas L; Li, Zhongyu

2017-12-01

Schwann cells are integral to the regenerative capacity of the peripheral nervous system, which declines after adolescence. The mechanisms underlying this decline are poorly understood. This study sought to compare the protein expression of Notch, c-Jun, and Krox-20 after nerve crush injury in adolescent and young adult rats. We hypothesized that these Schwann cell myelinating regulatory factors are down-regulated after nerve injury in an age-dependent fashion. Adolescent (2 months old) and young adult (12 months old) rats (n = 48) underwent sciatic nerve crush injury. Protein expression of Notch, c-Jun, and Krox-20 was quantified by Western blot analysis at 1, 3, and 7 days post-injury. Functional recovery was assessed in a separate group of animals (n = 8) by gait analysis (sciatic functional index) and electromyography (compound motor action potential) over an 8-week post-injury period. Young adult rats demonstrated a trend of delayed onset of the dedifferentiating regulatory factors, Notch and c-Jun, corresponding to the delayed functional recovery observed in young adult rats compared to adolescent rats. Compound motor action potential area was significantly greater in adolescent rats relative to young adult rats, while amplitude and velocity trended toward statistical significance. The process of Schwann cell dedifferentiation following peripheral nerve injury shows different trends with age. These trends of delayed onset of key regulatory factors responsible for Schwann cell myelination may be one of many possible factors mediating the significant differences in functional recovery between adolescent and young adult rats following peripheral nerve injury.

Schwann Cell Glycogen Selectively Supports Myelinated Axon Function

PubMed Central

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

2012-01-01

Objectives Interruption of energy supply to peripheral axons is a cause of axon loss. We determined if glycogen was present in mammalian peripheral nerve, and if it supported axon conduction during aglycemia. Methods We used biochemical assay and electron microscopy to determine the presence of glycogen, and electrophysiology to monitor axon function. Results Glycogen was present in sciatic nerve, its concentration varying directly with ambient [glucose]. Electron microscopy detected glycogen granules primarily in myelinating Schwann cell cytoplasm and these diminished after exposure to aglycemia. During aglycemia, conduction failure in large myelinated axons (A fibers) mirrored the time-course of glycogen loss. Latency to CAP failure was directly related to nerve glycogen content at aglycemia onset. Glycogen did not benefit the function of slow-conducting, small diameter unmyelinated axons (C fibers) during aglycemia. Blocking glycogen breakdown pharmacologically accelerated CAP failure during aglycemia in A fibers, but not in C fibers. Lactate was as effective as glucose in supporting sciatic nerve function, and was continuously released into the extracellular space in the presence of glucose and fell rapidly during aglycemia. Interpretation Our findings indicated that glycogen is present in peripheral nerve, primarily in myelinating Schwann cells, and exclusively supports large diameter, myelinated axon conduction during aglycemia. Available evidence suggests that peripheral nerve glycogen breaks down during aglycemia and is passed, probably as lactate, to myelinated axons to support function. Unmyelinated axons are not protected by glycogen and are more vulnerable to dysfunction during periods of hypoglycemia. PMID:23034913

Immunostaining of skin biopsy adds no diagnostic value in MGUS-associated peripheral neuropathy.

PubMed

Al-Zuhairy, Ali; Schrøder, Henrik Daa; Plesner, Torben; Abildgaard, Niels; Sindrup, Søren H

