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Sample records for optic nerve regeneration

  1. Regeneration of Optic Nerve

    Directory of Open Access Journals (Sweden)

    Kwok-Fai So

    2011-05-01

    Full Text Available The optic nerve is part of the central nervous system (CNS and has a structure similar to other CNS tracts. The axons that form the optic nerve originate in the ganglion cell layer of the retina and extend through the optic tract. As a tissue, the optic nerve has the same organization as the white matter of the brain in regard to its glia. There are three types of glial cells: Oligodendrocytes, astrocytes, and microglia. Little structural and functional regeneration of the CNS takes place spontaneously following injury in adult mammals. In contrast, the ability of the mammalian peripheral nervous system (PNS to regenerate axons after injury is well documented. A number of factors are involved in the lack of CNS regeneration, including: (i the response of neuronal cell bodies against the damage; (ii myelin-mediated inhibition by oligodendrocytes; (iii glial scarring, by astrocytes; (iv macrophage infiltration; and (v insufficient trophic factor support. The fundamental difference in the regenerative capacity between CNS and PNS neuronal cell bodies has been the subject of intensive research. In the CNS the target normally conveys a retrograde trophic signal to the cell body. CNS neurons die because of trophic deprivation. Damage to the optic nerve disconnects the neuronal cell body from its target-derived trophic peptides, leading to the death of retinal ganglion cells. Furthermore, the axontomized neurons become less responsive to the peptide trophic signals they do receive. On the other hand, adult PNS neurons are intrinsically responsive to neurotrophic factors and do not lose trophic responsiveness after axotomy. In this talk different strategies to promote optic-nerve regeneration in adult mammals are reviewed. Much work is still needed to resolve many issues. This is a very important area of neuroregeneration and neuroprotection, as currently there is no cure after traumatic optic nerve injury or retinal disease such as glaucoma, which

  2. Intrinsic determinants of optic nerve regeneration

    Institute of Scientific and Technical Information of China (English)

    ZHU Rui-lin; CHO Kin-Sang; GUO Chen-ying; CHEW Justin; CHEN Dong-feng; YANG Liu

    2013-01-01

    Objective To review the functions of these intracellular signals in their regulation of retinal ganglion cell (RGC) axon regeneration.Data sources Relevant articles published in English or Chinese from 1970 to present were selected from PubMed.Searches were made using the terms "intrinsic determinants,axon regeneration,RGC,optic nerve regeneration,and central nervous system axon regeneration."Study selection Articles studying the mechanisms controlling RGC and central nervous system (CNS) axon regeneration were reviewed.Articles focusing on the intrinsic determinants of axon regeneration were selected.Results Like other CNS neurons of mammals,RGCs undergo a developmental loss in their ability to grow axons as they mature,which is a critical contributing factor to the failure of nerve regeneration and repair after injury.This growth failure can be attributed,at least in part,by the induction of molecular programs preventing cellular overgrowth and termination of axonal growth upon maturation.Key intracellular signals and transcription factors,including B cell lymphoma/leukemia 2,cyclic adenine monophosphate,mammalian target of rapamycin,and Krüppel-like transcription factors,have been identified to play central roles in this process.Conclusions Intense effort and substantial progress have been made to identify the various intrinsic growth pathways that regulate RGC axon regeneration.More work is needed to elucidate the mechanisms of and the interrelationship between the actions of these factors and to successfully achieve regeneration and repair of the severed RGC axons.

  3. Neutrophils express oncomodulin and promote optic nerve regeneration

    National Research Council Canada - National Science Library

    Kurimoto, Takuji; Yin, Yuqin; Habboub, Ghaith; Gilbert, Hui-Ya; Li, Yiqing; Nakao, Shintaro; Hafezi-Moghadam, Ali; Benowitz, Larry I

    2013-01-01

    .... In a widely studied instance of this phenomenon, proinflammatory agents have been shown to cause retinal ganglion cells, the projection neurons of the eye, to regenerate lengthy axons through the injured optic nerve...

  4. Characterization of Optic Nerve Regeneration using transgenic Zebrafish

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    Heike eDiekmann

    2015-04-01

    Full Text Available In contrast to the adult mammalian central nervous system (CNS, fish are able to functionally regenerate severed axons upon injury. Although the zebrafish is a well-established model vertebrate for genetic and developmental studies, its use for anatomical studies of axon regeneration has been hampered by the paucity of appropriate tools to visualize re-growing axons in the adult CNS. On this account, we used transgenic zebrafish that express enhanced green fluorescent protein (GFP under the control of a GAP-43 promoter. In adult, naïve retinae, GFP was restricted to young retinal ganglion cells (RGCs and their axons. Within the optic nerve, these fluorescent axons congregated in a distinct strand at the nerve periphery, indicating age-related order. Upon optic nerve crush, GFP expression was markedly induced in RGC somata and intra-retinal axons at 4 to at least 14 days post injury. Moreover, individual axons were visualized in their natural environment of the optic nerve using wholemount tissue clearing and confocal microscopy. With this novel approach, regenerating axons were clearly detectable beyond the injury site as early as 2 days after injury and grew past the optic chiasm by 4 days. Regenerating axons in the entire optic nerve were labelled from 6 to at least 14 days after injury, thereby allowing detailed visualization of the complete regeneration process. Therefore, this new approach could now be used in combination with expression knockdown or pharmacological manipulations to analyze the relevance of specific proteins and signaling cascades for axonal regeneration in vivo. In addition, the RGC-specific GFP expression facilitated accurate evaluation of neurite growth in dissociated retinal cultures. This fast in vitro assay now enables the screening of compound and expression libraries. Overall, the presented methodologies provide exciting possibilities to investigate the molecular mechanisms underlying successful CNS regeneration in

  5. Role of inflammation in the relationship between OM and regeneration of optic nerves

    Directory of Open Access Journals (Sweden)

    Lin-Kun Ma

    2017-07-01

    Full Text Available Oncomodulin(OMis known by us progressively as a Calcium binding protein. Recently, OM has been found that it is secreted by inflammatory cells(neutrophilic granulocyte, and a signal which can promote cell growth between innate immunity and neurons, and a key to regenerate the damaged optical nerves by activating inflammation. The function of promoting the regeneration progress of axons has become a hot issue in recent years. This article summarized the mechanism of OM and the relationship between inflammation-induced OM and optic nerve regeneration research and progress were reviewed.

  6. Upregulation of leukemia inhibitory factor (LIF during the early stage of optic nerve regeneration in zebrafish.

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    Kazuhiro Ogai

    Full Text Available Fish retinal ganglion cells (RGCs can regenerate their axons after optic nerve injury, whereas mammalian RGCs normally fail to do so. Interleukin 6 (IL-6-type cytokines are involved in cell differentiation, proliferation, survival, and axon regrowth; thus, they may play a role in the regeneration of zebrafish RGCs after injury. In this study, we assessed the expression of IL-6-type cytokines and found that one of them, leukemia inhibitory factor (LIF, is upregulated in zebrafish RGCs at 3 days post-injury (dpi. We then demonstrated the activation of signal transducer and activator of transcription 3 (STAT3, a downstream target of LIF, at 3-5 dpi. To determine the function of LIF, we performed a LIF knockdown experiment using LIF-specific antisense morpholino oligonucleotides (LIF MOs. LIF MOs, which were introduced into zebrafish RGCs via a severed optic nerve, reduced the expression of LIF and abrogated the activation of STAT3 in RGCs after injury. These results suggest that upregulated LIF drives Janus kinase (Jak/STAT3 signaling in zebrafish RGCs after nerve injury. In addition, the LIF knockdown impaired axon sprouting in retinal explant culture in vitro; reduced the expression of a regeneration-associated molecule, growth-associated protein 43 (GAP-43; and delayed functional recovery after optic nerve injury in vivo. In this study, we comprehensively demonstrate the beneficial role of LIF in optic nerve regeneration and functional recovery in adult zebrafish.

  7. A study of degeneration, scar formation and regeneration after section of the optic nerve in the frog, Rana pipiens.

    OpenAIRE

    Scott, T. M.; Foote, J

    1981-01-01

    Degeneration, scar formation and regeneration have been studied after section of the optic nerve in the frog. In the normal optic nerve two types of macroglial cell were identified: astrocytes and oligodendroglia. Degeneration after injury proceeded rapidly in comparison with mammals but did not lead to the production of a dense scar. Before much scarring had developed, regenerating axons penetrated the lesioned area.

  8. Report on the National Eye Institute Audacious Goals Initiative: Regenerating the Optic Nerve.

    Science.gov (United States)

    Goldberg, Jeffrey L; Guido, William

    2016-03-01

    The National Eye Institute (NEI) hosted a workshop on November 19, 2014, as part of the Audacious Goals Initiative (AGI), an NEI-led effort to rapidly expand therapies for eye diseases through coordinated research funding. The central audacious goal aims to demonstrate by 2025 the restoration of usable vision in humans through the regeneration of neurons and neural connections in the eye and visual system. This workshop focused on identifying promising strategies for optic nerve regeneration. Its principal objective was to solicit input on future AGI-related funding announcements, and specifically to ask, where are we now in our scientific progress, and what progress should we reach for in the coming years? A full report was generated as a white paper posted on the NEI Web site; this report summarizes the discussion and outcomes from the meeting and serves as guidance for future funding of research that focuses on optic nerve regeneration.

  9. Application of tissue clearing and light sheet fluorescence microscopy to assess optic nerve regeneration in unsectioned tissues.

    Science.gov (United States)

    Luo, Xueting; Yungher, Benjamin; Park, Kevin K

    2014-01-01

    Optic nerve crush injury, as a model to study central nervous system (CNS) injury, is widely used to assess potential therapeutic strategies, aimed at promoting axon regeneration and neuronal survival. Traditional methods to evaluate optic nerve regeneration rely on histological sectioning. However, tissue sectioning results in inevitable loss of three-dimensional (3D) information, such as axonal trajectories and terminations. Here we describe a protocol for whole-tissue assessment of optic nerve regeneration in adult mice without the need for histological sectioning.

  10. Jak/Stat Signaling Stimulates Zebrafish Optic Nerve Regeneration and Overcomes the Inhibitory Actions of Socs3 and Sfpq

    Science.gov (United States)

    Elsaeidi, Fairouz; Bemben, Michael A.; Zhao, Xiao-Feng

    2014-01-01

    The regenerative failure of mammalian optic axons is partly mediated by Socs3-dependent inhibition of Jak/Stat signaling (Smith et al., 2009, 2011). Whether Jak/Stat signaling is part of the normal regenerative response observed in animals that exhibit an intrinsic capacity for optic nerve regeneration, such as zebrafish, remains unknown. Nor is it known whether the repression of regenerative inhibitors, such as Socs3, contributes to the robust regenerative response of zebrafish to optic nerve damage. Here we report that Jak/Stat signaling stimulates optic nerve regeneration in zebrafish. We found that IL-6 family cytokines, acting via Gp130-coupled receptors, stimulate Jak/Stat3 signaling in retinal ganglion cells after optic nerve injury. Among these cytokines, we found that CNTF, IL-11, and Clcf1/Crlf1a can stimulate optic axon regrowth. Surprisingly, optic nerve injury stimulated the expression of Socs3 and Sfpq (splicing factor, proline/glutamine rich) that attenuate optic nerve regeneration. These proteins were induced in a Jak/Stat-dependent manner, stimulated each other's expression and suppressed the expression of regeneration-associated genes. In vivo, the injury-dependent induction of Socs3 and Sfpq inhibits optic nerve regeneration but does not block it. We identified a robust induction of multiple cytokine genes in zebrafish retinal ganglion cells that may contribute to their ability to overcome these inhibitory factors. These studies not only identified mechanisms underlying optic nerve regeneration in fish but also suggest new molecular targets for enhancing optic nerve regeneration in mammals. PMID:24523552

  11. Is the capacity for optic nerve regeneration related to continued retinal ganglion cell production in the frog?

    Science.gov (United States)

    Taylor, J S; Jack, J L; Easter, S S

    1989-01-01

    In the central nervous system of fish and frogs, some, but not all, axons can regenerate. Retinal ganglion cells are among those that can. The retinae of fish and frogs produce new retinal neurons, including ganglion cells, for months or years after hatching. We have evaluated the hypothesis that retinal axonal regeneration is obligatorily linked to continued production of new ganglion cells. We used bromodeoxyuridine immunocytochemistry to assess retinal neurogenesis in juvenile, yearling, and 10 year old Xenopus laevis. Retinal ganglion cell genesis was vigorous in the marginal retina of the juveniles, but in the yearlings and the 10 year olds, no new ganglion cells were produced there. Cellular proliferation in the central retina was evident at all three ages, but none of the cells produced centrally were in the ganglion cell layer. Regeneration was examined in vivo by cutting one optic nerve and then, weeks later, injecting the eye with tritiated proline. Autoradiographs of brain sections showed that the optic nerves of all three ages regenerated. Regeneration in vitro was assessed using retinal explants from frogs of all three ages. In all cases, the cultures produced neurites, with some age-specific differences in the patterns of outgrowth. We conclude that retinal axonal regeneration is not linked obligatorily to maintained neurogenesis.

  12. Progesterone and peripheral nerve regeneration

    Institute of Scientific and Technical Information of China (English)

    Fei Fan; Haichao Li; Yuwei Wang; Yanglin Zheng; Lianjun Jia; Zhihui Wang

    2006-01-01

    OBJECTIVE: To explore the effect of progesterone on peripheral nerve regeneration.DATA SOURCES: An online search of Medline and OVID databases was under taken to identify articles about progesterone and peripheral nerve regeneration published in English between January 1990 and June 2004 by using the keywords of "peripheral nerve, injury, progesterone, regeneration".STUDY SELECTION: The data were primarily screened, those correlated with progesterone and peripheral nerve regeneration were involved, and their original articles were further searched, the repetitive studies or reviews were excluded.DATA EXTRACTION: Totally 59 articles about progesterone and peripheral nerve regeneration were collected, and 26 of them were involved, the other 33 excluded ones were the repetitive studies or reviews.DATA SYNTHESIS: Recent researches found that certain amount of progesterone could be synthetized in peripheral nervous system, and the expression of progesterone receptor could be found in sensory neurons and Schwann cells. After combined with the receptor, endogenous and exogenous progesterone can accelerate the formation of peripheral nerve myelin sheath, also promote the axonal regeneration.CONCLUSION: Progesterone plays a role in protecting neurons, increasing the sensitivity of nerve tissue to nerve growth factor, and accelerating regeneration of nerve in peripheral nerve regeneration, which provides theoretical references for the treatment of demyelinated disease and nerve injury, as well as the prevention of neuroma, especially that the in vivo level of progesterone should be considered for the elderly people accompanied by neuropathy and patients with congenital luteal phase defect, which is of positive significance in guiding the treatment.

  13. Distribution of mesenchymal stem cells and effects on neuronal survival and axon regeneration after optic nerve crush and cell therapy.

    Directory of Open Access Journals (Sweden)

    Louise Alessandra Mesentier-Louro

    Full Text Available Bone marrow-derived cells have been used in different animal models of neurological diseases. We investigated the therapeutic potential of mesenchymal stem cells (MSC injected into the vitreous body in a model of optic nerve injury. Adult (3-5 months old Lister Hooded rats underwent unilateral optic nerve crush followed by injection of MSC or the vehicle into the vitreous body. Before they were injected, MSC were labeled with a fluorescent dye or with superparamagnetic iron oxide nanoparticles, which allowed us to track the cells in vivo by magnetic resonance imaging. Sixteen and 28 days after injury, the survival of retinal ganglion cells was evaluated by assessing the number of Tuj1- or Brn3a-positive cells in flat-mounted retinas, and optic nerve regeneration was investigated after anterograde labeling of the optic axons with cholera toxin B conjugated to Alexa 488. Transplanted MSC remained in the vitreous body and were found in the eye for several weeks. Cell therapy significantly increased the number of Tuj1- and Brn3a-positive cells in the retina and the number of axons distal to the crush site at 16 and 28 days after optic nerve crush, although the RGC number decreased over time. MSC therapy was associated with an increase in the FGF-2 expression in the retinal ganglion cells layer, suggesting a beneficial outcome mediated by trophic factors. Interleukin-1β expression was also increased by MSC transplantation. In summary, MSC protected RGC and stimulated axon regeneration after optic nerve crush. The long period when the transplanted cells remained in the eye may account for the effect observed. However, further studies are needed to overcome eventually undesirable consequences of MSC transplantation and to potentiate the beneficial ones in order to sustain the neuroprotective effect overtime.

  14. Requirement of retinoic acid receptor β for genipin derivative-induced optic nerve regeneration in adult rat retina.

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    Yoshiki Koriyama

    Full Text Available Like other CNS neurons, mature retinal ganglion cells (RGCs are unable to regenerate their axons after nerve injury due to a diminished intrinsic regenerative capacity. One of the reasons why they lose the capacity for axon regeneration seems to be associated with a dramatic shift in RGCs' program of gene expression by epigenetic modulation. We recently reported that (1R-isoPropyloxygenipin (IPRG001, a genipin derivative, has both neuroprotective and neurite outgrowth activities in murine RGC-5 retinal precursor cells. These effects were both mediated by nitric oxide (NO/S-nitrosylation signaling. Neuritogenic activity was mediated by S-nitrosylation of histone deacetylase-2 (HDAC2, which subsequently induced retinoic acid receptor β (RARβ expression via chromatin remodeling in vitro. RARβ plays important roles of neural growth and differentiation in development. However, the role of RARβ expression during adult rat optic nerve regeneration is not clear. In the present study, we extended this hypothesis to examine optic nerve regeneration by IPRG001 in adult rat RGCs in vivo. We found a correlation between RARβ expression and neurite outgrowth with age in the developing rat retina. Moreover, we found that IPRG001 significantly induced RARβ expression in adult rat RGCs through the S-nitrosylation of HDAC2 processing mechanism. Concomitant with RARβ expression, adult rat RGCs displayed a regenerative capacity for optic axons in vivo by IPRG001 treatment. These neuritogenic effects of IPRG001 were specifically suppressed by siRNA for RARβ. Thus, the dual neuroprotective and neuritogenic actions of genipin via S-nitrosylation might offer a powerful therapeutic tool for the treatment of RGC degenerative disorders.

  15. Dock3 overexpression and p38 MAPK inhibition synergistically stimulate neuroprotection and axon regeneration after optic nerve injury.

    Science.gov (United States)

    Semba, Kentaro; Namekata, Kazuhiko; Kimura, Atsuko; Harada, Chikako; Katome, Takashi; Yoshida, Hiroshi; Mitamura, Yoshinori; Harada, Takayuki

    2014-10-03

    The dedicator of cytokinesis 3 (Dock3) is an atypical guanine nucleotide exchange factor that is predominantly expressed in the CNS. Dock3 exerts neuroprotective effects and stimulates optic nerve regeneration. The p38 mitogen-activated protein kinase acts downstream of apoptosis signal-regulating kinase 1 (ASK1) signaling and plays an important role in neural cell death. We assessed a therapeutic efficacy of Dock3 stimulation and p38 inhibition in retinal degeneration induced by optic nerve injury (ONI). In vivo retinal imaging using optical coherence tomography revealed that ONI-induced retinal degeneration was ameliorated in SB203580 (a p38 inhibitor)-treated WT mice and PBS-treated Dock3 overexpressing (Dock3 Tg) mice, and SB203580 further stimulated retinal protection in Dock3 Tg mice. In addition, SB203580 increased the number of regenerating axons after ONI in both WT and Dock3 Tg mice. ONI-induced phosphorylation of ASK1, p38 and the N-methyl-d-aspartate receptor 2B subunit were suppressed in the retina of Dock3 Tg mice. Inhibition of the ASK1 pathway in Dock3 Tg mice suggests that Dock3 may have an antioxidant-like property. These results indicate that overexpression of Dock3 and pharmacological interruption of p38 have synergistic effects for both neuroprotection and axon regeneration, thus combined application may be beneficial for the treatment of ONI. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  16. Erythropoietin promotes axonal regeneration after optic nerve crush in vivo by inhibition of RhoA/ROCK signaling pathway.

    Science.gov (United States)

    Tan, Haibo; Zhong, Yisheng; Shen, Xi; Cheng, Yu; Jiao, Qin; Deng, Lianfu

    2012-11-01

    We investigated whether the RhoA/ROCK pathway was involved in the effect of erythropoietin (EPO) to promote retinal ganglion cells (RGCs) axonal regeneration in a rat optic nerve crush (ONC) model. We demonstrated that both EPO and ROCK inhibitor Y-27632 significantly enhanced RGCs survival and axon regeneration in vivo, and the effects of these agents were additive. Expression of active-RhoA was decreased after EPO or Y-27632 per pull down assay and affinity precipitation. Administration of EPO and Y-27632 cocktail resulted in even more RhoA inactivation, decreased expression of ROCK-1 and ROCK-2, and increased expression of growth associated protein-43 (GAP-43) protein per immunohistochemistry and western blot analysis. Down-regulation of active-RhoA, ROCK-1, and ROCK-2 expression by EPO coincided with the appearance of larger numbers of regenerating axons. In conclusion, the RhoA/ROCK signaling pathway was involved in the EPO effect to promote RGCs axon regeneration after ONC.

  17. Nerves Regulate Cardiomyocyte Proliferation and Heart Regeneration

    OpenAIRE

    Mahmoud, Ahmed I.; O’Meara, Caitlin C.; Gemberling, Matthew; Zhao, Long; Bryant, Donald M.; Zheng, Ruimao; Gannon, Joseph B.; Cai, Lei; Choi, Wen-Yee; Egnaczyk, Gregory F.; Burns, Caroline E.; Burns, C. Geoffrey; MacRae, Calum A.; Poss, Kenneth D.; Lee, Richard T.

    2015-01-01

    Some organisms, such as adult zebrafish and newborn mice, have the capacity to regenerate heart tissue following injury. Unraveling the mechanisms of heart regeneration is fundamental to understanding why regeneration fails in adult humans. Numerous studies have revealed that nerves are crucial for organ regeneration, thus we aimed to determine whether nerves guide heart regeneration. Here, we show using transgenic zebrafish that inhibition of cardiac innervation leads to reduction of myocyte...

  18. Tissue engineering and peripheral nerve regeneration (III) -- Sciatic nerve regeneration with PDLLA nerve guide

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The biodegradation rate and biocompatibility of poly(d, l -lactide) (PDLLA) in vivo were evaluated. The aim of this study was to establish a nerve guide constructed by the PDLLA with 3-D microenvironment and to repair a 10 mm of sciatic nerve gap in rats. The process of the nerve regeneration was investigated by histological assessment, electrophysiological examination, and determination of wet weight recovery rate of the gastrocnemius muscle. After 3 weeks, the nerve guide had changed from a transparent to an opaque status. The conduit was degraded and absorbed partly and had lost their strength with breakage at the 9th week of postoperation. At the conclusion of 12 weeks, proximal and distal end of nerves were anastomosed by nerve regeneration and the conduit vanished completely. The results suggest that PDLLA conduits may serve for peripheral nerve regeneration and PDLLA is a sort of hopeful candidate for tissue engineering.

  19. Acellular nerve allograft promotes selective regeneration

    Institute of Scientific and Technical Information of China (English)

    Haili Xin; Guanjun Wang; Xinrong He; Jiang Peng; Quanyi Guo; Wenjing Xu

    2011-01-01

    Acellular nerve allograft preserves the basilar membrane tube and extracellular matrix, which pro-motes selective regeneration of neural defects via bridging. In the present study, a Sprague Dawley rat sciatic nerve was utilized to prepare acellular nerve allografts through the use of the chemical extraction method. Subsequently, the allograft was transplanted into a 10-mm sciatic nerve defect in Wistar rats, while autologous nerve grafts from Wistar rats served as controls. Compared with autologous nerve grafts, the acellular nerve allografts induced a greater number of degenerated nerve fibers from sural nerves, as well as a reduced misconnect rate in motor fibers, fewer acetyl-choline esterase-positive sural nerves, and a greater number of carbonic anhydrase-positive senso-ry nerve fibers. Results demonstrated that the acellular nerve allograft exhibited significant neural selective regeneration in the process of bridging nerve defects.

  20. Comprehensive evaluation of peripheral nerve regeneration in the acute healing phase using tissue clearing and optical microscopy in a rodent model.

    Science.gov (United States)

    Jung, Yookyung; Ng, Joanna H; Keating, Cameron P; Senthil-Kumar, Prabhu; Zhao, Jie; Randolph, Mark A; Winograd, Jonathan M; Evans, Conor L

    2014-01-01

    Peripheral nerve injury (PNI), a common injury in both the civilian and military arenas, is usually associated with high healthcare costs and with patients enduring slow recovery times, diminished quality of life, and potential long-term disability. Patients with PNI typically undergo complex interventions but the factors that govern optimal response are not fully characterized. A fundamental understanding of the cellular and tissue-level events in the immediate postoperative period is essential for improving treatment and optimizing repair. Here, we demonstrate a comprehensive imaging approach to evaluate peripheral nerve axonal regeneration in a rodent PNI model using a tissue clearing method to improve depth penetration while preserving neural architecture. Sciatic nerve transaction and end-to-end repair were performed in both wild type and thy-1 GFP rats. The nerves were harvested at time points after repair before undergoing whole mount immunofluorescence staining and tissue clearing. By increasing the optic depth penetration, tissue clearing allowed the visualization and evaluation of Wallerian degeneration and nerve regrowth throughout entire sciatic nerves with subcellular resolution. The tissue clearing protocol did not affect immunofluorescence labeling and no observable decrease in the fluorescence signal was observed. Large-area, high-resolution tissue volumes could be quantified to provide structural and connectivity information not available from current gold-standard approaches for evaluating axonal regeneration following PNI. The results are suggestive of observed behavioral recovery in vivo after neurorrhaphy, providing a method of evaluating axonal regeneration following repair that can serve as an adjunct to current standard outcomes measurements. This study demonstrates that tissue clearing following whole mount immunofluorescence staining enables the complete visualization and quantitative evaluation of axons throughout nerves in a PNI model

  1. Nerves Regulate Cardiomyocyte Proliferation and Heart Regeneration.

    Science.gov (United States)

    Mahmoud, Ahmed I; O'Meara, Caitlin C; Gemberling, Matthew; Zhao, Long; Bryant, Donald M; Zheng, Ruimao; Gannon, Joseph B; Cai, Lei; Choi, Wen-Yee; Egnaczyk, Gregory F; Burns, Caroline E; Burns, C Geoffrey; MacRae, Calum A; Poss, Kenneth D; Lee, Richard T

    2015-08-24

    Some organisms, such as adult zebrafish and newborn mice, have the capacity to regenerate heart tissue following injury. Unraveling the mechanisms of heart regeneration is fundamental to understanding why regeneration fails in adult humans. Numerous studies have revealed that nerves are crucial for organ regeneration, thus we aimed to determine whether nerves guide heart regeneration. Here, we show using transgenic zebrafish that inhibition of cardiac innervation leads to reduction of myocyte proliferation following injury. Specifically, pharmacological inhibition of cholinergic nerve function reduces cardiomyocyte proliferation in the injured hearts of both zebrafish and neonatal mice. Direct mechanical denervation impairs heart regeneration in neonatal mice, which was rescued by the administration of neuregulin 1 (NRG1) and nerve growth factor (NGF) recombinant proteins. Transcriptional analysis of mechanically denervated hearts revealed a blunted inflammatory and immune response following injury. These findings demonstrate that nerve function is required for both zebrafish and mouse heart regeneration.

  2. Complement components of nerve regeneration conditioned fluid influence the microenvironment of nerve regeneration

    Directory of Open Access Journals (Sweden)

    Guang-shuai Li

    2016-01-01

    Full Text Available Nerve regeneration conditioned fluid is secreted by nerve stumps inside a nerve regeneration chamber. A better understanding of the proteinogram of nerve regeneration conditioned fluid can provide evidence for studying the role of the microenvironment in peripheral nerve regeneration. In this study, we used cylindrical silicone tubes as the nerve regeneration chamber model for the repair of injured rat sciatic nerve. Isobaric tags for relative and absolute quantitation proteomics technology and western blot analysis confirmed that there were more than 10 complement components (complement factor I, C1q-A, C1q-B, C2, C3, C4, C5, C7, C8ß and complement factor D in the nerve regeneration conditioned fluid and each varied at different time points. These findings suggest that all these complement components have a functional role in nerve regeneration.

  3. Complement components of nerve regeneration conditioned lfuid inlfuence the microenvironment of nerve regeneration

    Institute of Scientific and Technical Information of China (English)

    Guang-shuai Li; Qing-feng Li; Ming-min Dong; Tao Zan; Shuang Ding; Lin-bo Liu

    2016-01-01

    Nerve regeneration conditioned lfuid is secreted by nerve stumps inside a nerve regeneration chamber. A better understanding of the pro-teinogram of nerve regeneration conditioned lfuid can provide evidence for studying the role of the microenvironment in peripheral nerve regeneration. In this study, we used cylindrical silicone tubes as the nerve regeneration chamber model for the repair of injured rat sciatic nerve. Isobaric tags for relative and absolute quantitation proteomics technology and western blot analysis conifrmed that there were more than 10 complement components (complement factor I, C1q-A, C1q-B, C2, C3, C4, C5, C7, C8β and complement factor D) in the nerve regeneration conditioned lfuid and each varied at different time points. These ifndings suggest that all these complement components have a functional role in nerve regeneration.

  4. Characterization of the domains of zRICH, a protein induced during optic nerve regeneration in zebrafish.

    Science.gov (United States)

    Challa, Madhavi; Chapa, Gloria R; Govindaraju, Suman; González-García, Maribel; Ballestero, Rafael P

    2006-07-19

    Teleost fish show a remarkable capability of nerve regeneration in their CNS, while injuries to axon fibers in the CNS of mammals result in degeneration and loss of function. Understanding this difference has biomedical consequences to humans. Both extrinsic factors from the neuronal environment and intrinsic neuronal factors seem to play a role in successful nerve regeneration. Among the intrinsic factors, a number of proteins termed axonal growth associated proteins (GAPs) are strongly induced during axon regeneration. RICH proteins are axonal GAPs that show homology to mammalian myelin marker proteins termed CNPases. Sequence analysis distinguishes three domains in these proteins. In this report, mutant versions of zebrafish RICH proteins were generated to study the roles of the domains of the protein at biochemical and cellular levels. The central CNPase homology domain was sufficient for catalytic activity. The amino terminal acidic domain causes the anomalous electrophoretic migration observed for RICH proteins. The small C-terminal domain bears an isoprenylation motif and is necessary for the interaction of zRICH with cellular membranes. At the cellular level, expression of wild-type zRICH protein in PC12 cells did not induce neurite generation. Additionally, neither the expression of wild-type zRICH nor the expression of mutant versions of the protein interfered with the levels of differentiation of PC12 cells induced by nerve growth factor, suggesting that, at least in this model of neuronal differentiation, zRICH proteins do not participate in the process of generation of neurites.

  5. Adipose derived stem cells and nerve regeneration

    Institute of Scientific and Technical Information of China (English)

    Alessandro Faroni; Richard JP Smith; Adam J Reid

    2014-01-01

    Injuries to peripheral nerves are common and cause life-changing problems for patients along-side high social and health care costs for society. Current clinical treatment of peripheral nerve injuries predominantly relies on sacriifcing a section of nerve from elsewhere in the body to pro-vide a graft at the injury site. Much work has been done to develop a bioengineered nerve graft, precluding sacriifce of a functional nerve. Stem cells are prime candidates as accelerators of re-generation in these nerve grafts. This review examines the potential of adipose-derived stem cells to improve nerve repair assisted by bioengineered nerve grafts.

  6. Optic nerve oxygenation

    DEFF Research Database (Denmark)

    Stefánsson, Einar; Pedersen, Daniella Bach; Jensen, Peter Koch

    2005-01-01

    at similar levels of perfusion pressure. The levels of perfusion pressure that lead to optic nerve hypoxia in the laboratory correspond remarkably well to the levels that increase the risk of glaucomatous optic nerve atrophy in human glaucoma patients. The risk for progressive optic nerve atrophy in human...... glaucoma patients is six times higher at a perfusion pressure of 30 mmHg, which corresponds to a level where the optic nerve is hypoxic in experimental animals, as compared to perfusion pressure levels above 50 mmHg where the optic nerve is normoxic. Medical intervention can affect optic nerve oxygen......-oxygenase inhibitor, indomethacin, which indicates that prostaglandin metabolism plays a role. Laboratory studies suggest that carbonic anhydrase inhibitors might be useful for medical treatment of optic nerve and retinal ischemia, potentially in diseases such as glaucoma and diabetic retinopathy. However, clinical...

  7. Optic nerve oxygenation

    DEFF Research Database (Denmark)

    Stefánsson, Einar; Pedersen, Daniella Bach; Jensen, Peter Koch;

    2005-01-01

    at similar levels of perfusion pressure. The levels of perfusion pressure that lead to optic nerve hypoxia in the laboratory correspond remarkably well to the levels that increase the risk of glaucomatous optic nerve atrophy in human glaucoma patients. The risk for progressive optic nerve atrophy in human...... glaucoma patients is six times higher at a perfusion pressure of 30 mmHg, which corresponds to a level where the optic nerve is hypoxic in experimental animals, as compared to perfusion pressure levels above 50 mmHg where the optic nerve is normoxic. Medical intervention can affect optic nerve oxygen......-oxygenase inhibitor, indomethacin, which indicates that prostaglandin metabolism plays a role. Laboratory studies suggest that carbonic anhydrase inhibitors might be useful for medical treatment of optic nerve and retinal ischemia, potentially in diseases such as glaucoma and diabetic retinopathy. However, clinical...

  8. Chitosan Conduit for Peripheral Nerve Regeneration

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    Chitosan, the N-deacetylated form of chitin, has good biocompatibility and biodegradability.This paper investigates the feasibility of using chitosan conduits for peripheral nerve regeneration.Cell culture experiments were used to test the material's cytotoxicity and affinity to nerve cells.Conduit implantation experiments were used to study the degradation of the material and the regeneration of injured sciatic nerves.The primary results indicate that chitosan has good mechanical properties, biocompatibility, and biodegradability and it may be a promising biomaterial for peripheral nerve regeneration.

  9. Neuromodulatory nerve regeneration: adipose tissue-derived stem cells and neurotrophic mediation in peripheral nerve regeneration.

    Science.gov (United States)

    Widgerow, Alan D; Salibian, Ara A; Lalezari, Shadi; Evans, Gregory R D

    2013-12-01

    Peripheral nerve injury requiring nerve gap reconstruction remains a major problem. In the quest to find an alternative to autogenous nerve graft procedures, attempts have been made to differentiate mesenchymal stem cells into neuronal lineages in vitro and utilize these cellular constructs for nerve regeneration. Unfortunately, this has produced mixed results, with no definitive procedure matching or surpassing traditional nerve grafting procedures. This review presents a different approach to nerve regeneration. The literature was reviewed to evaluate current methods of using adipose-derived stem cells (ADSCs) for peripheral nerve regeneration in in vivo models of animal peripheral nerve injury. The authors present cited evidence for directing nerve regeneration through paracrine effects of ADSCs rather than through in vitro nerve regeneration. The paracrine effects rely mainly, but not solely, on the elaboration of nerve growth factors and neurotrophic mediators that influence surrounding host cells to orchestrate in vivo nerve regeneration. Although this paradigm has been indirectly referred to in a host of publications, few major efforts for this type of neuromodulatory nerve regeneration have been forthcoming. The ADSCs are initially "primed" in vitro using specialized controlled medium (not for neuronal differentiation but for sustainability) and then incorporated into a hydrogel base matrix designed for this purpose. This core matrix is then introduced into a natural collagen-based nerve conduit. The prototype design concepts, evidence for paracrine influences, and regulatory hurdles that are avoided using this approach are discussed. Copyright © 2013 Wiley Periodicals, Inc.

  10. Nanofibrous nerve conduit-enhanced peripheral nerve regeneration.

    Science.gov (United States)

    Jiang, Xu; Mi, Ruifa; Hoke, Ahmet; Chew, Sing Yian

    2014-05-01

    Fibre structures represent a potential class of materials for the formation of synthetic nerve conduits due to their biomimicking architecture. Although the advantages of fibres in enhancing nerve regeneration have been demonstrated, in vivo evaluation of fibre size effect on nerve regeneration remains limited. In this study, we analyzed the effects of fibre diameter of electrospun conduits on peripheral nerve regeneration across a 15-mm critical defect gap in a rat sciatic nerve injury model. By using an electrospinning technique, fibrous conduits comprised of aligned electrospun poly (ε-caprolactone) (PCL) microfibers (981 ± 83 nm, Microfiber) or nanofibers (251 ± 32 nm, Nanofiber) were obtained. At three months post implantation, axons regenerated across the defect gap in all animals that received fibrous conduits. In contrast, complete nerve regeneration was not observed in the control group that received empty, non-porous PCL film conduits (Film). Nanofiber conduits resulted in significantly higher total number of myelinated axons and thicker myelin sheaths compared to Microfiber and Film conduits. Retrograde labeling revealed a significant increase in number of regenerated dorsal root ganglion sensory neurons in the presence of Nanofiber conduits (1.93 ± 0.71 × 10(3) vs. 0.98 ± 0.30 × 10(3) in Microfiber, p regeneration. These results could provide useful insights for future nerve guide designs.

