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Peripheral Nerves (peripheral + nerve)
Terms modified by Peripheral Nerves Selected AbstractsTissue Engineering Strategies Designed to Realize the Endogenous Regenerative Potential of Peripheral NervesADVANCED MATERIALS, Issue 46 2009Vivek Mukhatyar Abstract http://doi.wiley.com/10.1002/adma.v21:32/33 Bridging peripheral nerve gaps without the use of autografts has significant clinical importance. But in order to rationally design novel scaffolds, a good understanding of the nerve regeneration process is vital. Appropriate amount of structural and chemical cues are required to stimulate the endogenous mechanisms of repair and functional recovery. Synthetic and natural materials present various opportunities to induce the growth of supporting cells as well as promote axon regeneration. An overview of tissue engineering strategies currently being explored that stimulate the different steps of the regenerative sequence is presented. [source] Macrophage-Related Demyelination In Peripheral Nerves Of Mice Deficient In The Gap Junction Protein Connexin 32JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 3 2002I Kobsar Mice deficient in the gap junction protein connexin 32 (Cx32) develop a slowly progressing demyelinating neuropathy, with enlarged periaxonal collars, abnormal non-compacted myelin domains and axonal sprouts. These mice serve as a model for the X-linked form of inherited demyelin- ating neuropathies in humans. Based on our previous findings that macrophages are involved in demyelination in other myelin mutants (i.e. mice heterozygously deficient in P0), we considered the possibility that macrophages might be also mediators of demyelination in Cx32-deficient mice. Indeed, we detected an age-related increase in the number of macrophages in demyelinating nerves of Cx32-deficient mice. In addition, immunoelectron microscopy revealed macrophages in an apposition to degenerating myelin reminiscent of a macrophage-mediated demyelinating neuropathy. We conclude that involvement of macrophages might be a widespread phenomenon in genetically-determined demyelination. [source] Radiofrequency Treatment of Peripheral NervesPAIN PRACTICE, Issue 3 2002O.J.J.M. Rohof MD Neurolysis by surgical, chemical, cryogenic, or thermal means may be considered as an option on seldom occasions, because of the risk of neuritis and deafferentation pain, motor deficit, and potential unintentional damage to nontargeted tissue. To our knowledge, there is only 1 report concerning selective radiofrequency (RF) treatment of the obturator and femoral nerves that was published. The introduction of the non-neurodestructive pulsed radiofrequency technique has provided new possibilities for the treatment of peripheral nerves. Today there is some experience with the management of chronic shoulder pain and additional case reports on other indications. [source] Poster Session C10: Peripheral NervesBRAIN PATHOLOGY, Issue 4 2000Article first published online: 5 APR 200 No abstract is available for this article. [source] Migration of cells into and out of peripheral nerve isografts in the peripheral and central nervous systems of the adult mouseEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2001Natalie A. Symons Abstract Peripheral nerve (PN) isografts provide a favourable environment for axon regeneration after peripheral and central nervous system (CNS) injury, but definitive information on the extent of cellular intermixing between donor and host tissues is lacking. We wished to compare migration patterns in fresh and predegenerate PN grafts, and also compare the extent of cell migration after transplantation to peripheral nervous system (PNS) versus CNS. To discern how host and donor cells interact after PN transplantation, sciatic nerve segments were transplanted from inbred adult mice into PN defects (PN,PN grafts) or into lesioned cerebral cortex of opposite gender siblings. Migrating male cells were identified using a Y-chromosome-specific probe and in situ hybridization methods, and characterized immunohistochemically. The extent of donor and host cellular intermixing was similar in fresh and predegenerate PN,PN isografts. There was substantial intermixing of donor and host cells by 8 days. Many host cells migrating into epineurial regions of grafts were immunopositive for F4/80 (macrophages). The endoneurium of grafted PN was also colonized by host cells; some were F4/80+ but many were immunostained with S-100 (Schwann cell marker). Donor S-100+ Schwann cells rapidly migrated out into proximal and distal host PN and by 12 weeks were found at least 2 mm from the grafts. Endoneurial microvessels in grafts were mostly donor-derived. By comparison, in male PN grafts to female CNS, even after 6 weeks few donor cells had migrated out into surrounding host cortex, despite the observation that almost all grafts contained regenerating axons and were thus attached to host CNS tissue. [source] Molecular architecture of myelinated peripheral nerves is supported by calorie restriction with agingAGING CELL, Issue 2 2009Sunitha Rangaraju Summary Peripheral nerves from aged animals exhibit features of degeneration, including marked fiber loss, morphological irregularities in myelinated axons and notable reduction in the expression of myelin proteins. To investigate how protein homeostatic mechanisms change with age within the peripheral nervous system, we isolated Schwann cells from the sciatic nerves of young and old rats. The responsiveness of cells from aged nerves to stress stimuli is weakened, which in part may account for the observed age-associated alterations in glial and axonal proteins in vivo. Although calorie restriction is known to slow the aging process in the central nervous system, its influence on peripheral nerves has not been investigated in detail. To determine if dietary restriction is beneficial for peripheral nerve health and glial function, we studied sciatic nerves from rats of four distinct ages (8, 18, 29 and 38 months) kept on an ad libitum (AL) or a 40% calorie restricted diet. Age-associated reduction in the expression of the major myelin proteins and widening of the nodes of Ranvier are attenuated by the dietary intervention, which is paralleled with the maintenance of a differentiated Schwann cell phenotype. The improvements in nerve architecture with diet restriction, in part, are underlined by sustained expression of protein chaperones and markers of the autophagy,lysosomal pathway. Together, the in vitro and in vivo results suggest that there might be an age-limit by which dietary intervention needs to be initiated to elicit a beneficial response on peripheral nerve health. [source] Nerve conduits and growth factor delivery in peripheral nerve repairJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 2 2007Lukas A. Pfister Abstract Peripheral nerves possess the capacity of self-regeneration after traumatic injury. Transected peripheral nerves can be bridged by direct surgical coaptation of the two nerve stumps or by interposing autografts or biological (veins) or synthetic nerve conduits (NC). NC are tubular structures that guide the regenerating axons to the distal nerve stump. Early synthetic NC have primarily been made of silicone because of the relative flexibility and biocompatibility of this material and because medical-grade silicone tubes were readily available in various dimensions. Nowadays, NC are preferably made of biodegradable materials such as collagen, aliphatic polyesters, or polyurethanes. Although NC assist in guiding regenerating nerves, satisfactory functional restoration of severed nerves may further require exogenous growth factors. Therefore, authors have proposed NC with integrated delivery systems for growth factors or growth factor,producing cells. This article reviews the most important designs of NC with integrated delivery systems for localized release of growth factors. The various systems discussed comprise NC with growth factors being released from various types of matrices, from transplanted cells (Schwann cells or mesenchymal stem cells), or through genetic modification of cells naturally present at the site of injured tissue. Acellular delivery systems for growth factors include the NC wall itself, biodegradable microspheres seeded onto the internal surface of the NC wall, or matrices that are filled into the lumen of the NC and immobilize the growth factors through physical-chemical interactions or specific ligand-receptor interactions. A very promising and elegant system appears to be longitudinally aligned fibers inserted in the lumen of a NC that deliver the growth factors and provide additional guidance for Schwann cells and axons. This review also attempts to appreciate the most promising approaches and emphasize the importance of growth factor delivery kinetics. [source] Leprous neuropathy: a clinical and neurophysiological studyJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 2 2004E Ghiglione Leprosy is one of the most common treatable causes of neuropathy in the world. Peripheral nerves and skin are commonly affected. We reported the clinical features and electrophysiological findings in 46 patients with leprosy. The aim of our study was to evaluate the nature of damage in the nerve fibres, especially in the first phase of disease. Forty-six patients (mean age: 44.8 ± 17.8) with diagnosed leprosy were studied by neurological examination and nerve conduction studies (NCS). Twenty-eight patients were examined for a mean period of 34.8 months. The number of tests for patients varied from 1 to 13 controls. Amplitude of sensory and motor action potentials (SNAP and MAP), sensory-motor conduction velocity of median, ulnar, tibialis, peroneal and sural nerves were evaluated. Abnormalities were found in 282 of 647 nerves investigated (37.56%), sensory nerve abnormalities being more frequent than motor (50.16% 29.45). Of 282 nerves with neurophysiological abnormalities, 123 were clinically asymptomatic (43.62%). A statistically significant correlation between duration of disease and number of electrophysiological abnormalities was demonstrated. In 19 nerves partial "conduction-block"(reduction of cMAP > 50% in the proximal response) was individuated. The first electrophysiological alteration, suggesting segmental demyelination, was detected in 41 nerves of 21 patients (33.3 %). According to this view, our data support the hypothesis that leprosy induces a neuropathy of demyelinating nature in the first phase. [source] Biopsy of the posterior interosseous nerve: a low morbidity method for assessment of peripheral nerve disordersDIABETIC MEDICINE, Issue 1 2009N. O. B. Thomsen Abstract Aims The sural nerve is the commonest peripheral nerve biopsied to help in the diagnosis of peripheral neuropathy of unknown cause. However, associated complications limit its use. The aim was, as an alternative, to asses biopsy of the terminal branch of the posterior interosseous nerve (PIN) in the forearm. Methods PIN pathology was morphometrically quantified in 10 male patients with Type 2 diabetes and compared with six PIN biopsy specimens taken post mortem from male cadavers with no history of neuropathy or trauma. Results The PIN biopsy procedure provides a long (approximately 3 cm) mono- or bifascicular nerve biopsy with generous epineurial tissue and adjacent vessels. Our results show a significantly lower myelinated fibre density in subjects with diabetes [5782 (3332,9060)/mm2] compared with autopsy control material [9256 (6593,12 935)/mm2, P < 0.007]. No postoperative discomfort or complications were encountered. Conclusions A reduction in myelinated fibre density has previously been shown to be a clinically meaningful measure of neuropathy in diabetic patients. We demonstrate similar findings using the PIN biopsy. The PIN biopsy procedure fulfils the criteria for nerve biopsy and was well tolerated by the patients. It may be a possible alternative to sural nerve biopsy to allow for diagnosis