2015-02-15

For several decades an association between MGUS, IgM-MGUS in particular, and peripheral neuropathy has been suspected. Several histopathology studies have shown binding of IgM to myelin and a secondary widening of myelin lamellae in cutaneous nerves and in the sural nerve of patients with IgM-MGUS, or Waldenström's Macroglobulinaemia (WM), and peripheral neuropathy. In this retrospective study we investigated the value of skin biopsy examination in the diagnosis of MGUS- and WM-associated peripheral neuropathy. A total of 117 patients, who were examined for an M-component in serum with associated nerve symptoms, had a skin biopsy taken and examined for immunoglobulin deposition in cutaneous nerves. Thirty-five patients were diagnosed with MGUS or WM and peripheral neuropathy with no other cause of neuropathy. Nineteen patients had MGUS but no peripheral neuropathy. Of the 35 patients with MGUS or WM and peripheral neuropathy, four had immunoglobulin deposition in the skin biopsy, all of whom had an IgM gammopathy. In the control group of 19 without peripheral neuropathy, three had immunoglobulin deposition in the skin biopsy, all of whom had IgM-MGUS. In both groups, there was a trend towards higher IgM blood levels in patients with immunoglobulin deposition. Half of the patients with IgM gammopathy in the neuropathy group had anti-MAG reactivity, whereas only one in the control group had weak anti-MAG reactivity. Our study indicates that examination of skin biopsies for immunoglobulin deposition does not add significant diagnostic value in the evaluation of neuropathies suspected to be caused by MGUS or WM. IgM immunoglobulin deposition in skin biopsy might merely be an epiphenomenon secondary to high IgM blood levels. Copyright © 2014 Elsevier B.V. All rights reserved.

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

Ultrasound-Guided Cryoanalgesia of Peripheral Nerve Lesions.

PubMed

Djebbar, Sahlya; Rossi, Ignacio M; Adler, Ronald S

2016-11-01

The real-time nature of ultrasound makes it ideally suited to provide guidance for a variety of musculoskeletal interventional procedures involving peripheral nerves. Continuous observation of the needle ensures proper placement and allows continuous monitoring when performing localized ablative therapy and therefore more accurate positioning of a cryoprobe, use of smaller needles, as well as access to small structures. We describe our experience performing cryoablative procedures. Patients undergoing cryoneurolysis have largely reported varying degrees of long-term pain relief and improvement in function; no serious complications have yet been identified. Ultrasound-guided cryoneurolysis can provide a useful, safe alternative to other ablative techniques to achieve long-term analgesia from painful peripheral nerve lesions. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Neurotrophically Induced Mesenchymal Progenitor Cells Derived from Induced Pluripotent Stem Cells Enhance Neuritogenesis via Neurotrophin and Cytokine Production

PubMed Central

Brick, Rachel M.; Sun, Aaron X.

2017-01-01

Abstract Adult tissue‐derived mesenchymal stem cells (MSCs) are known to produce a number of bioactive factors, including neurotrophic growth factors, capable of supporting and improving nerve regeneration. However, with a finite culture expansion capacity, MSCs are inherently limited in their lifespan and use. We examined here the potential utility of an alternative, mesenchymal‐like cell source, derived from induced pluripotent stem cells, termed induced mesenchymal progenitor cells (MiMPCs). We found that several genes were upregulated and proteins were produced in MiMPCs that matched those previously reported for MSCs. Like MSCs, the MiMPCs secreted various neurotrophic and neuroprotective factors, including brain‐derived neurotrophic factor (BDNF), interleukin‐6 (IL‐6), leukemia inhibitory factor (LIF), osteopontin, and osteonectin, and promoted neurite outgrowth in chick embryonic dorsal root ganglia (DRG) cultures compared with control cultures. Cotreatment with a pharmacological Trk‐receptor inhibitor did not result in significant decrease in MiMPC‐induced neurite outgrowth, which was however inhibited upon Jak/STAT3 blockade. These findings suggest that the MiMPC induction of DRG neurite outgrowth is unlikely to be solely dependent on BDNF, but instead Jak/STAT3 activation by IL‐6 and/or LIF is likely to be critical neurotrophic signaling pathways of the MiMPC secretome. Taken together, these findings suggest MiMPCs as a renewable, candidate source of therapeutic cells and a potential alternative to MSCs for peripheral nerve repair, in view of their ability to promote nerve growth by producing many of the same growth factors and cytokines as Schwann cells and signaling through critical neurotrophic pathways. stem cells translational Medicine 2018;7:45–58 PMID:29215199

VAGUS NERVE STIMULATION REGULATES HEMOSTASIS IN SWINE

PubMed Central

Czura, Christopher J.; Schultz, Arthur; Kaipel, Martin; Khadem, Anna; Huston, Jared M.; Pavlov, Valentin A.; Redl, Heinz; Tracey, Kevin J.