  11. The neurochemistry of peripheral nerve regeneration

    Science.gov (United States)

    Benga, Andreea; Zor, Fatih; Korkmaz, Ahmet; Marinescu, Bogdan; Gorantla, Vijay

    2017-01-01

    Peripheral nerve injuries (PNIs) can be most disabling, resulting in the loss of sensitivity, motor function and autonomic control in the involved anatomical segment. Although injured peripheral nerves are capable of regeneration, sub-optimal recovery of function is seen even with the best reconstruction. Distal axonal degeneration is an unavoidable consequence of PNI. There are currently few strategies aimed to maintain the distal pathway and/or target fidelity during regeneration across the zone of injury. The current state of the art approaches have been focussed on the site of nerve injury and not on their distal muscular targets or representative proximal cell bodies or central cortical regions. This is a comprehensive literature review of the neurochemistry of peripheral nerve regeneration and a state of the art analysis of experimental compounds (inorganic and organic agents) with demonstrated neurotherapeutic efficacy in improving cell body and neuron survival, reducing scar formation and maximising overall nerve regeneration. PMID:28615804

  12. A small molecule screen identifies in vivo modulators of peripheral nerve regeneration in zebrafish

    Science.gov (United States)

    Skinner, Julianne; Granato, Michael

    2017-01-01

    Adult vertebrates have retained the ability to regenerate peripheral nerves after injury, although regeneration is frequently incomplete, often leading to functional impairments. Small molecule screens using whole organisms have high potential to identify biologically relevant targets, yet currently available assays for in vivo peripheral nerve regeneration are either very laborious and/or require complex technology. Here we take advantage of the optical transparency of larval zebrafish to develop a simple and fast pectoral fin removal assay that measures peripheral nerve regeneration in vivo. Twenty-four hours after fin amputation we observe robust and stereotyped nerve regrowth at the fin base. Similar to laser mediated nerve transection, nerve regrowth after fin amputation requires Schwann cells and FGF signaling, confirming that the fin amputation assay identifies pathways relevant for peripheral nerve regeneration. From a library of small molecules with known targets, we identified 21 compounds that impair peripheral nerve regeneration. Several of these compounds target known regulators of nerve regeneration, further validating the fin removal assay. Twelve of the identified compounds affect targets not previously known to control peripheral nerve regeneration. Using a laser-mediated nerve transection assay we tested ten of those compounds and confirmed six of these compounds to impair peripheral nerve regeneration: an EGFR inhibitor, a glucocorticoid, prostaglandin D2, a retinoic acid agonist, an inhibitor of calcium channels and a topoisomerase I inhibitor. Thus, we established a technically simple assay to rapidly identify valuable entry points into pathways critical for vertebrate peripheral nerve regeneration. PMID:28575069

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

    Science.gov (United States)

    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

  14. Nerve growth factor and injured peripheral nerve regeneration

    Institute of Scientific and Technical Information of China (English)

    Endong Shi; Bingchen Wang; Qingshan Sun

    2008-01-01

    Nerve growth factor (NGF) exhibits many biological activities, such as supply of nutrients, neuroprotection, and the generation and rehabilitation of injured nerves. The neuroprotective and neurotrophic qualities of NGF are generally recognized. NGF may enhance axonal regeneration and myelination of peripheral nerves, as well as cooperatively promote functional recovery of injured nerves and limbs. The clinical efficacy of NGF and its therapeutic potentials are reviewed here. This paper also reviews the latest NGF research developments for repairing injured peripheral nerve, thereby providing scientific evidence for the appropriate clinical application of NGF.

  15. Immunobiology of Facial Nerve Repair and Regeneration

    Institute of Scientific and Technical Information of China (English)

    QUAN Shi-ming; GAO Zhi-qiang

    2006-01-01

    Immunobiological study is a key to revealing the important basis of facial nerve repair and regeneration for both research and development of clinic treatments. The microenvironmental changes around an injuried facial motoneuron, i.e., the aggregation and expression of various types of immune cells and molecules in a dynamic equilibrium, impenetrate from the start to the end of the repair of an injured facial nerve. The concept of "immune microenvironment for facial nerve repair and regeneration", mainly concerns with the dynamic exchange between expression and regulation networks and a variaty of immune cells and immune molecules in the process of facial nerve repair and regeneration for the maintenance of a immune microenvironment favorable for nerve repair.Investigation on microglial activation and recruitment, T cell behavior, cytokine networks, and immunological cellular and molecular signaling pathways in facial nerve repair and regeneration are the current hot spots in the research on immunobiology of facial nerve injury. The current paper provides a comprehensive review of the above mentioned issues. Research of these issues will eventually make immunological interventions practicable treatments for facial nerve injury in the clinic.

  16. Magnetoneurographic evaluation of peripheral nerve regeneration

    NARCIS (Netherlands)

    P.D.L. Kuypers (Paul)

    1998-01-01

    textabstractWhen a peripheral nerve is reconstructed after it has been damaged. it is important to assess, in an early stage, whether the nerve is regenerating across the lesion. However, at present for this purpose an adequate method is not available. In this study short term changes in the proxima

  17. Photofabricated gelatin-based nerve conduits: nerve tissue regeneration potentials.

    Science.gov (United States)

    Gámez, Eduardo; Goto, Yoshinobu; Nagata, Kengo; Iwaki, Toru; Sasaki, Tomio; Matsuda, Takehisa

    2004-01-01

    There is a strong demand for development of nerve guide conduit with prompt nerve regeneration potential for injury-induced nerve defect. Prior to study on nerve tissue engineering using Schwann cells or nerve stem cells, the effectiveness of photofabricated scaffolds based on photocurable gelatin was examined. This study describes the evaluation of in vivo nerve tissue regeneration potentials of three custom-designed and -fabricated prostheses (inner diameter, 1.2 mm; outer diameter, 2.4 mm; wall thickness, 0.60 mm; and length, 15 mm) made of photocured gelatin: a plain photocured gelatin tube (model I), a photocured gelatin tube packed with bioactive substances (laminin, fibronectin, and nerve growth factor) coimmobilized in a photocured gelatin rod (model II), and a photocured gelatin tube packed with bioactive substances coimmobilized in multifilament fibers (model III). These prostheses were implanted between the proximal and distal stumps 10 mm of the dissected right sciatic nerve of 70 adult male Lewis rats for up to 1 year. The highest regenerative potentials were found using the model III prosthesis, followed by the model II prosthesis. Markedly retarded neural regeneration was observed using the model I prosthesis. These were evaluated from the viewpoints of functional recovery, electrophysiological responses, and tissue morphological regeneration. The significance of the synergistic cooperative functions of multifilaments, which serve as a platform that provides contact guidance to direct longitudinal cell movement and tissue ingrowth and as a cell adhesive matrix with high surface area, and immobilized bioactive substances, which enhance nerve regeneration via biological stimulation, is discussed.

  18. The nuclear events guiding successful nerve regeneration

    Directory of Open Access Journals (Sweden)

    Sumiko eKiryu-Seo

    2011-12-01

    Full Text Available Peripheral nervous system (PNS neurons survive and regenerate after nerve injury, whereas central nervous system (CNS neurons lack the capacity to do so. The inability of the CNS to regenerate results from a lack of intrinsic growth activity and a permissive environment. To achieve CNS regeneration, we can learn from successful nerve regeneration in the PNS. Neurons in the PNS elicit dynamic changes in gene expression in response to permissive environmental cues following nerve injury. To switch gene expression on and off in injured neurons, transcription factors and their networks should be carefully orchestrated according to the regeneration program. This is the so-called intrinsic power of axonal growth. There is an increasing repertoire of candidate transcription factors induced by nerve injury. Some of them potentiate the survival and axonal regeneration of damaged neurons in vivo; however, our knowledge of transcriptional events in injured neurons is still limited. How do these transcription factors communicate with each other? How does the transcriptional machinery regulate the wide variety of regeneration-associated genes (RAGs in the properly coordinated manner? In this review, we describe our current understanding of the injury-inducible transcriptional factors that enhance the intrinsic growth capacity, and propose a potential role for specificity protein 1 (Sp1, which provides a platform to recruit injury-inducible transcription factors, in simultaneous gene regulation. Finally, we discuss an additional mechanism that is involved in epigenetic modifications in damaged neurons. A comprehensive understanding of the nuclear events in injured neurons will provide clues to clinical interventions for successful nerve regeneration.

  19. Optic nerve oxygen tension

    DEFF Research Database (Denmark)

    la Cour, M; Kiilgaard, Jens Folke; Eysteinsson, T

    2000-01-01

    To investigate the influence of acute changes in intraocular pressure on the oxygen tension in the vicinity of the optic nerve head under control conditions and after intravenous administration of 500 mg of the carbonic anhydrase inhibitor dorzolamide....

  20. Drug Delivery for Peripheral Nerve Regeneration

    Science.gov (United States)

    2015-11-01

    and diffusion hole follow sterilization . The manufactured PLGA devices were sterilized using 70% ethanol (n=42), ethylene oxide (ETO) (n=46), and a...hydrogels. The shortcomings of current devices in terms of burst effect , nonuniform dosage, and uneven drug delivery, necessitates a new approach to...Specific Aim 2 -- To evaluate the effectiveness of the conduit-drug delivery device to enhance nerve regeneration across a 15mm nerve gap in a rat sciatic

  1. Electrical Stimulation to Promote Peripheral Nerve Regeneration.

    Science.gov (United States)

    Willand, Michael P; Nguyen, May-Anh; Borschel, Gregory H; Gordon, Tessa

    2016-06-01

    Peripheral nerve injury afflicts individuals from all walks of life. Despite the peripheral nervous system's intrinsic ability to regenerate, many patients experience incomplete functional recovery. Surgical repair aims to expedite this recovery process in the most thorough manner possible. However, full recovery is still rarely seen especially when nerve injury is compounded with polytrauma where surgical repair is delayed. Pharmaceutical strategies supplementary to nerve microsurgery have been investigated but surgery remains the only viable option. Brief low-frequency electrical stimulation of the proximal nerve stump after primary repair has been widely investigated. This article aims to review the currently known biological basis for the regenerative effects of acute brief low-frequency electrical stimulation on axonal regeneration and outline the recent clinical applications of the electrical stimulation protocol to demonstrate the significant translational potential of this modality for repairing peripheral nerve injuries. The review concludes with a discussion of emerging new advancements in this exciting area of research. The current literature indicates the imminent clinical applicability of acute brief low-frequency electrical stimulation after surgical repair to effectively promote axonal regeneration as the stimulation has yielded promising evidence to maximize functional recovery in diverse types of peripheral nerve injuries. © The Author(s) 2015.

  2. Extracellular matrix components in peripheral nerve regeneration.

    Science.gov (United States)

    Gonzalez-Perez, Francisco; Udina, Esther; Navarro, Xavier

    2013-01-01

    Injured axons of the peripheral nerve are able to regenerate and, eventually, reinnervate target organs. However, functional recovery is usually poor after severe nerve injuries. The switch of Schwann cells to a proliferative state, secretion of trophic factors, and the presence of extracellular matrix (ECM) molecules (such as collagen, laminin, or fibronectin) in the distal stump are key elements to create a permissive environment for axons to grow. In this review, we focus attention on the ECM components and their tropic role in axonal regeneration. These components can also be used as molecular cues to guide the axons through artificial nerve guides in attempts to better mimic the natural environment found in a degenerating nerve. Most used scaffolds tested are based on natural molecules that form the ECM, but use of synthetic polymers and functionalization of hydrogels are bringing new options. Progress in tissue engineering will eventually lead to the design of composite artificial nerve grafts that may replace the use of autologous nerve grafts to sustain regeneration over long gaps.

  3. Protein phosphorylation: Localization in regenerating optic axons

    Energy Technology Data Exchange (ETDEWEB)

    Larrivee, D. (Cornell Univ. Medical College, New York, NY (USA))

    1990-09-01

    A number of axonal proteins display changes in phosphorylation during goldfish optic nerve regeneration. (1) To determine whether the phosphorylation of these proteins was closely linked to their synthesis in the retinal ganglion cell body, cycloheximide was injected intraocularly into goldfish whose optic nerves had been regenerating for 3 weeks. Cycloheximide reduced the incorporation of (3H)proline and 32P orthophosphate into total nerve protein by 84% and 46%, respectively. Of the 20 individual proteins examined, 17 contained less than 15% of the (3H)proline label measured in corresponding controls, whereas 18 proteins contained 50% or more of the 32P label, suggesting that phosphorylation was largely independent of synthesis. (2) To determine whether the proteins were phosphorylated in the ganglion cell axons, axonal transport of proteins was blocked by intraocular injection of vincristine. Vincristine reduced (3H)proline labeling of total protein by 88% and 32P labeling by 49%. Among the individual proteins (3H)proline labeling was reduced by 90% or more in 18 cases but 32P labeling was reduced only by 50% or less. (3) When 32P was injected into the cranial cavity near the ends of the optic axons, all of the phosphoproteins were labeled more intensely in the optic tract than in the optic nerve. These results suggest that most of the major phosphoproteins that undergo changes in phosphorylation in the course of regeneration are phosphorylated in the optic axons.

  4. Nerve Cross-Bridging to Enhance Nerve Regeneration in a Rat Model of Delayed Nerve Repair

    Science.gov (United States)

    2015-01-01

    There are currently no available options to promote nerve regeneration through chronically denervated distal nerve stumps. Here we used a rat model of delayed nerve repair asking of prior insertion of side-to-side cross-bridges between a donor tibial (TIB) nerve and a recipient denervated common peroneal (CP) nerve stump ameliorates poor nerve regeneration. First, numbers of retrogradely-labelled TIB neurons that grew axons into the nerve stump within three months, increased with the size of the perineurial windows opened in the TIB and CP nerves. Equal numbers of donor TIB axons regenerated into CP stumps either side of the cross-bridges, not being affected by target neurotrophic effects, or by removing the perineurium to insert 5-9 cross-bridges. Second, CP nerve stumps were coapted three months after inserting 0-9 cross-bridges and the number of 1) CP neurons that regenerated their axons within three months or 2) CP motor nerves that reinnervated the extensor digitorum longus (EDL) muscle within five months was determined by counting and motor unit number estimation (MUNE), respectively. We found that three but not more cross-bridges promoted the regeneration of axons and reinnervation of EDL muscle by all the CP motoneurons as compared to only 33% regenerating their axons when no cross-bridges were inserted. The same 3-fold increase in sensory nerve regeneration was found. In conclusion, side-to-side cross-bridges ameliorate poor regeneration after delayed nerve repair possibly by sustaining the growth-permissive state of denervated nerve stumps. Such autografts may be used in human repair surgery to improve outcomes after unavoidable delays. PMID:26016986

  5. Nerve cross-bridging to enhance nerve regeneration in a rat model of delayed nerve repair.

    Science.gov (United States)

    Gordon, Tessa; Hendry, Michael; Lafontaine, Christine A; Cartar, Holliday; Zhang, Jennifer J; Borschel, Gregory H

    2015-01-01

    There are currently no available options to promote nerve regeneration through chronically denervated distal nerve stumps. Here we used a rat model of delayed nerve repair asking of prior insertion of side-to-side cross-bridges between a donor tibial (TIB) nerve and a recipient denervated common peroneal (CP) nerve stump ameliorates poor nerve regeneration. First, numbers of retrogradely-labelled TIB neurons that grew axons into the nerve stump within three months, increased with the size of the perineurial windows opened in the TIB and CP nerves. Equal numbers of donor TIB axons regenerated into CP stumps either side of the cross-bridges, not being affected by target neurotrophic effects, or by removing the perineurium to insert 5-9 cross-bridges. Second, CP nerve stumps were coapted three months after inserting 0-9 cross-bridges and the number of 1) CP neurons that regenerated their axons within three months or 2) CP motor nerves that reinnervated the extensor digitorum longus (EDL) muscle within five months was determined by counting and motor unit number estimation (MUNE), respectively. We found that three but not more cross-bridges promoted the regeneration of axons and reinnervation of EDL muscle by all the CP motoneurons as compared to only 33% regenerating their axons when no cross-bridges were inserted. The same 3-fold increase in sensory nerve regeneration was found. In conclusion, side-to-side cross-bridges ameliorate poor regeneration after delayed nerve repair possibly by sustaining the growth-permissive state of denervated nerve stumps. Such autografts may be used in human repair surgery to improve outcomes after unavoidable delays.

  6. POROSITY OF THE WALL OF A NEUROLAC (R) NERVE CONDUIT HAMPERS NERVE REGENERATION

    NARCIS (Netherlands)

    Meek, Marcel F.; Den Dunnen, Wilfred F. A.

    2009-01-01

    One way to improve nerve regeneration and bridge longer nerve gaps may be the use of semipermeable/porous conduits. With porosity less biomaterial is used for the nerve conduit. We evaluated the short-term effects of porous Neurolac (R) nerve conduits for in vivo peripheral nerve regeneration. In 10

  7. Neuronal differentiation of PC12 cells induced by sciatic nerve and optic nerve conditioned medium

    Institute of Scientific and Technical Information of China (English)

    DU Chan; YANG De-mei; ZHANG Pei-xun; DENG Lei; JIANG Bao-guo

    2010-01-01

    Background Previous work has shown that optic nerve and sciatic nerve conditional medium had neurotrophic activity on neurons. In order to find if the optic nerve conditioned media (CM) had a similar activity to make PC12 cells differentiate as sciatic nerve CM did, we explored the neurotrophic activity in optic nerve CM in the same in vitro system and compared the neurotrophin expression levels in optic and sciatic nerves under both conditions.Methods PC12 cells were used to examine the effects of neurotrophins secreted by the sciatic nerve and optic nerve. RT-PCR and real-time QPCR showed that the sciatic nerve and optic nerve produced a range of neurotrophins including nerve growth factor (NGF), brain derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3).Results The effects of sciatic nerve and optic nerve CM on neurite outgrowth were tested against a range of neurotrophins, and they had different neuritogenic activities. Only NGF and sciatic nerve CM had obvious neuritogenic activities, although the concentration of NGF in the sciatic nerve CM was very low.Conclusions Our experiment showed that sciatic nerve CM had a higher neurotrophic activity on PC12 cells than optic nerve CM. These results suggested that peripheral nervous system (PNS) and central nervous system (CNS) had different expression levels of neurotrophin, which may in part explain the lack of ability to regenerate the CNS.

  8. Optic nerve oxygen tension

    DEFF Research Database (Denmark)

    Kiilgaard, Jens Folke; Pedersen, D B; Eysteinsson, T

    2004-01-01

    The authors have previously reported that carbonic anhydrase inhibitors such as acetazolamide and dorzolamide raise optic nerve oxygen tension (ONPO(2)) in pigs. The purpose of the present study was to investigate whether timolol, which belongs to another group of glaucoma drugs called beta...

  9. Optic nerve oxygen tension

    DEFF Research Database (Denmark)

    Kiilgaard, Jens Folke; Pedersen, D B; Eysteinsson, T

    2004-01-01

    The authors have previously reported that carbonic anhydrase inhibitors such as acetazolamide and dorzolamide raise optic nerve oxygen tension (ONPO(2)) in pigs. The purpose of the present study was to investigate whether timolol, which belongs to another group of glaucoma drugs called beta block...

  10. Effects of subcutaneous implant of peripheral nerve allograft on the regeneration of defected sciatic nerve

    Institute of Scientific and Technical Information of China (English)

    Mingtang Gao; Dianming Jiang; Hong An

    2006-01-01

    BACKGROUND: Some experimental studies demonstrate that subcutaneous implant of allograft can significantly decrease lymphocyte infiltration and reduce immunological reaction. However, compared with autologous nerve grafting, what is the effect of nerve regeneration after repair?OBJECTIVE: To observe the local nervous status of the detected part of sciatic nerve repaired through subcutaneously implanting peripheral nerve allograft, and compare the effect with fresh autologous nerve grafting.DESIGN: Contrast observation.SETTING: Departments of Orthopaedics of Zhengzhou Fifth People's Hospital and First Hospital Affiliated to Chongqing Medical University.MATERIALS: Totally 30 healthy adult Wistar male rats, with body mass of (200±20)g, were enrolled. Optical microscope (Olympus biological microscope BHS, Japan), Electron microscope (H-600, Japan),CM-2000 biomedical image analysis system (CM-2000,Beihang) and myoelectricity scanner (KEYPOINT,Denmark) were used in this experiment.METHODS: This experiment was carried out in the Orthopaedic Laboratory of Chongqing Medical University between October 2000 and April 2002. ① Six rats were chosen as the donors for allogenic nerve grafting,and 15 mm sciatic nerve segment was chosen as graft. The other rats were randomly divided into two groups: allogenic nerve grafting group and autologous nerve grafting group, with 12 rats in each group. In the allogenic nerve grafting group, a skin incision was made on the posterior side of right thigh, and subcutaneous blunt dissection was performed prorsally a little, then allograft was implanted. Two weeks later, sciatic nerve was exposed at the posterior side of left thigh and cut respectively at 5 mm and another 10 mm away from pelvis. The donor nerve (with connective tissue veil) implanted subcutaneously on the right thigh was taken out. Sectioned connective tissue at the proximal end was trimmed and that at the distal end as done but reserved 10 mm in length, and inosculated

  11. Optic nerve hypoplasia

    Directory of Open Access Journals (Sweden)

    Savleen Kaur

    2013-01-01

    Full Text Available Optic nerve hypoplasia (ONH is a congenital anomaly of the optic disc that might result in moderate to severe vision loss in children. With a vast number of cases now being reported, the rarity of ONH is obviously now refuted. The major aspects of ophthalmic evaluation of an infant with possible ONH are visual assessment, fundus examination, and visual electrophysiology. Characteristically, the disc is small, there is a peripapillary double-ring sign, vascular tortuosity, and thinning of the nerve fiber layer. A patient with ONH should be assessed for presence of neurologic, radiologic, and endocrine associations. There may be maternal associations like premature births, fetal alcohol syndrome, maternal diabetes. Systemic associations in the child include endocrine abnormalities, developmental delay, cerebral palsy, and seizures. Besides the hypoplastic optic nerve and chiasm, neuroimaging shows abnormalities in ventricles or white- or gray-matter development, septo-optic dysplasia, hydrocephalus, and corpus callosum abnormalities. There is a greater incidence of clinical neurologic abnormalities in patients with bilateral ONH (65% than patients with unilateral ONH. We present a review on the available literature on the same to urge caution in our clinical practice when dealing with patients with ONH. Fundus photography, ocular coherence tomography, visual field testing, color vision evaluation, neuroimaging, endocrinology consultation with or without genetic testing are helpful in the diagnosis and management of ONH. (Method of search: MEDLINE, PUBMED.

  12. Let-7 microRNAs regenerate peripheral nerve regeneration by targeting nerve growth factor.

    Science.gov (United States)

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

    2015-03-01

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

  13. LONG-TERM EVALUATION OF NERVE REGENERATION IN A BIODEGRADABLE NERVE GUIDE

    NARCIS (Netherlands)

    DENDUNNEN, WFA; VANDERLEI, B; SCHAKENRAAD, JM; BLAAUW, EH; STOKROOS, [No Value; PENNINGS, AJ; ROBINSON, PH

    1993-01-01

    Nerve regeneration using artificial biodegradable conduits is of increasing interest. The aim of this study is to evaluate the regeneration and maturation of a nerve after long-term implantation (2 years) of a biodegradable poly-L-lactide/poly-E-caprolactone (PLLA/PCL) copolymeric nerve guide in the

  14. LONG-TERM EVALUATION OF NERVE REGENERATION IN A BIODEGRADABLE NERVE GUIDE

    NARCIS (Netherlands)

    DENDUNNEN, WFA; VANDERLEI, B; SCHAKENRAAD, JM; BLAAUW, EH; STOKROOS, [No Value; PENNINGS, AJ; ROBINSON, PH

    1993-01-01

    Nerve regeneration using artificial biodegradable conduits is of increasing interest. The aim of this study is to evaluate the regeneration and maturation of a nerve after long-term implantation (2 years) of a biodegradable poly-L-lactide/poly-E-caprolactone (PLLA/PCL) copolymeric nerve guide in the

  15. Dilong: Role in Peripheral Nerve Regeneration

    Directory of Open Access Journals (Sweden)

    Yung-Ming Chang

    2011-01-01

    Full Text Available Dilong, also known as earthworm, has been widely used in traditional Chinese medicine (TCM for thousands of years. Schwann cell migration and proliferation are critical for the regeneration of injured nerves and Schwann cells provide an essentially supportive role for neuron regeneration. However, the molecular mechanisms of migration and proliferation induced by dilongs in Schwann cells remain unclear. Here, we discuss the molecular mechanisms that includes (i migration signaling, MAPKs (mitogen-activated protein kinases, mediated PAs and MMP2/9 pathway; (ii survival and proliferative signaling, IGF-I (insulin-like growth factor-I-mediated PI3K/Akt pathways and (iii cell cycle regulation. Dilong stimulate RSC96 cell proliferation and migration. It can induce phosphorylation of ERK1/2 and p38, but not JNK, and activate the downstream signaling expression of PAs (plasminogen activators and MMPs (matrix metalloproteinases in a time-dependent manner. In addition, Dilong stimulated ERK1/2 and p38 phosphorylation was attenuated by pretreatment with chemical inhibitors (U0126 and SB203580, and small interfering ERK1/2 and p38 RNA, resulting in migration and uPA-related signal pathway inhibition. Dilong also induces the phosphorylation of IGF-I-mediated PI3K/Akt pathway, activates protein expression of PCNA (proliferating cell nuclear antigen and cell cycle regulatory proteins (cyclin D1, cyclin E and cyclin A in a time-dependent manner. In addition, it accelerates G1-phase progression with earlier S-phase entry and significant numbers of cells entered the S-phase. The siRNA-mediated knockdown of PI3K that significantly reduces PI3K protein expression levels, resulting in Bcl2 survival factor reduction, revealing a marked blockage of G1 to S transition in proliferating cells. These results reveal the unknown RSC96 cell migration and proliferation mechanism induced by dilong, which find use as a new medicine for nerve regeneration.

  16. Motonuclear changes after cranial nerve injury and regeneration.

    Science.gov (United States)

    Fernandez, E; Pallini, R; Lauretti, L; La Marca, F; Scogna, A; Rossi, G F

    1997-09-01

    Little is known about the mechanisms at play in nerve regeneration after nerve injury. Personal studies are reported regarding motonuclear changes after regeneration of injured cranial nerves, in particular of the facial and oculomotor nerves, as well as the influence that the natural molecule acetyl-L-carnitine (ALC) has on post-axotomy cranial nerve motoneuron degeneration after facial and vagus nerve lesions. Adult and newborn animal models were used. Massive motoneuron response after nerve section and reconstruction was observed in the motonuclei of all nerves studied. ALC showed to have significant neuroprotective effects on the degeneration of axotomized motoneurons. Complex quantitative, morphological and somatotopic nuclear changes occurred that sustain new hypotheses regarding the capacities of motoneurons to regenerate and the possibilities of new neuron proliferation. The particularities of such observations are described and discussed.

  17. Role of metallothioneins in peripheral nerve function and regeneration

    DEFF Research Database (Denmark)

    Ceballos, D; Lago, N; Verdú, E;

    2003-01-01

    The physiological role of the metallothionein (MT) family of proteins during peripheral nerve injury and regeneration was examined in Mt1+ 2 and Mt3 knockout (KO) mice. To this end, the right sciatic nerve was crushed, and the regeneration distance was evaluated by the pinch test 2-7 days...

  18. Impaired Prosaposin Secretion During Nerve Regeneration in Diabetic Rats and Protection of Nerve Regeneration by a Prosaposin-Derived Peptide

    Science.gov (United States)

    Jolivalt, Corinne G.; Vu, Yvonne; Mizisin, Leah M.; Mizisin, Andrew P.; Calcutt, Nigel A.

    2009-01-01

    Prosaposin is both a precursor of sphingolipid activator proteins and a secreted neurotrophic and myelinotrophic factor. Because peripheral nerve regeneration is impaired in diabetes mellitus, we measured prosaposin protein levels from control and streptozotocin-diabetic rats by collecting endoneurial fluid secreted into a bridging tube connecting the ends of transected sciatic nerve. Prosaposin protein levels were significantly reduced in endoneurial fluid from diabetic rats and increased in the proximal nerve stump compared to controls. To investigate whether a prosaposin-derived peptide could improve nerve regeneration, rats were treated with prosaptide TX14(A) following sciatic nerve crush. In control rats, TX14(A) was without effect in the uninjured nerve but shortened toe spread recovery time after nerve crush. In diabetic rats, efficacy of prosaptide TX14(A) was confirmed by correction of thermal hypoalgesia, formalin-evoked hyperalgesia and conduction slowing in the uninjured nerve. The peptide also prevented diabetes-induced abnormalities in nerve regeneration distance and mean axonal diameter of regenerated axons, whereas delayed recovery of toe spread was not improved. Muscle denervation atrophy was attenuated by TX14(A) in both control and diabetic rats. These results suggest that reduced prosaposin secretion after nerve injury may contribute to impaired regeneration rates in diabetic rats and that prosaptide TX14(A) can improve aspects of nerve regeneration. PMID:18596543

  19. Impaired prosaposin secretion during nerve regeneration in diabetic rats and protection of nerve regeneration by a prosaposin-derived peptide.

    Science.gov (United States)

    Jolivalt, Corinne G; Vu, Yvonne; Mizisin, Leah M; Mizisin, Andrew P; Calcutt, Nigel A

    2008-07-01

    Prosaposin is both a precursor of sphingolipid activator proteins and a secreted neurotrophic and myelinotrophic factor. Because peripheral nerve regeneration is impaired in diabetes mellitus, we measured prosaposin protein levels from control and streptozotocin-diabetic rats by collecting endoneurial fluid secreted into a bridging tube connecting the ends of transected sciatic nerve. Prosaposin protein levels were significantly reduced in endoneurial fluid from diabetic rats and increased in the proximal nerve stump compared to controls. To investigate whether a prosaposin-derived peptide could improve nerve regeneration, rats were treated with prosaptide TX14(A) after sciatic nerve crush. In control rats, TX14(A) was without effect in the uninjured nerve but shortened toe spread recovery time after nerve crush. In diabetic rats, efficacy of prosaptide TX14(A) was confirmed by correction of thermal hypoalgesia, formalin-evoked hyperalgesia, and conduction slowing in the uninjured nerve. The peptide also prevented diabetes-induced abnormalities in nerve regeneration distance and mean axonal diameter of regenerated axons, whereas delayed recovery of toe spread was not improved. Muscle denervation atrophy was attenuated by TX14(A) in both control and diabetic rats. These results suggest that reduced prosaposin secretion after nerve injury may contribute to impaired regeneration rates in diabetic rats, and that prosaptide TX14(A) can improve aspects of nerve regeneration.

  20. The potential roles for adipose tissue in peripheral nerve regeneration.

    Science.gov (United States)

    Walocko, Frances M; Khouri, Roger K; Urbanchek, Melanie G; Levi, Benjamin; Cederna, Paul S

    2016-01-01

    This review summarizes current understanding about the role of adipose-derived tissues in peripheral nerve regeneration and discusses potential advances that would translate this approach into the clinic. We searched PubMed for in vivo, experimental studies on the regenerative effects of adipose-derived tissues on peripheral nerve injuries. We summarized the methods and results for the 42 experiments. Adipose-derived tissues enhanced peripheral nerve regeneration in 86% of the experiments. Ninety-five percent evaluated purified, cultured, or differentiated adipose tissue. These approaches have regulatory and scaling burdens, restricting clinical usage. Only one experiment tested the ability of adipose tissue to enhance nerve regeneration in conjunction with nerve autografts, the clinical gold standard. Scientific studies illustrate that adipose-derived tissues enhance regeneration of peripheral nerves. Before this approach achieves clinical acceptance, fat processing must become automated and regulatory approval achieved. Animal studies using whole fat grafts are greatly needed for clinical translation. © 2015 Wiley Periodicals, Inc.

  1. Biodegradable magnesium wire promotes regeneration of compressed sciatic nerves.

    Science.gov (United States)

    Li, Bo-Han; Yang, Ke; Wang, Xiao

    2016-12-01

    Magnesium (Mg) wire has been shown to be biodegradable and have anti-inflammatory properties. It can induce Schwann cells to secrete nerve growth factor and promote the regeneration of nerve axons after central nervous system injury. We hypothesized that biodegradable Mg wire may enhance compressed peripheral nerve regeneration. A rat acute sciatic nerve compression model was made, and AZ31 Mg wire (3 mm diameter; 8 mm length) bridged at both ends of the nerve. Our results demonstrate that sciatic functional index, nerve growth factor, p75 neurotrophin receptor, and tyrosine receptor kinase A mRNA expression are increased by Mg wire in Mg model. The numbers of cross section nerve fibers and regenerating axons were also increased. Sciatic nerve function was improved and the myelinated axon number was increased in injured sciatic nerve following Mg treatment. Immunofluorescence histopathology showed that there were increased vigorous axonal regeneration and myelin sheath coverage in injured sciatic nerve after Mg treatment. Our findings confirm that biodegradable Mg wire can promote the regeneration of acute compressed sciatic nerves.

  2. Identification of proteins in fluid collected from nerve regeneration chambers

    Directory of Open Access Journals (Sweden)

    Ye Yilin

    2014-01-01

    Full Text Available We examined whether there are novel neurotrophic factors (NTFs in nerve regeneration conditioned fluid (NRCF. Nerve regeneration chamber models were established in the sciatic nerves of 25 New Zealand rabbits, and NRCF was extracted from the chambers l week postoperatively. Proteins in NRCF were separated by native polyacrylamide gel electrophoresis (PAGE, and Western blot and ELISA were used to identify the proteins. A novel NTF was identified in a protein fraction corresponding to 220 kDa.

  3. Peripheral nerve regeneration: experimental strategies and future perspectives.

    Science.gov (United States)

    Faroni, Alessandro; Mobasseri, S Atefeh; Kingham, Paul J; Reid, Adam J

    2015-03-01

    Peripheral nerve injuries represent a substantial clinical problem with insufficient or unsatisfactory treatment options. This review summarises all the events occurring after nerve damage at the level of the cell body, the site of injury and the target organ. Various experimental strategies to improve neuronal survival, axonal regeneration and target reinnervation are described including pharmacological approaches and cell-based therapies. Given the complexity of nerve regeneration, further studies are needed to address the biology of nerve injury, to improve the interaction with implantable scaffolds, and to implement cell-based therapies in nerve tissue engineering. Copyright © 2014. Published by Elsevier B.V.

  4. Visualizing peripheral nerve regeneration by whole mount staining.

    Directory of Open Access Journals (Sweden)

    Xin-peng Dun

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

  5. Visualizing Peripheral Nerve Regeneration by Whole Mount Staining

    Science.gov (United States)

    Dun, Xin-peng; Parkinson, David B.

    2015-01-01

    Peripheral nerve trauma triggers a well characterised sequence of events both proximal and distal to the site of injury. Axons distal to the injury degenerate, Schwann cells convert to a repair supportive phenotype and macrophages enter the nerve to clear myelin and axonal debris. Following these events, axons must regrow through the distal part of the nerve, re-innervate and finally are re-myelinated by Schwann cells. For nerve crush injuries (axonotmesis), in which the integrity of the nerve is maintained, repair may be relatively effective whereas for nerve transection (neurotmesis) repair will likely be very poor as few axons may be able to cross between the two parts of the severed nerve, across the newly generated nerve bridge, to enter the distal stump and regenerate. Analysing axon growth and the cell-cell interactions that occur following both nerve crush and cut injuries has largely been carried out by staining sections of nerve tissue, but this has the obvious disadvantage that it is not possible to follow the paths of regenerating axons in three dimensions within the nerve trunk or nerve bridge. To try and solve this problem, we describe the development and use of a novel whole mount staining protocol that allows the analysis of axonal regeneration, Schwann cell-axon interaction and re-vascularisation of the repairing nerve following nerve cut and crush injuries. PMID:25738874

  6. Peripheral nerve regeneration through P(DLLA-epsilon-CL) nerve guides

    NARCIS (Netherlands)

    Den Dunnen, WFA; Meek, MF; Robinson, PH; Schakernraad, JM

    1998-01-01

    P(DLLA-epsilon-CL) nerve guides can be used perfectly for short nerve gaps in rats, and are even better than short autologous nerve grafts. The tube dimensions, such as the internal diameter and wall thickness, are very important for the final outcome of peripheral nerve regeneration, as well as the

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

    Directory of Open Access Journals (Sweden)

    Tessa Gordon

    2015-01-01

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

  8. Engineering Bi-Layer Nanofibrous Conduits for Peripheral Nerve Regeneration

    Science.gov (United States)

    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

  9. Stimulated regeneration of the crushed adult rat optic nerve correlates with attenuated expression of the protein tyrosine phosphatases RPTPalpha, STEP, and LAR.