of neuropathy. [source] Polyacrylamide gel electrophoresis followed by sodium dodecyl sulfate gradient polyacrylamide gel electrophoresis for the study of the dimer to monomer transition of human transthyretinELECTROPHORESIS, Issue 14 2003Klaus Altland Abstract Familial amyloidotic polyneuropathy (FAP) is caused by mutations which destabilize transthyretin (TTR) and facilitate the aggregation into extracellular amyloid fibrils preferentially in peripheral nerve and heart tissues. Therapeutic and preventive trials for FAP at the plasma TTR level require a careful study of the destabilization of TTR under variable conditions. We have developed a simple double one-dimensional (D1-D) electrophoretic procedure with polyacrylamide gel electrophoresis (PAGE) followed by sodium dodecylsulfate (SDS) gradient PAGE to study the dimer to monomer transition. TTR is first isolated by PAGE from other plasma proteins. The gel strip containing the TTR fraction is incubated in 2% SDS under varying conditions of temperature, buffer composition, pH, and additives like urea and/or a sulfhydryl-reactive agent, followed by SDS-gradient PAGE for the separation of TTR dimers and monomers. We demonstrate that an unidirectional dimer to monomer transition of normal TTR is achieved at 70,80°C in neutral to mild alkaline buffers or at 37°C and slightly acidic pH (6,7). Addition of urea favors the transition into monomers. Amyloidogenic mutations like amyloidogenic TTR (ATTR)-V30M or ATTR-I107V favor the transition into monomers in buffer systems close to the physiological pH of human plasma. We conclude that this finding has to be considered by any hypothesis on ATTR-derived amyloidogenesis. [source] The future of magnetic resonance-based techniques in neurologyEUROPEAN JOURNAL OF NEUROLOGY, Issue 1 2001European Federation of Neurological Societies Task Force Magnetic resonance techniques have become increasingly important in neurology for defining: 1,brain, spinal cord and peripheral nerve or muscle structure; 2,pathological changes in tissue structures and properties; and 3,dynamic patterns of functional activation of the brain. New applications have been driven in part by advances in hardware, particularly improvements in magnet and gradient coil design. New imaging strategies allow novel approaches to contrast with, for example, diffusion imaging, magnetization transfer imaging, perfusion imaging and functional magnetic resonance imaging. In parallel with developments in hardware and image acquisition have been new approaches to image analysis. These have allowed quantitative descriptions of the image changes to be used for a precise, non-invasive definition of pathology. With the increasing capabilities and specificity of magnetic resonance techniques it is becoming more important that the neurologist is intimately involved in both the selection of magnetic resonance studies for patients and their interpretation. There is a need for considerably improved access to magnetic resonance technology, particularly in the acute or intensive care ward and in the neurosurgical theatre. This report illustrates several key developments. The task force concludes that magnetic resonance imaging is a major clinical tool of growing significance and offers recommendations for maximizing the potential future for magnetic resonance techniques in neurology. [source] Axon behaviour at Schwann cell , astrocyte boundaries: manipulation of axon signalling pathways and the neural adhesion molecule L1 can enable axons to crossEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2004Kathryn H. Adcock Abstract Axon regeneration in vivo is blocked at boundaries between Schwann cells and astrocytes, such as occur at the dorsal root entry zone and around peripheral nerve or Schwann cell grafts. We have created a tissue culture model of these boundaries in Schwann cell , astrocyte monolayer co-cultures. Axon behaviour resembles that in vivo, with axons showing a strong preference for Schwann cells over astrocytes. At boundaries between the two cell types, axons growing on astrocytes cross readily onto Schwann cells, but only 15% of axons growing on Schwann cells are able to cross onto astrocytes. Treatment with chondroitinase or chlorate to reduce inhibition by proteoglycans did not change this behaviour. The neural adhesion molecule L1 is present on Schwann cells and not astrocytes, and manipulation of L1 by application of an antibody, L1-Fc in solution, or adenoviral transduction of L1 into astrocytes increased the proportion of axons able to cross onto astrocytes to 40,50%. Elevating cAMP levels increased crossing from Schwann cells onto astrocytes in live and fixed cultures, and had a co-operative effect with NT-3 but not with NGF. Inactivation of Rho with a cell-permeant form of C3 exoenzyme also increased crossing from Schwann cells to astrocytes. Our experiments indicate that the preference of axons for Schwann cells is largely mediated by the presence of L1 on Schwann cells but not astrocytes, and that manipulation of growth cone signalling pathways can allow axons to disregard boundaries between the two cell types. [source] How does the Schwann cell lineage form tumors in NF1?GLIA, Issue 14 2008Steven L. Carroll Abstract Neurofibromas are benign tumors of peripheral nerve that occur sporadically or in patients with the autosomal dominant tumor predisposition syndrome neurofibromatosis type 1 (NF1). Multiple neurofibroma subtypes exist which differ in their site of occurrence, their association with NF1, and their tendency to undergo transformation to become malignant peripheral nerve sheath tumors (MPNSTs), the most common malignancy associated with NF1. Most NF1 patients carry a constitutional mutation of the NF1 tumor suppressor gene. Neurofibromas develop in these patients when an unknown cell type in the Schwann cell lineage loses its remaining functional NF1 gene and initiates a complex series of interactions with other cell types; these interactions may be influenced by aberrant