2010-01-01

The central nervous system regulates peripheral immune responses via the vagus nerve, the primary neural component of the cholinergic anti-inflammatory pathway. Electrical stimulation of the vagus nerve suppresses pro-inflammatory cytokine release in response to endotoxin, I/R injury, and hypovolemic shock and protects against lethal hypotension. To determine the effect of vagus nerve stimulation on coagulation pathways, anesthetized pigs were subjected to partial ear resection before and after electrical vagus nerve stimulation. We observed that electrical vagus nerve stimulation significantly decreased bleeding time (pre–electrical vagus nerve stimulation = 1033 ± 210 s versus post–electrical vagus nerve stimulation = 585 ± 111 s; P < 0.05) and total blood loss (pre–electrical vagus nerve stimulation = 48.4 ± 6.8 mL versus post–electrical vagus nerve stimulation = 26.3 ± 6.7 mL; P < 0.05). Reduced bleeding time after vagus nerve stimulation was independent of changes in heart rate or blood pressure and correlated with increased thrombin/antithrombin III complex generation in shed blood. These data indicate that electrical stimulation of the vagus nerve attenuates peripheral hemorrhage in a porcine model of soft tissue injury and that this protective effect is associated with increased coagulation factor activity. PMID:19953009

Stereological analysis of sciatic nerve in chickens following neonatal pinealectomy: an experimental study

PubMed Central

2010-01-01

Background Although the injury to the peripheral nervous system is a common clinical problem, understanding of the role of melatonin in nerve degeneration and regeneration is incomplete. Methods The current study investigated the effects of neonatal pinealectomy on the sciatic nerve microarchitecture in the chicken. The chickens were divided into two equal groups: unpinealectomized controls and pinealectomized chickens. At the end of the study, biochemical examination of 10 sciatic nerve samples from both groups was performed and a quantitative stereological evaluation of 10 animals in each group was performed. The results were compared using Mann-Whitney test. Results In this study, the results of axon number and thickness of the myelin sheath of a nerve fiber in newly hatched pinealectomy group were higher than those in control group. Similarly, surgical pinealectomy group had significantly larger axonal cross-sectional area than the control group (p < 0.05). In addition, the average hydroxyproline content of the nerve tissue in neonatal pinealectomy group was higher than those found in control group. Our results suggest that melatonin may play a role on the morphologic features of the peripheral nerve tissue and that melatonin deficiency might be a pathophysiological mechanism in some degenerative diseases of peripheral nerves. The changes demonstrated by quantitative morphometric methods and biochemical analysis has been interpreted as a reflection of the effects of melatonin upon nerve tissue. Conclusion In the light of these results from present animal study, changes in sciatic nerve morphometry may be indicative of neuroprotective feature of melatonin, but this suggestion need to be validated in the human setting. PMID:20409336

The beneficial effect of genetically engineered Schwann cells with enhanced motility in peripheral nerve regeneration: review.

PubMed

Gravvanis, A I; Lavdas, A A; Papalois, A; Tsoutsos, D A; Matsas, R

2007-01-01

The importance of Schwann cells in promoting nerve regeneration across a conduit has been extensively reported in the literature, and Schwann cell motility has been acknowledged as a prerequisite for myelination of the peripheral nervous system during regeneration after injury. Review of recent literature and retrospective analysis of our studies with genetically modified Schwann Cells with increased motility in order to identify the underlying mechanism of action and outline the future trends in peripheral nerve repair. Schwann cell transduction with the pREV-retrovirus, for expression of Sialyl-Transferase-X, resulting in conferring Polysialyl-residues (PSA) on NCAM, increases their motility in-vitro and ensures nerve regeneration through silicone tubes after end-to-side neurorraphy in the rat sciatic nerve model, thus significantly promoting fiber maturation and functional outcome. An artificial nerve graft consisting of a type I collagen tube lined with the genetically modified Schwann cells with increased motility, used to bridge a defect in end-to-end fashion in the rat sciatic nerve model, was shown to promote nerve regeneration to a level equal to that of a nerve autograft. The use of genetically engineered Schwann cells with enhanced motility for grafting endoneural tubes promotes axonal regeneration, by virtue of the interaction of the transplanted cells with regenerating axonal growth cones as well as via the recruitment of endogenous Schwann cells. It is envisaged that mixed populations of Schwann cells, expressing PSA and one or more trophic factors, might further enhance the regenerating and remyelinating potential of the lesioned nerves.