    NARCIS (Netherlands)

    Lorber, B.; Berry, M.; Hendriks, W.J.A.J.; Hertog, J.F. den; Pulido, R.; Logan, A.

    2004-01-01

    We have evaluated the spatial and temporal expression patterns of three protein tyrosine phosphatases (PTPs), receptor PTPalpha (RPTPalpha), striatal enriched phosphatase (STEP), and leucocyte common antigen-related phosphatase (LAR), in the retina and optic nerve (ON) of adult rats in which the cru

  10. Nerve dependence in tissue, organ, and appendage regeneration.

    Science.gov (United States)

    Kumar, Anoop; Brockes, Jeremy P

    2012-11-01

    Many regeneration contexts require the presence of regenerating nerves as a transient component of the progenitor cell niche. Here we review nerve involvement in regeneration of various structures in vertebrates and invertebrates. Nerves are also implicated as persistent determinants in the niche of certain stem cells in mammals, as well as in Drosophila. We consider our present understanding of the cellular and molecular mechanisms underlying nerve dependence, including evidence of critical interactions with glia and non-neural cell types. The example of the salamander aneurogenic limb illustrates that developmental interactions between the limb bud and its innervation can be determinative for adult regeneration. These phenomena provide a different perspective on nerve cells to that based on chemical and electrical excitability.

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

    Science.gov (United States)

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

    2015-12-01

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

  12. Intermediate filaments of zebrafish retinal and optic nerve astrocytes and Müller glia: differential distribution of cytokeratin and GFAP

    OpenAIRE

    Mosier Amanda L; Koke Joseph R; García Dana M

    2010-01-01

    Abstract Background Optic nerve regeneration (ONR) following injury is a model for central nervous system regeneration. In zebrafish, ONR is rapid - neurites cross the lesion and enter the optic tectum within 7 days; in mammals regeneration does not take place unless astrocytic reactivity is suppressed. Glial fibrillary acidic protein (GFAP) is used as a marker for retinal and optic nerve astrocytes in both fish and mammals, even though it has long been known that astrocytes of optic nerves i...

  13. The role of exosomes in peripheral nerve regeneration

    Directory of Open Access Journals (Sweden)

    Rosanna C Ching

    2015-01-01

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

  14. The role of exosomes in peripheral nerve regeneration

    Institute of Scientific and Technical Information of China (English)

    Rosanna C Ching; Paul J Kingham

    2015-01-01

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

  15. Nanotechnology and bio-functionalisation for peripheral nerve regeneration

    Institute of Scientific and Technical Information of China (English)

    Tina Sedaghati; Alexander M Seifalian

    2015-01-01

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

  16. Optic nerve atrophy

    Science.gov (United States)

    Optic atrophy; Optic neuropathy ... There are many causes of optic atrophy. The most common is poor blood flow. This is called ischemic optic neuropathy. The problem most often affects older adults. The optic ...

  17. Promoting nerve regeneration through long gaps using a small nerve tissue graft.

    Science.gov (United States)

    Saito, Ikuo; Oka, Yoshinori; Odaka, Mitsuaki

    2003-03-01

    If nerve tissue is capable of inducing regeneration, as suggested by the neurotropism theory, then even small pieces of nerve tissue should have the potential to induce nerve regeneration. Therefore, long gaps might presumably be bridged via the neurotrophic potential of small pieces of nerve tissue grafted into the middle of the nerve gap. It is necessary to confirm the validity of the neurotropism theory and to also explore the potential usefulness of small nerve grafting through long gaps. A small piece of nerve tissue was grafted into a silicone tube bridging a relatively long nerve gap in an attempt to promote nerve regeneration. A 15-mm gap was created in the left sciatic nerve of 31 Wistar rats (8 weeks of age). The experimental groups included one with nonvascularized nerve tissue grafted into a silicone tube with no distal nerve suturing (NV-A), another with vascularized nerve tissue grafted into a silicone tube with no distal nerve suturing (V-A), a third group with nonvascularized nerve tissue grafted into a silicone tube with distal nerve suturing (NV-P), a fourth group with vascularized nerve tissue grafted into a silicone tube with distal nerve suturing (V-P), and a group with no nerve segment grafted into the silicone tube (control). Electrophysiologic and histologic examinations were performed 10 weeks after the operation. No regeneration was obtained in the control group. Nerve regeneration was evident at the proximal end of the tube in the NV-A, V-A, NV-P, and V-P groups, and at the distal end in the NV-P and V-P groups. The degree of distal regeneration was extremely slight in the NV-A and V-A groups. An electrophysiologic examination performed in the NV-P and V-P groups revealed better results in the latter group. Small nerve grafts are capable of inducing nerve regeneration even over a long nerve gap, by grafting nerve tissue into the middle of the lesion using a silicone tube.

  18. A novel internal fixator device for peripheral nerve regeneration.

    Science.gov (United States)

    Chuang, Ting-Hsien; Wilson, Robin E; Love, James M; Fisher, John P; Shah, Sameer B

    2013-06-01

    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.

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

    Science.gov (United States)

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

    2016-10-01

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

  20. Guided regeneration with resorbable conduits in experimental peripheral nerve injuries

    OpenAIRE

    Nicoli Aldini, N.; Fini, M; Rocca, M; Giavaresi, G.; Giardino, R.

    2000-01-01

    Guided tissue regeneration is a new approach in the reconstructive surgery of peripheral nerves. Artificial conduits can be constructed from biodegradable polymers. Lactic/caproic acid copolymers and polyphospazenes are biocompatible materials with a slow resorption rate. Conduits made from either poly-[l-lactide-co-6-caprolatone] or poly-[bis-(ethylalanate)-phosphazene] were assessed for use as guides for nerve regeneration in experimental animals. Under general anesthesia and by using a mic...

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

    Science.gov (United States)

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

    2017-01-01

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

  2. Factors that influence peripheral nerve regeneration

    DEFF Research Database (Denmark)

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

    2002-01-01

    median nerve lesions (n = 46) in nonhuman primates over 3 to 4 years, a time span comparable with such lesions in humans. Nerve gap distances of 5, 20, or 50mm were repaired with nerve grafts or collagen-based nerve guide tubes, and three electrophysiological outcome measures were followed: (1) compound...

  3. Polymer scaffolds with preferential parallel grooves enhance nerve regeneration.

    Science.gov (United States)

    Mobasseri, Atefeh; Faroni, Alessandro; Minogue, Ben M; Downes, Sandra; Terenghi, Giorgio; Reid, Adam J

    2015-03-01

    We have modified the surface topography of poly ɛ-caprolactone (PCL) and polylactic acid (PLA) blended films to improve cell proliferation and to guide the regeneration of peripheral nerves. Films with differing shaped grooves were made using patterned silicon templates, sloped walls (SL), V-shaped (V), and square-shaped (SQ), and compared with nongrooved surfaces with micropits. The solvent cast films were tested in vitro using adult adipose-derived stem cells differentiated to Schwann cell-like cells. Cell attachment, proliferation, and cell orientation were all improved on the grooved surfaces, with SL grooves giving the best results. We present in vivo data on Sprague-Dawley rat sciatic nerve injury with a 10-mm gap, evaluating nerve regeneration at 3 weeks across a polymer nerve conduit modified with intraluminal grooves (SL, V, and SQ) and differing wall thicknesses (70, 100, 120, and 210 μm). The SL-grooved nerve conduit showed a significant improvement over the other topographical-shaped grooves, while increasing the conduit wall thickness saw no positive effect on the biological response of the regenerating nerve. Furthermore, the preferred SL-grooved conduit (C) with 70 μm wall thickness was compared with the current clinical gold standard of autologous nerve graft (Ag) in the rat 10-mm sciatic nerve gap model. At 3 weeks postsurgery, all nerve gaps across both groups were bridged with regenerated nerve fibers. At 16 weeks, features of regenerated axons were comparable between the autograft (Ag) and conduit (C) groups. End organ assessments of muscle weight, electromyography, and skin reinnervation were also similar between the groups. The comparable experimental outcome between conduit and autograft, suggests that the PCL/PLA conduit with inner lumen microstructured grooves could be used as a potential alternative treatment for peripheral nerve repair.

  4. Recent Strategies in Tissue Engineering for Guided Peripheral Nerve Regeneration.

    Science.gov (United States)

    Belanger, Kayla; Dinis, Tony M; Taourirt, Sami; Vidal, Guillaume; Kaplan, David L; Egles, Christopher

    2016-04-01

    The repair of large crushed or sectioned segments of peripheral nerves remains a challenge in regenerative medicine due to the complexity of the biological environment and the lack of proper biomaterials and architecture to foster reconstruction. Traditionally such reconstruction is only achieved by using fresh human tissue as a surrogate for the absence of the nerve. However, recent focus in the field has been on new polymer structures and specific biofunctionalization to achieve the goal of peripheral nerve regeneration by developing artificial nerve prostheses. This review presents various tested approaches as well their effectiveness for nerve regrowth and functional recovery.

  5. Do you have the nerves to regenerate? The importance of neural signalling in the regeneration process.

    Science.gov (United States)

    Pirotte, Nicky; Leynen, Nathalie; Artois, Tom; Smeets, Karen

    2016-01-01

    The importance of nerve-derived signalling for correct regeneration has been the topic of research for more than a hundred years, but we are just beginning to identify the underlying molecular pathways of this process. Within the current review, we attempt to provide an extensive overview of the neural influences during early and late phases of both vertebrate and invertebrate regeneration. In general, denervation impairs limb regeneration, but the presence of nerves is not essential for the regeneration of aneurogenic extremities. This observation led to the "neurotrophic factor(s) hypothesis", which states that certain trophic factors produced by the nerves are necessary for proper regeneration. Possible neuron-derived factors which regulate regeneration as well as the denervation-affected processes are discussed. Copyright © 2015. Published by Elsevier Inc.

  6. All optical regeneration using semiconductor devices

    DEFF Research Database (Denmark)

    Mørk, Jesper; Öhman, Filip; Tromborg, Bjarne

    All-optical regeneration is a key functionality for implementing all-optical networks. We present a simple theory for the bit-error-rate in links employing all-optical regenerators, which elucidates the interplay between the noise and and nonlinearity of the regenerator. A novel device structure ...... is analyzed, emphasizing general aspects of active semiconductor waveguides....

  7. Optical Regeneration and Noise in Semiconductor Devices

    DEFF Research Database (Denmark)

    Öhman, Filip

    2005-01-01

    In this report all-optical 2R-regeneration in optical communication systems is investigated. A simple regenerator device based on concatenated semiconductor optical amplifiers (SOAs) and electro absorbers (EAs) is introduced and examined. Experiments show that the monolithic SOA-EA 2R-regenerator......In this report all-optical 2R-regeneration in optical communication systems is investigated. A simple regenerator device based on concatenated semiconductor optical amplifiers (SOAs) and electro absorbers (EAs) is introduced and examined. Experiments show that the monolithic SOA-EA 2R...

  8. Tumors of the optic nerve

    DEFF Research Database (Denmark)

    Lindegaard, Jens; Heegaard, Steffen

    2009-01-01

    A variety of lesions may involve the optic nerve. Mainly, these lesions are inflammatory or vascular lesions that rarely necessitate surgery but may induce significant visual morbidity. Orbital tumors may induce proptosis, visual loss, relative afferent pupillary defect, disc edema and optic...... tumor-specific histologic features are given. Finally, treatment modalities and prognosis are discussed....

  9. Carbon nanomaterials for nerve tissue stimulation and regeneration.

    Science.gov (United States)

    Fraczek-Szczypta, Aneta

    2014-01-01

    Nanotechnology offers new perspectives in the field of innovative medicine, especially for reparation and regeneration of irreversibly damaged or diseased nerve tissues due to lack of effective self-repair mechanisms in the peripheral and central nervous systems (PNS and CNS, respectively) of the human body. Carbon nanomaterials, due to their unique physical, chemical and biological properties, are currently considered as promising candidates for applications in regenerative medicine. This chapter discusses the potential applications of various carbon nanomaterials including carbon nanotubes, nanofibers and graphene for regeneration and stimulation of nerve tissue, as well as in drug delivery systems for nerve disease therapy. © 2013.

  10. Rabbit facial nerve regeneration in NGF-containing silastic tubes.

    Science.gov (United States)

    Spector, J G; Lee, P; Derby, A; Frierdich, G E; Neises, G; Roufa, D G

    1993-05-01

    Previous reports suggest that exogenous nerve growth factor (NGF) enhanced nerve regeneration in rabbit facial nerves. Rabbit facial nerve regeneration in 10-mm Silastic tubes prefilled with NGF was compared to cytochrome C (Cyt. C), bridging an 8-mm nerve gap. Three weeks following implantation, NGF-treated regenerates exhibited a more mature fascicular organization and more extensive neovascularization than cytochrome-C-treated controls. Morphometric analysis at the midtube of 3- and 5-week regenerates revealed no significant difference in the mean number of myelinated or unmyelinated axons between NGF- and cytochrome-C-treated implants. However, when the number of myelinated fibers in 5-week regenerates were compared to their respective preoperative controls, NGF-treated regenerates had recovered a significantly greater percentage of myelinated axons than cytochrome-C--treated implants (46% vs. 18%, respectively). In addition, NGF-containing chambers reinnervated a higher percentage of myelinated axons in the distal transected neural stumps (49% vs. 34%). Behavioral and electrophysiologic studies demonstrated spontaneous and induced activities in the target muscles when approximately one third of the myelinated axons were recovered in the midchamber (1280 axons). Horseradish peroxidase (HRP) studies demonstrated retrograde axonal transport to the midchamber and proximal transected neural stump. PC12 bioassay demonstrated persistent NGF activity in the intrachamber fluids at 3 (5:1 dilution) and 5 (2:1 dilution) weeks of entubation. Electrophysiologic tests demonstrated a slow conduction velocity of a propagated electrical impulse (43.5 m/s-1 vs. 67 m/s-1) and shallow wide compound action potential. In wider defects (15-mm chambers) and longer entubation periods (7 weeks), no regeneration or NGF activity was seen. Therefore, exogenous NGF provides an early but limited neurotrophic effect on the regeneration of the rabbit buccal division of the facial nerve and a

  11. Combination of acellular nerve graft and schwann cells-like cells for rat sciatic nerve regeneration.

    Science.gov (United States)

    Gao, Songtao; Zheng, Yan; Cai, Qiqing; Deng, Zhansheng; Yao, Weitao; Wang, Jiaqiang; Wang, Xin; Zhang, Peng

    2014-01-01

    To investigate the effect of tissue engineering nerve on repair of rat sciatic nerve defect. Forty-five rats with defective sciatic nerve were randomly divided into three groups. Rats in group A were repaired by acellular nerve grafts only. Rats in group B were repaired by tissue engineering nerve. In group C, rats were repaired by autogenous nerve grafts. After six and twelve weeks, sciatic nerve functional index (SFI), neural electrophysiology (NEP), histological and transmission electron microscope observation, recovery ratio of wet weight of gastrocnemius muscle, regenerated myelinated nerve fibers number, nerve fiber diameter, and thickness of the myelin sheath were measured to assess the effect. After six and twelve weeks, the recovery ratio of SFI and wet weight of gastrocnemius muscle, NEP, and the result of regenerated myelinated nerve fibers in groups B and C were superior to that of group A (P 0.05). The tissue engineering nerve composed of acellular allogenic nerve scaffold and Schwann cells-like cells can effectively repair the nerve defect in rats and its effect was similar to that of the autogenous nerve grafts.

  12. Imaging of the optic nerve

    Energy Technology Data Exchange (ETDEWEB)

    Becker, Minerva [Head and Neck and Maxillofacial Radiology, Department of Radiology, Geneva University Hospital, Rue Gabrielle-Perret-Gentil 4, CH - 1211 Geneva 14 (Switzerland)], E-mail: minerva.becker@hcuge.ch; Masterson, Karen [Head and Neck and Maxillofacial Radiology, Department of Radiology, Geneva University Hospital, Rue Gabrielle-Perret-Gentil 4, CH - 1211 Geneva 14 (Switzerland); Delavelle, Jacqueline [Neuroradiology, Department of Radiology, Geneva University Hospital, Rue Gabrielle-Perret-Gentil 4, CH - 1211 Geneva 14 (Switzerland); Viallon, Magalie [Department of Radiology, Geneva University Hospital, Rue Gabrielle-Perret-Gentil 4, CH - 1211 Geneva 14 (Switzerland); Vargas, Maria-Isabel [Neuroradiology, Department of Radiology, Geneva University Hospital, Rue Gabrielle-Perret-Gentil 4, CH - 1211 Geneva 14 (Switzerland); Becker, Christoph D. [Department of Radiology, Geneva University Hospital, Rue Gabrielle-Perret-Gentil 4, CH - 1211 Geneva 14 (Switzerland)

    2010-05-15

    This article provides an overview of the imaging findings of diseases affecting the optic nerve with special emphasis on clinical-radiological correlation and on the latest technical developments in MR imaging and CT. The review deals with congenital malformations, tumors, toxic/nutritional and degenerative entities, inflammatory and infectious diseases, compressive neuropathy, vascular conditions and trauma involving the optic nerve from its ocular segment to the chiasm. The implications of imaging findings on patient management and outcome and the importance of performing high-resolution tailored examinations adapted to the clinical situation are discussed.

  13. Effect of Surface Pore Structure of Nerve Guide Conduit on Peripheral Nerve Regeneration

    Science.gov (United States)

    Oh, Se Heang; Kim, Jin Rae; Kwon, Gu Birm; Namgung, Uk; Song, Kyu Sang

    2013-01-01

    Polycaprolactone (PCL)/Pluronic F127 nerve guide conduits (NGCs) with different surface pore structures (nano-porous inner surface vs. micro-porous inner surface) but similar physical and chemical properties were fabricated by rolling the opposite side of asymmetrically porous PCL/F127 membranes. The effect of the pore structure on peripheral nerve regeneration through the NGCs was investigated using a sciatic nerve defect model of rats. The nerve fibers and tissues were shown to have regenerated along the longitudinal direction through the NGC with a nano-porous inner surface (Nanopore NGC), while they grew toward the porous wall of the NGC with a micro-porous inner surface (Micropore NGC) and, thus, their growth was restricted when compared with the Nanopore NGC, as investigated by immunohistochemical evaluations (by fluorescence microscopy with anti-neurofilament staining and Hoechst staining for growth pattern of nerve fibers), histological evaluations (by light microscopy with Meyer's modified trichrome staining and Toluidine blue staining and transmission electron microscopy for the regeneration of axon and myelin sheath), and FluoroGold retrograde tracing (for reconnection between proximal and distal stumps). The effect of nerve growth factor (NGF) immobilized on the pore surfaces of the NGCs on nerve regeneration was not so significant when compared with NGCs not containing immobilized NGF. The NGC system with different surface pore structures but the same chemical/physical properties seems to be a good tool that is used for elucidating the surface pore effect of NGCs on nerve regeneration. PMID:22871377

  14. Effect of surface pore structure of nerve guide conduit on peripheral nerve regeneration.

    Science.gov (United States)

    Oh, Se Heang; Kim, Jin Rae; Kwon, Gu Birm; Namgung, Uk; Song, Kyu Sang; Lee, Jin Ho

    2013-03-01

    Polycaprolactone (PCL)/Pluronic F127 nerve guide conduits (NGCs) with different surface pore structures (nano-porous inner surface vs. micro-porous inner surface) but similar physical and chemical properties were fabricated by rolling the opposite side of asymmetrically porous PCL/F127 membranes. The effect of the pore structure on peripheral nerve regeneration through the NGCs was investigated using a sciatic nerve defect model of rats. The nerve fibers and tissues were shown to have regenerated along the longitudinal direction through the NGC with a nano-porous inner surface (Nanopore NGC), while they grew toward the porous wall of the NGC with a micro-porous inner surface (Micropore NGC) and, thus, their growth was restricted when compared with the Nanopore NGC, as investigated by immunohistochemical evaluations (by fluorescence microscopy with anti-neurofilament staining and Hoechst staining for growth pattern of nerve fibers), histological evaluations (by light microscopy with Meyer's modified trichrome staining and Toluidine blue staining and transmission electron microscopy for the regeneration of axon and myelin sheath), and FluoroGold retrograde tracing (for reconnection between proximal and distal stumps). The effect of nerve growth factor (NGF) immobilized on the pore surfaces of the NGCs on nerve regeneration was not so significant when compared with NGCs not containing immobilized NGF. The NGC system with different surface pore structures but the same chemical/physical properties seems to be a good tool that is used for elucidating the surface pore effect of NGCs on nerve regeneration.

  15. An effect of wrapping peripheral nerve anastomosis with pedicled muscle flap on nerve regeneration in experiment

    Directory of Open Access Journals (Sweden)

    Naumenko L.Yu.

    2010-01-01

    Full Text Available Despite intrinsic capacity of peripheral nerves to regenerate, functional outcomes of peripheral nerves injury remain poor. Nerve ischemia, intra-/perineurial fibrosis and neuroma formation contribute a lot to that. Several authors demonstrated beneficial effects of increased vascularization at the site of injury on peripheral nerves regeneration. The use of highly vascularized autologous tissues (greater omentum as a source of peripheral nerves neovascularization shows promising re-sults. We proposed a surgical technique in which injured peripheral nerves anastomosis was wrapped in a pedicled muscular flap and performed morphological assessment of the efficacy of such technique with the aid of immunohistochemistry. 14 rats (which underwent sciatic nerve transection were operated according to proposed technique. Another 14 rats, in which only end-to-end nerve anastomosis (without muscular wrapping was performed served as controls. Morphological changes were evaluated at 3 weeks and 3 months periods. Higher blood vessel and axon counts were observed in experimental groups at both checkpoints. There was also an increase in Schwann cells and macrophages counts, and less collagen content in pe-ripheral nerves of experimental groups. Axons in neuromas of experimental groups showed a higher degree of arrangement. We conclude that proposed surgical technique provides better vascularisation of injured peripheral nerves, which is beneficial for nerve regeneration.

  16. Semiconductor devices for all-optical regeneration

    DEFF Research Database (Denmark)

    Öhman, Filip; Bischoff, Svend; Tromborg, Bjarne

    2003-01-01

    We review different implementations of semiconductor devices for all-optical regeneration. A general model will be presented for all-optical regeneration in fiber links, taking into consideration the trade-off between non-linearity and noise. Furthermore we discuss a novel regenerator type, based...

  17. Optic nerve invasion of uveal melanoma

    DEFF Research Database (Denmark)

    Lindegaard, Jens; Isager, Peter; Prause, Jan Ulrik

    2007-01-01

    The aim of the study was to identify the histopathological characteristics associated with the invasion of the optic nerve of uveal melanoma and to evaluate the association between invasion of the optic nerve and survival. In order to achieve this, all uveal melanomas with optic nerve invasion...... in Denmark between 1942 and 2001 were reviewed (n=157). Histopathological characteristics and depth of optic nerve invasion were recorded. The material was compared with a control material from the same period consisting of 85 cases randomly drawn from all choroidal/ciliary body melanomas without optic nerve......; and 4) in one case a tumor spread along the inner limiting membrane to the optic nerve through the lamina cribrosa. Invasion of the optic nerve had no impact on all-cause mortality or melanoma-related mortality in multivariate analyses. The majority of melanomas invading the optic nerve are large...

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

    Directory of Open Access Journals (Sweden)

    Rodrigo Guerra Sabongi

    2015-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    Rodrigo Guerra Sabongi; Marcela Fernandes; Joo Baptista Gomes dos Santos

    2015-01-01

    Treatment of peripheral nerve injuries remains a challenge to modern medicine due to the com-plexity 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 au-tologous 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.

  20. Spreading of hemiretinal projections in the ipsilateral tectum following unilateral enucleation: a study of optic nerve regeneration in Xenopus with one compound eye.

    Science.gov (United States)

    Straznicky, C; Tay, D

    1981-02-01

    Right compound eyes were formed in Xenopus embryos at stages 32-33 by the fusion of two nasal (NN), two ventral (VV) or two temporal (TT) halves. Shortly after metamorphosis the optic nerve from the compound eye was sectioned and the left intact eye removed. The retinotectal projections from the compound eye to the contralateral and ipsilateral tecta were studied by [3H]proline autoradiography and electrophysiological mapping between 6 weeks and 5 months after the postmetamorphic surgery. The results showed that NN and VV eyes projected to the entire extent of both tecta. In contrast, optic fibre projection from TT eyes, although more extensive than the normal temporal hemiretinal projection, failed to cover the caudomedial portion of the tecta. The visuotectal projections in all three combinations corresponded to typical reduplicated maps to be expected from such compound eyes, where each of the hemiretinae projected across the contralateral and ipsilateral tecta in an overlapping fashion. The rapid expansion of the hemiretinal projections of the compound eyes in the ipsilateral tectum following the removal of the resident optic fibre projection suggests that tectal markers may be carried and deployed by the incoming optic fibres themselves.

  1. The role of peripheral nerves in urodele limb regeneration.

    Science.gov (United States)

    Stocum, David L

    2011-09-01

    Nerve axons and the apical epidermal cap (AEC) are both essential for the formation of an accumulation blastema by amputated limbs of urodele salamanders. The AEC forms in the absence of axons, but is not maintained, and blastema formation fails. Growth stages of the blastema become nerve-independent for morphogenesis, but remain dependent on the nerve for blastema growth. Denervated growth stage blastemas form smaller than normal skeletal parts, owing to diminished mitosis, but form the full proximodistal array of skeletal elements. This difference in nerve dependency of morphogenesis and proliferation is hypothesized to be the result of a dependence of the AEC on nerves for blastema cell proliferation but not for blastema morphogenesis. Regenerating axons induce the synthesis and secretion of the anterior gradient protein (AGP) by distal Schwann cells during dedifferentiation and by the gland cells of the AEC during blastema growth stages. AGP promotes the regeneration of a denervated limb to digit stages when electroporated into the limb during dedifferentiation. Once a critical mass of blastema cells has been attained, the blastema can undergo morphogenesis in the absence of the nerve, but the regenerate will be a miniature, because the nerve is no longer inducing the AEC to carry out its AGP-mediated proliferative function. AGP expression by both Schwann cells and the AEC is induced by axons, but the nature of the inductive agent is unclear.

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

    Science.gov (United States)

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

    2016-09-07

    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.

  3. Advances and Future Applications of Augmented Peripheral Nerve Regeneration

    Directory of Open Access Journals (Sweden)

    Salazar Jones

    2016-09-01

    Full Text Available 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.

  4. Collagen Type I Conduits for the Regeneration of Nerve Defects

    Directory of Open Access Journals (Sweden)

    Silvan Klein

    2016-03-01

    Full Text Available To date, reliable data to support the general use of biodegradable materials for bridging nerve defects are still scarce. We present the outcome of nerve regeneration following type I collagen conduit nerve repair in patients with large-diameter nerve gaps. Ten patients underwent nerve repair using a type I collagen nerve conduit. Patients were re-examined at a minimal follow-up of 14.0 months and a mean follow-up of 19.9 months. Regeneration of nerve tissue within the conduits was assessed by nerve conduction velocity (NCV, a static two-point discrimination (S2PD test, and as disability of arm shoulder and hand (DASH outcome measure scoring. Quality of life measures including patients’ perceived satisfaction and residual pain were evaluated using a visual analog scale (VAS. No implant-related complications were observed. Seven out of 10 patients reported being free of pain, and the mean VAS was 1.1. The mean DASH score was 17.0. The S2PD was below 6 mm in 40%, between 6 and 10 mm in another 40% and above 10 mm in 20% of the patients. Eight out of 10 patients were satisfied with the procedure and would undergo surgery again. Early treatment correlated with lower DASH score levels. The use of type I collagen in large-diameter gaps in young patients and early treatment presented superior functional outcomes.

  5. Extrinsic and intrinsic determinants of nerve regeneration

    Directory of Open Access Journals (Sweden)

    Toby A. Ferguson

    2011-01-01

    Full Text Available After central nervous system (CNS injury axons fail to regenerate often leading to persistent neurologic deficit although injured peripheral nervous system (PNS axons mount a robust regenerative response that may lead to functional recovery. Some of the failures of CNS regeneration arise from the many glial-based inhibitory molecules found in the injured CNS, whereas the intrinsic regenerative potential of some CNS neurons is actively curtailed during CNS maturation and limited after injury. In this review, the molecular basis for extrinsic and intrinsic modulation of axon regeneration within the nervous system is evaluated. A more complete understanding of the factors limiting axonal regeneration will provide a rational basis, which is used to develop improved treatments for nervous system injury.

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

    Directory of Open Access Journals (Sweden)

    Mohammadi Rahim

    2013-12-01

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

  7. Optic Nerve Decompression for Orbitofrontal Fibrous Dysplasia

    OpenAIRE

    Abe, Takumi; Sato, Kaneshige; Otsuka, Takaharu; Kawamura, Noriyoshi; Shimazu, Motohiko; Izumiyama, Hitoshi; Matsumoto, Kiyoshi

    2002-01-01

    Orbitofrontal fibrous dysplasia often involves the bony orbit and the optic canal. Although fibrous dysplasia reportedly produces compression of the optic nerve leading to visual distrubances, optic nerve decompression in patients without clinical signs of optic neuropathy is still controversial. We describe two patients with orbitofrontal fibrous dysplasia without signs of visual disturbance and one patient with McCune-Albright syndrome and progressive visual impairment. Optic nerve decompre...

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

    Science.gov (United States)

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

    2013-01-01

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

  9. Impaired Prosaposin Secretion During Nerve Regeneration in Diabetic Rats and Protection of Nerve Regeneration by a Prosaposin-Derived Peptide

    OpenAIRE

    2008-01-01

    Prosaposin is both a precursor of sphingolipid activator proteins and a secreted neurotrophic and myelinotrophic factor. Because peripheral nerve regeneration is impaired in diabetes mellitus, we measured prosaposin protein levels from control and streptozotocin-diabetic rats by collecting endoneurial fluid secreted into a bridging tube connecting the ends of transected sciatic nerve. Prosaposin protein levels were significantly reduced in endoneurial fluid from diabetic rats and increased in...

  10. Sciatic nerve regeneration in rats subjected to ketogenic diet.

    Science.gov (United States)

    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.

  11. Lipofilling may induce nerve regeneration after previous traumatic injury : a clinical case with remarkable outcome

    NARCIS (Netherlands)

    Nanninga, Geraldine L.; Nijhuis, Tim H.; Schols, Rutger M.; Paulusma, Sjoerd B.; Coert, J. Henk; Jaquet, Jean Bart

    2016-01-01

    Despite the fast amount of techniques, which promote nerve regeneration, the outcomes of high ulnar nerve injuries are still poor. This case report illuminates the usability of lipofilling in peripheral nerve regeneration. In the case described, we encountered a successful regeneration with return o

  12. Morphology of nerve fiber regeneration along a biodegradable poly (DLLA-epsilon-CL) nerve guide filled with fresh skeletal muscle.

    Science.gov (United States)

    Varejão, Artur S P; Cabrita, António M; Meek, Marcel F; Fornaro, Michele; Geuna, Stefano; Giacobini-Robecchi, Maria G

    2003-01-01

    Previous morphological and morphometrical studies showed that fresh-skeletal-muscle-enriched vein segments are good conduits for leading peripheral nerve regeneration. In the present study, we investigated the morphological features of peripheral nerve fibers regenerated along a 10-mm-long biodegradable poly (DLLA-epsilon-CL) nerve guide enriched with fresh skeletal muscle, comparing them to nerve fiber regeneration along 10-mm-long phosphate-buffered saline (PBS)-enriched poly (DLLA-epsilon-CL) tubes. Repaired nerves were analyzed at weeks 6 and 24 postoperatively. Structural and ultrastructural observation showed that good nerve fiber regeneration occurred in both PBS-enriched and fresh-skeletal-muscle-enriched nerve guides, and histomorphometrical analysis of regenerated myelinated fibers revealed no statistically significant differences between the two experimental groups at week 24 after surgery. The employment of fresh-muscle-enriched conduits for the repair of nerve defects is critically discussed in the light of these results.

  13. Comparison of rabbit facial nerve regeneration in nerve growth factor-containing silicone tubes to that in autologous neural grafts.

    Science.gov (United States)

    Spector, J G; Lee, P; Derby, A; Roufa, D G

    1995-11-01

    Previous reports suggest that nerve growth factor (NGF) enhanced nerve regeneration in rabbit facial nerves. We compared rabbit facial nerve regeneration in 10-mm silicone tubes prefilled with NGF or cytochrome C (Cyt C), bridging an 8-mm nerve gap, to regeneration of 8-mm autologous nerve grafts. Three weeks following implantation, NGF-treated regenerates exhibited a more mature fascicular organization and more extensive neovascularization than Cyt C-treated controls. Morphometric analysis at the middle of the tube of 3- and 5-week regenerates revealed no significant difference in the mean number of myelinated or unmyelinated axons between NGF- and Cyt C-treated implants. However, when the numbers of myelinated fibers in 5-week regenerates were compared to those in their respective preoperative controls, NGF-treated regenerates had recovered a significantly greater percentage of myelinated axons than Cyt C-treated implants (46% versus 18%, respectively). The number of regenerating myelinated axons in the autologous nerve grafts at 5 weeks was significantly greater than the number of myelinated axons in the silicone tubes. However, in the nerve grafts the majority of the axons were found in the extrafascicular connective tissue (66%). The majority of these myelinated fibers did not find their way into the distal nerve stump. Thus, although the number of regenerating myelinated axons within the nerve grafts is greater than that of axons within silicone tube implants, functional recovery of autologous nerve graft repairs may not be superior to that of intubational repairs.

  14. Effect of low-level laser therapy (LLLT) on peripheral nerve regeneration using fibrin glue derived from snake venom.

    Science.gov (United States)

    Buchaim, Rogerio Leone; Andreo, Jesus Carlos; Barraviera, Benedito; Ferreira Junior, Rui Seabra; Buchaim, Daniela Vieira; Rosa Junior, Geraldo Marco; de Oliveira, Alexandre Leite Rodrigues; de Castro Rodrigues, Antonio

    2015-04-01

    The purpose of this study was to assess whether the adhesive permits the collateral repair of axons originating from a vagus nerve to the interior of a sural nerve graft, and whether low-level laser therapy (LLLT) assists in the regeneration process. Study sample consisted of 32 rats randomly separated into three groups: Control Group (CG; n=8), from which the intact sural nerve was collected; Experimental Group (EG; n=12), in which one of the ends of the sural nerve graft was coapted to the vagus nerve using the fibrin glue; and Experimental Group Laser (EGL; n=12), in which the animals underwent the same procedures as those in EG with the addition of LLLT. Ten weeks after surgery, the animals were euthanized. Morphological analysis by means of optical and electron microscopy, and morphometry of the regenerated fibers were employed to evaluate the results. Collateral regeneration of axons was observed from the vagus nerve to the interior of the autologous graft in EG and EGL, and in CG all dimensions measured were greater and presented a significant difference in relation to EG and EGL, except for the area and thickness of the myelin sheath, that showed significant difference only in relation to the EG. The present study demonstrated that the fibrin glue makes axonal regeneration feasible and is an efficient method to recover injured peripheral nerves, and the use of low-level laser therapy enhances nerve regeneration. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Quantitative STIR of muscle for monitoring nerve regeneration

    NARCIS (Netherlands)

    Viddeleer, Alain R.; Sijens, Paul E.; van Ooijen, Peter M. A.; Kuypers, Paul D. l.; Hovius, Steven E. R.; De Deyn, Peter P.; Oudkerk, Matthijs

    PurposeTo assess whether short tau inversion recovery (STIR) MRI sequences can provide a tool for monitoring peripheral nerve regeneration, by comparing signal intensity changes in reinnervated muscle over time, and to determine potential clinical time points for monitoring. Materials and MethodsFor

  16. Nanofiber Nerve Guide for Peripheral Nerve Repair and Regeneration

    Science.gov (United States)

    2015-01-01

    guide conduits (NGCs) made of biodegradable materials offer a potential solution to this problem. Based on our previous accomplishments in developing...microscopy laboratory for plastic embedding, sectioning and staining. We have not counted the number of regenerated axons, as we want to wait and

  17. Neural tissue engineering options for peripheral nerve regeneration.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2014-09-01

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

  19. A polylactic acid non-woven nerve conduit for facial nerve regeneration in rats.

    Science.gov (United States)

    Matsumine, Hajime; Sasaki, Ryo; Yamato, Masayuki; Okano, Teruo; Sakurai, Hiroyuki

    2014-06-01

    This study developed a biodegradable nerve conduit with PLA non-woven fabric and evaluated its nerve regeneration-promoting effect. The buccal branch of the facial nerve of 8 week-old Lewis rats was exposed, and a 7 mm nerve defect was created. A nerve conduit made of either PLA non-woven fabric (mean fibre diameter 460 nm), or silicone tube filled with type I collagen gel, or an autologous nerve, was implanted into the nerve defect, and their nerve regenerative abilities were evaluated 13 weeks after the surgery. The number of myelinated neural fibres in the middle portion of the regenerated nerve was the highest for PLA tubes (mean ± SD, 5051 ± 2335), followed by autologous nerves (4233 ± 590) and silicone tubes (1604 ± 148). Axon diameter was significantly greater in the PLA tube group (5.17 ± 1.69 µm) than in the silicone tube group (4.25 ± 1.60 µm) and no significant difference was found between the PLA tube and autograft (5.53 ± 1.93 µm) groups. Myelin thickness was greatest for the autograft group (0.65 ± 0.24 µm), followed by the PLA tube (0.54 ± 0.18 µm) and silicone tube (0.38 ± 0.12 µm) groups, showing significant differences among the three groups. The PLA non-woven fabric tube, composed of randomly-connected PLA fibres, is porous and has a number of advantages, such as sufficient strength to maintain luminal structure. The tube has demonstrated a comparable ability to induce peripheral nerve regeneration following autologous nerve transplantation.