expression of growth factors and growth factor receptors and the action of modifier genes. Cells within certain neurofibroma subtypes subsequently accumulate additional mutations affecting the p19ARF -MDM2-TP53 and p16INK4A-Rb signaling cascades, mutations of other as yet unidentified genes, and amplification of growth factor receptor genes, resulting in their transformation into MPNSTs. These observations have been validated using a variety of transgenic and knockout mouse models that recapitulate neurofibroma and MPNST pathogenesis. A new generation of mouse models is also providing important new insights into the identity of the cell type in the Schwann cell lineage that gives rise to neurofibromas. Our improving understanding of the mechanisms underlying the pathogenesis of neurofibromas and MPNSTs raises intriguing new questions about the origin and pathogenesis of these neoplasms and establishes models for the development of new therapies targeting these neoplasms. © 2008 Wiley-Liss, Inc. [source] Increase of MCP-1 (CCL2) in myelin mutant Schwann cells is mediated by MEK-ERK signaling pathwayGLIA, Issue 8 2008Stefan Fischer Abstract Macrophages are critically involved in the pathogenesis of genetically caused demyelination, as it occurs in inherited demyelinating neuropathies. On the basis of the observation that upregulation of the Schwann cell-derived chemokine MCP-1 (CCL2) is a pathologically relevant mechanism for macrophage activation in mice heterozygously deficient for the myelin component P0 (P0+/,), we posed the question of the intracellular signaling cascade involved. By using western blot analysis of peripheral nerve lysates the MAP-kinases extracellular signal-regulated kinase 1/2 (ERK1/2) and MAP kinase/ERK kinase 1/2 (MEK1/2) showed an early and constantly increasing activation in P0 mutants. Furthermore, in nerve fibers from the P0+/, mutants, Schwann cell nuclei were much more often positive for phosphorylated ERK1/2 than in nerve fibers from wild type mice. In vitro experiments using the MEK1/2-inhibitor CI-1040 decreased ERK1/2-phosphorylation and MCP-1 expression in a Schwann cell-derived cell line. Finally, systemic application of CI-1040 lead to a decreased ERK1/2-phosphorylation and substantially reduced MCP-1-production in peripheral nerves of P0+/, mutant mice. Our study identifies MEK1/2-ERK1/2 signaling as an important intracellular pathway that connects the Schwann cell mutation with the activation of pathogenetically relevant macrophages in the peripheral nerves. These findings may have important implications for the treatment of inherited peripheral neuropathies in humans. © 2008 Wiley-Liss, Inc. [source] Retroviral labeling of Schwann cells: In vitro characterization and in vivo transplantation to improve peripheral nerve regenerationGLIA, Issue 1 2001Afshin Mosahebi Abstract Transplantation of Schwann cells (SCs) is a promising treatment modality to improve neuronal regeneration. Identification of the transplanted cells is an important step when studying the development of this method. Genetic labeling is the most stable and reliable method of cell identification, but it is still unclear whether it has deleterious effect on SC characteristics. Our aim was to achieve a stable population of SCs transduced with the lacZ gene at a high frequency using a retroviral vector in vitro, and to follow the labeled SC in vitro to assess their viability and phenotypic marker expression. Furthermore, we transplanted lacZ -labeled SCs in a conduit to repair peripheral nerve to investigate their effect on nerve regeneration in vivo. Rat and human SCs were cultured and transduced with an MFG lacZ nls marker gene, achieving a transduction rate of 80% and 70%, respectively. Rat SCs were kept in culture for 27 weeks and examined every 4 weeks for expression of lacZ, viability, and phenotypic marker expression of GFAP, p75, MHC I and II. Throughout this period, transduced rat SCs remained viable and continued to proliferate. The proportion of cells expressing lacZ dropped only by 10% and the expression of phenotypic markers remained stable. Transduced human SCs were followed up for 4 weeks in culture. They proliferated and continued to express the lacZ gene and phenotypic marker expression of GFAP and p75 was preserved. Primary culture of transduced rat SCs were transplanted, syngeneically, in a conduit to bridge a 10 mm gap in sciatic nerve and the grafts were examined after 3 weeks for the presence and participation of labeled SCs and for axonal regeneration distance. Transplanted transduced rat SCs were clearly identified, taking part in the regeneration process and enhancing the axonal regeneration rate by 100% (at the optimal concentration) compared to conduits without SCs. Thus, retroviral introduction of lacZ gene has no deleterious effect on SCs in vitro and these SCs take part and enhance nerve regeneration in vivo. GLIA 34:8,17, 2001. © 2001 Wiley-Liss, Inc. [source] Relationship between fascicle size and perineurial collagen IV content in diabetic and control human peripheral nerveHISTOPATHOLOGY, Issue 6 2000P E Williams Aim: The relationship between perineurial collagen IV content and fascicle size was determined in diabetic and control human peripheral nerve. Methods and results Age-matched diabetic and control sural nerve samples were immunostained using antibodies to collagen IV. The number of cell layers and the perimeter of the fascicle were measured and the collagen IV content of the perineurium determined. Using this method, a comparison could be made of collagen IV content in the perineuria of fascicles of different size. A positive linear relationship was found between fascicle size and the amount of collagen IV per unit of perineurium. The number of perineurial cell layers and the collagen IV content of the diabetic nerve did not differ from control values. Conclusions The linear relationship between fascicle size and perineurial collagen IV content per unit of perineurium underlines the importance