Ultrastructural aspects of mouse nerve-muscle preparation exposed to Bothrops jararacussu and Bothrops bilineatus venoms and their toxins BthTX-I and Bbil-TX: Unknown myotoxic effects.

PubMed

Melaré, Rodolfo; Floriano, Rafael Stuani; Gracia, Marta; Rodrigues-Simioni, Léa; Cruz-Höfling, Maria Alice da; Rocha, Thalita

2016-11-01

Bites by Bothrops snakes normally induce local pain, haemorrhage, oedema and myonecrosis. Mammalian isolated nerve-muscle preparations exposed to Bothrops venoms and their phospholipase A 2 toxins (PLA 2 ) can exhibit a neurotoxic pattern as increase in frequency of miniature end-plate potentials (MEPPs) as well as in amplitude of end-plate potentials (EPPs); neuromuscular facilitation followed by complete and irreversible blockade without morphological evidence for muscle damage. In this work, we analysed the ultrastructural damage induced by Bothrops jararacussu and Bothrops bilineatus venoms and their PLA 2 toxins (BthTX-I and Bbil-TX) in mouse isolated nerve-phrenic diaphragm preparations (PND). Under transmission electron microscopy (TEM), PND preparations previously exposed to B. jararacussu and B. bilineatus venoms and BthTX-I and Bbil-TX toxins showed hypercontracted and loosed myofilaments; unorganized sarcomeres; clusters of edematous sarcoplasmic reticulum and mitochondria; abnormal chromatin distribution or apoptotic-like nuclei. The principal affected organelles, mitochondria and sarcoplasmic reticulum, were those related to calcium buffering and, resulting in sarcomeres and myofilaments hypercontraction. Schwann cells were also damaged showing edematous axons and mitochondria as well as myelin sheath alteration. These ultrastructural changes caused by both of Bothrops venoms and toxins indicate that the neuromuscular blockade induced by them in vitro can also be associated with nerve and muscle degeneration. © 2016 Wiley Periodicals, Inc.

Presynaptic Proteins as Markers of the Neurotoxic Activity of BmjeTX-I and BmjeTX-II Toxins from Bothrops marajoensis (Marajó Lancehead) Snake Venom.

PubMed

Lisboa, Antonio; Melaré, Rodolfo; Franco, Junia R B; Bis, Carolina V; Gracia, Marta; Ponce-Soto, Luis A; Marangoni, Sérgio; Rodrigues-Simioni, Léa; da Cruz-Höfling, Maria Alice; Rocha, Thalita

2016-01-01

Neuromuscular preparations exposed to B. marajoensis venom show increases in the frequency of miniature end-plate potentials and twitch tension facilitation followed by presynaptic neuromuscular paralysis, without evidences of muscle damage. Considering that presynaptic toxins interfere into the machinery involved in neurotransmitter release (synaptophysin, synaptobrevin, and SNAP25 proteins), the main objective of this communication is to analyze, by immunofluorescence and western blotting, the expression of the synaptic proteins, synaptophysin, synaptobrevin, and SNAP25 and by myography, light, and transmission electron microscopy the pathology of motor nerve terminals and skeletal muscle fibres of chick biventer cervicis preparations (CBC) exposed in vitro to BmjeTX-I and BmjeTX-II toxins from B. marajoensis venom. CBC incubated with toxins showed irreversible twitch tension blockade and unaffected KCl- and ACh-evoked contractures, and the positive colabelling of acetylcholine receptors confirmed that their action was primarily at the motor nerve terminal. Hypercontraction and loose myofilaments and synaptic vesicle depletion and motor nerve damage indicated that the toxins displayed both myotoxic and neurotoxic effect. The blockade resulted from interference on synaptophysin, synaptobrevin, and SNAP25 proteins leading to the conclusion that BmjeTX-I and BmjeTX-II affected neurotransmitter release machinery by preventing the docking of synaptic vesicles to the axolemma of the nerve terminal.