  20. Low-intensity ultrasound for regeneration of injured peripheral nerve

    Institute of Scientific and Technical Information of China (English)

    Wei Zhou; Wenzhi Chen; Kun Zhou; Zhibiao Wang

    2006-01-01

    BACKGROUND: Ultrasound is a kind of mechanical wave and characterized by mechanical effect,heat affect and physical and chemical effect.Ultrasound can promote regeneration of peripheral nerves after a slight injury based on its mechanical effect.However,whether it can promote regeneration of peripheral nerves after a severe injury or not is still unclear.OBJECTIVE: To study the effect of low-intensity ultrasound(LIU)on regeneration of injured peripheral nerve,throgh examining sciatic nerve function index,the sensory nerve conduction velocity and the thickness of myelin sheath.DESIGN: Single factor design of contrast observation.SETTING: Institute of Ultrasound Engineering,Chongqing Medical University.MATERIALS:A total of 64 female Wistar rats,of clean grade,age 3 moths,weighing 200-250g ,were provided by Experimental Animal Center of Chongqing Medical University. All rats were randomly divided into treatment group and control group with 32 in each group. In addition rats were observed at 4 time points, including 2,4,6 and 8 weeks,with 8 at each time point.The main equipments were detailed as follows:forceps (Medical Treatment Apparatus Company,Chongqing),low-intensity ultrasound treatment instrument(Institute of Ulrasound Engineering in Medicine),the analysis instrument of diagram resembles and arithmetic figure(the United States Bio-RAD Company),ultrasound coupling agent(Xunde Image material factory,Hangzhou),Osmium Tetraoxide(Next Chimicam,South Africa).METHODS:The experiment was carried out in Institute of Ultrasound Engineering of Chongqing Medical University from December 2003 to May 2004.The right sciatic nerves of 64 rats were crushed with forceps for 30 s to form the experimental animal models.Then they were treated at 3 days after operation.Rats in the treatment group received the LIU exposure.LIU was applied every other day to the crush site of rats,which had a spatial peak,time-averaged intensity of 0.25 W/cm2 operated at 1 MHz for 1 minute per

  1. Nerve regeneration by human corneal stromal keratocytes and stromal fibroblasts

    Science.gov (United States)

    Yam, Gary Hin-Fai; Williams, Geraint P.; Setiawan, Melina; Yusoff, Nur Zahirah Binte M.; Lee, Xiao-wen; Htoon, Hla Myint; Zhou, Lei; Fuest, Matthias; Mehta, Jodhbir S.

    2017-01-01

    Laser refractive surgeries reshape corneal stroma to correct refractive errors, but unavoidably affect corneal nerves. Slow nerve regeneration and atypical neurite morphology cause desensitization and neuro-epitheliopathy. Following injury, surviving corneal stromal keratocytes (CSKs) are activated to stromal fibroblasts (SFs). How these two different cell types influence nerve regeneration is elusive. Our study evaluated the neuro-regulatory effects of human SFs versus CSKs derived from the same corneal stroma using an in vitro chick dorsal root ganglion model. The neurite growth was assessed by a validated concentric circle intersection count method. Serum-free conditioned media (CM) from SFs promoted neurite growth dose-dependently, compared to that from CSKs. We detected neurotrophic and pro-inflammatory factors (interleukin-8, interleukin-15, monocyte chemoattractant protein-1, eotaxin, RANTES) in SFCM by Bio-Plex Human Cytokine assay. More than 130 proteins in SFCM and 49 in CSKCM were identified by nanoLC-MS/MS. Proteins uniquely present in SFCM had reported neuro-regulatory activities and were predicted to regulate neurogenesis, focal adhesion and wound healing. Conclusively, this was the first study showing a physiological relationship between nerve growth and the metabolically active SFs versus quiescent CSKs from the same cornea source. The dose-dependent effect on neurite growth indicated that nerve regeneration could be influenced by SF density. PMID:28349952

  2. Tacrolimus reduces scar formation and promotes sciatic nerve regeneration

    Institute of Scientific and Technical Information of China (English)

    Jun Que; Quan Cao; Tao Sui; Shihao Du; Ailiang Zhang; Dechao Kong; Xiaojian Cao

    2012-01-01

    A sciatic nerve transection and repair model was established in Sprague-Dawley rats by transecting the tendon of obturator internus muscle in the greater sciatic foramen and suturing with nylon sutures. The models were treated with tacrolimus gavage (4 mg/kg per day) for 0, 2, 4 and 6 weeks. Specimens were harvested at 6 weeks of intragastric administration. Masson staining revealed that the collagen fiber content and scar area in the nerve anastomosis of the sciatic nerve injury rats were significantly reduced after tacrolimus administration. Hematoxylin-eosin staining showed that tacrolimus significantly increased myelinated nerve fiber density, average axon diameter and myelin sheath thickness. Intragastric administration of tacrolimus also led to a significant increase in the recovery rate of gastrocnemius muscle wet weight and the sciatic functional index after sciatic nerve injury. The above indices were most significantly improved at 6 weeks after of tacrolimus gavage. The myelinated nerve fiber density in the nerve anastomosis and the sciatic nerve functions had a significant negative correlation with the scar area, as detected by Spearman’s rank correlation analysis. These findings indicate that tacrolimus can promote peripheral nerve regeneration and accelerate the recovery of neurological function through the reduction of scar formation.

  3. Nerve growth factor loaded heparin/chitosan scaffolds for accelerating peripheral nerve regeneration.

    Science.gov (United States)

    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.

  4. Drug Delivery for Peripheral Nerve Regeneration

    Science.gov (United States)

    2014-09-01

    and connect the two tubes; (b) A scanning electron microscope image of the transverse cross-sectional view of the PLGA nerve conduit. The filter is...reprints of manuscripts and abstracts, a curriculum vitae, patent applications, study questionnaires, and surveys, etc. Bioresorbable Multi-Drug

  5. Ginsenoside Rg1 promotes peripheral nerve regeneration in rat model of nerve crush injury.

    Science.gov (United States)

    Ma, Junxiong; Li, Wenxian; Tian, Ruifeng; Lei, Wei

    2010-07-05

    Searching for effective drugs which are capable of promoting nerve regeneration after nerve injuries has gained extensive attention. Ginsenoside Rg1 (GRg1) is one of the bioactive compounds extracted from ginseng. GRg1 has been shown to be neuroprotective in many in vitro studies, which raises the possibility of using GRg1 as a neuroprotective agent after nerve injuries. However, such a possibility has never been tested in in vivo studies. The present study was designed to investigate the efficacy of GRg1 in promoting nerve regeneration after nerve crush injury in rats. All rats were randomly divided into four groups (n=8 in each group) after crush injury and were intraperitoneally administrated daily for 4 weeks with 1mg/kg, or 5mg/kg GRg1 (low or high dose GRg1 groups), or 100mug/kg mecobalamin or normal saline, respectively. The axonal regeneration was investigated by retrograde labeling and morphometric analysis. The motor functional recovery was evaluated by electrophysiological studies, behavioral tests and histological appearance of the target muscles. Our data showed that high dose GRg1 achieved better axonal regeneration and functional recovery than those achieved by low dose GRg1 and mecobalamin. The final outcome of low dose GRg1 and mecobalamin was similar in both morphological and functional items, which was significantly better than that in saline group. These findings show that GRg1 is capable of promoting nerve regeneration after nerve injuries, suggesting the possibility of developing GRg1 a neuroprotective drug for peripheral nerve repair applications.

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

    Directory of Open Access Journals (Sweden)

    Gholam Hossein Farjah

    2013-08-01

    Full Text Available Objective(s:  The aim of this study was to evaluate the final outcome of nerve regeneration across the eggsell membrane (ESM tube conduit in comparison with autograft. Materials and Methods: Thirty adult male rats (250-300 g were randomized into (1 ESM conduit, (2 autograft, and (3 sham surgery groups. The eggs submerged in 5% acetic acid. The decalcifying membranes were cut into four pieces, rotated over the teflon mandrel and dried at   37°C. The left sciatic nerve was surgically cut. A 10-mm nerve segment was cut and removed. In the ESM group, the proximal and distal cut ends of the sciatic nerve were telescoped into the nerve guides. In the autograft group, the 10 mm nerve segment was reversed and used as an autologous nerve graft. All animals were evaluated by sciatic functional index (SFI and electrophysiology testing.  Results:The improvement in SFI from the first to the last evalution in ESM and autograft groups were evaluated. On days 49 and 60 post-operation, the mean SFI of ESM group was significantly greater than the autograft group (P 0.05. Conclusion:These findings demonstrate that ESM effectively enhances nerve regeneration and promotes functional recovery in injured sciatic nerve of rat.

  7. Effect of neurotrophic factor, MDP, on rats' nerve regeneration.

    Science.gov (United States)

    Fornazari, A A; Rezende, M R de; Mattar Jr, R; Taira, R I; Santos, G B dos; Paulos, R G

    2011-04-01

    Our objective was to determine the immune-modulating effects of the neurotrophic factor N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) on median nerve regeneration in rats. We used male Wistar rats (120-140 days of age, weighing 250-332 g) and compared the results of three different techniques of nerve repair: 1) epineural neurorrhaphy using sutures alone (group S - 10 rats), 2) epineural neurorrhaphy using sutures plus fibrin tissue adhesive (FTA; group SF - 20 rats), and 3) sutures plus FTA, with MDP added to the FTA (group SFM - 20 rats). Functional assessments using the grasp test were performed weekly for 12 weeks to identify recovery of flexor muscle function in the fingers secondary to median nerve regeneration. Histological analysis was also utilized. The total number and diameter of myelinated fibers were determined in each proximal and distal nerve segment. Two indices, reported as percentage, were calculated from these parameters, namely, the regeneration index and the diameter change index. By the 8th week, superiority of group SFM over group S became apparent in the grasping test (P = 0.005). By the 12th week, rats that had received MDP were superior in the grasping test compared to both group S (P MDP obtained better function, in the absence of any significant histological differences.

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

    Science.gov (United States)

    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.

  9. Nanofiber Nerve Guide for Peripheral Nerve Repair and Regeneration

    Science.gov (United States)

    2014-01-01

    months 24-33) 3d. Retrograde labeling and tissue harvesting (months 32-33) 3e. Nerve morphometry (months 33-35) 3f. Histopathological evaluations...divided into specific tasks related to various components of optimization schemes. In vitro fiber size dependent Schwann cell migration for...5/7/13 17 4 S(design medium 1200 0 Uniform 6/27/13 Tier(5 18 4 S(Design medium 1200 0 Shallow(Gradient(60L180 6/28/13 19 8 S(Design medium 1200 0

  10. Development of Nanofiber Sponges-Containing Nerve Guidance Conduit for Peripheral Nerve Regeneration in Vivo.

    Science.gov (United States)

    Sun, Binbin; Zhou, Zifei; Wu, Tong; Chen, Weiming; Li, Dawei; Zheng, Hao; El-Hamshary, Hany; Al-Deyab, Salem S; Mo, Xiumei; Yu, Yinxian

    2017-08-16

    In the study of hollow nerve guidance conduit (NGC), the dispersion of regenerated axons always confused researchers. To address this problem, filler-containing NGC was prepared, which showed better effect in the application of nerve tissue engineering. In this study, nanofiber sponges with abundant macropores, high porosity, and superior compressive strength were fabricated by electrospinning and freeze-drying. Poly(l-lactic acid-co-ε-caprolactone)/silk fibroin (PLCL/SF) nanofiber sponges were used as filler to prepare three-dimensional nanofiber sponges-containing (NS-containing) NGC. In order to study the effect of fillers for nerve regeneration, hollow NGC was set as control. In vitro cell viability studies indicated that the NS-containing NGC could enhance the proliferation of Schwann cells (SCs) due to the macroporous structure. The results of hematoxylin-eosin (HE) and immunofluorescence staining confirmed that SCs infiltrated into the nanofiber sponges. Subsequently, the NS-containing NGC was implanted in a rat sciatic nerve defect model to evaluate the effect in vivo. NS-containing NGC group performed better in nerve function recovery than hollow NGC group. In consideration of the walking track and triceps weight analysis, NS-containing NGC was close to the autograft group. In addition, histological and morphological analyses with HE and toluidine blue (TB) staining, and transmission electron microscope (TEM) were conducted. Better nerve regeneration was observed on NS-containing NGC group both quantitatively and qualitatively. Furthermore, the results of three indexes' immuno-histochemistry and two indexes' immunofluorescence all indicated good nerve regeneration of NS-containing NGC as well, compared with hollow NGC. The results demonstrated NS-containing NGC had great potential in the application of peripheral nerve repair.

  11. Ferulic Acid Enhances Peripheral Nerve Regeneration across Long Gaps

    Directory of Open Access Journals (Sweden)

    Sheng-Chi Lee

    2013-01-01

    Full Text Available This study investigated the effect of ferulic acid (FA on peripheral nerve injury. In the in vitro test, the effect of FA on viability of Schwann cells was studied. In the in vivo test, right sciatic nerves of the rats were transected, and a 15 mm nerve defect was created. A nerve conduit made of silicone rubber tube filled with FA (5 and 25 μg/mL, or saline (control, was implanted into the nerve defect. Results show that the number of proliferating Schwann cells increased significantly in the FA-treated group at 25 μg/mL compared to that in the control group. After 8 weeks, the FA-treated group at 25 μg/mL had a higher rate of successful regeneration across the wide gap, a significantly calcitonin gene-related peptide (CGRP staining of the lamina I-II regions in the dorsal horn ipsilateral to the injury, a significantly diminished number of macrophages recruited, and a significantly shortening of the latency and an acceleration of the nerve conductive velocity (NCV of the evoked muscle action potentials (MAPs compared with the controls. In summary, the FA may be useful in the development of future strategies for the treatment of peripheral nerve injury.

  12. Sciatic nerve regeneration in rats by a promising electrospun collagen/poly(ε-caprolactone nerve conduit with tailored degradation rate

    Directory of Open Access Journals (Sweden)

    Jiang Xinquan

    2011-07-01

    Full Text Available Abstract Background To cope with the limitations faced by autograft acquisitions particularly for multiple nerve injuries, artificial nerve conduit has been introduced by researchers as a substitute for autologous nerve graft for the easy specification and availability for mass production. In order to best mimic the structures and components of autologous nerve, great efforts have been made to improve the designation of nerve conduits either from materials or fabrication techniques. Electrospinning is an easy and versatile technique that has recently been used to fabricate fibrous tissue-engineered scaffolds which have great similarity to the extracellular matrix on fiber structure. Results In this study we fabricated a collagen/poly(ε-caprolactone (collagen/PCL fibrous scaffold by electrospinning and explored its application as nerve guide substrate or conduit in vitro and in vivo. Material characterizations showed this electrospun composite material which was made of submicron fibers possessed good hydrophilicity and flexibility. In vitro study indicated electrospun collagen/PCL fibrous meshes promoted Schwann cell adhesion, elongation and proliferation. In vivo test showed electrospun collagen/PCL porous nerve conduits successfully supported nerve regeneration through an 8 mm sciatic nerve gap in adult rats, achieving similar electrophysiological and muscle reinnervation results as autografts. Although regenerated nerve fibers were still in a pre-mature stage 4 months postoperatively, the implanted collagen/PCL nerve conduits facilitated more axons regenerating through the conduit lumen and gradually degraded which well matched the nerve regeneration rate. Conclusions All the results demonstrated this collagen/PCL nerve conduit with tailored degradation rate fabricated by electrospinning could be an efficient alternative to autograft for peripheral nerve regeneration research. Due to its advantage of high surface area for cell attachment, it

  13. Sciatic nerve regeneration in rats by a nerve conduit engineering with a membrane derived from natural latex.

    Science.gov (United States)

    Ganga, Marcos Vinícius Muniz; Coutinho-Netto, Joaquim; Colli, Benedicto Oscar; Marques Junior, Wilson; Catalão, Carlos Henrique Rocha; Santana, Ricardo Torres; Oltramari, Marcos Roberto Pedron; Carraro, Kleber Tadeu; Lachat, João-José; Lopes, Luiza da Silva

    2012-12-01

    To evaluate the capacity of natural latex membrane to accelerate and improve the regeneration quality of the of rat sciatic nerves. Forty male adult Wistar rats were used, anesthetized and operated to cut the sciatic nerve and receive an autograft or a conduit made with a membrane derived from natural latex (Hevea brasiliensis). Four or eight weeks after surgery, to investigate motor nerve recovery, we analyzed the neurological function by walking pattern (footprints analysis and computerized treadmill), electrophysiological evaluation and histological analysis of regenerated nerve (autologous nerve graft or tissue cables between the nerve stumps), and anterior tibial and gastrocnemius muscles. All functional and morphological analysis showed that the rats transplanted with latex conduit had a better neurological recovery than those operated with autologous nerve: quality of footprints, performance on treadmill (pregeneration. The data reported showed behavioral and functional recovery in rats implanted with latex conduit for sciatic nerve repair, supporting a complete morphological and physiological regeneration of the nerve.

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

    Science.gov (United States)

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

    2013-12-01

    The present study aims to investigate the potential of brief electrical stimulation (ES; 3 V, 20 Hz, 20 min) in improving functional recovery in delayed nerve injury repair (DNIR). The sciatic nerve of Sprague Dawley rats was transected, and the repair of nerve injury was delayed for different time durations (2, 4, 12 and 24 weeks). Brief depolarizing ES was applied to the proximal nerve stump when the transected nerve stumps were bridged with a hollow nerve conduit (5 mm in length) after delayed periods. We found that the diameter and number of regenerated axons, the thickness of myelin sheath, as well as the number of Fluoro-Gold retrograde-labeled motoneurons and sensory neurons were significantly increased by ES, suggesting that brief ES to proximal nerve stumps is capable of promoting nerve regeneration in DNIR with different delayed durations, with the longest duration of 24 weeks. In addition, the amplitude of compound muscle action potential (gastrocnemius muscle) and nerve conduction velocity were also enhanced, and gastrocnemius muscle atrophy was partially reversed by brief ES, indicating that brief ES to proximal nerve stump was able to improve functional recovery in DNIR. Furthermore, brief ES was capable of increasing brain-derived neurotrophic factor (BDNF) expression in the spinal cord in DNIR, suggesting that BDNF-mediated neurotrophin signaling might be one of the contributing factors to the beneficial effect of brief ES on DNIR. In conclusion, the present findings indicate the potential of using brief ES as a useful method to improve functional recovery for delayed repair of peripheral nerve lesions. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  15. Effect of arecoline on regeneration of injured peripheral nerves.

    Science.gov (United States)

    Lee, Sheng-Chi; Tsai, Chin-Chuan; Yao, Chun-Hsu; Hsu, Yuan-Man; Chen, Yueh-Sheng; Wu, Ming-Chang

    2013-01-01

    The present study provides in vitro and in vivo evaluation of arecoline on peripheral nerve regeneration. In the in vitro study, we found that arecoline at 50 μg/ml could significantly promote the survival and outgrowth of cultured Schwann cells as compared to the controls treated with culture medium only. In the in vivo study, we evaluated peripheral nerve regeneration across a 10-mm gap in the sciatic nerve of the rat, using a silicone rubber nerve chamber filled with the arecoline solution. In the control group, the chambers were filled with normal saline only. At the end of the fourth week, morphometric data revealed that the arecoline-treated group at 5 μg/ml significantly increased the number and the density of myelinated axons as compared to the controls. Immunohistochemical staining in the arecoline-treated animals at 5 μg/ml also showed their neural cells in the L4 and L5 dorsal root ganglia ipsilateral to the injury were strongly retrograde-labeled with fluorogold and lamina I-II regions in the dorsal horn ipsilateral to the injury were significantly calcitonin gene-related peptide-immunolabeled compared with the controls. In addition, we found that the number of macrophages recruited in the distal sciatic nerve was increased as the concentration of arecoline was increased. Electrophysiological measurements showed the arecoline-treated groups at 5 and 50 μg/ml had a relatively larger nerve conductive velocity of the evoked muscle action potentials compared to the controls. These results indicate that arecoline could stimulate local inflammatory conditions, improving the recovery of a severe peripheral nerve injury.

  16. Magnetic resonance imaging of optic nerve

    Directory of Open Access Journals (Sweden)

    Foram Gala

    2015-01-01

    Full Text Available Optic nerves are the second pair of cranial nerves and are unique as they represent an extension of the central nervous system. Apart from clinical and ophthalmoscopic evaluation, imaging, especially magnetic resonance imaging (MRI, plays an important role in the complete evaluation of optic nerve and the entire visual pathway. In this pictorial essay, the authors describe segmental anatomy of the optic nerve and review the imaging findings of various conditions affecting the optic nerves. MRI allows excellent depiction of the intricate anatomy of optic nerves due to its excellent soft tissue contrast without exposure to ionizing radiation, better delineation of the entire visual pathway, and accurate evaluation of associated intracranial pathologies.

  17. Nerve Degeneration and Regeneration Associated with NF1 Tumors

    Science.gov (United States)

    2014-09-01

    Associated with NF1 Tumors PRINCIPAL INVESTIGATOR: David F. Muir CONTRACTING ORGANIZATION: University of Florida...NUMBER Nerve Degeneration and Regeneration Associated with NF1 Tumors 5b. GRANT NUMBER W81XWH-11-1-0145 5c...for  the   eradication  of  PNSTs.    Our  preliminary  studies  indicate  that  PDT  effectively  kills  human   NF1

  18. Primary optic nerve sheath meningioma

    Energy Technology Data Exchange (ETDEWEB)

    Jeremic, Branislav [International Atomic Energy Agency, Vienna (Austria); Pitz, Susanne (eds.) [University Eye Hospital, Mainz (Germany)

    2008-07-01

    Optic nerve sheath meningioma (ONSM) is a rare tumour. Cases are usually separated into primary ONSM, which arises either intraorbitally or, less commonly, intracanalicularly, and secondary ONSM, which arises intracranially and subsequently invades the optic canal and orbit. This is the first book to cover all important aspects of the diagnosis and treatment of primary ONSM. After a general introduction, individual chapters discuss the clinical presentation, clinical examination and diagnosis, imaging, and histology. Treatment options are then addressed in detail, with special emphasis on external beam radiation therapy, and in particular stereotactic fractionated radiation therapy. The latter has recently produced consistently good results and is now considered the emerging treatment of choice for the vast majority of patients with primary ONSM. This well-illustrated book will prove invaluable to all practitioners who encounter primary ONSM in their clinical work. (orig.)

  19. Swimming Exercise in the Acute or Late Phase after Sciatic Nerve Crush Accelerates Nerve Regeneration

    Directory of Open Access Journals (Sweden)

    Rosana Macher Teodori

    2011-01-01

    Full Text Available There is no consensus about the best time to start exercise after peripheral nerve injury. We evaluated the morphological and functional characteristics of the sciatic nerves of rats that began to swim immediately after crush nerve injury (CS1, those that began to swim 14 days after injury (CS14, injured rats not submitted to swimming (C, and uninjured rats submitted to swimming (S. After 30 days the number of axons in CS1 and CS14 was lower than in C (P0.05. Swimming exercise applied during the acute or late phase of nerve injury accelerated nerve regeneration and synaptic elimination after axonotmesis, suggesting that exercise may be initiated immediately after injury.

  20. Swimming Exercise in the Acute or Late Phase after Sciatic Nerve Crush Accelerates Nerve Regeneration

    Science.gov (United States)

    Teodori, Rosana Macher; Betini, Joice; de Oliveira, Larissa Salgado; Sobral, Luciane Lobato; Takeda, Sibele Yoko Mattozo; Montebelo, Maria Imaculada de Lima

    2011-01-01

    There is no consensus about the best time to start exercise after peripheral nerve injury. We evaluated the morphological and functional characteristics of the sciatic nerves of rats that began to swim immediately after crush nerve injury (CS1), those that began to swim 14 days after injury (CS14), injured rats not submitted to swimming (C), and uninjured rats submitted to swimming (S). After 30 days the number of axons in CS1 and CS14 was lower than in C (P 0.05). Swimming exercise applied during the acute or late phase of nerve injury accelerated nerve regeneration and synaptic elimination after axonotmesis, suggesting that exercise may be initiated immediately after injury. PMID:21876821

  1. The mechanism of astragaloside IV promoting sciatic nerve regeneration

    Institute of Scientific and Technical Information of China (English)

    Xiaohong Zhang; Jiajun Chen

    2013-01-01

    3-O-beta-D-xylopyranosyl-6-O-beta-D-glucopyranosyl-cycloastragenol (astragaloside IV), the main active component of the traditional Chinese medicine astragalus membranaceus, has been shown to be neuroprotective. This study investigated whether astragaloside IV could promote the repair of injured sciatic nerve. Denervated sciatic nerve of mice was subjected to anastomosis. The mice were intraperitoneal y injected with 10, 5, 2.5 mg/kg astragaloside IV per day for 8 consecutive days. Western blot assay and real-time PCR results demonstrated that growth-associated protein-43 ex-pression was upregulated in mouse spinal cord segments L 4–6 after intervention with 10, 5, 2.5 mg/kg astragaloside IV per day in a dose-dependent manner. Luxol fast blue staining and elec-trophysiological detection suggested that astragaloside IV elevated the number and diameter of myelinated nerve fibers, and simultaneously increased motor nerve conduction velocity and action potential amplitude in the sciatic nerve of mice. These results indicated that astragaloside IV con-tributed to sciatic nerve regeneration and functional recovery in mice. The mechanism underlying this effect may be associated with the upregulation of growth-associated protein-43 expression.

  2. Histochemical discrimination of fibers in regenerating rat infraorbital nerve

    Science.gov (United States)

    Wilke, R. A.; Riley, D. A.; Sanger, J. R.

    1992-01-01

    In rat dorsal root ganglia, histochemical staining of carbonic anhydrase (CA) and cholinesterase (CE) yields a reciprocal pattern of activity: Sensory processes are CA positive and CE negative, whereas motor processes are CA negative and CE positive. In rat infraorbital nerve (a sensory peripheral nerve), we saw extensive CA staining of nearly 100% of the myelinated axons. Although CE reactivity in myelinated axons was extremely rare, we did observe CE staining of unmyelinated autonomic fibers. Four weeks after transection of infraorbital nerves, CA-stained longitudinal sections of the proximal stump demonstrated 3 distinct morphological zones. A fraction of the viable axons retained CA activity to within 2 mm of the distal extent of the stump, and the stain is capable of resolving growth sprouts being regenerated from these fibers. Staining of unmyelinated autonomic fibers in serial sections shows that CE activity was not retained as far distally as is the CA sensory staining.

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

    Directory of Open Access Journals (Sweden)

    Maria Veronica de Souza

    1996-12-01

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

  4. Electrically conductive biodegradable polymer composite for nerve regeneration: electricity-stimulated neurite outgrowth and axon regeneration.

    Science.gov (United States)

    Zhang, Ze; Rouabhia, Mahmoud; Wang, Zhaoxu; Roberge, Christophe; Shi, Guixin; Roche, Phillippe; Li, Jiangming; Dao, Lê H

    2007-01-01

    Normal and electrically stimulated PC12 cell cultures and the implantation of nerve guidance channels were performed to evaluate newly developed electrically conductive biodegradable polymer composites. Polypyrrole (PPy) doped by butane sulfonic acid showed a significantly higher number of viable cells compared with PPy doped by polystyrenesulfonate after a 6-day culture. The PC12 cells were left to proliferate for 6 days, and the PPy-coated membranes, showing less initial cell adherence, recorded the same proliferation rate as did the noncoated membranes. Direct current electricity at various intensities was applied to the PC12 cell-cultured conductive membranes. After 7 days, the greatest number of neurites appeared on the membranes with a current intensity approximating 1.7-8.4 microA/cm. Nerve guidance channels made of conductive biodegradable composite were implanted into rats to replace 8 mm of sciatic nerve. The implants were harvested after 2 months and analyzed with immunohistochemistry and transmission electron microscopy. The regenerated nerve tissue displayed myelinated axons and Schwann cells that were similar to those in the native nerve. Electrical stimulation applied through the electrically conductive biodegradable polymers therefore enhanced neurite outgrowth in a current-dependent fashion. The conductive polymers also supported sciatic nerve regeneration in rats.

  5. Chemoattractive capacity of different lengths of nerve fragments bridging regeneration chambers for the repair of sciatic nerve defects

    Institute of Scientific and Technical Information of China (English)

    Jiren Zhang; Yubo Wang; Jincheng Zhang

    2012-01-01

    A preliminary study by our research group showed that 6-mm-long regeneration chamber bridging is equivalent to autologous nerve transplantation for the repair of 12-mm nerve defects.In this study,we compared the efficacy of different lengths (6,8,10 mm) of nerve fragments bridging 6-mm regeneration chambers for the repair of 12-mm-long nerve defects.At 16 weeks after the regeneration chamber was implanted,the number,diameter and myelin sheath thickness of the regenerated nerve fibers,as well as the conduction velocity of the sciatic nerve and gastrocnemius muscle wet weight ratio,were similar to that observed with autologous nerve transplantation.Our results demonstrate that 6-,8-and 10-mm-long nerve fragments bridging 6-mm regeneration chambers effectively repair 12-mm-long nerve defects.Because the chemoattractive capacity is not affected by the length of the nerve fragment,we suggest adopting 6-mm-long nerve fragments for the repair of peripheral nerve defects.

  6. Degeneration and regeneration of motor and sensory nerves: a stereological study of crush lesions in rat facial and mental nerves

    DEFF Research Database (Denmark)

    Barghash, Ziad; Larsen, Jytte Overgaard; Al-Bishri, Awad

    2013-01-01

    The aim of this study was to evaluate the degeneration and regeneration of a sensory nerve and a motor nerve at the histological level after a crush injury. Twenty-five female Wistar rats had their mental nerve and the buccal branch of their facial nerve compressed unilaterally against a glass rod...... in the degenerative pattern; however, at day 19 the buccal branch had regenerated to the normal number of axons, whereas the mental nerve had only regained 50% of the normal number of axons. We conclude that the regenerative process is faster and/or more complete in the facial nerve (motor function) than...... for 30 s. Specimens of the compressed nerves and the corresponding control nerves were dissected at 3, 7, and 19 days after surgery. Nerve cross-sections were stained with osmium tetroxide and toluidine blue and analysed using two-dimensional stereology. We found differences between the two nerves both...

  7. Improvement in nerve regeneration through a decellularized nerve graft by supplementation with bone marrow stromal cells in fibrin.

    Science.gov (United States)

    Zhao, Zhe; Wang, Yu; Peng, Jiang; Ren, Zhiwu; Zhang, Li; Guo, Quanyi; Xu, Wenjing; Lu, Shibi

    2014-01-01

    Acellular nerve grafting is often inferior as well as an inadequate alternative to autografting for the repair of long gaps in peripheral nerves. Moreover, the injection method is not perfect. During the injection of cells, the syringe can destroy the acellular nerve structure and the limited accumulation of seed cells. To resolve this problem, we constructed a nerve graft by acellular nerve grafting. Bone marrow-mesenchymal stromal cells (BM-MSCs) were affixed with fibrin glue and injected inside or around the graft, which was then used to repair a 15-mm nerve defect in rats. The acellular nerve graft maintained its structure and composition, and its tensile strength was decreased, as determined by two-photon microscopy and a tensile testing device. In vitro, MSCs embedded in fibrin glue survived and secreted growth factors such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). We repaired 15-mm Sprague-Dawley rat sciatic nerve defects using this nerve graft construction, and MSCs injected around the graft helped improve nerve regeneration and functional recovery of peripheral nerve lesions as determined by functional analysis and histology. Therefore, we conclude that supplying MSCs in fibrin glue around acellular nerves is successful in maintaining the nerve structure and can support nerve regeneration similar to the direct injection of MSCs into the acellular nerve for long nerve defects but may avoid destroying the nerve graft. The technique is simple and is another option for stem cell transplantation.

  8. Effect of neurotrophic factor, MDP, on rats’ nerve regeneration

    Directory of Open Access Journals (Sweden)

    A.A. Fornazari

    2011-04-01

    Full Text Available Our objective was to determine the immune-modulating effects of the neurotrophic factor N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP on median nerve regeneration in rats. We used male Wistar rats (120-140 days of age, weighing 250-332 g and compared the results of three different techniques of nerve repair: 1 epineural neurorrhaphy using sutures alone (group S - 10 rats, 2 epineural neurorrhaphy using sutures plus fibrin tissue adhesive (FTA; group SF - 20 rats, and 3 sutures plus FTA, with MDP added to the FTA (group SFM - 20 rats. Functional assessments using the grasp test were performed weekly for 12 weeks to identify recovery of flexor muscle function in the fingers secondary to median nerve regeneration. Histological analysis was also utilized. The total number and diameter of myelinated fibers were determined in each proximal and distal nerve segment. Two indices, reported as percentage, were calculated from these parameters, namely, the regeneration index and the diameter change index. By the 8th week, superiority of group SFM over group S became apparent in the grasping test (P = 0.005. By the 12th week, rats that had received MDP were superior in the grasping test compared to both group S (P < 0.001 and group SF (P = 0.001. Moreover, group SF was better in the grasping test than group S (P = 0.014. However, no significant differences between groups were identified by histological analysis. In the present study, rats that had received MDP obtained better function, in the absence of any significant histological differences.

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

    Science.gov (United States)

    Mottaghitalab, Fatemeh; Farokhi, Mehdi; Zaminy, Arash; Kokabi, Mehrdad; Soleimani, Masoud; Mirahmadi, Fereshteh; Shokrgozar, Mohammad Ali; Sadeghizadeh, Majid

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Fatemeh Mottaghitalab

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

  11. Retrobulbar diameter of optic nerve in glaucoma

    Directory of Open Access Journals (Sweden)

    Stefanović Ivan

    2009-01-01

    Full Text Available Introduction. The ultrasound diagnostics of the optic nerve includes the analysis of the optic nerve disc (PNO and measuring of its retrobulbar diameter. With B-scan, by Schraeder's method, it is possible to measure very precisely the optic nerve, the pial diameter, the normal values for the pial diameter being 2.8-4.1 mm. In glaucoma, the disease that is most frequently associated with higher intraocular pressure, there comes the destruction of nerve fibres, which can be visualized as the excavation of the optic nerve disc. Objective. In this paper, we were interested in finding whether in glaucoma, and in what phase of the disease, the optic nerve starts growing thinner. Aware of many forms of this very complex disease, we were interested in knowing if the visualization of excavation on the optic nerve disc is related to diminishing of the pial diameter of the retrobulbar nerve part. Methods. There were treated the patients who had already had the diagnosis of glaucoma and the visualized excavation of the optic disc of various dimensions. Echographically, there was measured the thickness of the retrobulbar part of the optic nerve and the finding compared in relation to the excavation of the optic disc. Results. In all eyes with glaucoma, a normal size of the retrobulbar part of the optic nerve was measured, ranging from 3.01 to 3.91 mm with the median of 3.36 mm. Also, by testing the correlation between the thickness of the optic nerve and the excavation of the PNO, by Pearson test, we found that there was no correlation between these two parameters (r=0.109; p>0.05. Conclusion. In the patients with glaucoma, the retrobulbar part of the optic nerve is not thinner (it has normal values, even not in the cases with a totally excavated optic disc. There is no connection between the size of the PNO excavation and the thickness of the retrobulbar part of the optic nerve.