of taking fascicle size into account when determining changes in basement membrane components associated with neuropathy. The results indicate that increased deposition of collagen IV is not involved in the early changes in the perineurial cell basement membrane and is thus not the primary factor involved in altered nerve function associated with diabetic neuropathy. [source] Peripheral Nerve pericytes originating from the blood,nerve barrier expresses tight junctional molecules and transporters as barrier-forming cellsJOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2008Fumitaka Shimizu The objective of this study was to establish pure blood,nerve barrier (BNB)-derived peripheral nerve pericyte cell lines and to investigate their unique properties as barrier-forming cells. We isolated peripheral nerve, brain, and lung pericytes from transgenic rats harboring the temperature-sensitive simian virus 40 large T-antigen gene. These cell lines expressed several pericyte markers such as ,-smooth muscle actin, NG2, osteopontin, and desmin, whereas they did not express endothelial cell markers such as vWF and PECAM. In addition, these cell lines expressed several tight junction molecules such as occludin, claudin-12, ZO-1, and ZO-2. In particular, the expression of occludin was detected in peripheral nerve and brain pericytes, although it was not detected in lung pericytes by a Western blot analysis. An immunocytochemical analysis confirmed that occludin and ZO-1 were localized at the cell,cell boundaries among the pericytes. Brain and peripheral nerve pericytes also showed significantly higher trans-pericyte electrical resistance values and lower inulin clearances than lung pericytes. We considered that occludin localized at the cell,cell boundaries among the pericytes might mechanically stabilize the microvessels of the BNB and the blood,brain barrier. Furthermore, we also showed that these cell lines expressed many barrier-related transporters. ABCG2, p-gp, MRP-1, and Glut-1 were detected by a Western blot analysis and were observed in the cytoplasm and outer membrane by an immunocytochemical analysis. These transporters on pericytes might facilitate the peripheral nerve-to-blood efflux and blood-to-peripheral nerve influx transport of substrates in cooperation with those on endothelial cells in order to maintain peripheral nerve homeostasis. J. Cell. Physiol. 217: 388,399, 2008. © 2008 Wiley-Liss, Inc. [source] Impact of a regional anesthesia rotation on ultrasonographic identification of anatomic structures by anesthesiology residentsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 3 2009S. L. OREBAUGH Objective: The specific aim of this study was to determine the ability of anesthesiology residents to independently identify a series of anatomic structures in a live model using ultrasound, both before and after a 4-week regional anesthesia rotation that incorporates a standardized ultrasound training curriculum for peripheral nerve blockade. Methods: Ten CA2 and CA3 anesthesiology residents volunteered to participate in this study. Each resident was subjected to a pre-rotation practical exam, in which he attempted to identify 15 structures at four sites of peripheral nerve blockade, in a test subject. Each resident then received specific training for ultrasound-guided nerve blocks during a 4-week regional anesthesia rotation, and then completed a post-rotation exam. The mean number of structures correctly identified on the exams was compared for significant differences utilizing a paired t -test. Results: Residents were able to identify significantly more anatomic structures on the post-rotation exam as compared with the pre-rotation exam (mean 14.1 vs. 9.9, P<.001), as well as more peripheral nerve targets. The most frequently misidentified structures on the pre-rotation exam were the subclavian vein, the sciatic nerve in the popliteal fossa, and the femur. Conclusions: Ultrasound-naïve anesthesiology residents, who received instruction and experience with ultrasound-guided peripheral nerve blocks on a 4-week regional anesthesia rotation, significantly improved their ability to independently identify relevant anatomic structures with ultrasonography. [source] Microneurography of human median nerveJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 6 2005Mehmet Bilgen PhD Abstract Purpose To examine the possibility of performing high-resolution MRI (microneurography) on peripheral nerves. Materials and Methods A specific radio frequency (RF) coil was developed to probe the human median nerve at a magnetic field strength of 9.4 T and tested on three excised samples by acquiring microneurograms. Results The microneurograms revealed neuronal tissue constituents at subfascicular level. The contrast features on proton-density and T1- and T2-weighted images were described and compared. The microscopic water movement was quantified using diffusion weighting parallel and orthogonal to the neuronal fiber orientation. The characteristics of anisotropic diffusion in the median nerve were comparable to those reported from other biological tissues (white matter and kidney). Conclusion The results overall suggest that microneurography might provide new noninvasive insights into microscopic gross anatomy of the peripheral nerve, injury evaluation, and efficacy of repair, although the feasibility at current clinically relevant field strengths is yet to be determined. J. Magn. Reson. Imaging 2005;21:826,830. © 2005 Wiley-Liss, Inc. [source] Correction of protein kinase C activity and macrophage migration in peripheral nerve by pioglitazone, peroxisome proliferator activated-,-ligand, in insulin-deficient diabetic ratsJOURNAL OF NEUROCHEMISTRY, Issue 2 2008Shin-Ichiro Yamagishi Abstract Pioglitazone, one of thiazolidinediones, a peroxisome proliferator-activated receptor (PPAR)-, ligand, is known to have beneficial effects on macrovascular complications in diabetes, but the effect on diabetic neuropathy is not well addressed. We demonstrated the