The Association Between the Levels of Thyroid Hormones and Peripheral Nerve Conduction in Patients with Type 2 Diabetes Mellitus.

PubMed

Zhu, Fan-Fan; Yang, Li-Zhen

2018-06-26

Type 2 diabetes has an underlying pathology with thyroid dysfunction. However, few studies have investigated the association between thyroid hormones and diabetic peripheral neuropathy. Our aim was to evaluate the relationship between thyroid hormones and electrophysiological properties of peripheral nerves in type 2 diabetes. The medical records of 308 patients with type 2 diabetes were enrolled in this study. Subjects stratified by sex were divided into subgroups based on the diagnosis of nerve conduction study. The nerve conduction parameters were separately described with the spectrum of thyroid hormones. Multivariate regression models to analyze the potential links between thyroid hormones and nerve conduction parameters. The serum free triiodine thyronine levels between normal and abnormal nerve conduction groups were statistically different in total (4.55±0.65 vs 4.37±0.63, P<0.05) and female diabetic patients (4.46±0.50 vs 4.14±0.57, P<0.01). Moreover, the summed amplitude and velocity Z score of female and male increased with free triiodine thyronine levels (P<0.05). Sex-specific binary logistic regression models showed that free triiodine thyronine levels were associated with decreased odds of abnormal nerve conduction diagnosis (odds ratio [95%CI]=0.151[0.047-0.186]) and low tertile of summed amplitude Z score (odds ratio [95%CI]=0.283[0.099-0.809]) in female. In total patients, free triiodine thyronine level was negatively associated with odds of abnormal nerve conduction (odds ratio [95%CI]=0.436 [0.226-0.842]), low tertile of summed velocity (odds ratio [95%CI]=0.44[0.226-0.858]) and amplitude (odds ratio [95%CI]=0.436[0.227-0.838) Z score. Serum free triiodine thyronine level is associated with nerve conduction in diabetes. Low free triiodine thyronine may be a potential risk for diabetic peripheral neuropathy. © Georg Thieme Verlag KG Stuttgart · New York.

Supplemental Interscalene Blockade to General Anesthesia for Shoulder Arthroscopy: Effects on Fast Track Capability, Analgesic Quality, and Lung Function.

PubMed

Zoremba, Martin; Kratz, Thomas; Dette, Frank; Wulf, Hinnerk; Steinfeldt, Thorsten; Wiesmann, Thomas

2015-01-01

After shoulder surgery performed in patients with interscalene nerve block (without general anesthesia), fast track capability and postoperative pain management in the PACU are improved compared with general anesthesia alone. However, it is not known if these evidence-based benefits still exist when the interscalene block is combined with general anesthesia. We retrospectively analyzed a prospective cohort data set of 159 patients undergoing shoulder arthroscopy with general anesthesia alone (n = 60) or combined with an interscalene nerve block catheter (n = 99) for fast track capability time. Moreover, comparisons were made for VAS scores, analgesic consumption in the PACU, pain management, and lung function measurements. The groups did not differ in mean time to fast track capability (22 versus 22 min). Opioid consumption in PACU was significantly less in the interscalene group, who had significantly better VAS scores during PACU stay. Patients receiving interscalene blockade had a significantly impaired lung function postoperatively, although this did not affect postoperative recovery and had no impact on PACU times. The addition of interscalene block to general anesthesia for shoulder arthroscopy did not enhance fast track capability. Pain management and VAS scores were improved in the interscalene nerve block group.

Electroactive biodegradable polyurethane significantly enhanced Schwann cells myelin gene expression and neurotrophin secretion for peripheral nerve tissue engineering.