  12. The impact of optic nerve movement on optic nerve magnetic resonance diffusion parameters

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    Anand Moodley

    2014-04-01

    Full Text Available Background: Optic nerve diffusion imaging is a useful investigational tool of optic nerve microstructure, but is limited by eye-movement-induced optic nerve movement and artifacts from surrounding cerebrospinal fluid, fat, bone and air. Attempts at improving patient cooperation, thus voluntarily limiting eye movement during a standard diffusion imagingsequence, are usually futile. The aim of this study was to establish the impact of optic nerve movement on clinical diffusion parameters of the optic nerve.Method: Twenty-nine healthy volunteers with intact vision and intact conjugate gaze were recruited and subjected to magnetic resonance diffusion-weighted imaging (DWI and diffusion-tensor imaging (DTI of the optic nerves. Twenty right eyes had nerve tracking done using single-shot echo-planar imaging at 20 time points over 3 minutes. Optic nerve movement measurements were correlated with diffusion parameters of apparent diffusion coefficient (ADC, mean diffusivity (MD, fractional anisotropy (FA and anisotropic index(AI using Spearman’s rank correlation.Results: No significant correlations were noted between optic nerve movement parameters and ADC in the axial plane and MD of the optic nerve. Low to moderate negative correlations were noted between optic nerve movement parameters and AI and FA and positive correlation with ADC in the radial plane.Conclusion: Optic nerve movement documented during the timespan of standard diffusion sequences (DWI and DTI has a negative effect on the anisotropic diffusion parameters of the optic nerve. With greater eye movement, optic nerve diffusion appears less anisotropic owing to greater radial diffusion.

  13. A dual laminin/collagen receptor acts in peripheral nerve regeneration.

    OpenAIRE

    Toyota, B; Carbonetto, S; David, S.

    1990-01-01

    A regeneration chamber was created in vivo by suturing a synthetic tube sealed at its distal end onto the proximal stump of a severed rat sciatic nerve. Nerves regenerated into tubes coated with laminin at a rate of 0.33 mm/day after a lag of about 2 days. At 25 days, regenerating nerves had extended 23% farther into laminin-coated tubes as compared with uncoated ones. Monoclonal antibody 3A3, which functionally interferes with a dual laminin/collagen receptor, inhibited nerve regeneration in...

  14. The optic nerve sheath on MRI in acute optic neuritis

    Energy Technology Data Exchange (ETDEWEB)

    Hickman, S.J. [University College London, NMR Research Unit, Department of Neuroinflammation, Institute of Neurology, London (United Kingdom); Moorfields Eye Hospital, Department of Neuro-Ophthalmology, London (United Kingdom); Miszkiel, K.A. [National Hospital for Neurology and Neurosurgery, Lysholm Department of Neuroradiology, London (United Kingdom); Plant, G.T. [Moorfields Eye Hospital, Department of Neuro-Ophthalmology, London (United Kingdom); Miller, D.H. [University College London, NMR Research Unit, Department of Neuroinflammation, Institute of Neurology, London (United Kingdom)

    2005-01-01

    Optic nerve sheath dilatation or gadolinium-enhancement on magnetic resonance imaging in acute optic neuritis have been previously reported but have been thought to be rare occurrences. This study recruited 33 patients with acute unilateral optic neuritis. All had their optic nerves imaged with fat-saturated fast spin-echo (FSE) imaging, and 28 had imaging before and after triple-dose gadolinium-enhanced fat-saturated T{sub 1}-weighted imaging. Follow-up imaging was performed on 20 patients (15 following gadolinium). A dilated subarachnoid space at the anterior end of the symptomatic optic nerve on FSE imaging was seen in 15/33 cases. In three of these cases, dilatation was visible on short-term follow-up. Optic nerve sheath enhancement was seen in 21/28 cases acutely: seven at the anterior end of the lesion only, five at the posterior end only and nine at both ends. Optic sheath enhancement was seen in 13 patients on follow-up. This study suggests that optic nerve sheath dilatation on FSE images and optic nerve sheath enhancement on triple-dose gadolinium-enhanced images are common findings in acute optic neuritis. Optic nerve sheath dilatation may be due to inflammation of the optic nerve, with its associated swelling, interrupting the communication between the subarachnoid space of the diseased optic nerve and the chiasmal cistern. Optic nerve sheath enhancement suggests that meningeal inflammation occurs in optic neuritis, in agreement with pathological studies of both optic neuritis and multiple sclerosis. (orig.)

  15. Ultrastructural analysis of guided nerve regeneration using progesterone- and pregnenolone-loaded chitosan prostheses.

    Science.gov (United States)

    Chávez-Delgado, M E; Gomez-Pinedo, U; Feria-Velasco, A; Huerta-Viera, M; Castañeda, S Castro; Toral, F A López-Dellamary; Parducz, A; Anda, S Luquín-De; Mora-Galindo, J; García-Estrada, J

    2005-07-01

    Recently, numerous guide chambers for the treatment of injured nerves made up of different biomaterials have been designed, capable of hosting living cells or carrying neurotrophic or neuroactive substances to be directly released to the injured tissue. In this study, chitosan prostheses containing neurosteroids (progesterone and pregnenolone) were used for bridging a 10-mm gap in the rabbit facial nerve. Gas chromatography was used to quantify neurosteroid content in the prostheses prior to and after subcutaneous implantation at different periods of up to 60 days. The regeneration of the nerve fibers were evaluated at 15 and 45 days after axotomy by means of ultrastructural morphometric analysis. Different nerve fibers regenerative patterns were seen depending the groups studied and the analyzed stages. At 15 days after axotomy, the newly regenerating tissue revealed Schwann cells holding nonmyelinated nerve fiber bundles in an incipient and organized regenerative pattern. At 45 days, the regenerating tissue showed myelinated nerve fibers of different sizes, shapes, and myelin sheath thickness. Although the regeneration of the nerve fibers under neurosteroid treatment showed statistically significant differences in comparison with vehicle regenerated tissue, progesterone-loaded chitosan prostheses produced the best guided nerve regeneration response. These findings indicate that chitosan prostheses allowed regeneration of nerve fibers in their lumen, and when containing neurosteroids produced a faster guided nerve regeneration acting as a long-lasting release delivery vehicle.

  16. Congenital optic nerve anomalies and hereditary optic neuropathies.

    Science.gov (United States)

    Heidary, Gena

    2014-12-01

    Congenital and hereditary optic nerve anomalies represent a significant cause of visual dysfunction. While some optic nerve abnormalities affect the visual system alone, others may be associated with neurologic and systemic findings. Correct identification of the optic nerve disease therefore is crucial both for developing a treatment plan with respect to visual rehabilitation, but also for initiating the appropriate multidisciplinary evaluation. The purpose of this review is to highlight common examples of congenital and inherited optic nerve abnormalities in an effort to familiarize the clinician with salient clinical features of these diseases and to review important systemic testing when relevant.

  17. Unilateral optic nerve aplasia associated with microphthalmos

    Directory of Open Access Journals (Sweden)

    Stanković-Babić Gordana

    2012-01-01

    Full Text Available Intraduction. Optic nerve aplasia is a rare developmental anomaly characterised by the congenital absence of the optic nerve, central retinal vessels and retinal ganglion cells that is seen most often in a unilaterally malformed eye. Case report. We reported a girl with a very rare anomaly of the eye, unilateral aplasia of the optic nerve and microphthalmia. We carried out a complete ophthalmological examination, A- and Bscan ultrasonography, magnetic resonance imaging (MRI of the orbit and brain, pediatrician, neurological examinations and karyotype determination. The examined child was a third child from the third regular pregnancy, born at term (39 GS, BM 3100 g. Family ocular history was negative. The right corneal diameter was 7.5 mm and left 10 mm. On dilated fundus examination, the right eye showed the absence of optic nerve and central retinal vessels. B-scan echography showed a small right globe (axial length 13.80 mm, normal size left globe (axial length 18.30 mm and the absence of optic nerve on the right eye. Physical and neurological findings and karyotype was normal. MRI of the orbits and brain marked asymmetry of globe size and unilateral absence of the optic nerve. The patient is under the control of a competent ophthalmologist and prosthetic. Conclusion. Further aesthetic and functional development of a young person is the primary goal in tracking this rare congenital optic nerve anomalies in the malformed eye.

  18. In vivo MRI monitoring nerve regeneration of acute peripheral nerve traction injury following mesenchymal stem cell transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Duan, Xiao-Hui, E-mail: duanxiaohui-128@163.com [Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yanjiang Road West, Guangzhou 510120, Guangdong (China); Cheng, Li-Na, E-mail: kobe10716@163.com [Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yanjiang Road West, Guangzhou 510120, Guangdong (China); Zhang, Fang, E-mail: xinxin110007@yahoo.com.cn [Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yanjiang Road West, Guangzhou 510120, Guangdong (China); Liu, Jun, E-mail: docliujun@hotmail.com [Department of Neurology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yanjiang Road West, Guangzhou 510120, Guangdong (China); Guo, Ruo-Mi, E-mail: guoruomi-521@163.com [Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yanjiang Road West, Guangzhou 510120, Guangdong (China); Zhong, Xiao-Mei, E-mail: enough300@yahoo.com.cn [Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yanjiang Road West, Guangzhou 510120, Guangdong (China); Wen, Xue-Hua, E-mail: xuehuasuqian@126.com [Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yanjiang Road West, Guangzhou 510120, Guangdong (China); Shen, Jun, E-mail: junshenjun@hotmail.com [Department of Radiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, No. 107 Yanjiang Road West, Guangzhou 510120, Guangdong (China)

    2012-09-15

    Objective: To assess the continuous process of nerve regeneration in acute peripheral nerve traction injury treated with mesenchymal stem cells (MSCs) transplantation using MRI. Materials and methods: 1 week after acute nerve traction injury was established in the sciatic nerve of 48 New Zealand white rabbits, 5 × 10{sup 5} MSCs and vehicle alone were grafted to the acutely distracted sciatic nerves each in 24 animals. Serial MRI and T1 and T2 measurements of the injured nerves were performed with a 1.5-T scanner and functional recovery was recorded over a 10-week follow-up period, with histological assessments performed at regular intervals. Results: Compared with vehicle control, nerves grafted with MSCs had better functional recovery and showed improved nerve regeneration, with a sustained increase of T1 and T2 values during the phase of regeneration. Conclusion: MRI could be used to monitor the enhanced nerve regeneration in acute peripheral nerve traction injury treated with MSC transplantation, reflected by a prolonged increase in T1 and T2 values of the injured nerves.

  19. Promoting central nervous system regeneration: lessons from cranial nerve I.

    Science.gov (United States)

    Ruitenberg, Marc J; Vukovic, Jana

    2008-01-01

    The olfactory nerve differs from cranial nerves III-XII in that it contains a specialised type of glial cell, called 'olfactory ensheathing cell' (OEC), rather than Schwann cells. In addition, functional neurogenesis persists postnatally in the olfactory system, i.e. the primary olfactory pathway continuously rebuilds itself throughout adult life. The presence of OECs in the olfactory nerve is thought to be critical to this continuous growth process. Because of this intrinsic capacity for self-repair, the mammalian olfactory system has proved as a useful model in neuroregeneration studies. In addition, OECs have been used in transplantation studies to promote pathway regeneration elsewhere in the nervous system. Here, we have reviewed the parameters that allow for repair within the primary olfactory pathway and the role that OECs are thought to play in this process. We conclude that, in addition to intrinsic growth potential, the presence of an aligned substrate to the target structure is a fundamental prerequisite for appropriate restoration of connectivity with the olfactory bulb. Hence, strategies to promote regrowth of injured nerve pathways should incorporate usage of aligned, oriented substrates of OECs or other cellular conduits with additional intervention to boost neuronal cell body responses to injury and/or neutralisation of putative inhibitors.

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

    Directory of Open Access Journals (Sweden)

    Pei-xun Zhang

    2015-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    Pei-xun Zhang; Li-ya A; Yu-hui Kou; Xiao-feng Yin; Feng Xue#; Na Han; Tian-bing Wang; Bao-guo Jiang

    2015-01-01

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

  2. Mandibular branch of the facial nerve in wistar rats: new experimental model to assess facial nerve regeneration.

    Science.gov (United States)

    Bento, Ricardo Ferreira; Salomone, Raquel; Nascimento, Silvia Bona do; Ferreira, Ricardo Jose Rodriguez; Silva, Ciro Ferreira da; Costa, Heloisa Juliana Zabeu Rossi

    2014-07-01

    Introduction The ideal animal model for nerve regeneration studies is the object of controversy, because all models described by the literature have advantages and disadvantages. Objective To describe the histologic and functional patterns of the mandibular branch of the facial nerve of Wistar rats to create a new experimental model of facial nerve regeneration. Methods Forty-two male rats were submitted to a nerve conduction test of the mandibular branch to obtain the compound muscle action potential. Twelve of these rats had the mandibular branch surgically removed and submitted to histologic analysis (number, partial density, and axonal diameter) of the proximal and distal segments. Results There was no statistically significant difference in the functional and histologic variables studied. Conclusion These new histologic and functional standards of the mandibular branch of the facial nerve of rats establish an objective, easy, and greatly reproducible model for future facial nerve regeneration studies.

  3. The Influence of a Fibrin-Coating Inside a Biodegradable Poly(DL-Lactide-ε-Caprolactone) Nerve Guide on Peripheral Nerve Regeneration

    OpenAIRE

    den Dunnen, W F A; Schakenraad, J.M.; Lei, B; Pennings, A.J.; Robinson, P. H.

    1996-01-01

    The aim of this study was to evaluate the effect of a fibrin-coating on the inner surface of a biodegradable poly(DL-lactide-E-caprolactone) nerve guide on the speed and quality of the nerve regeneration. The nerve regeneration and orientation of the nerve fibers, as well as the fibrous tissue formation were evaluated. On the short term, nerve regeneration was slightly faster in the non-coated nerve guide. After longer implantation periods (≥ 4 weeks), nerve regeneration in the fibrin-coated ...

  4. Nerve regeneration following implantation of axotomized nerves pretreated with gamma radiation

    Institute of Scientific and Technical Information of China (English)

    Xinyuan Wang; Dehai Chang; Shihua Xie; Chunming Han; Jinsheng Sheng

    2008-01-01

    BACKGROUND: It has been shown that irradiation to the neurolemma can reduce immunogenicity. However, it is still poorly understood whether the degenerated nerve can affect peripheral nerve regeneration.OBJECTIVE: To observe the effect of radiation-damaged nerve transplantation on functional recovery of the peripheral nerve.DESIGN, TIME AND SETTING: Self-control animal trial was performed at the Experimental Center of Orthopedics, Tangdu Hospital of Fourth Military Medical University from January to October 2005.MATERIALS: Fifty-four healthy, Chinese rabbits, irrespective of gender, were randomly divided into experimental (n = 36) and control (n = 18) groups. A60 Co γ -radiation machine and NDI-200 nerve electromyograph were provided by the Experimental Center of Orthopedics, Tangdu Hospital of Fourth Military Medical University.METHODS: A median incision was made in the posterior right thigh of rabbits after abdominal anesthesia. A 30-mm segment of sciatic nerve was excised from the inferior margin of the piriform muscle to the tibiofibular intersection. The sciatic nerve in the experimental group was sterilely radiated with 350 Gy for 9.5 minutes. The damaged nerve segment was then re-transplanted. In the control group, the sciatic nerve was re-transplanted directly following excision. Nerve conduction velocity was determined at 4, 6, and 8 months post-surgery.MAIN OUTCOME MEASURES: Functional assessments, such as gait, nutritional status of skin on dorsum of foot, toe spreading reflex, and foot holding, were made between 1 and 180 days post-surgery. The common peroneal nerve and tibial nerve reflexes under clamping were observed at 4, 6, and 8 months post-surgery to evaluate functional restoration of the peripheral nerve. Eiectromyogram was performed to observe nerve conduction velocity.RESULTS: From postoperative days 1 to 26, the limbs that were transplanted with irradiated nerve exhibited dragged walking, foot drop, sole ulcers, depilation, self

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

    Science.gov (United States)

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

    2014-04-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Lei; Liu, Yi; Zhao, Hua; Zhang, Wen; Guo, Ying-Jun; Nie, Lin, E-mail: chengleiyx@126.com

    2013-10-18

    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-mediated 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

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

    Science.gov (United States)

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

    2016-02-01

    Many bioartificial nerve guides have been investigated pre-clinically for their nerve regeneration-supporting function, often in comparison to autologous nerve transplantation, which is still regarded as the current clinical gold standard. Enrichment of these scaffolds with cells intended to support axonal regeneration has been explored as a strategy to boost axonal regeneration across these nerve guides Ansselin et al. (1998). In the present study, 20 mm rat sciatic nerve defects were implanted with a cell-seeded microstructured collagen nerve guide (Perimaix) or an autologous nerve graft. Under the influence of seeded, pre-differentiated mesenchymal stromal cells, axons regenerated well into the Perimaix nerve guide. Myelination-related parameters, like myelin sheath thickness, benefitted from an additional seeding with pre-differentiated mesenchymal stromal cells. Furthermore, both the number of retrogradely labelled sensory neurons and the axon density within the implant were elevated in the cell-seeded scaffold group with pre-differentiated mesenchymal stromal cells. However, a pre-differentiation had no influence on functional recovery. An additional cell seeding of the Perimaix nerve guide with mesenchymal stromal cells led to an extent of functional recovery, independent of the differentiation status, similar to autologous nerve transplantation. These findings encourage further investigations on pre-differentiated mesenchymal stromal cells as a cellular support for peripheral nerve regeneration. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  8. Synergistic effects of ultrashort wave and bone marrow stromal cells on nerve regeneration with acellular nerve allografts.

    Science.gov (United States)

    Pang, Chao-Jian; Tong, Lei; Ji, Li-Li; Wang, Zhen-Yu; Zhang, Xu; Gao, Hai; Jia, Hua; Zhang, Li-Xin; Tong, Xiao-Jie

    2013-10-01

    Acellular nerve allografts (ANA) possess bioactivity and neurite promoting factors in nerve tissue engineering. Previously we reported that low dose ultrashort wave (USW) radiation could enhance the rate and quality of peripheral nerve regeneration with ANA repairing sciatic nerve defects. Meanwhile, ANA implanted with bone marrow stromal cells (BMSCs) exhibited a similar result. Thus, it is interesting to know whether it might yield a synergistic effect when USW radiation is combined with BMSCs-laden ANA. Here we investigated the effectiveness of ANA seeded with BMSCs, combined with USW therapy on repairing peripheral nerve injuries. Adult male Wistar rats were randomly divided into four groups: Dulbecco's modified Eagle's medium (DMEM) control group, BMSCs-laden group, ultrashort wave (USW) group and BMSC + USW group. The regenerated nerves were assayed morphologically and functionally, and growth-promoting factors in the regenerated tissues following USW administration or BMSCs integration were also detected. The results indicated that the combination therapy caused much better beneficial effects evidenced by increased myelinated nerve fiber number, myelin sheath thickness, axon diameter, sciatic function index, nerve conduction velocity, and restoration rate of tibialis anterior wet weight. Moreover, the mRNA levels of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) in the spinal cord and muscles were elevated significantly. In conclusion, we found a synergistic effect of USW radiation and BMSCs treatment on peripheral nerve regeneration, which may help establish novel strategies for repairing peripheral nerve defects. Copyright © 2013 Wiley Periodicals, Inc.

  9. Peripheral nerve grafts support regeneration after spinal cord injury.

    Science.gov (United States)

    Côté, Marie-Pascale; Amin, Arthi A; Tom, Veronica J; Houle, John D

    2011-04-01

    Traumatic insults to the spinal cord induce both immediate mechanical damage and subsequent tissue degeneration leading to a substantial physiological, biochemical, and functional reorganization of the spinal cord. Various spinal cord injury (SCI) models have shown the adaptive potential of the spinal cord and its limitations in the case of total or partial absence of supraspinal influence. Meaningful recovery of function after SCI will most likely result from a combination of therapeutic strategies, including neural tissue transplants, exogenous neurotrophic factors, elimination of inhibitory molecules, functional sensorimotor training, and/or electrical stimulation of paralyzed muscles or spinal circuits. Peripheral nerve grafts provide a growth-permissive substratum and local neurotrophic factors to enhance the regenerative effort of axotomized neurons when grafted into the site of injury. Regenerating axons can be directed via the peripheral nerve graft toward an appropriate target, but they fail to extend beyond the distal graft-host interface because of the deposition of growth inhibitors at the site of SCI. One method to facilitate the emergence of axons from a graft into the spinal cord is to digest the chondroitin sulfate proteoglycans that are associated with a glial scar. Importantly, regenerating axons that do exit the graft are capable of forming functional synaptic contacts. These results have been demonstrated in acute injury models in rats and cats and after a chronic injury in rats and have important implications for our continuing efforts to promote structural and functional repair after SCI.

  10. Schwann-like cells seeded in acellular nerve grafts improve nerve regeneration.

    Science.gov (United States)

    Fan, Lihong; Yu, Zefeng; Li, Jia; Dang, Xiaoqian; Wang, Kunzheng

    2014-05-21

    This study evaluated whether Schwann-like cells (SLCs) induced from bone marrow-derived mesenchymal stem cells (BM-MSCs) transplanted into acellular nerve grafts (ANGs) could repair nerve defects compared with nerve isografts and ANGs with BM-MSCs. BM-MSCs extracted, separated and purified from the bone marrow of rats, and some of the BM-MSCs were cultured with mixed induction agents that could induce BM-MSCs into SLCs. Either SLCs or BM-MSCs were seeded onto 10-mm ANGs, and the isografts were chosen as the control. The walking-track test, tibialis anterior muscle weight measurement, electrophysiological examination, toluidine blue staining, transmission electron micrographs and immunostaining of S-100 and VEGF in these three groups were evaluated in a 10-mm rat sciatic injury-repair model. The walking-track test, tibialis anterior muscle weight measurement and electrophysiological examination of the sciatic nerve suggested the groups of ANGs with SLCs and isografts obtained better results than the BM-MSC group (P0.05). All the histomorphometric analyses (toluidine blue staining, transmission electron micrographs and immunostaining of S-100 and VEGF) showed that there were more regenerating nerve fibers in the group of ANGs with SLCs than the BM-MSCs (P0.05). SLCs seeded in ANGs and isografts show better functional regeneration compared with BM-MSCs seeded in ANGs. Additionally, SLCs combined with ANGs present almost the same outcome as the isografts. Therefore, SLCs with ANGs can be a good choice in nerve defect repairs.

  11. Rat-derived processed nerve allografts support more axon regeneration in rat than human-derived processed nerve xenografts.

    Science.gov (United States)

    Wood, Matthew D; Kemp, Stephen W P; Liu, Edward H; Szynkaruk, Mark; Gordon, Tessa; Borschel, Gregory H

    2014-04-01

    Processed nerve allografts are increasingly used as "off the shelf" nerve replacements for surgically bridging nerve gaps. Benchmarking the regenerative capacity of a commercially available human-derived nerve or xenograft in a rat nerve injury model would provide a convenient platform for future studies seeking to modify the processed nerve graft. Human and rat processed nerve grafts were used to bridge a 14 mm defect in a Sprague-Dawley rat sciatic nerve. Reversed autografts served as a positive control group. Twelve weeks following surgery, the distal nerve stumps were retrograde labeled and harvested for histology and histomorphometry. The cross-sectional areas of the human- and rat-derived processed nerve grafts were similar. Neuron counts and myelinated axon counts following use of the human-derived processed xenografts were decreased compared with those obtained from both the rat-derived processed nerve allografts and the autografts; the rat-derived processed nerve allografts were statistically equivalent to autografts. Measures of nerve fiber diameter and myelination revealed inferior axon regeneration maturity in both processed nerve grafts compared with autografts. Processed xenografts showed significantly reduced regeneration compared with autografts or processed allografts indicating that cross-species immunological reactions are important considerations in this rat model. Copyright © 2013 Wiley Periodicals, Inc.

  12. Optic Nerve Avulsion after Blunt Trauma

    Directory of Open Access Journals (Sweden)

    Hacı Halil Karabulut

    2014-05-01

    Full Text Available Optic nerve avulsion is an uncommon presentation of ocular trauma with a poor prognosis. It can be seen as complete or partial form due to the form of trauma. We assessed the complete optic nerve avulsion in a 16-year-old female patient complaining of loss of vision in her left eye after a traffic accident. (Turk J Ophthalmol 2014; 44: 249-51

  13. Ultrasound-stimulated peripheral nerve regeneration within asymmetrically porous PLGA/Pluronic F127 nerve guide conduit.

    Science.gov (United States)

    Park, Sang Chul; Oh, Se Heang; Seo, Tae Beom; Namgung, Uk; Kim, Jin Man; Lee, Jin Ho

    2010-08-01

    Recently, we developed a novel method to fabricate a nerve guide conduit (NGC) with asymmetrical pore structure and hydrophilicity using poly(lactic-co-glycolic acid) (PLGA) and Pluronic F127 by a modified immersion precipitation method. From the animal study using a rat model (sciatic nerve defect of rat), we recognized that the unique PLGA/Pluronic F127 tube provided good environments for nerve regeneration. In this study, we applied low-intensity pulsed ultrasound as a simple and noninvasive stimulus at the PLGA/F127 NGC-implanted site transcutaneously in rats to investigate the feasibility of ultrasound for the enhanced nerve regeneration through the tube. The nerve regeneration behaviors within the ultrasound-stimulated PLGA/Pluronic F127 NGCs were compared with the NGCs without the ultrasound treatment as well as normal nerve by histological and immunohistochemical observations. It was observed that the PLGA/Pluronic F127 tube-implanted group applied with the ultrasound had more rapid nerve regeneration behavior (approximately 0.71 mm/day) than the tube-implanted group without the ultrasound treatment (approximately 0.48 mm/day). The ultrasound-treated tube group also showed greater neural tissue area as well as larger axon diameter and thicker myelin sheath than the tube group without the ultrasound treatment, indicating better nerve regeneration. The better nerve regeneration behavior in the our NGC/ultrasound system may be caused by the synergistic effect of the asymmetrically porous PLGA/Pluronic F127 tube with unique properties (selective permeability, hydrophilicity, and structural stability, which can provide good environment for nerve regeneration) and physical stimulus (stimulation of the Schwann cells and activation of the neurotrophic factors).

  14. Active Nerve Regeneration with Failed Target Reinnervation Drives Persistent Neuropathic Pain

    Science.gov (United States)

    Xie, Wenrui

    2017-01-01

    Abstract Peripheral nerves can regenerate and, when injured, may cause neuropathic pain. We propose that the active regeneration process plays a pivotal role in the maintenance of neuropathic pain. In one commonly used rodent neuropathic pain model, pronounced pain behaviors follow ligation and cutting of the L5 spinal nerve. We found that the injured nerve regenerates into the sciatic nerve and functionally reinnervates target tissues: the regenerated nerve conducts electrical signals, mechanical responses, and tracers between the leg/hindpaw and axotomized sensory ganglion. The regenerating nerve is the primary source of abnormal spontaneous activity detected in vivo. Disrupting the regeneration inhibited pain. First, semaphorin 3A, an inhibitory axonal guidance molecule, reduced functional regeneration, spontaneous activity, and pain behaviors when applied to the injury site in vivo. Second, knockdown of the upregulated growth-associated protein 43 (GAP43) with siRNA injected into the axotomized sensory ganglion reduced pain behaviors. We next examined the spared nerve injury model, in which pain behaviors are essentially permanent. The regeneration resulted in tangled GAP43-positive neuromas at the nerve injury site without target reinnervation. Perfusing the nerve stump with semaphorin 3A, but not removing the tangled fibers, prevented or reversed pain behaviors. This effect far outlasted the semaphorin 3A perfusion. Hence, in this model the long-lasting chronic pain may reflect the anatomical inability of regenerating nerves to successfully reinnervate target tissues, resulting in an ongoing futile regeneration process. We propose that specifically targeting the regeneration process may provide effective long-lasting pain relief in patients when functional reinnervation becomes impossible. PMID:28197545

  15. The Dilator Naris Muscle as a Reporter of Facial Nerve Regeneration in a Rat Model

    NARCIS (Netherlands)

    Weinberg, J.S.; Kleiss, I.J.; Knox, C.J.; Heaton, J.T.; Hadlock, T.A.

    2016-01-01

    OBJECTIVE: Many investigators study facial nerve regeneration using the rat whisker pad model, although widely standardized outcomes measures of facial nerve regeneration in the rodent have not yet been developed. The intrinsic whisker pad "sling" muscles producing whisker protraction, situated at t

  16. Regeneration of unmyelinated and myelinated sensory nerve fibres studied by a retrograde tracer method

    DEFF Research Database (Denmark)

    Lozeron, Pierre; Krarup, Christian; Schmalbruch, Henning

    2004-01-01

    Regeneration of myelinated and unmyelinated sensory nerve fibres after a crush lesion of the rat sciatic nerve was investigated by means of retrograde labelling. The advantage of this method is that the degree of regeneration is estimated on the basis of sensory somata rather than the number...

  17. Optical coherence tomographic findings in optic nerve hypoplasia

    Directory of Open Access Journals (Sweden)

    Daruchi Moon

    2013-01-01

    Full Text Available We investigated a case of unilateral optic nerve hypoplasia using spectral domain optical coherence tomography (SDOCT. Optical coherence tomography was done on both eyes using 5-line Raster scan for the fovea to analyze the retinal nerve fiber layer thickness, inner retinal layer thickness, outer retinal layer thickness, and optic disc cube scan for the disc. Retinal nerve fiber layer thickness, inner retinal layer thickness, and outer retinal layer thickness were manually measured at 21-points of each five lines, and results were compared between both eyes. Retinal nerve fiber layer thickness and inner retinal layer thickness of optic nerve hypoplasia were significantly thinner than the opposite eye, but there was no significant difference in the thickness of the outer retinal layer between both eyes.

  18. A study on peripheral nerve regeneration via biomimetic conduits loaded with Schwann cells and nerve growth factor

    Institute of Scientific and Technical Information of China (English)

    ZHAO Fengyi; ZHOU Peilan; WANG Ruilin; YANG Mingfu; ZHAO Weisheng; WEI Dian; ZHANG Tieliang; YAO Kangde; CUI Yuanlu

    2001-01-01

    @@ Guided tissue regeneration is a new approach in the reconstructive surgery of peripheral nerves. Biomimetic conducts were construct from the expanded vein onwhose inner surface composited with amnion filaments (cf. Fig 1).

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

    Science.gov (United States)

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

    2014-08-01

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

  20. Degeneration and regeneration of motor and sensory nerves: a stereological study of crush lesions in rat facial and mental nerves.

    Science.gov (United States)

    Barghash, Z; Larsen, J O; Al-Bishri, A; Kahnberg, K-E

    2013-12-01

    The aim of this study was to evaluate the degeneration and regeneration of a sensory nerve and a motor nerve at the histological level after a crush injury. Twenty-five female Wistar rats had their mental nerve and the buccal branch of their facial nerve compressed unilaterally against a glass rod for 30s. Specimens of the compressed nerves and the corresponding control nerves were dissected at 3, 7, and 19 days after surgery. Nerve cross-sections were stained with osmium tetroxide and toluidine blue and analysed using two-dimensional stereology. We found differences between the two nerves both in the normal anatomy and in the regenerative pattern. The mental nerve had a larger cross-sectional area including all tissue components. The mental nerve had a larger volume fraction of myelinated axons and a correspondingly smaller volume fraction of endoneurium. No differences were observed in the degenerative pattern; however, at day 19 the buccal branch had regenerated to the normal number of axons, whereas the mental nerve had only regained 50% of the normal number of axons. We conclude that the regenerative process is faster and/or more complete in the facial nerve (motor function) than it is in the mental nerve (somatosensory function).

  1. Laminin-modified and aligned PHBV/PEO nanofibrous nerve conduits promote peripheral nerve regeneration.

    Science.gov (United States)

    Zhang, Xiao-Feng; Liu, Hai-Xia; Ortiz, Lazarus Santiago; Xiao, Zhong-Dang; Huang, Ning-Ping

    2016-11-12

    Poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) has received much attention for its biodegradability and biocompatibility, characteristics which are required in tissue engineering. In this study, polyethylene oxide (PEO)-incorporated PHBV nanofibers with random or aligned orientation were obtained by electrospinning. For further use in vivo, the nanofiber films were made into nerve conduits after treated with NH3 plasma, which could improve the hydrophilicity of inner surfaces of nerve conduits and then facilitate laminin adsorption via electrostatic interaction for promoting cell adhesion and proliferation. Morphology of the surfaces of modified PHBV/PEO nanofibrous scaffolds were examined by scanning electron microscopy. Schwann cell viability assay was conducted and the results confirmed that the functionalized nanofibers were favorable for cell growth. Morphology of Schwann cells cultured on scaffolds showed that aligned nanofibrous scaffolds provided topographical guidance for cell orientation and elongation. Furthermore, 3D PHBV/PEO nerve conduits made from aligned and random-oriented nanofibers were implanted into 12-mm transected sciatic nerve rat model and subsequent analysis were conducted at 1 and 2 months post-surgery. The above functionalized PHBV/PEO scaffolds provide a novel and promising platform for peripheral nerve regeneration.

  2. Nerve guidance conduits from aligned nanofibers: improvement of nerve regeneration through longitudinal nanogrooves on a fiber surface.

    Science.gov (United States)

    Huang, Chen; Ouyang, Yuanming; Niu, Haitao; He, Nanfei; Ke, Qinfei; Jin, Xiangyu; Li, Dawei; Fang, Jun; Liu, Wanjun; Fan, Cunyi; Lin, Tong

    2015-04-08

    A novel fibrous conduit consisting of well-aligned nanofibers with longitudinal nanogrooves on the fiber surface was prepared by electrospinning and was subjected to an in vivo nerve regeneration study on rats using a sciatic nerve injury model. For comparison, a fibrous conduit having a similar fiber alignment structure without surface groove and an autograft were also conducted in the same test. The electrophysiological, walking track, gastrocnemius muscle, triple-immunofluorescence, and immunohistological analyses indicated that grooved fibers effectively improved sciatic nerve regeneration. This is mainly attributed to the highly ordered secondary structure formed by surface grooves and an increase in the specific surface area. Fibrous conduits made of longitudinally aligned nanofibers with longitudinal nanogrooves on the fiber surface may offer a new nerve guidance conduit for peripheral nerve repair and regeneration.

  3. Regeneration of the nerves in the aerial cavity with an artificial nerve conduit --reconstruction of chorda tympani nerve gaps-.

    Directory of Open Access Journals (Sweden)

    Toshiaki Yamanaka

    Full Text Available Due to its anatomical features, the chorda tympani nerve (CTN is sometimes sacrificed during middle ear surgery, resulting in taste dysfunction. We examined the effect of placing an artificial nerve conduit, a polyglycolic acid (PGA-collagen tube, across the gap in the section of the resected chorda tympani nerve (CTN running through the tympanic cavity.The CTN was reconstructed with a PGA-collagen tube in three patients with taste disturbance who underwent CTN resection. To evaluate the effect of the reconstruction procedure on the patients' gustatory function, we measured the patients' electrogustometry (EGM thresholds. The patients were followed-up for at least two years.Gustatory function was completely restored in all of the patients after the reconstruction. The patients' EGM thresholds exhibited early improvements within one to two weeks and had returned to their normal ranges within three months. They subsequently remained stable throughout the two-year follow-up period. In a patient who underwent a second surgical procedure, it was found that the PGA-collagen tube used in the first surgical procedure had been absorbed and replaced by new CTN fibers with blood vessels on their surfaces.These results suggest that reconstruction of the CTN with an artificial nerve conduit, a PGA-collagen tube, allows functional and morphological regeneration of the nerve and facilitates the recovery of taste function. PGA-collagen tubes might be useful for repairing CTNs that are resected during middle ear surgery. Further research is required to confirm these preliminary results although this is the first report to describe the successful regeneration of a nerve running through an aerial space.