expression of PPAR-, in Schwann cells and vascular walls in peripheral nerve and then evaluated the effect of pioglitazone treatment for 12 weeks (10 mg/kg/day, orally) on neuropathy in streptozotocin-diabetic rats. At end, pioglitazone treatment improved nerve conduction delay in diabetic rats without affecting the expression of PPAR-,. Diabetic rats showed suppressed protein kinase C (PKC) activity of endoneurial membrane fraction with decreased expression of PKC-,. These alterations were normalized in the treated group. Enhanced expression of phosphorylated extracellular signal-regulated kinase detected in diabetic rats was inhibited by the treatment. Increased numbers of macrophages positive for ED-1 and 8-hydroxydeoxyguanosine-positive Schwann cells in diabetic rats were also corrected by the treatment. Pioglitazone lowered blood lipid levels of diabetic rats, but blood glucose and nerve sorbitol levels were not affected by the treatment. In conclusion, our study showed that pioglitazone was beneficial for experimental diabetic neuropathy via correction of impaired PKC pathway and proinflammatory process, independent of polyol pathway. [source] Oxidative stress in the pathogenesis of experimental diabetic neuropathyJOURNAL OF NEUROCHEMISTRY, Issue 2003P. A. Low We evaluated the effects of chronic hyperglycemia on L5 DRG neurons. Experimental diabetic neuropathy (EDN) was induced by streptozotocin. We studied peripheral nerve after 1, 3, 12 months of diabetes. A conduction deficit was present from the first month and persisted over 12 months, affecting mainly sensory fibers. 8-Hydroxy-deoxyguanosine labeling was significantly increased at all time points in DRG neurons, indicating oxidative injury. Caspase-3 labeling was increased at all three time-points, indicating commitment to the efferent limb of the apoptotic pathway. Apoptosis was confirmed by a significant increase in the percent of neurons undergoing apoptosis (TUNEL staining) at 1 month (8%), 3 months (7%) and 12 months (11%). Morphometry of DRG showed a selective loss (42%) of the largest neurons. These findings support the concept that oxidative stress leads to oxidative injury of DRG neurons, with mitochondrium as a specific target, leading to apoptosis and a predominantly sensory neuropathy. [source] Involvement of nerve injury and activation of peripheral glial cells in tetanic sciatic stimulation-induced persistent pain in ratsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 13 2010Lingli Liang Abstract Tetanic stimulation of the sciatic nerve (TSS) produces long-lasting pain hypersensitivity in rats. Long-term potentiation (LTP) of C- and A-fiber-evoked field potentials in the spinal cord has been explored as contributing to central sensitization in pain pathways. However, the peripheral mechanism underlying TSS-induced pain hypersensitivity remains largely unknown. We investigated the effect of TSS on peripheral nerve and the expression of activating transcription factor 3 (ATF3) in dorsal root ganglion (DRG) as a marker of neuronal injury. TSS induced a mechanical allodynia for at least 35 days and induced ATF3 expression in the ipsilateral DRG. ATF3 is colocalized with NF200-labeled myelinated DRG neurons or CGRP- and IB4-labeled unmyelinated ones. Furthermore, we found that TSS induced Wallerian degeneration of sciatic nerve at the level of myelinisation by S100 protein (to label Schwann cells) immunohistochemistry, luxol fast blue staining, and electron microscopy. TSS also elicited the activation of satellite glial cells (SGCs) and enhanced the colocalization of GFAP and P2X7 receptors. Repeated local treatment with tetrodotoxin decreased GFAP expression in SGCs and behavioral allodynia induced by TSS. Furthermore, reactive microglia and astrocytes were found in the spinal dorsal horn after TSS. These results suggest that TSS-induced nerve injury and glial activation in the DRG and spinal dorsal horn may be involved in cellular mechanisms underlying the development of persistent pain after TSS and that TSS-induced nerve injury may be used as a novel neuropathic pain model. © 2010 Wiley-Liss, Inc. [source] Investigating mechanical behaviour at a core,sheath interface in peripheral nerveJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 4 2004Rachel L. Tillett Abstract As peripheral nerves bend and stretch, internal elements need to move in relation to each other. However, the way in which intraneural components interact is poorly understood. Previous work identified a distinct core and sheath in the rat sciatic nerve and provides a useful model with which to investigate this interaction. Here we have focused on identifying the mechanical and anatomical characteristics of the interface between core and sheath. Nerve samples, 15 and 20 mm long, of rat sciatic nerves were harvested and placed in a purpose-built jig, and a tensile testing machine was used to pull core from sheath. Mechanical tests of specimens in which core had been previously pulled from sheath by 25% of its initial length achieved a mean pull-out force approximately six times smaller than that achieved using intact controls. These results are consistent with the proposal that core,sheath interactions involve physical connections rather than a viscous fluid interface. Anatomical features of this interface were characterised using transmission electron microscopy. It appeared that sheath was derived from epineurium and most of the perineurium, whilst core consisted of endoneurium and a small proportion of the perineurium: the plane of cleavage appeared to involve the innermost perineurial cell layer. [source] Unravelling the molecular basis of CMT4B pathologyJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 2 2004A Bolis Charcot-Marie-Tooth type 4B (CMT4B) disease is a severe autosomal recessive peripheral neuropathy with childhood onset, characterised by progressive muscular atrophy and weakness in the distal extremities, sensory loss, severely decreased nerve conduction velocities, and