PubMed

Wu, Yaobin; Wang, Ling; Guo, Baolin; Shao, Yongpin; Ma, Peter X

2016-05-01

Myelination of Schwann cells (SCs) is critical for the success of peripheral nerve regeneration, and biomaterials that can promote SCs' neurotrophin secretion as scaffolds are beneficial for nerve repair. Here we present a biomaterials-approach, specifically, a highly tunable conductive biodegradable flexible polyurethane by polycondensation of poly(glycerol sebacate) and aniline pentamer, to significantly enhance SCs' myelin gene expression and neurotrophin secretion for peripheral nerve tissue engineering. SCs are cultured on these conductive polymer films, and the biocompatibility of these films and their ability to enhance myelin gene expressions and sustained neurotrophin secretion are successfully demonstrated. The mechanism of SCs' neurotrophin secretion on conductive films is demonstrated by investigating the relationship between intracellular Ca(2+) level and SCs' myelination. Furthermore, the neurite growth and elongation of PC12 cells are induced by adding the neurotrophin medium suspension produced from SCs-laden conductive films. These data suggest that these conductive degradable polyurethanes that enhance SCs' myelin gene expressions and sustained neurotrophin secretion perform great potential for nerve regeneration applications. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

PubMed Central

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

2013-01-01

The purpose of this study was to investigate the influence of implanting collagen with a supramolecular organization on peripheral nerve regeneration, using the sciatic nerve tubulization technique. For this purpose, adult female Sprague Dawley rats were divided into five groups: (1) TP – sciatic nerve repaired with empty polyethylene tubular prothesis (n = 10), (2) TPCL – nerve repair with empty polycaprolactone (PCL) tubing (n = 8), (3) TPCLF – repair with PCL tubing filled with an implant of collagen with a supramolecular organization (n = 10), (4) AG – animals that received a peripheral nerve autograft (n = 8), and (5) Normal nerves (n = 8). The results were assessed by quantification of the regenerated fibers, nerve morphometry, and transmission electron microscopy, 60 days after surgery. Immunohistochemistry and polarization microscopy were also used to analyze the regenerated nerve structure and cellular elements. The results showed that the AG group presented a larger number of regenerated axons. However, the TPCL and TPCLF groups presented more compact regenerated fibers with a morphometric profile closer to normal, both at the tube midpoint and 2 mm distal to the prosthesis. These findings were reinforced by polarization microscopy, which indicated a better collagen/axons suprastructural organization in the TPCLF derived samples. In addition, the immunohistochemical results obtained using the antibody anti-p75NTR as a Schwann cell reactivity marker demonstrated that the Schwann cells were more reactive during the regenerative process in the TPCLF group as compared to the TPCL group and the normal sciatic nerve. Altogether, the results of this study indicated that the implant of collagen with a supramolecular organization positively influenced and stimulated the regeneration process through the nerve gap, resulting in the formation of a better morphologically arranged tissue. PMID:24381812

The Effectiveness of Aerobic Exercise in Improving Peripheral Nerve Functions in Type 2 Diabetes Mellitus: An Evidence Based Case Report.

PubMed

Mirtha, Listya Tresnanti; Permatahati, Viandini

2018-01-01

peripheral neuropathy is known as one of most common complication in diabetes mellitus type 2 patient. This complication is caused by uncontrolled condition of blood glucose level in long periode. Regular physical activity in moderate to high intensity is beneficial in management of diabetes mellitus. This report aimed to know the effectiveness of aerobic exercise in causing improved peripheral functions in type 2 diabetes mellitus. literature searching using several related keywords in Medline®, Pubmed®, and Cochrane library, following inclusion and exclusion criteria. Dixit et al suggested that a heart rate intensity of 40-60% aerobic exercise of 30-45 min duration per session for eight weeks suggest an important impact in controlling diabetic peripheral neuropathy. Kluding PM et al suggested that significantly improved selected measures of peripheral nerve function ("worst" pain levels and MNSI score), glycemic control (HbA1c), and resting heart rate. the studies showed significant benefit of aerobic exercise, despite the short duration of exercise being used as intervention towards improvement in peripheral nerve function. However, further studies with large samples and longer duration of intervention are needed to confirm the finding.