  4. Optic nerve decompression for orbitofrontal fibrous dysplasia.

    Science.gov (United States)

    Abe, Takumi; Sato, Kaneshige; Otsuka, Takaharu; Kawamura, Noriyoshi; Shimazu, Motohiko; Izumiyama, Hitoshi; Matsumoto, Kiyoshi

    2002-08-01

    Orbitofrontal fibrous dysplasia often involves the bony orbit and the optic canal. Although fibrous dysplasia reportedly produces compression of the optic nerve leading to visual distrubances, optic nerve decompression in patients without clinical signs of optic neuropathy is still controversial. We describe two patients with orbitofrontal fibrous dysplasia without signs of visual disturbance and one patient with McCune-Albright syndrome and progressive visual impairment. Optic nerve decompression was performed prophylactically for two patients and therapeutically for one patient through the transcranial extradural route. Dystopias and craniofacial deformities induced by fibrous dysplasia also were corrected. The micropressure suction-irrigation system was especially effective for decreasing heat transfer and thereby preventing thermal injury of the optic nerve. The orbitofrontal area was reconstructed from cranial bone, iliac bone, and ribs. Postoperative follow-up revealed no disturbances in visual function and no evidence of cerebrospinal fluid leakage. These findings suggest that optic nerve decompression may be effective in preventing visual disturbances with minimal risk of other neurological sequelae. Subsequent orbital reconstruction yielded satisfactory cosmetic results.

  5. Peripheral nerve regeneration within an asymmetrically porous PLGA/Pluronic F127 nerve guide conduit.

    Science.gov (United States)

    Oh, Se Heang; Kim, Jun Ho; Song, Kyu Sang; Jeon, Byeong Hwa; Yoon, Jin Hwan; Seo, Tae Beom; Namgung, Uk; Lee, Il Woo; Lee, Jin Ho

    2008-04-01

    Asymmetrically porous tubes with selective permeability and hydrophilicity as nerve guide conduits (NGCs) were fabricated using poly(lactic-co-glycolic acid) (PLGA) and Pluronic F127 by a modified immersion precipitation method. The inner surface of the tube had nano-size pores ( approximately 50nm) which can effectively prevent from fibrous tissue infiltration but permeate nutrients and retain neurotrophic factors, while the outer surface had micro-size pores ( approximately 50microm) which can allow vascular ingrowth for effective supply of nutrients into the tube. From the animal study using a rat model, the hydrophilized PLGA/F127 (3wt%) tube showed better nerve regeneration behavior than the control silicone or hydrophobic PLGA tubes, as investigated by immunohistochemical observation (by fluorescent microscopy with anti-neurofilament staining), histological observations (by light microscopy with toluidine blue staining and transmission electron microscopy), and electrophysiological evaluation (by compound muscle action potential measurement). This is probably owing to the effective permeation of nutrients and prevention of fibrous scar tissue invasion as well as the good mechanical strength of the tube to maintain a stable support structure for the nerve regeneration.

  6. Nerve-dependent and -independent events in blastema formation during Xenopus froglet limb regeneration.

    Science.gov (United States)

    Suzuki, Makoto; Satoh, Akira; Ide, Hiroyuki; Tamura, Koji

    2005-10-01

    Blastema formation, the initial stage of epimorphic limb regeneration in amphibians, is an essential process to produce regenerates. In our study on nerve dependency of blastema formation, we used forelimb of Xenopus laevis froglets as a system and applied some histological and molecular approaches in order to determine early events during blastema formation. We also investigated the lateral wound healing in comparison to blastema formation in limb regeneration. Our study confirmed at the molecular level that there are nerve-dependent and -independent events during blastema formation after limb amputation, Tbx5 and Prx1, reliable markers of initiation of limb regeneration, that start to be expressed independently of nerve supply, although their expressions cannot be maintained without nerve supply. We also found that cell proliferation activity, cell survival and expression of Fgf8, Fgf10 and Msx1 in the blastema were affected by denervation, suggesting that these events specific for blastema outgrowth are controlled by the nerve supply. Wound healing, which is thought to be categorized into tissue regeneration, shares some nerve-independent events with epimorphic limb regeneration, although the healing process results in simple restoration of wounded tissue. Overall, our results demonstrate that dedifferentiated blastemal cells formed at the initial phase of limb regeneration must enter the nerve-dependent epimorphic phase for further processes, including blastema outgrowth, and that failure of entry results in a simple redifferentiation as tissue regeneration.

  7. Axonal autophagy during regeneration of the rat sciatic nerve

    Institute of Scientific and Technical Information of China (English)

    Kangrong Lu; Zhongxian Piao; Zhenxi Liu; Weiwang Gu; Wanshan Wang; Nngjie Piao

    2008-01-01

    BACKGROUND: The removal of degenerated axonal debris during Wallerian degeneration is very important for nerve regeneration. However, the mechanism by which debris is removed is not been completely understood. Considerable controversy remains as to the clearance pathway and cells that are involved. OBJECTIVE: To investigate axonal autophagy during removal of degenerated axonal debris by transecting the sciatic nerve in a rat Wallerian degeneration model.DESIGN, TIME AND SETTING: Experimental neuropathological analysis. The experiment was conducted at the Laboratory Animal Service Center of the Southern Medical University between January and June 2005. MATERIALS: Fifty-four adult, Wistar rats of either sex, weighing 180-250 g, were obtained from the Laboratory Animal Service Center of the Southern Medical University. Animals were randomly divided into nine groups of six rats. METHODS: Wallerian degeneration was induced by transecting the rat sciatic nerve, and tissue samples from the distal stump were obtained 0.2, 0.4, 1, 2, 3, 4, 7, 10, and 15 days post-transection. Ultrathin sections were prepared for electron microscopy to study ultrastructure and enzyme cytochemistry staining. MAIN OUTCOME MEASURES: Ultrastructure (axon body, autophagic body, and cystoskeleton) of axons and myelin sheaths observed with electron microscopy; acidic phosphatase activity detected by Gomori staining using electron microscopy. RESULTS: The major changes of degenerating axons after transection were axoplasm swelling and separation of axons from their myelin sheath between five hours and two days post-transection. At four days post-transection, the axoplasm condensed and axons were completely separated from the myelin sheath, forming dissociative axon bodies. Vacuoles of different sizes formed in axons during the early phase after lesion. Larger dissociative axon bodies were formed when the axons were completely separated from the myelin sheath during a late phase. The axolemma

  8. The optic nerve head in hereditary optic neuropathies.

    Science.gov (United States)

    O'Neill, Evelyn C; Mackey, David A; Connell, Paul P; Hewitt, Alex W; Danesh-Meyer, Helen V; Crowston, Jonathan G

    2009-05-01

    Hereditary optic neuropathies are a prominent cause of blindness in both children and adults. The disorders in this group share many overlapping clinical characteristics, including morphological changes that occur at the optic nerve head. Accurate and prompt clinical diagnosis, supplemented with imaging when indicated, is essential for optimum management of the relevant optic neuropathy and appropriate counseling of the patient on its natural history. Patient history, visual field assessment, optic disc findings and imaging are the cornerstones of a correct diagnosis. This Review highlights the characteristic optic nerve head features that are common to the various hereditary optic neuropathies, and describes the features that enable the conditions to be differentiated.

  9. Acceleration of Peripheral Nerve Regeneration through Asymmetrically Porous Nerve Guide Conduit Applied with Biological/Physical Stimulation

    Science.gov (United States)

    Kim, Jin Rae; Oh, Se Heang; Kwon, Gu Birm; Namgung, Uk; Song, Kyu Sang; Jeon, Byeong Hwa

    2013-01-01

    Sufficient functional restoration of damaged peripheral nerves is a big clinical challenge. In this study, a nerve guide conduit (NGC) with selective permeability was prepared by rolling an asymmetrically porous polycaprolactone/Pluronic F127 membrane fabricated using a novel immersion precipitation method. Dual stimulation (nerve growth factor [NGF] as a biological stimulus and low-intensity pulse ultrasound [US] as a physical stimulus) was adapted to enhance nerve regeneration through an NGC. The animal study revealed that each stimulation (NGF or US) has a positive effect to promote the peripheral nerve regeneration through the NGC, however, the US-stimulated NGC group allowed more accelerated nerve regeneration compared with the NGF-stimulated group. The NGC group that received dual stimulation (NGF and US) showed more effective nerve regeneration behavior than the groups that received a single stimulation (NGF or US). The asymmetrically porous NGC with dual NGF and US stimulation may be a promising strategy for the clinical treatment of delayed and insufficient functional recovery of a peripheral nerve. PMID:23859225

  10. Acceleration of peripheral nerve regeneration through asymmetrically porous nerve guide conduit applied with biological/physical stimulation.

    Science.gov (United States)

    Kim, Jin Rae; Oh, Se Heang; Kwon, Gu Birm; Namgung, Uk; Song, Kyu Sang; Jeon, Byeong Hwa; Lee, Jin Ho

    2013-12-01

    Sufficient functional restoration of damaged peripheral nerves is a big clinical challenge. In this study, a nerve guide conduit (NGC) with selective permeability was prepared by rolling an asymmetrically porous polycaprolactone/Pluronic F127 membrane fabricated using a novel immersion precipitation method. Dual stimulation (nerve growth factor [NGF] as a biological stimulus and low-intensity pulse ultrasound [US] as a physical stimulus) was adapted to enhance nerve regeneration through an NGC. The animal study revealed that each stimulation (NGF or US) has a positive effect to promote the peripheral nerve regeneration through the NGC, however, the US-stimulated NGC group allowed more accelerated nerve regeneration compared with the NGF-stimulated group. The NGC group that received dual stimulation (NGF and US) showed more effective nerve regeneration behavior than the groups that received a single stimulation (NGF or US). The asymmetrically porous NGC with dual NGF and US stimulation may be a promising strategy for the clinical treatment of delayed and insufficient functional recovery of a peripheral nerve.

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

    KAUST Repository

    Morrison, Brett M.

    2015-01-01

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

  12. High-resolution CT of lesions of the optic nerve

    Energy Technology Data Exchange (ETDEWEB)

    Peyster, R.G.; Hoover, E.D.; Hershey, B.L.; Haskin, M.E.

    1983-05-01

    The optic nerves are well demonstrated by high-resolution computed tomography. Involvement of the optic nerve by optic gliomas and optic nerve sheath meningiomas is well known. However, nonneoplastic processes such as increased intracranial pressure, optic neuritis, Grave ophthalmopathy, and orbital pseudotumor may also alter the appearance of the optic nerve/sheath on computed tomography. Certain clinical and computed tomographic features permit distinction of these nonneoplastic tumefactions from tumors.

  13. Anatomy of the optic nerve head and glaucomatous optic neuropathy.

    Science.gov (United States)

    Radius, R L

    1987-01-01

    The mechanism of axon damage in eyes with glaucomatous optic neuropathy remains undefined. Interestingly, it has been observed that, although the entire nerve cross-section may be involved by the nerve damage, in many instances, the superior and inferior axon bundles are preferentially affected by the pressure insult. Thus, recent studies by many investigators have stressed a re-examination of the optic nerve head anatomy, including the nerve head microcirculation, the glial and connective tissue elements within the nerve head, and the morphology of the axons themselves. Any correlation between regional differences in this anatomy and the preferential involvement by specific axon bundles within the nerve head by the pressure insult may suggest some further insight into the mechanisms underlying the pressure-induced axon loss in glaucomatous eyes.

  14. Synergistic effects of bone mesenchymal stem cells and chondroitinase ABC on nerve regeneration after acellular nerve allograft in rats.

    Science.gov (United States)

    Wang, Ying; Jia, Hua; Li, Wen-Yuan; Tong, Xiao-Jie; Liu, Gui-Bo; Kang, Si-Wen

    2012-04-01

    This study aimed to evaluate whether combination therapy of bone marrow stromal cells (BMSCs) transplantation and chondroitinase ABC (ChABC) treatment further enhances axonal regeneration and functional recovery after acellular nerve allograft repair of the sciatic nerve gap in rats. Eight Sprague-Dawley rats were used as nerve donors, and 32 Wistar rats were randomly divided into four groups: Group I: acellular rat sciatic nerve (ARSN) group; Group II: ChABC treatment; Group III: BMSCs transplantation; and Group IV: ChABC treatment and BMSCs transplantation. The results showed that compared with ARSN control group, BMSC transplantation promoted axonal regeneration, the secretion of neural trophic factors NGF, BDNF and axon angiogenesis in nerve graft. ChABC treatment degraded chondroitin sulfate proteoglycans in ARSN in vitro and in vivo and improved BMSCs survival in ARSN. The combination therapy caused much better beneficial effects evidenced by increasing sciatic function index, nerve conduction velocity, restoration rate of tibialis anterior wet muscle weight, and myelinated nerve number, but did not further boost the therapeutic effects on neurotrophic factor production, axon angiogenesis, and sensory functional recovery by BMSC transplantation. Taken together, for the first time, we demonstrate the synergistic effects of BMSC transplantation and BMSCs treatment on peripheral nerve regeneration, and our findings may help establish novel strategies for cell transplantation therapy for peripheral nerve injury.

  15. Experimental study on the effect of electrostimulation on neural regeneration after oculomotor nerve injury.

    Science.gov (United States)

    Zhu, Ningxi; Zhang, Chunmei; Li, Zhen; Meng, Youqiang; Feng, Baohui; Wang, Xuhui; Yang, Min; Wan, Liang; Ning, Bo; Li, Shiting

    2014-12-01

    The oculomotor nerve can regenerate anatomically and histologically after injury; however, the degree of functional recovery of extraocular muscles and the pupil sphincter muscle was not satisfactory. Electrostimulation was one potential intervention that was increasingly being studied for use in nerve injury settings. However, the effect of electrostimulation on regeneration of the injured oculomotor nerve was still obscure. In this study, we studied the effects of electrostimulation on neural regeneration in terms of neurofunction, myoelectrophysiology, neuroanatomy, and neurohistology after oculomotor nerve injury and found that electrostimulation on the injured oculomotor nerve enhanced the speed and final level of its functional and electrophysiological recovery, promoted neural regeneration, and enhanced the selectivity and specificity of reinnervation of the regenerated neuron, the conformity among the electrophysiological and functional recovery of extraocular muscles, and neural regeneration, and that the function of extraocular muscles recovered slower than electrophysiology. Thus, we speculated that electrostimulation on the injured oculomotor nerve produced a marked effect on all phases of neural regeneration including neuronal survival, sprout formation, axonal elongation, target reconnection, and synaptogenesis. We think that neural electrostimulation can be used in oculomotor nerve injury.

  16. Biological performance of a novel biodegradable polyamidoamine hydrogel as guide for peripheral nerve regeneration.

    Science.gov (United States)

    Magnaghi, Valerio; Conte, Vincenzo; Procacci, Patrizia; Pivato, Giorgio; Cortese, Paolo; Cavalli, Erika; Pajardi, Giorgio; Ranucci, Elisabetta; Fenili, Fabio; Manfredi, Amedea; Ferruti, Paolo

    2011-07-01

    Polyamidoamines (PAAs) are a well-known family of synthetic biocompatible and biodegradable polymers, which can be prepared as soft hydrogels characterized by low interfacial tension and tunable elasticity. For the first time we report here on the in vivo performance of a PAA hydrogel implant as scaffold for tissue engineering. In particular, an amphoteric agmatine-deriving PAA hydrogel shaped as small tubing was obtained by radical polymerization of a soluble functional oligomeric precursor and used as conduit for nerve regeneration in a rat sciatic nerve cut model. The animals were analyzed at 30, 90, and 180 days post-surgery. PAA tubing proved to facilitate nerve regeneration. Good surgical outcomes were achieved with no signs of inflammation or neuroma. Moreover, nerve regeneration was morphologically sound and the quality of functional recovery satisfactory. In conclusion, PAA hydrogel scaffolds may represent a novel and promising material for peripheral nerve regeneration.

  17. Collagen scaffolds modified with CNTF and bFGF promote facial nerve regeneration in minipigs.

    Science.gov (United States)

    Cui, Yi; Lu, Chao; Meng, Danqing; Xiao, Zhifeng; Hou, Xianglin; Ding, Wenyong; Kou, Depeng; Yao, Yao; Chen, Bing; Zhang, Zhen; Li, Jiayin; Pan, Juli; Dai, Jianwu

    2014-09-01

    Most experiments of peripheral nerve repair after injury have been conducted in the rodent model but the translation of findings from rodent studies to clinical practice is needed partly because the nerve regeneration must occur over much longer distances in humans than in rodents. The reconstruction of long distance nerve injuries still represents a great challenge to surgeons who is engaged in peripheral nerve surgery. Here we used the functional nerve conduit (collagen scaffolds incorporated with neurocytokines CNTF and bFGF) to bridge a 35 mm long facial nerve gap in minipig models. At 6 months after surgery, electrophysiology assessment and histological examination were conducted to evaluate the regeneration of peripheral facial nerves. Based on functional and histological observations, the results indicated that the functional collagen scaffolds promoted nerve reconstruction. The number and arrangement of regenerated nerve fibers, myelination, and nerve function reconstruction was better in the CNTF + bFGF conduit group than the single factor CNTF or bFGF conduit group. The functional composite conduit, which exhibited favorable mechanical properties, may promote facial nerve regeneration in minipigs effectively. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. The optic nerve head in glaucoma

    Directory of Open Access Journals (Sweden)

    Rupert RA Bourne

    2006-09-01

    Full Text Available ll types of glaucoma involve glaucomatous optic neuropathy. The key to detection and management of glaucoma is understanding how to examine the optic nerve head (ONH. This pictorial glossary addresses the following issues: how to examine the ONH; normal characteristics of the ONH; characteristics of a glaucomatous ONH; how to tell if the glaucomatous optic neuropathy is getting worse;‘pitfalls and pearls’.

  19. Immune system augmentation by glatiramer acetate of peripheral nerve regeneration-crush versus transection models of rat sciatic nerve.

    Science.gov (United States)

    Luria, Shai; Cohen, Avraham; Safran, Ori; Firman, Shimon; Liebergall, Meir

    2013-10-01

    Immune system augmentation, using the antigen glatiramer acetate (GA), which is known to affect cellular immunity, has been shown to have a positive effect on peripheral nerve regeneration. We aimed to compare the effect of GA on the regeneration of crushed versus transected nerves. Wild-type rats underwent crush or transection and repair of the sciatic nerve. They were examined 3 weeks postinjury histologically (axon count) and functionally (tibialis anterior muscle weight and footprint analysis). GA was found to augment regeneration both histologically and functionally. In the transected nerve, a significant increase in axon count distal to the injury site was seen in the GA group versus control. A similar yet statistically insignificant trend was found in the crushed nerve. Improvement was found in the footprint analysis between the GA and control groups in both crush and transected nerve groups. We found improvement in the footprint analysis in the crush versus transection group. GA was found to improve the regeneration of the peripheral nerve. Histologically, this was more pronounced in the transection injury. The discrepancy between the different functional measures examined may be explained by the distance of the reinnervated muscles evaluated from the injury site. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

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

    DEFF Research Database (Denmark)

    Moldovan, Mihai; Sørensen, Jesper; Krarup, Christian

    2006-01-01

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

  1. Survey of Current Experimental Studies of Effects of Traditional Chinese Medicine on Peripheral Nerve Regeneration

    Institute of Scientific and Technical Information of China (English)

    WU Qun-li; LIANG Xiao-chun

    2006-01-01

    The repairing and regeneration of peripheral nerves is a very complex biological and cytological process, its mechanism is unclear so far, and thus results in the lack of specific and effectual therapy and medicament. Chinese herbs and their effective components have their own inimitable predominance in promoting peripheral nerve regeneration, such as their multi-factorial, multi-target and multi-functional action, abundant source, inexpensive, etc. In this paper, the experimental studies reported in recent 5 years concerning the effects of Chinese herbs or their active components on peripheral nerve repairing and regeneration are reviewed in respects of the integral level, cellular level, molecular level and gene level.

  2. Skin nerve regeneration and burn wound healing following spinal nerve root incision

    Institute of Scientific and Technical Information of China (English)

    Yibing Wang; Pengfei Guo; Yongqiang Feng; Yongqian Cao; Shourong Zhu; Rui Zhang

    2011-01-01

    Burn wounds were produced on two sides on the backs of Wistar rats, in addition to denervation on one side. The skin neural regeneration at the injury site and burn wound healing were evaluated following spinal nerve root incision. No nerve regeneration was observed in the burn wound region post-denervation, and the degree of epithelization was significantly less than the control group. With increasing time, expression of type Ⅰ collagen, which plays a supporting role, and collagen Ⅲ, which exhibits elastic properties, were significantly increased in the two groups, but the expression was less in the denervation group compared with the control group, and the wound healing was faster in the control group. The ratio of type Ⅰ collagen to type Ⅲ collagen was significantly lower in the denervation group compared with the control group. The ratio gradually decreased with prolonged time in the denervation group, but remained unchanged in the control group. However, the elasticity of the tissues in the denervation group was better than the control group. During burn wound healing, innervations can promote wound healing, but denervation can improve the quality of wound remodeling.

  3. Undifferentiated and differentiated adipose-derived stem cells improve nerve regeneration in a rat model of facial nerve defect.

    Science.gov (United States)

    Watanabe, Yorikatsu; Sasaki, Ryo; Matsumine, Hajime; Yamato, Masayuki; Okano, Teruo

    2017-02-01

    Autologous nerve grafting is the current procedure used for repairing facial nerve gaps. As an alternative to this method, tissue engineering cell-based therapy using induced pluripotent stem cells, Schwann cells and bone marrow-derived mesenchymal stem cells has been proposed. However, these cells have major problems, including tumorigenesis in induced pluripotent stem cells and invasiveness and limited tissue associated with harvesting for the other cells. Here, we investigated the therapeutic potential of adipose-derived stem cells (ASCs), which can be harvested easily and repeatedly by a minimally invasive liposuction procedure. The ASCs had characteristics of mesenchymal tissue lineages and could differentiate into Schwann-like cells that were relatively simple to isolate and expand in culture. In an in vivo study, a silicone conduit containing undifferentiated ASCs, differentiated ASCs or Schwann cells were transplanted, embedded in a collagen gel and the efficacy of repair of a 7 mm-gap in the rat facial nerve examined. Morphometric quantification analysis of regenerated facial nerves after a regeneration period of 13 weeks showed that undifferentiated ASCs, differentiated ASCs, and Schwann cells had similar potential for nerve regeneration. Furthermore, the functional recovery of facial nerve regeneration using a rat facial palsy scoring system in the three groups was close to that in autologous nerve graft positive controls. These findings suggest that undifferentiated and differentiated ASCs may both have therapeutic potential in facial nerve regeneration as a source of Schwann cells in cell-based therapy performed as an alternative to autologous nerve grafts. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.

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

    Science.gov (United States)

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

    2014-12-01

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

  5. Glatiramer acetate immune system augmentation for peripheral nerve regeneration in rat crushed sciatic nerve model.

    Science.gov (United States)

    Luria, Shai; Waitayawinyu, Thanapong; Conniff, James; Morton, H Josette; Nemechek, Nicholas M; Sonnen, Joshua A; Katolik, Leonid I; Trumble, Thomas E

    2010-02-01

    Protective antiself response to nervous system injury has been reported to be mediated by a T-cell subpopulation that can recognize self-antigens. Immune cells have been shown to play a role in the regulation of motor neuron survival after a peripheral nerve injury. The objective of the present study was to evaluate the effects of immune system augmentation with use of the antigen glatiramer acetate, which is known to affect T-cell immunity, on peripheral nerve regeneration. Wild-type and nude-type (T-cell-deficient) rats underwent crush injury of the sciatic nerve. Three and six weeks after the injury, the sciatic nerve was examined, both functionally (on the basis of footprint analysis and the tibialis anterior muscle response and weight) and histologically (on the basis of axon count). Significantly greater muscle responses were measured after three weeks in the group of wild-type rats that were treated with glatiramer acetate (control limb:injured limb ratio, 0.05 for the glatiramer acetate group [n = 9], compared with 0.51 for the saline solution group [n = 8]; p < 0.05). Higher axon counts were also found in this group (control limb:injured limb ratio, -0.07 for the glatiramer acetate group [n = 10], compared with 0.29 for the saline solution group [n = 8]; p < 0.05). The nude-type rats showed no response to the intervention after three weeks but showed a delayed response after six weeks. A second dose of glatiramer acetate, delivered forty-eight hours after the injury, did not result in an improved response as compared with the control groups. We found that a single treatment with glatiramer acetate resulted in accelerated functional and histological recovery after sciatic nerve crush injury. The role of T-cell immunity in the mechanism of glatiramer acetate was suggested by the partial and late response found in the T-cell-deficient rats.

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Science.gov (United States)

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

    2013-10-01

    The DLTIDDSYWYRI motif (Ln2-P3) of human laminin-2 has been reported to promote PC12 cell attachment through syndecan-1; however, the in vivo effects of Ln2-P3 have not been studied. In Schwann cells differentiated from skin-derived precursors, the peptide was effective in promoting cell attachment and spreading in vitro. To examine the effects of Ln2-P3 in peripheral nerve regeneration in vivo, we developed a dual-component poly(p-dioxanone) (PPD)/poly(lactic-co-glycolic acid) (PLGA) artificial nerve graft. The novel graft was coated with scrambled peptide or Ln2-P3 and used to bridge a 10 mm defect in rat sciatic nerves. The dual-component nerve grafts provided tensile strength comparable to that of a real rat nerve trunk. The Ln2-P3-treated grafts promoted early-stage peripheral nerve regeneration by enhancing the nerve regeneration rate and significantly increased the myelinated fibre density compared with scrambled peptide-treated controls. These findings indicate that Ln2-P3, combined with tissue-engineering scaffolds, has potential biomedical applications in peripheral nerve injury repair. Copyright © 2012 John Wiley & Sons, Ltd.

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

    Science.gov (United States)

    Gordon, Tessa; Gordon, Karen

    2010-01-01

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

  9. Light-microscopic and electron-microscopic evaluation of short-term nerve regeneration using a biodegradable poly(DL-lactide-epsilon-caprolacton) nerve guide

    NARCIS (Netherlands)

    denDunnen, WFA; Stokroos, [No Value; Blaauw, EH; Holwerda, A; Pennings, AJ; Robinson, PH; Schakenraad, JM

    1996-01-01

    The aim of this study was to evaluate short-term peripheral nerve regeneration across a IO-mm gap, using a biodegradable poly(DL-lactide-epsilon-caprolacton) nerve guide, with an internal diameter of 1.5 mm and a wall thickness of 0.30 mm. To do so, we evaluated regenerating nerves using light micro

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

    Science.gov (United States)

    Gordon, Tessa; Gordon, Karen

    2010-01-01

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

  11. Cell proliferation and apoptosis in optic nerve and brain integration centers of adult troutOncorhynchus mykiss after optic nerve injury

    Institute of Scientific and Technical Information of China (English)

    Evgeniya V Pushchina; Sachin Shukla; Anatoly A Varaksin; Dmitry K Obukhov

    2016-01-01

    Fishes have remarkable ability to effectively rebuild the structure of nerve cells and nerve ifbers after central nervous system injury. However, the underlying mechanism is poorly understood. In order to address this issue, we investigated the proliferation and apoptosis of cells in contralateral and ipsilateral optic nerves, after stab wound injury to the eye of an adult troutOncorhynchus mykiss. Heterogenous population of proliferating cells was investigated at 1 week after injury. TUNEL labeling gave a qualitative and quantita-tive assessment of apoptosis in the cells of optic nerve of trout 2 days after injury. After optic nerve injury, apoptotic response was investigated, and mass patterns of cell migration were found. The maximal con-centration of apoptotic bodies was detected in the areas of mass clumps of cells. It is probably indicative of massive cell death in the area of high phagocytic activity of macrophages/microglia. At 1 week after optic nerve injury, we observed nerve cell proliferation in the trout brain integration centers: the cerebellum and the optic tectum. In the optic tectum, proliferating cell nuclear antigen (PCNA)-immunopositive radial glia-like cells were identified. Proliferative activity of nerve cells was detected in the dorsal proliferative (matrix) area of the cerebellum and in parenchymal cells of the molecular and granular layers whereas local clusters of undifferentiated cells which formed neurogenic niches were observed in both the optic tectum and cerebellum after optic nerve injury.In vitro analysis of brain cells of trout showed that suspension cells compared with monolayer cells retain higher proliferative activity, as evidenced by PCNA immunolabeling. Phase contrast observation showed mitosis in individual cells and the formation of neurospheres which gradually increased during 1–4 days of culture. The present ifndings suggest that trout can be used as a novel model for studying neuronal regeneration.

  12. Remodeling of motor units after nerve regeneration studied by quantitative electromyography

    DEFF Research Database (Denmark)

    Krarup, Christian; Boeckstyns, Michel; Ibsen, Allan

    2016-01-01

    OBJECTIVE: Peripheral nerve has the capacity to regenerate after nerve lesions; during reinnervation of muscle motor units are gradually reestablished. The aim of this study was to follow the time course of reestablishing and remodeling of motor units in relation to recovery of force after...... different types of nerve repair. METHODS: Reinnervation of muscle was compared clinically and electrophysiologically in complete median or ulnar nerve lesions with short gap lengths in the distal forearm repaired with a collagen nerve conduit (11 nerves) or nerve suture (10 nerves). Reestablishment of motor...... and the number of motor units recovered to approximately 20% of normal. There was weak evidence of CMAP amplitude recovery after suture ahead of conduit repair but without treatment related differences at 2 years. CONCLUSIONS: Surgical repair of nerve lesions with a nerve conduit or suture supported recovery...

  13. Ultrastructural changes in the optic nerve and capillary vessels during early stages of optic nerve injury

    Institute of Scientific and Technical Information of China (English)

    Xuehong Ju; Xiuyun Li; Xiaoshuang Li; Hongtao Tang; Hongguo Liu

    2008-01-01

    BACKGROUND: Capillaries are the only blood supply for optic nerves, which makes the system more vulnerable to impaired blood circulation. OBJECTIVE: To observe the ultrastructural changes in the optic nerves and capillaries in rabbits following intracanalicular segment injury to the optic nerve. DESIGN, TIME AND SETTING: Comparative, observational, pathological morphology was performed at the Department of Anatomy, Weifang Medical College from September to November 2007. MATERIALS: Models of intracanalicular segment injury to the optic nerve were induced in the right eye of thirty healthy, adult rabbits by a flee-falling metal cylinder. The H-7500 transmission electron microscope was provided by Hitachi, Japan. METHODS: All rabbits were randomly assigned into experimental (n = 25) and control (n = 5) groups. Optic nerve specimens were obtained from the experimental group at 0.5, 6, 12, 48, and 96 hours, respectively, following injury. Uitrastructural changes to the optic nerves and their capillaries were observed by electron microscopy. Optic nerve injury was not established in the control group, but optic nerve specimens were collected similarly to the experimental group. MAIN OUTCOME MEASURES: Ultrastructural changes in the injured optic nerves and their capillaries. RESULTS: Thirty rabbits were included in the final analysis. In the control group, cross-sections of the optic nerves exhibited varied thicknesses with regularly arranged fibers. The axons appeared to be smooth with condensed myelin sheaths and oval mitochondria. The microtubules and mierofilaments were clearly seen. The lumens of the capillaries were regular with densely arranged endothelial cells and visible mitochondria. In the experimental group, 30 minutes after injury to the optic nerves, swollen axons, sparse myelin sheath, disordered microtubules and microfilaments, swollen mitochondria, and a decreased number of pinocytosis vesicles and microfilaments in endothelial cells of the capillaries

  14. Improvement of sciatic nerve regeneration using laminin-binding human NGF-beta.

    Directory of Open Access Journals (Sweden)

    Wenjie Sun

    Full Text Available BACKGROUND: Sciatic nerve injuries often cause partial or total loss of motor, sensory and autonomic functions due to the axon discontinuity, degeneration, and eventual death which finally result in substantial functional loss and decreased quality of life. Nerve growth factor (NGF plays a critical role in peripheral nerve regeneration. However, the lack of efficient NGF delivery approach limits its clinical applications. We reported here by fusing with the N-terminal domain of agrin (NtA, NGF-beta could target to nerve cells and improve nerve regeneration. METHODS: Laminin-binding assay and sustained release assay of NGF-beta fused with NtA (LBD-NGF from laminin in vitro were carried out. The bioactivity of LBD-NGF on laminin in vitro was also measured. Using the rat sciatic nerve crush injury model, the nerve repair and functional restoration by utilizing LBD-NGF were tested. FINDINGS: LBD-NGF could specifically bind to laminin and maintain NGF activity both in vitro and in vivo. In the rat sciatic nerve crush injury model, we found that LBD-NGF could be retained and concentrated at the nerve injury sites to promote nerve repair and enhance functional restoration following nerve damages. CONCLUSION: Fused with NtA, NGF-beta could bind to laminin specifically. Since laminin is the major component of nerve extracellular matrix, laminin binding NGF could target to nerve cells and improve the repair of peripheral nerve injuries.

  15. Beneficial Effect of Metformin on Nerve Regeneration and Functional Recovery After Sciatic Nerve Crush Injury in Diabetic Rats.

    Science.gov (United States)

    Ma, Junxiong; Liu, Jun; Yu, Hailong; Chen, Yu; Wang, Qi; Xiang, Liangbi

    2016-05-01

    Neuroprotective effects of metformin have been increasingly recognized in both diabetic and non-diabetic conditions. Thus far, no information has been available on the potential beneficial effects of metformin on peripheral nerve regeneration in diabetes mellitus. The present study was designed to investigate such a possibility. Diabetes was established by a single injection of streptozotocin at 50 mg/kg in rats. After sciatic nerve crush injury, the diabetic rats were intraperitoneally administrated daily for 4 weeks with metformin (30, 200 and 500 mg/kg), or normal saline, respectively. The axonal regeneration was investigated by morphometric analysis and retrograde labeling. The functional recovery was evaluated by electrophysiological studies and behavioral analysis. It was found that metformin significantly enhanced axonal regeneration and functional recovery compared to saline after sciatic nerve injury in diabetic rats. In addition, metformin at 200 and 500 mg/kg showed better performance than that at 30 mg/kg. Taken together, metformin is capable of promoting nerve regeneration after sciatic nerve injuries in diabetes mellitus, highlighting its therapeutic values for peripheral nerve injury repair in diabetes mellitus.

  16. Effects of a laminin peptide (YIGSR) immobilized on crab-tendon chitosan tubes on nerve regeneration.

    Science.gov (United States)

    Itoh, Soichiro; Matsuda, Atsushi; Kobayashi, Hisatoshi; Ichinose, Shizuko; Shinomiya, Kenichi; Tanaka, Junzo

    2005-05-01

    Thiolated and nonthiolated hydroxyapatite-coated crab-tendon chitosan (t-chitosan/HAp-SH and t-chitosan/HAp, respectively) tubes, both alone and conjugated with CDPGYIGSR (YIGSR) peptide, were compared, in order to determine their biocompatibility and efficacy as nerve conduits. YIGSR peptide was adsorbed on the t-chitosan/HAp (HAp) tubes, and covalently bound on the t-chitosan/HAp-SH (HAp-SH) tubes (Y/HAp and Y/HAp-SH tubes, respectively). HAp, HAp-SH, Y/HAp, or Y/HAp-SH tubes measuring 15 mm were bridge grafted into the sciatic nerve of SD rats. Grafting of 15-mm-long Type I atelocollagen tubes and isografting of sciatic nerves were also carried out (N = 6 in each group). After 12 weeks, evoked muscle action potentials were recorded to calculate the terminal latency quotient. Histological observation and analysis of myelinated axons were also carried out. Nerve-tissue regeneration did not occur directly on the tubes' surfaces in the YIGSR peptide-unconjugated groups. Transplantation of YIGSR-conjugated tubes, however, gave rise to regenerated nerve tissue attached to thin layers of epineurium-like structure formed on the inner-tube surface. Histological and electrophysiological analyses suggested that although thiolation retards nerve-tissue regeneration, adsorbed YIGSR, and, to a lesser extent, peptide that had been covalently bound onto the tube surfaces, enhance nerve regeneration, promoting sprouting from the proximal nerve stump and bridging of regenerated axons throughout the tube.