demyelination with myelin outfoldings in the peripheral nerve. We demonstrated that CMT4B is caused by loss of function mutations in the Myotubularin-related 2 gene, MTMR2, on chromosome 11q22 (Bolino et al., Nat Genet 25:17,19, 2000). MTMR2 belongs to the myotubularin family of protein phosphatases, of which, myotubularin (MTM), mutated in the X-linked myotubular myopathy (XLMTM) is the founder member. MTMR2 shows specific activity towards phosphatidylinositol 3-phosphate and 3,5-biphosphate, PI(3)P and PI(3,5)P2, respectively. However, how abrogation of this lipid phosphatase activity is leading to the specific disease phenotype has not yet been demonstrated. To elucidate the biological role of MTMR2 in the nerve, we performed an extensive expression analysis of this protein in the peripheral nervous system. Since MTMR2 was demonstrated to be ubiquitously expressed also within the nerve, we sought nerve-specific interactors using the yeast two-hybrid approach. The neurofilament light chain protein, NF-L, mutated in various CMTs including axonal type CMT2E, and demyelinating Dejerine-Sottas syndrome, was found to interact with MTMR2 in Schwann cells as well as in neurons. Since NF-L is specifically expressed in the nervous system, the interaction between MTMR2 and NF-L would explain why loss of a ubiquitously expressed phosphatase affects specifically the nerve (Previtali and Bolino, Hum Mol Genet 12:1713,1723, 2003). To model the CMT4B pathology, we generated a general knock-out mouse arising from inactivation f Mtmr2 in all cells. The characterisation of this animal model is underway. Overall, Mtmr2 null mice display a milder phenotype with respect to the human disorder. The morphological analysis of the peripheral nerve of this mouse line performed at P28 revealed the presence of myelin outfoldings, which are the hallmark of CMT4B pathology. [source] Ultrastructural identification of peripheral myelin proteins by a pre-embedding immunogold labeling methodJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2003Marie-Hélène Canron Abstract Ultrastructural immunolabeling of peripheral nervous system components is an important tool to study the relation between structure and function. Owing to the scarcity of certain antigens and the dense structure of the peripheral nerve, a pre-embedding technique is likely appropriate. After several investigations on procedures for pre-embedding immunolabeling, we propose a method that offers a good compromise between detection of antigenic sites and preservation of morphology at the ultrastructural level, and that is easy to use and suitable for investigations on peripheral nerve biopsies from humans. Pre-fixation by immersion in paraformaldehyde/glutaraldehyde is necessary to stabilize the ultrastructure. Then, ultrasmall gold particles with silver enhancement are advised. Antibodies against myelin protein zero and myelin basic protein were chosen for demonstration. The same technique was applied to localize a 35 kDa myelin protein. [source] HIV-associated neuropathies: role of HIV-1, CMV, and other virusesJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2001Dennis L. Kolson Abstract The role of the human immunodeficiency virus (HIV) and other viruses in the development of neuropathies associated with HIV infection is controversial. Distal symmetric polyneuropathy (DSP), the most common subtype of HIV-associated neuropathy, is characterized by an abundance of reactive macrophages within the peripheral nerve, but HIV replication is limited to a small percentage of the macrophages. Thus, the pathological destruction may be mediated by pro-inflammatory signals amplified by activated glial elements within the nerve, similar to the proposed mechanism of damage caused by HIV within the central nervous system. In contrast, in mononeuropathy multiplex (MM) and progressive polyneuropathy (PP), cytomegalovirus (CMV) replication in the peripheral nerve is consistently demonstrable, and this replication likely results in direct damage to the infected cells (neurons and glia). The rarest form of HIV-associated neuropathy, the diffuse infiltrative lymphocytosis syndrome (DILS), is characterized by an intense CD8+ T lymphocyte infiltration into the nerve and abundant HIV infection of macrophages. Finally, while other viruses (varicella zoster, herpes simplex) are associated with myelitis in HIV-infected individuals, there is little support for a role for these viruses in HIV-associated neuropathy. [source] Genes Differentially Expressed By Schwann Cells Of Motor Versus Sensory NervesJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2001D Imperiale Charcot-Marie-Tooth (CMT) disease includes a heterogeneous group of inherited demyelinating peripheral neuropathies related to genetic defects of myelin-forming Schwann cells (SC). In CMT, as in other common acquired demyelinating neuropathies (Guillain Barré syndrome, chronic inflammatory demyelinating polyneuropathy), motor nerves are invariably more involved than sensory nerves. Also in transgenic mouse models of peripheral neuropathy, there is a preferential demyelination of motor districts independent of the type of genetic alteration. The basis for differential susceptibility to demyelination is unknown. The aim of this study was to identify differences in gene and protein expression that may underlie the differential susceptibility to demyelination of motor and sensory myelin-forming SC. Since spinal roots are the only portion of mammalian PNS in which motor and sensory axons are segregated, we extracted RNA from adult rat dorsal (sensory) and ventral (motor) spinal roots and compared corresponding cDNAs by an RNA fingerprint approach. Four differentially displayed bands were isolated. We first characterized the most differentially expressed band, which was highly enriched in sensory roots. Sequence analysis showed that the band encoded a portion of rat sarco/endoplasmic reticulum calcium transporting ATPase type 1 coding sequence (SERCA1). RT-PCR experiments