A histone deacetylase 3–dependent pathway delimits peripheral myelin growth and functional regeneration

PubMed Central

He, Xuelian; Zhang, Liguo; Queme, Luis F; Liu, Xuezhao; Lu, Andrew; Waclaw, Ronald R; Dong, Xinran; Zhou, Wenhao; Kidd, Grahame; Yoon, Sung-Ok; Buonanno, Andres; Rubin, Joshua B; Xin, Mei; Nave, Klaus-Armin; Trapp, Bruce D; Jankowski, Michael P; Lu, Q Richard

2018-01-01

Deficits in Schwann cell–mediated remyelination impair functional restoration after nerve damage, contributing to peripheral neuropathies. The mechanisms mediating block of remyelination remain elusive. Here, through small-molecule screening focusing on epigenetic modulators, we identified histone deacetylase 3 (HDAC3; a histone-modifying enzyme) as a potent inhibitor of peripheral myelinogenesis. Inhibition of HDAC3 enhanced myelin growth and regeneration and improved functional recovery after peripheral nerve injury in mice. HDAC3 antagonizes the myelinogenic neuregulin–PI3K–AKT signaling axis. Moreover, genome-wide profiling analyses revealed that HDAC3 represses promyelinating programs through epigenetic silencing while coordinating with p300 histone acetyltransferase to activate myelination-inhibitory programs that include the HIPPO signaling effector TEAD4 to inhibit myelin growth. Schwann cell–specific deletion of either Hdac3 or Tead4 in mice resulted in an elevation of myelin thickness in sciatic nerves. Thus, our findings identify the HDAC3–TEAD4 network as a dual-function switch of cell-intrinsic inhibitory machinery that counters myelinogenic signals and maintains peripheral myelin homeostasis, highlighting the therapeutic potential of transient HDAC3 inhibition for improving peripheral myelin repair. PMID:29431744

Schwannomas of the foot and ankle: a technical report.

PubMed

Kellner, Christopher P; Sussman, Eric; Bar-David, Tzvi; Winfree, Christopher J

2014-01-01

The present technical report provides a detailed description of open surgical resection of peripheral nerve sheath tumors in the foot and ankle. We present 3 cases to illustrate important differences in the technique based on the presentation, anatomic location, and intraoperative neurophysiologic monitoring findings. It is important for surgeons to understand that surgical excision of many peripheral nerve sheath tumors can be undertaken without en bloc resection of the entire nerve trunk. Copyright © 2014 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

An autopsy case of minamata disease (methylmercury poisoning)--pathological viewpoints of peripheral nerves.

PubMed

Eto, Komyo; Tokunaga, Hidehiro; Nagashima, Kazuo; Takeuchi, Tadao

2002-01-01

The outbreak of methylmercury poisoning in the geographic areas around Minamata Bay, Kumamoto, Japan in the 1950s has become known as Minamata disease. Based on earlier reports and extensive pathological studies on autopsied cases at the Kumamoto University School of Medicine, destructive lesions in the anterior portion of the calcarine cortex and depletion predominantly of granular cells in the cerebellar cortex came to be recognized as the hallmark and diagnostic yardstick of methylmercury poisoning in humans. As the number of autopsy cases of Minamata disease increased, it became apparent that the cerebral lesion was not restricted to the calcarine cortex but was relatively widespread. Less severe lesions, believed to be responsible for the motor symptoms of Minamata patients, were often found in the precentral, postcentral, and lateral temporal cortices. These patients also frequently presented with signs of sensory neuropathy affecting the distal extremities. Because of few sufficiently comprehensive studies, peripheral nerve degeneration has not been universally accepted as a cause of the sensory disturbances in Minamata patients. The present paper describes both biopsy and autopsy findings of the peripheral nerves in a male fisherman who died at the age of 64 years and showed the characteristic central nervous system lesions of Minamata disease at autopsy. A sural nerve biopsy with electron microscopy performed 1 month prior to his death showed endoneurial fibrosis and regenerated myelin sheaths. At autopsy the dorsal roots and sural nerve showed endoneurial fibrosis, loss of nerve fibers, and presence of Büngner's bands. The spinal cord showed Wallerian degeneration of the fasciculus gracilis (Goll's tract) with relative preservation of neurons in sensory ganglia. These findings support the contention that there is peripheral nerve degeneration in Minamata patients due to toxic injury from methylmercury.