  17. Cartilage Oligomeric Matrix Protein Angiopoeitin-1 Provides Benefits During Nerve Regeneration In Vivo and In Vitro.

    Science.gov (United States)

    Qiu, Longhai; He, Bo; Hu, Jun; Zhu, Zhaowei; Liu, Xiaolin; Zhu, Jiakai

    2015-12-01

    Our group pioneered the study of nerve regeneration in China and has successfully developed human "acellular nerve grafts (ACNGs)". However, our clinical studies revealed that the effects of ACNGs for long and large nerve defects are far from satisfactory. To improve the efficacy of ACNGs, we combined Cartilage oligomeric matrix protein angiopoietin-1 (COMP-Ang1) with ACNGs in rat sciatic nerve injury models and observed the outcomes via angiographic, morphological, and functional analyses. Co-cultures of endothelial cells (ECs) and dorsal root ganglion neurons (DRGs) were also used to characterize the relationship between neovascularization and nerve regeneration. The results showed significant improvements in early neovascularization, nerve regeneration, and functional outcomes in vivo in the ACNG + COMP-Ang1 group. In vitro, neurite length, and density as well as the expression levels of neurofilament 68 (NF68) and phosphorylated-Tie-2 (p-Tie-2) significantly increased when ECs were co-cultured with DRGs using COMP-Ang1. p-Tie-2 expression dramatically decreased after treatment with a Tie-2 kinase inhibitor (S157701), which consequently decreased the level of NF68. COMP-Ang1 can be concluded to promote early neovascularization followed by brisk nerve regeneration, and the mechanism of this regeneration may involve the modulation of the p-Tie-2 and Tie-2 receptors on ECs. These findings demonstrate that ACNGs can be modified using COMP-Ang1 to improve their efficacy in repairing peripheral nerve defects in clinical trials.

  18. Mesenchymal stem cells in a polycaprolactone conduit promote sciatic nerve regeneration and sensory neuron survival after nerve injury.

    Science.gov (United States)

    Frattini, Flávia; Lopes, Fatima Rosalina Pereira; Almeida, Fernanda Martins; Rodrigues, Rafaela Fintelman; Boldrini, Leonardo Cunha; Tomaz, Marcelo A; Baptista, Abrahão Fontes; Melo, Paulo A; Martinez, Ana Maria Blanco

    2012-10-01

    Despite the fact that the peripheral nervous system is able to regenerate after traumatic injury, the functional outcomes following damage are limited and poor. Bone marrow mesenchymal stem cells (MSCs) are multipotent cells that have been used in studies of peripheral nerve regeneration and have yielded promising results. The aim of this study was to evaluate sciatic nerve regeneration and neuronal survival in mice after nerve transection followed by MSC treatment into a polycaprolactone (PCL) nerve guide. The left sciatic nerve of C57BL/6 mice was transected and the nerve stumps were placed into a biodegradable PCL tube leaving a 3-mm gap between them; the tube was filled with MSCs obtained from GFP+ animals (MSC-treated group) or with a culture medium (Dulbecco's modified Eagle's medium group). Motor function was analyzed according to the sciatic functional index (SFI). After 6 weeks, animals were euthanized, and the regenerated sciatic nerve, the dorsal root ganglion (DRG), the spinal cord, and the gastrocnemius muscle were collected and processed for light and electron microscopy. A quantitative analysis of regenerated nerves showed a significant increase in the number of myelinated fibers in the group that received, within the nerve guide, stem cells. The number of neurons in the DRG was significantly higher in the MSC-treated group, while there was no difference in the number of motor neurons in the spinal cord. We also found higher values of trophic factors expression in MSC-treated groups, especially a nerve growth factor. The SFI revealed a significant improvement in the MSC-treated group. The gastrocnemius muscle showed an increase in weight and in the levels of creatine phosphokinase enzyme, suggesting an improvement of reinnervation and activity in animals that received MSCs. Immunohistochemistry documented that some GFP+ -transplanted cells assumed a Schwann-cell-like phenotype, as evidenced by their expression of the S-100 protein, a Schwann cell

  19. Spider silk constructs enhance axonal regeneration and remyelination in long nerve defects in sheep.

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    Christine Radtke

    Full Text Available BACKGROUND: Surgical reapposition of peripheral nerve results in some axonal regeneration and functional recovery, but the clinical outcome in long distance nerve defects is disappointing and research continues to utilize further interventional approaches to optimize functional recovery. We describe the use of nerve constructs consisting of decellularized vein grafts filled with spider silk fibers as a guiding material to bridge a 6.0 cm tibial nerve defect in adult sheep. METHODOLOGY/PRINCIPAL FINDINGS: The nerve constructs were compared to autologous nerve grafts. Regeneration was evaluated for clinical, electrophysiological and histological outcome. Electrophysiological recordings were obtained at 6 months and 10 months post surgery in each group. Ten months later, the nerves were removed and prepared for immunostaining, electrophysiological and electron microscopy. Immunostaining for sodium channel (NaV 1.6 was used to define nodes of Ranvier on regenerated axons in combination with anti-S100 and neurofilament. Anti-S100 was used to identify Schwann cells. Axons regenerated through the constructs and were myelinated indicating migration of Schwann cells into the constructs. Nodes of Ranvier between myelin segments were observed and identified by intense sodium channel (NaV 1.6 staining on the regenerated axons. There was no significant difference in electrophysiological results between control autologous experimental and construct implantation indicating that our construct are an effective alternative to autologous nerve transplantation. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that spider silk enhances Schwann cell migration, axonal regrowth and remyelination including electrophysiological recovery in a long-distance peripheral nerve gap model resulting in functional recovery. This improvement in nerve regeneration could have significant clinical implications for reconstructive nerve surgery.

  20. Spider Silk Constructs Enhance Axonal Regeneration and Remyelination in Long Nerve Defects in Sheep

    Science.gov (United States)

    Radtke, Christine; Allmeling, Christina; Waldmann, Karl-Heinz; Reimers, Kerstin; Thies, Kerstin; Schenk, Henning C.; Hillmer, Anja; Guggenheim, Merlin; Brandes, Gudrun; Vogt, Peter M.

    2011-01-01

    Background Surgical reapposition of peripheral nerve results in some axonal regeneration and functional recovery, but the clinical outcome in long distance nerve defects is disappointing and research continues to utilize further interventional approaches to optimize functional recovery. We describe the use of nerve constructs consisting of decellularized vein grafts filled with spider silk fibers as a guiding material to bridge a 6.0 cm tibial nerve defect in adult sheep. Methodology/Principal Findings The nerve constructs were compared to autologous nerve grafts. Regeneration was evaluated for clinical, electrophysiological and histological outcome. Electrophysiological recordings were obtained at 6 months and 10 months post surgery in each group. Ten months later, the nerves were removed and prepared for immunostaining, electrophysiological and electron microscopy. Immunostaining for sodium channel (NaV 1.6) was used to define nodes of Ranvier on regenerated axons in combination with anti-S100 and neurofilament. Anti-S100 was used to identify Schwann cells. Axons regenerated through the constructs and were myelinated indicating migration of Schwann cells into the constructs. Nodes of Ranvier between myelin segments were observed and identified by intense sodium channel (NaV 1.6) staining on the regenerated axons. There was no significant difference in electrophysiological results between control autologous experimental and construct implantation indicating that our construct are an effective alternative to autologous nerve transplantation. Conclusions/Significance This study demonstrates that spider silk enhances Schwann cell migration, axonal regrowth and remyelination including electrophysiological recovery in a long-distance peripheral nerve gap model resulting in functional recovery. This improvement in nerve regeneration could have significant clinical implications for reconstructive nerve surgery. PMID:21364921

  1. Agarose and methylcellulose hydrogel blends for nerve regeneration applications

    Science.gov (United States)

    Martin, Benton C.; Minner, Eric J.; Wiseman, Sherri L.; Klank, Rebecca L.; Gilbert, Ryan J.

    2008-06-01

    Trauma sustained to the central nervous system is a debilitating problem for thousands of people worldwide. Neuronal regeneration within the central nervous system is hindered by several factors, making a multi-faceted approach necessary. Two factors contributing to injury are the irregular geometry of injured sites and the absence of tissue to hold potential nerve guides and drug therapies. Biocompatible hydrogels, injectable at room temperature, that rapidly solidify at physiological temperatures (37 °C) are beneficial materials that could hold nerve guidance channels in place and be loaded with therapeutic agents to aid wound healing. Our studies have shown that thermoreversible methylcellulose can be combined with agarose to create hydrogel blends that accommodate these properties. Three separate novel hydrogel blends were created by mixing methylcellulose with one of the three different agaroses. Gelation time tests show that the blends solidify at a faster rate than base methylcellulose at 37 °C. Rheological data showed that the elastic modulus of the hydrogel blends rapidly increases at 37 °C. Culturing experiments reveal that the morphology of dissociated dorsal root ganglion neurons was not altered when the hydrogels were placed onto the cells. The different blends were further assessed using dissolution tests, pore size evaluations using scanning electron microscopy and measuring the force required for injection. This research demonstrates that blends of agarose and methylcellulose solidify much more quickly than plain methylcellulose, while solidifying at physiological temperatures where agarose cannot. These hydrogel blends, which solidify at physiological temperatures naturally, do not require ultraviolet light or synthetic chemical cross linkers to facilitate solidification. Thus, these hydrogel blends have potential use in delivering therapeutics and holding scaffolding in place within the nervous system.

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

    Directory of Open Access Journals (Sweden)

    Carlos Rodrigo Camara-Lemarroy

    2012-01-01

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

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

    Science.gov (United States)

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

    2012-01-01

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

  4. Dark rearing maintains tyrosine hydroxylase expression in retinal amacrine cells following optic nerve transection

    Institute of Scientific and Technical Information of China (English)

    Wei Wan; Zhenghai Liu; Xiaosheng Wang; Xuegang Luo

    2012-01-01

    The present study examined changes in retinal tyrosine hydroxylase (TH) expression in rats having undergone optic nerve transection and housed under a normal day/night cycle or in the dark. The aim was to investigate the effects of amacrine cells on axonal regeneration in retinal ganglion cells and on the synapses that transmit visual signals. The results revealed that retinal TH expression gradually decreased following optic nerve transection in rats housed under a normal day/night cycle, reaching a minimum at 5 days. In contrast, retinal TH expression decreased to a minimum at 1 day following optic nerve transection in dark reared rats, gradually increasing afterward and reaching a normal level at 5-7 days. The number of TH-positive synaptic particles correlated with the TH levels, indicating that dark rearing can help maintain TH expression during the synaptic degeneration stage (5-7 days after optic nerve injury) in retinal amacrine cells.

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

    Science.gov (United States)

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

    1998-01-01

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

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

    Science.gov (United States)

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

    1998-01-01

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

  7. Low-Level Laser Irradiation Improves Functional Recovery and Nerve Regeneration in Sciatic Nerve Crush Rat Injury Model

    Science.gov (United States)

    Wang, Chau-Zen; Chen, Yi-Jen; Wang, Yan-Hsiung; Yeh, Ming-Long; Huang, Mao-Hsiung; Ho, Mei-Ling; Liang, Jen-I; Chen, Chia-Hsin

    2014-01-01

    The development of noninvasive approaches to facilitate the regeneration of post-traumatic nerve injury is important for clinical rehabilitation. In this study, we investigated the effective dose of noninvasive 808-nm low-level laser therapy (LLLT) on sciatic nerve crush rat injury model. Thirty-six male Sprague Dawley rats were divided into 6 experimental groups: a normal group with or without 808-nm LLLT at 8 J/cm2 and a sciatic nerve crush injury group with or without 808-nm LLLT at 3, 8 or 15 J/cm2. Rats were given consecutive transcutaneous LLLT at the crush site and sacrificed 20 days after the crush injury. Functional assessments of nerve regeneration were analyzed using the sciatic functional index (SFI) and hindlimb range of motion (ROM). Nerve regeneration was investigated by measuring the myelin sheath thickness of the sciatic nerve using transmission electron microscopy (TEM) and by analyzing the expression of growth-associated protein 43 (GAP43) in sciatic nerve using western blot and immunofluorescence staining. We found that sciatic-injured rats that were irradiated with LLLT at both 3 and 8 J/cm2 had significantly improved SFI but that a significant improvement of ROM was only found in rats with LLLT at 8 J/cm2. Furthermore, the myelin sheath thickness and GAP43 expression levels were significantly enhanced in sciatic nerve-crushed rats receiving 808-nm LLLT at 3 and 8 J/cm2. Taken together, these results suggest that 808-nm LLLT at a low energy density (3 J/cm2 and 8 J/cm2) is capable of enhancing sciatic nerve regeneration following a crush injury. PMID:25119457

  8. Regeneration of the radial nerve cord in the sea cucumber Holothuria glaberrima

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    García-Arrarás José E

    2009-01-01

    Full Text Available Abstract Background Regeneration of neurons and fibers in the mammalian spinal cord has not been plausible, even though extensive studies have been made to understand the restrictive factors involved. New experimental models and strategies are necessary to determine how new nerve cells are generated and how fibers regrow and connect with their targets in adult animals. Non-vertebrate deuterostomes might provide some answers to these questions. Echinoderms, with their amazing regenerative capacities could serve as model systems; however, very few studies have been done to study the regeneration of their nervous system. Results We have studied nerve cord regeneration in the echinoderm Holothuria glaberrima. These are sea cucumbers or holothurians members of the class Holothuroidea. One radial nerve cord, part of the echinoderm CNS, was completely transected using a scalpel blade. Animals were allowed to heal for up to four weeks (2, 6, 12, 20, and 28 days post-injury before sacrificed. Tissues were sectioned in a cryostat and changes in the radial nerve cord were analyzed using classical dyes and immmuohistochemistry. In addition, the temporal and spatial distribution of cell proliferation and apoptosis was assayed using BrdU incorporation and the TUNEL assay, respectively. We found that H. glaberrima can regenerate its radial nerve cord within a month following transection. The regenerated cord looks amazingly similar in overall morphology and cellular composition to the uninjured cord. The cellular events associated to radial cord regeneration include: (1 outgrowth of nerve fibers from the injured radial cord stumps, (2 intense cellular division in the cord stumps and in the regenerating radial nerve cords, (3 high levels of apoptosis in the RNC adjacent to the injury and within the regenerating cord and (4 an increase in the number of spherule-containing cells. These events are similar to those that occur in other body wall tissues during wound

  9. Ischemic injury leads to extracellular matrix alterations in retina and optic nerve

    Science.gov (United States)

    Reinhard, Jacqueline; Renner, Marina; Wiemann, Susanne; Shakoor, Daniel A.; Stute, Gesa; Dick, H. Burkhard; Faissner, Andreas; Joachim, Stephanie C.

    2017-01-01

    Retinal ischemia occurs in a variety of eye diseases. Restrained blood flow induces retinal damage, which leads to progressive optic nerve degeneration and vision loss. Previous studies indicate that extracellular matrix (ECM) constituents play an important role in complex tissues, such as retina and optic nerve. They have great impact on de- and regeneration processes and represent major candidates of central nervous system glial scar formation. Nevertheless, the importance of the ECM during ischemic retina and optic nerve neurodegeneration is not fully understood yet. In this study, we analyzed remodeling of the extracellular glycoproteins fibronectin, laminin, tenascin-C and tenascin-R and the chondroitin sulfate proteoglycans (CSPGs) aggrecan, brevican and phosphacan/RPTPβ/ζ in retinae and optic nerves of an ischemia/reperfusion rat model via quantitative real-time PCR, immunohistochemistry and Western blot. A variety of ECM constituents were dysregulated in the retina and optic nerve after ischemia. Regarding fibronectin, significantly elevated mRNA and protein levels were observed in the retina following ischemia, while laminin and tenascin-C showed enhanced immunoreactivity in the optic nerve after ischemia. Interestingly, CSPGs displayed significantly increased expression levels in the optic nerve. Our study demonstrates a dynamic expression of ECM molecules following retinal ischemia, which strengthens their regulatory role during neurodegeneration. PMID:28262779

  10. Optic Nerve Sheath Mechanics in VIIP Syndrome

    Science.gov (United States)

    Raykin, Julia; Forte, Taylor E.; Wang, Roy; Feola, Andrew; Samuels, Brian; Myers, Jerry; Nelson, Emily; Gleason, Rudy; Ethier, C. Ross

    2016-01-01

    Visual Impairment Intracranial Pressure (VIIP) syndrome is a major concern in current space medicine research. While the exact pathology of VIIP is not yet known, it is hypothesized that the microgravity-induced cephalad fluid shift increases intracranial pressure (ICP) and drives remodeling of the optic nerve sheath. To investigate this possibility, we are culturing optic nerve sheath dura mater samples under different pressures and investigating changes in tissue composition. To interpret results from this work, it is essential to first understand the biomechanical response of the optic nerve sheath dura mater to loading. Here, we investigated the effects of mechanical loading on the porcine optic nerve sheath.Porcine optic nerves (number: 6) were obtained immediately after death from a local abattoir. The optic nerve sheath (dura mater) was isolated from the optic nerve proper, leaving a hollow cylinder of connective tissue that was used for biomechanical characterization. We developed a custom mechanical testing system that allowed for unconfined lengthening, twisting, and circumferential distension of the dura mater during inflation and under fixed axial loading. To determine the effects of variations in ICP, the sample was inflated (0-60 millimeters Hg) and circumferential distension was simultaneously recorded. These tests were performed under variable axial loads (0.6 grams - 5.6 grams at increments of 1 gram) by attaching different weights to one end of the dura mater. Results and Conclusions: The samples demonstrated nonlinear behavior, similar to other soft connective tissue (Figure 1). Large increases in diameter were observed at lower transmural pressures (approximately 0 to 5 millimeters Hg), whereas only small diameter changes were observed at higher pressures. Particularly interesting was the existence of a cross-over point at a pressure of approximately 11 millimeters Hg. At this pressure, the same diameter is obtained for all axial loads applied

  11. Regenerated Sciatic Nerve Axons Stimulated through a Chronically Implanted Macro-Sieve Electrode

    Science.gov (United States)

    MacEwan, Matthew R.; Zellmer, Erik R.; Wheeler, Jesse J.; Burton, Harold; Moran, Daniel W.

    2016-01-01

    Sieve electrodes provide a chronic interface for stimulating peripheral nerve axons. Yet, successful utilization requires robust axonal regeneration through the implanted electrode. The present study determined the effect of large transit zones in enhancing axonal regeneration and revealed an intimate neural interface with an implanted sieve electrode. Fabrication of the polyimide sieve electrodes employed sacrificial photolithography. The manufactured macro-sieve electrode (MSE) contained nine large transit zones with areas of ~0.285 mm2 surrounded by eight Pt-Ir metallized electrode sites. Prior to implantation, saline, or glial derived neurotropic factor (GDNF) was injected into nerve guidance silicone-conduits with or without a MSE. The MSE assembly or a nerve guidance conduit was implanted between transected ends of the sciatic nerve in adult male Lewis rats. At 3 months post-operation, fiber counts were similar through both implant types. Likewise, stimulation of nerves regenerated through a MSE or an open silicone conduit evoked comparable muscle forces. These results showed that nerve regeneration was comparable through MSE transit zones and an open conduit. GDNF had a minimal positive effect on the quality and morphology of fibers regenerating through the MSE; thus, the MSE may reduce reliance on GDNF to augment axonal regeneration. Selective stimulation of several individual muscles was achieved through monopolar stimulation of individual electrodes sites suggesting that the MSE might be an optimal platform for functional neuromuscular stimulation. PMID:28008303

  12. Salicylic acid-based poly(anhydride-ester) nerve guidance conduits: Impact of localized drug release on nerve regeneration.

    Science.gov (United States)

    Lee, Yong S; Griffin, Jeremy; Masand, Shirley N; Shreiber, David I; Uhrich, Kathryn E

    2016-04-01

    Nerve guidance conduits (NGCs) can serve as physical scaffolds aligning and supporting regenerating cells while preventing scar tissue formation that often interferes with the regeneration process. Numerous studies have focused on functionalizing NGCs with neurotrophic factors, for example, to support nerve regeneration over longer gaps, but few directly incorporate therapeutic agents. Herein, we fabricated NGCs from a polyanhydride comprised of salicylic acid (SA), a nonsteroidal anti-inflammatory drug, then performed in vitro and in vivo assays. In vitro studies included cytotoxicity, anti-inflammatory response, and NGC porosity measurements. To prepare for implantation, type I collagen hydrogels were used as NGC luminal fillers to further enhance the axonal regeneration process. For the in vivo studies, SA-NGCs were implanted in femoral nerves of mice for 16 weeks and evaluated for functional recovery. The SA-based NGCs functioned as both a drug delivery vehicle capable of reducing inflammation and scar tissue formation because of SA release as well as a tissue scaffold that promotes peripheral nerve regeneration and functional recovery.

  13. Neuregulin-1 signaling is essential for nerve-dependent axolotl limb regeneration.

    Science.gov (United States)

    Farkas, Johanna E; Freitas, Polina D; Bryant, Donald M; Whited, Jessica L; Monaghan, James R

    2016-08-01

    The Mexican axolotl (Ambystoma mexicanum) is capable of fully regenerating amputated limbs, but denervation of the limb inhibits the formation of the post-injury proliferative mass called the blastema. The molecular basis behind this phenomenon remains poorly understood, but previous studies have suggested that nerves support regeneration via the secretion of essential growth-promoting factors. An essential nerve-derived factor must be found in the blastema, capable of rescuing regeneration in denervated limbs, and its inhibition must prevent regeneration. Here, we show that the neuronally secreted protein Neuregulin-1 (NRG1) fulfills all these criteria in the axolotl. Immunohistochemistry and in situ hybridization of NRG1 and its active receptor ErbB2 revealed that they are expressed in regenerating blastemas but lost upon denervation. NRG1 was localized to the wound epithelium prior to blastema formation and was later strongly expressed in proliferating blastemal cells. Supplementation by implantation of NRG1-soaked beads rescued regeneration to digits in denervated limbs, and pharmacological inhibition of NRG1 signaling reduced cell proliferation, blocked blastema formation and induced aberrant collagen deposition in fully innervated limbs. Taken together, our results show that nerve-dependent NRG1/ErbB2 signaling promotes blastemal proliferation in the regenerating limb and may play an essential role in blastema formation, thus providing insight into the longstanding question of why nerves are required for axolotl limb regeneration.

  14. Acupuncture Treatment for Optic Nerve Contusion

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ Optic nerve contusion is a commonly-seen eye injury, which is mostly caused by traffic accident, collision, and falling. Early diagnosis and timely emergency treatment can make such patients restore vision to a certain extent. Otherwise, there may appear optic atrophy or loss of vision. At present, in the treatment of this disease, cortical hormone, dehydrating agent, vasodilator, vitamin, energy mixture and neurotrophic agent, or surgical operation can all give certain therapeutic effect. In the recent 5 years, the Department of Ophthalmology of the Hospital Affiliated to Hubei College of Traditional Chinese Medicine has adopted acupuncture for treatment of optic nerve contusion, and obtained quite good therapeutic results. Some typical cases are reported in the following.

  15. The Role of Nerve Growth Factor in Ginsenoside Rg1-Induced Regeneration of Injured Rat Sciatic Nerve.

    Science.gov (United States)

    Huo, Dong-Sheng; Zhang, Ming; Cai, Zhi-Ping; Dong, Chao-Xuan; Wang, He; Yang, Zhan-Jun

    2015-01-01

    Sciatic nerve injury is commonly seen in clinical practice predominantly associated with trauma or sports injuries. Recent studies indicated that ginsenoside Rg1 (Gs Rg1), extracted from Chinese herbs, was found to promote regeneration of injured rat sciatic nerve and that nerve growth factor (NGF) may be involved in this process. The aim of this study was to examine the role that NGF may play in ginsenoside Rg1-induced regeneration of rat sciatic nerve following injury. Animals following surgical right sciatic nerve injury were subsequently administered intraperitoneally either saline (sham control) or different doses of 2, 4, 8, or 12 mg/kg daily GsRg1 for 2 to 8 wk. In addition, 100 μg/kg mecobalamin, a drug utilized to treat nerve injuries, was employed as a positive control. After 2, 4, or 8 wk, sciatic functional index (SFI) and mean nerve conduction velocity (MNCV), markers of sciatic nerve function, were assessed to determine whether recovery of injured sciatic nerve occurred. In addition, immunohistochemistry and Western blot methods were used to examine NGF protein expression changes. Results showed that all doses of GsRg1 significantly increased SFI and MNCV in injured sciatic-nerve-damaged rats in a manner similar to that noted with mecobalamin. It is of interest that the intermediate 4- and 8-mg/kg doses were more effective in restoring nerve functions. Immunohistochemistry and Western blot results also demonstrated a similar pattern with enhanced NGF protein expression at all doses, but greater effects were noted at 4 and 8 mg/kg GsRg1. Data suggest that GsRg1 promotes recovery of injured sciatic nerve functions within a specific dose range and that NGF may be involved in this physiological process.

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

    Science.gov (United States)

    2015-12-01

    impaired function . Nerve guidance conduits have been developed for use in surgery to bridge the gap between transected nerve ends and to support nerve...injuries such as traumatic nerve transections. Extremity trauma with nerve injury can be associated with long term functional limitations and impairments...dosing, except for the whole brain, brain stem, cerebellum, cerebrum , medulla oblongata, seminal vesicle, whole spinal cord, testes, urinary bladder

  17. IL-17 and VEGF are necessary for efficient corneal nerve regeneration

    Science.gov (United States)

    The contribution of acute inflammation to sensory nerve regeneration was investigated in the murine cornea using a model of corneal abrasion that removes the stratified epithelium and subbasal nerve plexus. Abrasion induced accumulation of IL-17(+) CCR6(+) yo T cells, neutrophils, and platelets in t...

  18. Growth-promoting activity of Hominis Placenta extract on regenerating sciatic nerve

    Institute of Scientific and Technical Information of China (English)

    Tae-beom SEO; Dong-hee KIM; Seung-kiel PARK; Deok-chun YANG; Uk NAMGUNG; In-sun HAN; Jin-hwan YOON; In-chan SEOL; Yun-sik KIM; Hyun-kyung JO; Joung-jo AN; Kwon-eui HONG; Young-bae SEO

    2006-01-01

    Aim: Extract of Hominis Placenta (HP) has been used in oriental medicine as an agent for improving physiological function. The present study was conducted to investigate whether HP treatment in an experimental sciatic nerve injury animal model produces growth-promoting effects on regenerating peripheral nerve fibers after injury. Methods: After HP was injected into a sciatic nerve injury site, changes in protein levels were analyzed in the regenerating nerve area by Western blotting and immunofluorescence staining analyses. For quantitative assessment of axonal regeneration, a retrograde tracing technique was used to identify the neuronal cell bodies corresponding to regenerating axons, and the extent of neurite outgrowth in cultured dorsal root ganglia (DRG) sensory neurons prepared from animals that had experienced a sciatic nerve crush injury 7 d before neuron collection was analyzed. Results: Induction levels of axonal growth-associated protein (GAP-43) in the injured sciatic nerves were elevated by HP treatment. HP treatment also upregulated cell division cycle 2 (Cdc2) protein levels in the distal stump of the injured sciatic nerve. Induced Cdc2 protein was detected in Schwann cells, suggesting that Cdc2 kinase activity may be involved in the growth-promoting activity of regenerating axons via Schwann cell proliferation. Cell body measurement by retrograde tracing indicated that HP treatment produced significant increases in regenerating motor axons. Finally, HP treatment of cultured DRG sensory neurons significantly increased neurite arborization and elongation.Conclusion: HP promotes the regeneration of injured sciatic axons by upregulating the synthesis of regeneration-related protein factors such as GAP-43 and Cdc2.

  19. Evaluation of the chitosan/glycerol-{beta}-phosphate disodium salt hydrogel application in peripheral nerve regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Zheng Lu; Zhang Xiufang; Gong Yandao [State Key Lab Biomembrane and Membrane Biotechnology, School of Life Sciences, Tsinghua University, Beijing 100084 (China); Ao Qiang; Han Hongyan, E-mail: gongyd@tsinghua.edu.c, E-mail: aoqiang@tsinghua.edu.c [Institute of Neurological Disorders, Yuquan Hospital, Tsinghua University, Beijing 100049 (China)

    2010-06-01

    Research efforts have been devoted to evaluating the application of the chitosan (CS)/glycerol-{beta}-phosphate (GP) disodium salt hydrogel in peripheral nerve regeneration. The gelation time was determined to be 770 s using ultraviolet spectrophotometry. A standard 10 mm long rat sciatic nerve defect model was employed, followed by bridging the proximal and distal stumps with chitosan conduits injected with the Schwann cell-containing hydrogel. Injections of the blank hydrogel, Schwann cell suspension and culture medium were used as controls. Two months later, electrophysiological assessment and fluorogold retrograde tracing showed that compound muscle action potentials (CMAPs) and fluorogold-labeled neurons were only detected in the Schwann cell suspension group and culture medium group. The rats were then killed, and implanted conduits were removed for examination. There were no regenerated nerves found in groups injected with the blank hydrogel or Schwann cell-containing hydrogel, while the other two groups clearly displayed regenerated nerves across the gaps. In the subsequent histological assessment, immunohistochemistry, toluidine blue staining and transmission electron microscopy were performed to evaluate the regenerated nerves. The relative wet weight ratio, Masson trichrome staining and acetylcholinesterase staining were employed for the examination of gastrocnemius muscles in all four groups. The Schwann cell suspension group showed the best results for all these indexes; the culture medium group ranked second and the two hydrogel-injected groups showed the least optimal results. In conclusion, our data revealed that the implanted CS/GP hydrogel actually impeded nerve regeneration, which is inconsistent with former in vitro reports and general supposition. We believe that the application of the CS/GP hydrogel in nerve regeneration requires a further study before a satisfactory result is obtained. In addition, the present study also confirmed that

  20. Xenotransplantation of human adipose-derived stem cells in the regeneration of a rabbit peripheral nerve.

    Science.gov (United States)

    Lasso, J M; Pérez Cano, R; Castro, Y; Arenas, L; García, J; Fernández-Santos, M E

    2015-12-01

    Adipose tissue-derived mesenchymal stem cells (AdMSCs) are useful in the regeneration of neural tissues. Furthermore, xenotransplantation of human adipose tissue-derived mesenchymal stem cells (hAdMSCs) into animal models has already been tested and the results encouraged us to study peripheral nerve regeneration in rabbits, in order to test the feasibility of a xenotransplantation of hAdMSCs. To promote end-to-end nerve fiber contacts of a 4-cm gap in the peroneal nerve of white New Zealand rabbits, an autologous vein conduit was used and three groups of animals were evaluated. In Group I, the gap was repaired with a vein conduit refilled with fibrin. Group II was similar, but the animals were treated with cyclosporine A. In Group III, a fibrin scaffold with hAdMSCs was placed inside the autologous vein conduit, and animals were treated with cyclosporine A. Neurofilament immunohistochemistry results showed 100% nerve regeneration at the vein guidance channel 90 days after the surgery in the hAdMSC-transplanted group but lesser neural regeneration in the neurofilaments of groups I and II. The analysis of variance (ANOVA) test showed statistically significant differences among all groups (p nerve regeneration through a vein conduit that connected a 4-cm gap created at the peroneal nerve of rabbits. Animals treated with hAdMSCs presented negative inflammatory response at the regenerated nerve gaps, but it was demonstrated that hAdMSCs were incorporated to the new nerve creating neural tissue and endothelial cells. However, hAdMSCs required immunosuppression with cyclosporine A to achieve axonal regeneration. Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  1. Study on Braiding Parameters of a Biodegradable Nerve Regeneration Conduit with Regular Braided Structure

    Institute of Scientific and Technical Information of China (English)

    LIU Guo-hua; ZHANG Pei-hua; WANG Wen-zu; FENG Xun-wei; LIU Hong-feng

    2004-01-01

    A biodegradable nerve regeneration conduit has been developed by the regular braided technique on a spindle-braiding machine. The geometry property indexes of braided nerve conduit consist of pitch, density, wall thickness and porosity etc. In this article, the influences of the braiding parameters i.e. the linear density of yarn, gear ratio and spindle number of the braiding machine on these geometry property indexes of nerve conduit were discussed from which the optimal braiding parameters were obtained.

  2. Regeneration of the vagus nerve after highly selective vagotomy, an autoradiographic study in the ferret stomach .

    OpenAIRE

    Al Muhtaseb, M. H. [محمد هاشم المحتسب; Abu-Khalaf, M.

    1995-01-01

    This study investigates the regeneration of the vagal nerve fibres after highly selective vagotomy in the ferret stomach by using the autoradiographic technique. Autoradiographic examination of the body of the stomach in the acute experimental animals has failed to show any labelled nerve fibres after highly selective vagotomy while the pylorus has shown many labelled nerve fibres . These observations indicate that the highly selective vagotomy has been performed properly and adequately. ...

  3. Histopathological Analysis Of Gangliosides Use In Peripheral Nerve Regeneration After Axonotmesis In Rats

    OpenAIRE

    Camila Maria Beder Ribeiro; Belmiro Cavalcanti do Egito Vasconcelos; Joaquim Celestino da Silva Neto; Valdemiro Amaro da Silva Júnior; Nancy Gurgel Figueiredo

    2008-01-01

    PURPOSE: To analyze the action of gangliosides in peripheral nerve regeneration in the sciatic nerve of the rat. METHODS: The sample was composed of 96 male Wistar rats. The animals were anaesthetized and, after identification of the anaesthesic plane, an incision was made in the posterior region of the thigh, followed by skin and muscle divulsion. The right sciatic nerve was isolated and compressed for 2 minutes. Continuous suture of the skin was performed. The animals were randomly divided ...

  4. Can preoperative MR imaging predict optic nerve invasion of retinoblastoma?

    Energy Technology Data Exchange (ETDEWEB)

    Song, Kyoung Doo, E-mail: kdsong0308@gmail.com [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50, Ilwon-Dong, Kangnam-Ku, Seoul 135-710 (Korea, Republic of); Eo, Hong, E-mail: rtombow@gmail.com [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50, Ilwon-Dong, Kangnam-Ku, Seoul 135-710 (Korea, Republic of); Kim, Ji Hye, E-mail: jhkate.kim@samsung.com [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50, Ilwon-Dong, Kangnam-Ku, Seoul 135-710 (Korea, Republic of); Yoo, So-Young, E-mail: sy1131.yoo@samsung.com [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50, Ilwon-Dong, Kangnam-Ku, Seoul 135-710 (Korea, Republic of); Jeon, Tae Yeon, E-mail: hathor97.jeon@samsung.com [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50, Ilwon-Dong, Kangnam-Ku, Seoul 135-710 (Korea, Republic of)

    2012-12-15

    Purpose: To evaluate the accuracy of pre-operative MRI for the detection of optic nerve invasion in retinoblastoma. Materials and methods: Institutional review board approval and informed consent were waived for this retrospective study. A total of 41 patients were included. Inclusion criteria were histologically proven retinoblastoma, availability of diagnostic-quality preoperative MR images acquired during the 4 weeks before surgery, unilateral retinoblastoma, and normal-sized optic nerve. Two radiologists retrospectively reviewed the MR images independently. Five imaging findings (diffuse mild optic nerve enhancement, focal strong optic nerve enhancement, optic sheath enhancement, tumor location, and tumor size) were evaluated against optic nerve invasion of retinoblastoma. The predictive performance of all MR imaging findings for optic nerve invasion was also evaluated by the receiver operating characteristic curve analysis. Results: Optic nerve invasion was histopathologically confirmed in 24% of study population (10/41). The differences in diffuse mild enhancement, focal strong enhancement, optic sheath enhancement, and tumor location between patients with optic nerve invasion and patients without optic nerve invasion were not significant. Tumor sizes were 16.1 mm (SD: 2.2 mm) and 14.9 mm (SD: 3.6 mm) in patients with and without optic nerve involvement, respectively (P = 0.444). P-Values from binary logistic regression indicated that all five imaging findings were not significant predictors of tumor invasion of optic nerve. The AUC values of all MR imaging findings for the prediction of optic nerve invasion were 0.689 (95% confidence interval: 0.499–0.879) and 0.653 (95% confidence interval: 0.445–0.861) for observer 1 and observer 2, respectively. Conclusion: Findings of MRI in patients with normal-sized optic nerves have limited usefulness in preoperatively predicting the presence of optic nerve invasion in retinoblastoma.

  5. Electrical stimulation promotes regeneration of defective peripheral nerves after delayed repair intervals lasting under one month.

    Science.gov (United States)

    Xu, Chungui; Kou, Yuhui; Zhang, Peixun; Han, Na; Yin, Xiaofeng; Deng, Jiuxu; Chen, Bo; Jiang, Baoguo

    2014-01-01

    Electrical stimulation (ES) has been proven to be an effective means of enhancing the speed and accuracy of nerve regeneration. However, these results were recorded when the procedure was performed almost immediately after nerve injury. In clinical settings, most patients cannot be treated immediately. Some patients with serious trauma or contaminated wounds need to wait for nerve repair surgery. Delays in nerve repair have been shown to be associated with poorer results than immediate surgery. It is not clear whether electrical stimulation still has any effect on nerve regeneration after enough time has elapsed. A delayed nerve repair model in which the rats received delayed nerve repair after 1 day, 1 week, 1 month, and 2 months was designed. At each point in time, the nerve stumps of half the rats were bridged with an absorbable conduit and the rats were given 1 h of weak electrical stimulation. The other half was not treated. In order to analyze the morphological and molecular differences among these groups, 6 ES rats and 6 sham ES rats per point in time were killed 5 days after surgery. The other rats in each group were allowed to recover for 6 weeks before the final functional test and tissue observation. The amounts of myelinated fibers in the distal nerve stumps decreased as the delay in repair increased for both ES rats and sham ES rats. In the 1-day-delay and 1-week-delay groups, there were more fibers in ES rats than in sham ES rats. And the compound muscle action potential (CMAP) and motor nerve conduction velocity (MNCV) results were better for ES rats in these two groups. In order to analyze the mechanisms underlying these differences, Masson staining was performed on the distal nerves and quantitative PCR on the spinal cords. Results showed that, after delays in repair of 1 month and 2 months, there was more collagen tissue hyperplasia in the distal nerve in all rats. The brain-derived neurotrophic factor (BDNF) and trkB expression levels in the

  6. Electrical stimulation promotes regeneration of defective peripheral nerves after delayed repair intervals lasting under one month.