confirmed SERCA1 enrichment in dorsal sensory roots. SERCA enzymes are ubiquitous calcium regulatory systems in muscle and non-muscle cells and SERCA1 is selectively enriched in skeletal muscle. To our knowledge, no studies have investigated SERCA isoform expression in peripheral nerve. Identification of a calcium regulatory molecule in SC is interesting, as calcium is essential for the proper structure and function of the nodal and paranodal portions of SC, as well as the myelin sheath. However, calcium homeostasis in SC is relatively unexplored. Experiments to localize SERCA1 transcript and protein in different PNS districts and to clarify its functional role in peripheral nerve are underway. [source] N-MYC Downstream-Regulated Gene 1 Is Mutated In Hereditary Motor And Sensory Neuropathy-LOMJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2001L Kalaydjieva Hereditary motor and sensory neuropathies, to which Charcot-Marie-Tooth (CMT) disease belongs, are a common cause of disability in adulthood. Growing awareness that axonal loss, rather than demyelination per se, is responsible for the neurological deficit in demyelinating CMT disease has focused research on the mechanisms of early development, cell differentiation, and cell-cell interactions in the peripheral nervous system. Autosomal recessive peripheral neuropathies are relatively rare but are clinically more severe than autosomal dominant forms of CMT, and understanding their molecular basis may provide a new perspective on these mechanisms. Here we report the identification of the gene responsible for hereditary motor and sensory neuropathy-Lom (HMSNL). HMSNL shows features of Schwann-cell dysfunction and a concomitant early axonal involvement, suggesting that impaired axon-glia interactions play a major role in its pathogenesis. The gene was previously mapped to 8q24.3, where conserved disease haplotypes suggested genetic homogeneity and a single founder mutation. We have reduced the HMSNL interval to 200 kb and have characterized it by means of large-scale genomic sequencing. Sequence analysis of two genes located in the critical region identified the founder HMSNL mutation: a premature-termination codon at position 148 of the N-myc downstream-regulated gene 1 (NDRG1). NDRG1 is ubiquitously expressed and has been proposed to play a role in growth arrest and cell differentiation, possibly as a signaling protein shuttling between the cytoplasm and the nucleus. We have studied expression in peripheral nerve and have detected particularly high levels in the Schwann cell. Taken together, these findings point to NDRG1 having a role in the peripheral nervous system, possibly in the Schwann-cell signaling necessary for axonal survival. [source] Enhanced B7 Costimulatory Molecule Expression In Inflammatory Human Sural Nerve BiopsiesJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2001R Kiefer Objectives-To define the role of the costimulatory molecules B7-1 and B7-2 in inflammatory disorders of the peripheral nervous system. B7 molecules are essential for effective antigen presentation and may determine the differentiation of T cells into a Th-1 or Th-2 phenotype, thus modulating immune response and disease course. Methods-Forty nine sural nerve biopsies from patients with neuroborreliosis, Guillain-Barre syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), CIDP variants and hereditary neuropathies, and those with no detectable abnormality were investigated. The expression of B7-1 and B7-2 mRNA and protein was investigated by polymerase chain reaction (PCR) and immunocytochemistry. Results-B7-1 mRNA was strongly upregulated in both cases of neuroborreliosis, in two cases of GBS and one case of variant CIDP. Moderate to low levels were detected in the remaining GBS and CIDP biopsies and were rarely found in a noninflammatory control group consisting of hereditary neuropathy and normal nerves. At the immunocytochemical level, strong expression of B7-1 protein was found in both neuroborreliosis cases, and moderate or low expression in six of eight GBS cases and seven of 17 CIDP cases investigated, whereas only one of five non-inflammatory control nerves showed staining, which was very weak. In neuroborreliosis, B7-1 protein was found very pronounced in epineurial infiltrates, whereas in CBS and CIDP, labelling was predominantly endoneurial and localised to putative macrophages. B7-2 mRNA and protein were expressed only at low levels in neuroborreliosis and selected autoimmune neuropathy cases, and were essentially absent from noninflammatory controls. Conclusions-B7 molecules are expressed in the peripheral nervous system and regulated during disease, and their presence in macrophages underlines the putative function of endoneurial macrophages as local antigen presenting cells in the immunopathology of peripheral nerve. B7-1 rather than B7-2 is preferentially upregulated, possibly promoting the induction of a Th-1-type T cell response within the nerve. [source] Prosaposin-derived peptides enhanced sprouting of sensory neurons in vitro and induced sprouting at motor endplates in vivoJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 3 2000W. Marie Campana Abstract Prosaposin exhibits neurotrophic factor properties that are localized to a 12-amino acid sequence located in the amino terminal portion of the saposin C domain. Prosaptides are peptides derived from the neurotrophic portion of prosaposin; these have been previously reported to be bioactive in neuroblastoma cell lines in vitro. We report that prosaptides were also bioactive in explants of adult primary sensory neurons by dose-dependently increasing both the number (3- to 4-fold) and elongation of these neurites by 50%. Local injection of prosaptides into the gluteus muscle of adult mice also induced sprouting at the motor endplate. Our results indicate that prosaptides are potent neuritogenic factors for both sensory and motor neurons of adult peripheral nerve. [source] | ||||||||||||||||||||||||||||||||||||||||