Proximal Neuropathy and Associated Skeletal Muscle Changes Resembling Denervation Atrophy in Hindlimbs of Chronic Hypoglycaemic Rats.

PubMed

Jensen, Vivi F H; Molck, Anne-Marie; Soeborg, Henrik; Nowak, Jette; Chapman, Melissa; Lykkesfeldt, Jens; Bogh, Ingrid B

2018-01-01

Peripheral neuropathy is one of the most common complications of diabetic hyperglycaemia. Insulin-induced hypoglycaemia (IIH) might potentially exacerbate or contribute to neuropathy as hypoglycaemia also causes peripheral neuropathy. In rats, IIH induces neuropathy associated with skeletal muscle changes. Aims of this study were to investigate the progression and sequence of histopathologic changes caused by chronic IIH in rat peripheral nerves and skeletal muscle, and whether such changes were reversible. Chronic IIH was induced by infusion of human insulin, followed by an infusion-free recovery period in some of the animals. Sciatic, plantar nerves and thigh muscle were examined histopathologically after four or eight weeks of infusion and after the recovery period. IIH resulted in high incidence of axonal degeneration in sciatic nerves and low incidence in plantar nerves indicating proximo-distal progression of the neuropathy. The neuropathy progressed in severity (sciatic nerve) and incidence (sciatic and plantar nerve) with the duration of IIH. The myopathy consisted of groups of angular atrophic myofibres which resembled histopathologic changes classically seen after denervation of skeletal muscle, and severity of the myofibre atrophy correlated with severity of axonal degeneration in sciatic nerve. Both neuropathy and myopathy were still present after four weeks of recovery, although the neuropathy was less severe. In conclusion, the results suggest that peripheral neuropathy induced by IIH progresses proximo-distally, that severity and incidence increase with duration of the hypoglycaemia and that these changes are partially reversible within four weeks. Furthermore, IIH-induced myopathy is most likely secondary to the neuropathy. © 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Positioning patients for spine surgery: Avoiding uncommon position-related complications

PubMed Central

Kamel, Ihab; Barnette, Rodger

2014-01-01

Positioning patients for spine surgery is pivotal for optimal operating conditions and operative-site exposure. During spine surgery, patients are placed in positions that are not physiologic and may lead to complications. Perioperative peripheral nerve injury (PPNI) and postoperative visual loss (POVL) are rare complications related to patient positioning during spine surgery that result in significant patient disability and functional loss. PPNI is usually due to stretch or compression of the peripheral nerve. PPNI may present as a brachial plexus injury or as an isolated injury of single nerve, most commonly the ulnar nerve. Understanding the etiology, mechanism and pattern of injury with each type of nerve injury is important for the prevention of PPNI. Intraoperative neuromonitoring has been used to detect peripheral nerve conduction abnormalities indicating peripheral nerve stress under general anesthesia and to guide modification of the upper extremity position to prevent PPNI. POVL usually results in permanent visual loss. Most cases are associated with prolonged spine procedures in the prone position under general anesthesia. The most common causes of POVL after spine surgery are ischemic optic neuropathy and central retinal artery occlusion. Posterior ischemic optic neuropathy is the most common cause of POVL after spine surgery. It is important for spine surgeons to be aware of POVL and to participate in safe, collaborative perioperative care of spine patients. Proper education of perioperative staff, combined with clear communication and collaboration while positioning patients in the operating room is the best and safest approach. The prevention of uncommon complications of spine surgery depends primarily on identifying high-risk patients, proper positioning and optimal intraoperative management of physiological parameters. Modification of risk factors extrinsic to the patient may help reduce the incidence of PPNI and POVL. PMID:25232519