    Directory of Open Access Journals (Sweden)

    Chungui Xu

    Full Text Available BACKGROUND: Electrical stimulation (ES has been proven to be an effective means of enhancing the speed and accuracy of nerve regeneration. However, these results were recorded when the procedure was performed almost immediately after nerve injury. In clinical settings, most patients cannot be treated immediately. Some patients with serious trauma or contaminated wounds need to wait for nerve repair surgery. Delays in nerve repair have been shown to be associated with poorer results than immediate surgery. It is not clear whether electrical stimulation still has any effect on nerve regeneration after enough time has elapsed. METHODS: A delayed nerve repair model in which the rats received delayed nerve repair after 1 day, 1 week, 1 month, and 2 months was designed. At each point in time, the nerve stumps of half the rats were bridged with an absorbable conduit and the rats were given 1 h of weak electrical stimulation. The other half was not treated. In order to analyze the morphological and molecular differences among these groups, 6 ES rats and 6 sham ES rats per point in time were killed 5 days after surgery. The other rats in each group were allowed to recover for 6 weeks before the final functional test and tissue observation. RESULTS: The amounts of myelinated fibers in the distal nerve stumps decreased as the delay in repair increased for both ES rats and sham ES rats. In the 1-day-delay and 1-week-delay groups, there were more fibers in ES rats than in sham ES rats. And the compound muscle action potential (CMAP and motor nerve conduction velocity (MNCV results were better for ES rats in these two groups. In order to analyze the mechanisms underlying these differences, Masson staining was performed on the distal nerves and quantitative PCR on the spinal cords. Results showed that, after delays in repair of 1 month and 2 months, there was more collagen tissue hyperplasia in the distal nerve in all rats. The brain-derived neurotrophic

  7. Functional evaluation of peripheral nerve regeneration and target reinnervation in animal models: a critical overview.

    Science.gov (United States)

    Navarro, Xavier

    2016-02-01

    Peripheral nerve injuries usually lead to severe loss of motor, sensory and autonomic functions in the patients. Due to the complex requirements for adequate axonal regeneration, functional recovery is often poorly achieved. Experimental models are useful to investigate the mechanisms related to axonal regeneration and tissue reinnervation, and to test new therapeutic strategies to improve functional recovery. Therefore, objective and reliable evaluation methods should be applied for the assessment of regeneration and function restitution after nerve injury in animal models. This review gives an overview of the most useful methods to assess nerve regeneration, target reinnervation and recovery of complex sensory and motor functions, their values and limitations. The selection of methods has to be adequate to the main objective of the research study, either enhancement of axonal regeneration, improving regeneration and reinnervation of target organs by different types of nerve fibres, or increasing recovery of complex sensory and motor functions. It is generally recommended to use more than one functional method for each purpose, and also to perform morphological studies of the injured nerve and the reinnervated targets. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  8. Optically-Induced Neuronal Activity Is Sufficient to Promote Functional Motor Axon Regeneration In Vivo.

    Directory of Open Access Journals (Sweden)

    Patricia J Ward

    Full Text Available Peripheral nerve injuries are common, and functional recovery is very poor. Beyond surgical repair of the nerve, there are currently no treatment options for these patients. In experimental models of nerve injury, interventions (such as exercise and electrical stimulation that increase neuronal activity of the injured neurons effectively enhance axon regeneration. Here, we utilized optogenetics to determine whether increased activity alone is sufficient to promote motor axon regeneration. In thy-1-ChR2/YFP transgenic mice in which a subset of motoneurons express the light-sensitive cation channel, channelrhodopsin (ChR2, we activated axons in the sciatic nerve using blue light immediately prior to transection and surgical repair of the sciatic nerve. At four weeks post-injury, direct muscle EMG responses evoked with both optical and electrical stimuli as well as the ratio of these optical/electrical evoked EMG responses were significantly greater in mice that received optical treatment. Thus, significantly more ChR2+ axons successfully re-innervated the gastrocnemius muscle in mice that received optical treatment. Sections of the gastrocnemius muscles were reacted with antibodies to Synaptic Vesicle Protein 2 (SV2 to quantify the number of re-occupied motor endplates. The number of SV2+ endplates was greater in mice that received optical treatment. The number of retrogradely-labeled motoneurons following intramuscular injection of cholera toxin subunit B (conjugated to Alexa Fluor 555 was greater in mice that received optical treatment. Thus, the acute (1 hour, one-time optical treatment resulted in robust, long-lasting effects compared to untreated animals as well as untreated axons (ChR2-. We conclude that neuronal activation is sufficient to promote motor axon regeneration, and this regenerative effect is specific to the activated neurons.

  9. Changes in microtubule-associated protein tau during peripheral nerve injury and regeneration.

    Science.gov (United States)

    Zha, Guang-Bin; Shen, Mi; Gu, Xiao-Song; Yi, Sheng

    2016-09-01

    Tau, a primary component of microtubule-associated protein, promotes microtubule assembly and/or disassembly and maintains the stability of the microtubule structure. Although the importance of tau in neurodegenerative diseases has been well demonstrated, whether tau is involved in peripheral nerve regeneration remains unknown. In the current study, we obtained sciatic nerve tissue from adult rats 0, 1, 4, 7, and 14 days after sciatic nerve crush and examined tau mRNA and protein expression levels and the location of tau in the sciatic nerve following peripheral nerve injury. The results from our quantitative reverse transcription polymerase chain reaction analysis showed that compared with the uninjured control sciatic nerve, mRNA expression levels for both tau and tau tubulin kinase 1, a serine/threonine kinase that regulates tau phosphorylation, were decreased following peripheral nerve injury. Our western blot assay results suggested that the protein expression levels of tau and phosphorylated tau initially decreased 1 day post nerve injury but then gradually increased. The results of our immunohistochemical labeling showed that the location of tau protein was not altered by nerve injury. Thus, these results showed that the expression of tau was changed following sciatic nerve crush, suggesting that tau may be involved in peripheral nerve repair and regeneration.

  10. Improvement of polydimethylsiloxane guide tube for nerve regeneration treatment by carbon negative-ion implantation

    Energy Technology Data Exchange (ETDEWEB)

    Tsuji, H. E-mail: tsuji@kuee.kyoto-u.ac.jp; Izukawa, M.; Ikeguchi, R.; Kakinoki, R.; Sato, H.; Gotoh, Y.; Ishikawa, J

    2003-05-01

    Modification of polydimethylsiloxane (PDMS) rubber by negative ion-implantation was investigated for improvement of nerve regeneration property. The PDMS rubber surface was found to have more hydrophilic property after carbon negative-ion implantation than before. At the conditions of 10 keV and 3.0 x 10{sup 15} ions/cm{sup 2}, the contact angle decreased to 83 deg. from 100 deg. . The reason of the hydrophilic modification is due to hydrophilic functional groups such as hydroxyl formed at the surface by radiation effect of ion implantation. The in vivo regeneration test of rat sciatic nerve was performed by using 18-mm-long PDMS rubber tubes with inner diameter of 2 mm, the inner surface of which was implanted with carbon negative ions at the above conditions. At 24 weeks after the clinical surgery, the sciatic nerve was regenerated through the tube between the proximal and distal nerve stumps.

  11. Regenerating nerve fiber innervation of extraocular muscles and motor functional changes following oculomotor nerve injuries at different sites

    Institute of Scientific and Technical Information of China (English)

    Wenchuan Zhang; Massimiliano Visocchi; Eduardo Fernandez; Xuhui Wang; Xinyuan Li; Shiting Li

    2011-01-01

    In the present study, the oculomotor nerves were sectioned at the proximal (subtentorial) and distal (superior orbital fissure) ends and repaired. After 24 weeks, vestibulo-ocular reflex evaluation confirmed that the regenerating nerve fibers following oculomotor nerve injury in the superior orbital fissure had a high level of specificity for innervating extraocular muscles. The level of functional recovery of extraocular muscles in rats in the superior orbital fissure injury group was remarkably superior over that in rats undergoing oculomotor nerve injuries at the proximal end (subtentorium). Horseradish peroxidase retrograde tracing through the right superior rectus muscle showed that the distribution of neurons in the nucleus of the oculomotor nerve was directly associated with the injury site, and that crude fibers were badly damaged. The closer the site of injury of the oculomotor nerve was to the extraocular muscle, the better the recovery of neurological function was. The mechanism may be associated with the aberrant number of regenerated nerve fibers passing through the injury site.

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

    Science.gov (United States)

    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

  13. Functional self-assembling peptide nanofiber hydrogel for peripheral nerve regeneration.

    Science.gov (United States)

    Wu, Xiaoli; He, Liumin; Li, Wen; Li, Heng; Wong, Wai-Man; Ramakrishna, Seeram; Wu, Wutian

    2017-02-01

    Peripheral nerves are fragile and easily damaged, usually resulting in nervous tissue loss, motor and sensory function loss. Advances in neuroscience and engineering have been significantly contributing to bridge the damage nerve and create permissive environment for axonal regrowth across lesions. We have successfully designed two self-assembling peptides by modifying RADA 16-I with two functional motifs IKVAV and RGD. Nanofiber hydrogel formed when combing the two neutral solutions together, defined as RADA 16-Mix that overcomes the main drawback of RADA16-I associated with low pH. In the present study, we transplanted the RADA 16-Mix hydrogel into the transected rat sciatic nerve gap and effect on axonal regeneration was examined and compared with the traditional RADA16-I hydrogel. The regenerated nerves were found to grow along the walls of the large cavities formed in the graft of RADA16-I hydrogel, while the nerves grew into the RADA 16-Mix hydrogel toward distal position. RADA 16-Mix hydrogel induced more axons regeneration and Schwann cells immigration than RADA16-I hydrogel, resulting in better functional recovery as determined by the gait-stance duration percentage and the formation of new neuromuscular junction structures. Therefore, our results indicated that the functional SAP RADA16-Mix nanofibrous hydrogel provided a better environment for peripheral nerve regeneration than RADA16-I hydrogel and could be potentially used in peripheral nerve injury repair.

  14. Optic Nerve Hemangioblastoma: A Case Report

    Directory of Open Access Journals (Sweden)

    Holly Zywicke

    2012-01-01

    Full Text Available Hemangioblastomas are World Health Organization (WHO grade I tumors of uncertain histologic origin. These central nervous system tumors are most often found in the posterior fossa, brainstem, and spinal cord. There are fewer than 20 reported cases of optic nerve hemangioblastomas in the literature. We present a patient with visual decline found to have a mass arising from within the posterior orbital canal that grossly involved the optic nerve sheath. Neuropathologic evaluation showed hemangioblastoma. Although not a common tumor in this location, consideration of hemangioblastoma in the differential diagnosis is important as they can have a more aggressive course than other tumors of this region and have a detrimental effect on visual prognosis.

  15. Increased axonal regeneration through a biodegradable amnionic tube nerve conduit: effect of local delivery and incorporation of nerve growth factor/hyaluronic acid media.

    Science.gov (United States)

    Mohammad, J A; Warnke, P H; Pan, Y C; Shenaq, S

    2000-01-01

    The authors emphasize the possible pharmacological enhancement of axonal regeneration using a specific growth factor/ extracellular media incorporated in a biodegradable nonneural nerve conduit material. They investigated the early effects on nerve regeneration of continuous local delivery of nerve growth factor (NGF) and the local incorporation of hyaluronic acid (HA) inside a newly manufactured nerve conduit material from fresh human amnionic membrane. Human amnionic membrane contains important biochemical factors that play a major neurotrophic role in the nerve regeneration process. The process of manufacturing a nerve conduit from fresh human amnionic membrane is described. This nerve conduit system was used in rabbits to bridge a 25-mm nerve gap over 3 months. NGF was released locally, over 28 days, at the distal end of the tube via a system of slow release, and HA was incorporated inside the lumen of the tube at the time of surgery. NGF/HA treatment promoted axonal regeneration across the amnionic tube nerve conduit (8,962 +/- 383 myelinated axons) 45% better than the nontreated amnionic tube group (6,180 +/- 353 myelinated axons). The authors demonstrate that NGF/HA media enhances additional axonal regeneration in the amnionic tube nerve conduit. This result is secondary to the effect of the amnion promoting biochemical factors, in combination with the NGF/HA effect on facilitating early events in the nerve regeneration process.

  16. Regeneration of unmyelinated and myelinated sensory nerve fibres studied by a retrograde tracer method

    DEFF Research Database (Denmark)

    Lozeron, Pierre; Krarup, Christian; Schmalbruch, Henning

    2004-01-01

    to large neurons after crush and regeneration than in controls, indicating that regeneration of small neurons was less complete than that of large ones. This contrasted with the fact that unmyelinated axons in the regenerated sural nerve after 74 days were only slightly reduced....... of axons. Axonal counts do not reflect the number of regenerated neurons because of axonal branching and because myelinated axons form unmyelinated sprouts. Two days to 10 weeks after crushing, the distal sural or peroneal nerves were cut and exposed to fluoro-dextran. Large and small dorsal root ganglion...... cells that had been labelled, i.e., that had regenerated axons towards or beyond the injection site, were counted in serial sections. Large and small neurons with presumably myelinated and unmyelinated axons, respectively, were classified by immunostaining for neurofilaments. The axonal growth rate...

  17. Network-Based Method for Identifying Co- Regeneration Genes in Bone, Dentin, Nerve and Vessel Tissues.

    Science.gov (United States)

    Chen, Lei; Pan, Hongying; Zhang, Yu-Hang; Feng, Kaiyan; Kong, XiangYin; Huang, Tao; Cai, Yu-Dong

    2017-10-02

    Bone and dental diseases are serious public health problems. Most current clinical treatments for these diseases can produce side effects. Regeneration is a promising therapy for bone and dental diseases, yielding natural tissue recovery with few side effects. Because soft tissues inside the bone and dentin are densely populated with nerves and vessels, the study of bone and dentin regeneration should also consider the co-regeneration of nerves and vessels. In this study, a network-based method to identify co-regeneration genes for bone, dentin, nerve and vessel was constructed based on an extensive network of protein-protein interactions. Three procedures were applied in the network-based method. The first procedure, searching, sought the shortest paths connecting regeneration genes of one tissue type with regeneration genes of other tissues, thereby extracting possible co-regeneration genes. The second procedure, testing, employed a permutation test to evaluate whether possible genes were false discoveries; these genes were excluded by the testing procedure. The last procedure, screening, employed two rules, the betweenness ratio rule and interaction score rule, to select the most essential genes. A total of seventeen genes were inferred by the method, which were deemed to contribute to co-regeneration of at least two tissues. All these seventeen genes were extensively discussed to validate the utility of the method.

  18. Traumatic globe luxation with optic nerve transection.

    Science.gov (United States)

    Bajaj, Mandeep S.; Kedar, Sachin; Sethi, Anita; Gupta, Vishal

    2000-09-01

    Luxation of the globe is a rare event that results from severe trauma to the orbit, often causing orbital rim and wall fractures. Though associated globe rupture often necessitates enucleation, repositioning of the globe can be attempted in these cases if the globe is intact. We report a case of globe luxation and optic nerve transection with its surgical management. A 17-year-old male presented with anterior luxation of the right globe and optic nerve transection following blunt trauma to the orbit. Computerized tomography revealed an anteriorly subluxated globe with complete transection of the optic nerve and multiple fractures of the orbital walls. The orbit was explored and the globe repositioned in the orbit with reattachment of the muscles. Postoperatively, the globe was in normal position with moderate motility and excellent overall cosmesis. Though the visual prognosis in these cases is usually extremely poor and depends on the extent and duration of injury, preservation of the globe not only helps the patient recover psychologically from the trauma but also allows better cosmesis.

  19. Chitosan-cross-linked nanofibrous PHBV nerve guide for rat sciatic nerve regeneration across a defect bridge.

    Science.gov (United States)

    Biazar, Esmaeil; Keshel, Saeed Heidari

    2013-01-01

    The aim of this study was to produce a chitosan-cross-linked nanofibrous biodegradable poly (3-hydroxybutyrate-co-3-hydroxyvalerate) nerve conduit. The artificial nerve scaffold designed by electrospinning method and cross-linked with chitosan by chemical method. Afterwards, the scaffolds were evaluated by microscopic, physical, and mechanical analyses and cell culture assays with Schwann cells. The conduits were implanted into a 10 mm gap in the sciatic nerves of the rats. Four months after surgery, the regenerated nerves were evaluated by macroscopic assessments and histology. This polymeric conduit had sufficiently good mechanical properties to serve as a nerve guide. Cellular experiments showed a better cell adhesion, growth, and proliferation inside the cross-linked nanofibrous scaffolds compared with un-cross-linked ones, also Schwann cells well attached on chitosan-cross-linked nanofibrous surface. The in vivo results demonstrated that in the nanofibrous graft, the sciatic nerve trunk had been reconstructed with restoration of nerve continuity and formatted nerve fibers with myelination. This neural conduit appears to have the right organization for testing in vivo nerve tissue engineering studies.

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

    Science.gov (United States)

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

    2014-04-30

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

  1. CT-diagnosis of optic nerve lesions. Differential diagnostic criteria

    Energy Technology Data Exchange (ETDEWEB)

    Unsoeld, R.

    1982-01-01

    Computed tomograms of 166 optic nerve lesions were analyzed: 97 were mainly orbital and 69 mainly intracranial. The criteria were clinical course, size, density and delineation of the optic nerve shadow, orbital and cerebral soft tissue abnormalities, and bony changes in the optic canal. Characteristic CT features are described of individual disease entities such as optic gliomas, optic nerve sheath meningiomas, neoplastic and inflammatory infiltrations. The differential diagnostic importance of individual CT criteria is evaluated and discussed. Simultaneous visualization of orbital and intracranial soft tissue changes as well as bony changes in the optic canal allow the location and identification of the majority of optic nerve lesions based on the criteria mentioned above, and optic nerve tumors can be differentiated. In 9 patients with optic neuritis due to clinically proven encephalitis and in 17 patients with total optic atrophy, no changes in the size of the optic nerve could be found. CT evaluation of the intraorbital portion of the optic nerve requires special examination techniques. Oblique computer reformations through the optic canal provide excellent visualization of bony changes in the optic canal. The exclusion of intracranial causes of optic nerve lesions requires intravenous injection of contrast material.

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

    Science.gov (United States)

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

    2016-10-01

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

  3. Stem Cell Transplantation for Peripheral Nerve Regeneration: Current Options and Opportunities

    Directory of Open Access Journals (Sweden)

    Liangfu Jiang

    2017-01-01

    Full Text Available Peripheral nerve regeneration is a complicated process highlighted by Wallerian degeneration, axonal sprouting, and remyelination. Schwann cells play an integral role in multiple facets of nerve regeneration but obtaining Schwann cells for cell-based therapy is limited by the invasive nature of harvesting and donor site morbidity. Stem cell transplantation for peripheral nerve regeneration offers an alternative cell-based therapy with several regenerative benefits. Stem cells have the potential to differentiate into Schwann-like cells that recruit macrophages for removal of cellular debris. They also can secrete neurotrophic factors to promote axonal growth, and remyelination. Currently, various types of stem cell sources are being investigated for their application to peripheral nerve regeneration. This review highlights studies involving the stem cell types, the mechanisms of their action, methods of delivery to the injury site, and relevant pre-clinical or clinical data. The purpose of this article is to review the current point of view on the application of stem cell based strategy for peripheral nerve regeneration.

  4. Stem Cell Transplantation for Peripheral Nerve Regeneration: Current Options and Opportunities.

    Science.gov (United States)

    Jiang, Liangfu; Jones, Salazar; Jia, Xiaofeng

    2017-01-05

    Peripheral nerve regeneration is a complicated process highlighted by Wallerian degeneration, axonal sprouting, and remyelination. Schwann cells play an integral role in multiple facets of nerve regeneration but obtaining Schwann cells for cell-based therapy is limited by the invasive nature of harvesting and donor site morbidity. Stem cell transplantation for peripheral nerve regeneration offers an alternative cell-based therapy with several regenerative benefits. Stem cells have the potential to differentiate into Schwann-like cells that recruit macrophages for removal of cellular debris. They also can secrete neurotrophic factors to promote axonal growth, and remyelination. Currently, various types of stem cell sources are being investigated for their application to peripheral nerve regeneration. This review highlights studies involving the stem cell types, the mechanisms of their action, methods of delivery to the injury site, and relevant pre-clinical or clinical data. The purpose of this article is to review the current point of view on the application of stem cell based strategy for peripheral nerve regeneration.

  5. Long-term survival and integration of transplanted engineered nervous tissue constructs promotes peripheral nerve regeneration.

    Science.gov (United States)

    Huang, Jason H; Cullen, D Kacy; Browne, Kevin D; Groff, Robert; Zhang, Jun; Pfister, Bryan J; Zager, Eric L; Smith, Douglas H

    2009-07-01

    Although peripheral nerve injury is a common consequence of trauma or surgery, there are insufficient means for repair. In particular, there is a critical need for improved methods to facilitate regeneration of axons across major nerve lesions. Here, we engineered transplantable living nervous tissue constructs to provide a labeled pathway to guide host axonal regeneration. These constructs consisted of stretch-grown, longitudinally aligned living axonal tracts inserted into poly(glycolic acid) tubes. The constructs (allogenic) were transplanted to bridge an excised segment of sciatic nerve in the rat, and histological analyses were performed at 6 and 16 weeks posttransplantation to determine graft survival, integration, and host regeneration. At both time points, the transplanted constructs were found to have maintained their pretransplant geometry, with surviving clusters of graft neuronal somata at the extremities of the constructs spanned by tracts of axons. Throughout the transplanted region, there was an intertwining plexus of host and graft axons, suggesting that the transplanted axons mediated host axonal regeneration across the lesion. By 16 weeks posttransplant, extensive myelination of axons was observed throughout the transplant region. Further, graft neurons had extended axons beyond the margins of the transplanted region, penetrating into the host nerve. Notably, this survival and integration of the allogenic constructs occurred in the absence of immunosuppression therapy. These findings demonstrate the promise of living tissue-engineered axonal constructs to bridge major nerve lesions and promote host regeneration, potentially by providing axon-mediated axonal outgrowth and guidance.

  6. ATF3 increases the intrinsic growth state of DRG neurons to enhance peripheral nerve regeneration.

    Science.gov (United States)

    Seijffers, Rhona; Mills, Charles D; Woolf, Clifford J

    2007-07-25

    Peripheral axons of dorsal root ganglion (DRG) neurons, but not their central axons in the dorsal columns, regenerate after injury. However, if the neurons are conditioned by a peripheral nerve injury into an actively growing state, the rate of peripheral axonal growth is accelerated and the injured central axons begin to regenerate. The growth-promoting effects of conditioning injuries have two components, increased axonal growth and a reduced response to inhibitory myelin cues. We have examined which transcription factors activated by peripheral axonal injury may mediate the conditioning effect by regulating expression of effectors that increase the intrinsic growth state of the neurons. Activating transcription factor 3 (ATF3) is a prime candidate because it is induced in all injured DRG neurons after peripheral, but not central, axonal damage. To investigate if ATF3 promotes regeneration, we generated transgenic mice that constitutively express this transcription factor in non-injured adult DRG neurons. The rate of peripheral nerve regeneration was enhanced in the transgenic mice to an extent comparable to that produced by a preconditioning nerve injury. The expression of some growth-associated genes, such as SPRR1A, but not others like GAP-43, was increased in the non-injured neurons. ATF3 increased DRG neurite elongation when cultured on permissive substrates but did not overcome the inhibitory effects of myelin or promote central axonal regeneration in the spinal cord in vivo. We conclude that ATF3 contributes to nerve regeneration by increasing the intrinsic growth state of injured neurons.

  7. Repairing nerve gaps by vein conduits filled with lipoaspirate-derived entire adipose tissue hinders nerve regeneration.

    Science.gov (United States)

    Papalia, Igor; Raimondo, Stefania; Ronchi, Giulia; Magaudda, Ludovico; Giacobini-Robecchi, Maria G; Geuna, Stefano

    2013-05-01

    In spite of great recent advancements, the definition of the optimal strategy for bridging a nerve defect, especially across long gaps, still remains an open issue since the amount of autologous nerve graft material is limited while the outcome after alternative tubulization techniques is often unsatisfactory. The aim of this study was to investigate a new tubulization technique based on the employment of vein conduits filled with whole subcutaneous adipose tissue obtained by lipoaspiration. In adult rats, a 1cm-long defect of the left median nerve was repaired by adipose tissue-vein-combined conduits and compared with fresh skeletal muscle tissue-vein-combined conduits and autologous nerve grafts made by the excised nerve segment rotated by 180°. Throughout the postoperative period, functional recovery was assessed using the grasping test. Regenerated nerve samples were withdrawn at postoperative month-6 and processed for light and electron microscopy and stereology of regenerated nerve fibers. Results showed that functional recovery was significantly slower in the adipose tissue-enriched group in comparison to both control groups. Light and electron microscopy showed that a large amount of adipose tissue was still present inside the vein conduits at postoperative month-6. Stereology showed that all quantitative morphological predictors analyzed performed significantly worse in the adipose tissue-enriched group in comparison to the two control groups. On the basis of this experimental study in the rat, the use of whole adipose tissue for tissue engineering of peripheral nerves should be discouraged. Pre-treatment of adipose tissue aimed at isolating stromal vascular fraction and/or adipose derived stem/precursor cells should be considered a fundamental requisite for nerve repair.

  8. Stromal vascular fraction combined with silicone rubber chamber improves sciatic nerve regeneration in diabetes

    Institute of Scientific and Technical Information of China (English)

    Rahim Mohammadi; Negin Sanaei; Sima Ahsan; Masoume Masoumi-Verki; Fatemeh Khadir; Aram Mokarizadeh

    2015-01-01

    Purpose:To study the effects of transplantation of characterized uncultured stromal vascular fraction (SVF) on sciatic nerve regeneration.Methods:A 10-mm sciatic nerve defect was bridged using a silicone conduit filled with SVF.In control group,silicone conduit was filled with phosphate-buffered saline alone.In sham-operated group,the sciatic nerve was only exposed and manipulated.The regenerated nerve fibers were studied 8 and 12 weeks after surgery.Results:Behavioral and functional studies confirmed faster recovery of regenerated axons in SVF transplanted animals than in control group (p < 0.05).Gastrocnemius muscle mass in SVF transplanted animal was found to be significantly more than that in control group.Morphometric indices of the regenerated fibers showed the number and diameter of the myelinated fibers to be significantly higher in SVF transplanted animals than in control group.In immunohistochemistry,the location of reactions to S-100 in SVF transplanted animals was clearly more positive than that in control group.Conclusion:SVF transplantation combined with silicone conduit could be considered as a readily accessible source of stromal cells that improves functional recovery of sciatic nerve.It may have clinical implications for the surgical management of acute diabetic patients after facial nerve transection.

  9. Concise review: tissue-engineered skin and nerve regeneration in burn treatment.

    Science.gov (United States)

    Blais, Mathieu; Parenteau-Bareil, Rémi; Cadau, Sébastien; Berthod, François

    2013-07-01

    Burns not only destroy the barrier function of the skin but also alter the perceptions of pain, temperature, and touch. Different strategies have been developed over the years to cover deep and extensive burns with the ultimate goal of regenerating the barrier function of the epidermis while recovering an acceptable aesthetic aspect. However, patients often complain about a loss of skin sensation and even cutaneous chronic pain. Cutaneous nerve regeneration can occur from the nerve endings of the wound bed, but it is often compromised by scar formation or anarchic wound healing. Restoration of pain, temperature, and touch perceptions should now be a major challenge to solve in order to improve patients' quality of life. In addition, the cutaneous nerve network has been recently highlighted to play an important role in epidermal homeostasis and may be essential at least in the early phase of wound healing through the induction of neurogenic inflammation. Although the nerve regeneration process was studied largely in the context of nerve transections, very few studies have been aimed at developing strategies to improve it in the context of cutaneous wound healing. In this concise review, we provide a description of the characteristics of and current treatments for extensive burns, including tissue-engineered skin approaches to improve cutaneous nerve regeneration, and describe prospective uses for autologous skin-derived adult stem cells to enhance recovery of the skin's sense of touch.

  10. Aligned Nanofibers for Regenerating Arteries, Nerves, and Muscles

    Science.gov (United States)

    McClendon, Mark Trosper

    . Furthermore, these nanofiber gels were used as a vehicle to deliver stem cells into muscle tissue. A specialized injector was designed to introduce aligned PA gels into mouse leg muscles in a 1cm long channel. Bioluminescence and histology showed that stem cell engraftment into myofibers was greatly enhanced when delivered by PA gels compared to saline solution. The final section of this thesis describes a new series of PA molecules designed to degrade upon exposure to UV lightstate here why is this of interest in the context of the work described in the thesis. This was done to understand the degradation behavior of PA nanofibers and provide a controlled approach to changing the rheological properties post gelation.The three PA molecules in this series contained the same peptide sequence V3A3E3, while varying the location of a nitrobenzyl UV-reactive group along the backbone of the molecule. This system allowed for a quick reaction that cleaves the molecule at the reactive nitrobenzyl site without introducing any other reactive molecules. While all three molecules produced nanofibers that remained intact upon UV exposure, the PA having its cleavage point nearest to the hydrophobic core resulted in the most dramatic drop in storage modulus. This work has demonstrated the control of alignment, macroscopic shape, and rheological properties of nanofiber gels tailored to assist in the regeneration of tissues with orientational order such as blood vessels, peripheral nerves, and muscle tissue.

  11. Side-To-Side Nerve Bridges Support Donor Axon Regeneration Into Chronically Denervated Nerves and Are Associated With Characteristic Changes in Schwann Cell Phenotype.

    Science.gov (United States)

    Hendry, J Michael; Alvarez-Veronesi, M Cecilia; Snyder-Warwick, Alison; Gordon, Tessa; Borschel, Gregory H

    2015-11-01

    Chronic denervation resulting from long nerve regeneration times and distances contributes greatly to suboptimal outcomes following nerve injuries. Recent studies showed that multiple nerve grafts inserted between an intact donor nerve and a denervated distal recipient nerve stump (termed "side-to-side nerve bridges") enhanced regeneration after delayed nerve repair. To examine the cellular aspects of axon growth across these bridges to explore the "protective" mechanism of donor axons on chronically denervated Schwann cells. In Sprague Dawley rats, 3 side-to-side nerve bridges were placed over a 10-mm distance between an intact donor tibial (TIB) nerve and a recipient denervated common peroneal (CP) distal nerve stump. Green fluorescent protein-expressing TIB axons grew across the bridges and were counted in cross section after 4 weeks. Immunofluorescent axons and Schwann cells were imaged over a 4-month period. Denervated Schwann cells dedifferentiated to a proliferative, nonmyelinating phenotype within the bridges and the recipient denervated CP nerve stump. As donor TIB axons grew across the 3 side-to-side nerve bridges and into the denervated CP nerve, the Schwann cells redifferentiated to the myelinating phenotype. Bridge placement led to an increased mass of hind limb anterior compartment muscles after 4 months of denervation compared with muscles whose CP nerve was not "protected" by bridges. This study describes patterns of donor axon regeneration and myelination in the denervated recipient nerve stump and supports a mechanism where these donor axons sustain a proregenerative state to prevent deterioration in the face of chronic denervation.

  12. Multicenter Clinical Trial of Keratin Biomaterials for Peripheral Nerve Regeneration

    Science.gov (United States)

    2013-10-01

    purity (size exclusion chromatography for molecular weight, amino acids analysis, ELISA for protein identification, and gel rheology ) and 2) a cell...distribution study. Labeled keratin gel will be placed inside nerve conduits. The ends of the conduits will be closed, and the conduits will be implanted in...Marra KG. Keratin gel filler for peripheral nerve repair in a rodent sciatic nerve injury model. Plast Reconstr Surg 2012;129:67-78. Pace LA

  13. Cooperative roles of BDNF expression in neurons and Schwann cells are modulated by exercise to facilitate nerve regeneration.

    Science.gov (United States)

    Wilhelm, Jennifer C; Xu, Mei; Cucoranu, Delia; Chmielewski, Sarah; Holmes, Tiffany; Lau, Kelly Shukkwan; Bassell, Gary J; English, Arthur W

    2012-04-04

    After peripheral nerve injury, neurotrophins play a key role in the regeneration of damaged axons that can be augmented by exercise, although the distinct roles played by neurons and Schwann cells are unclear. In this study, we evaluated the requirement for the neurotrophin, brain-derived neurotrophic factor (BDNF), in neurons and Schwann cells for the regeneration of peripheral axons after injury. Common fibular or tibial nerves in thy-1-YFP-H mice were cut bilaterally and repaired using a graft of the same nerve from transgenic mice lacking BDNF in Schwann cells (BDNF(-/-)) or wild-type mice (WT). Two weeks postrepair, axonal regeneration into BDNF(-/-) grafts was markedly less than WT grafts, emphasizing the importance of Schwann cell BDNF. Nerve regeneration was enhanced by treadmill training posttransection, regardless of the BDNF content of the nerve graft. We further tested the hypothesis that training-induced increases in BDNF in neurons allow regenerating axons to overcome a lack of BDNF expression in cells in the pathway through which they regenerate. Nerves in mice lacking BDNF in YFP(+) neurons (SLICK) were cut and repaired with BDNF(-/-) and WT nerves. SLICK axons lacking BDNF did not regenerate into grafts lacking Schwann cell BDNF. Treadmill training could not rescue the regeneration into BDNF(-/-) grafts if the neurons also lacked BDNF. Both Schwann cell- and neuron-derived BDNF are thus important for axon regeneration in cut peripheral nerves.

  14. Effect of glial cell line-derived neurotrophic factor on peripheral nerve regeneration in adult rat

    Institute of Scientific and Technical Information of China (English)

    CHEN Zhe-yu; LI Jian-hong; ZHENG Xing-dong; LU Chang-lin; HE Cheng

    2001-01-01

    Objective: To study the effect of glial cell line-derived neurotrophic (GDNF) on adult peripheral nerve regeneration. Methods: Transectioned sciatic nerve in adult rats was sutured into silicone channel. GDNF or SAL solution was injected into the silicone channels during operation. Four weeks later, the effect of GDNF on axonal regeneration was evaluated by degenerative neurofiber staining and HRP retrograde tracing. Results: Compared with SAL group, the percentage of degenerative neurofiber areas decreased from 17.3% to 1.9% ( P<0.01 ) and the ratio of labeled spinal somas number was significantly increased from 43.5% to 68.3% ( P<0.01 ) in GDNF group. Conclusion: The results suggest that exogenous GDNF can obviously enhance adult peripheral nerve regeneration.

  15. Cross-chest median nerve transfer: a new model for the evaluation of nerve regeneration across a 40 mm gap in the rat.

    Science.gov (United States)

    Sinis, Nektarios; Schaller, Hans-Eberhard; Becker, Stephan Thomas; Lanaras, Tatjana; Schulte-Eversum, Caterina; Müller, Hans-Werner; Vonthein, Reinhard; Rösner, Harald; Haerle, Max

    2006-09-30

    A new animal model for the study of nerve regeneration in rats across a 40 mm gap between both median nerves is described. For autologous grafting, the ulnar nerves were dissected and sutured together. From the left median nerve, they were transplanted across the chest to the right median nerve. Animals having undergone this operation were observed for 12 months and periodically assessed using the grasping test and measurements of body-weight. For histological analysis rats were sacrificed after this period and axon counts were determined at the suture points of operated animals and in the median nerve of non-operated animals. Functional recovery could be seen, although partially, beginning as early as the fifth postoperative month, as demonstrated by the grasping test. Quantification of the number of axons demonstrated axonal regeneration across all three coaptation points. This model provides a new approach for analysis of long distance peripheral nerve regeneration without impairment of behaviour.

  16. A case of amblyopia with contralateral optic nerve hypoplasia.

    Science.gov (United States)

    Frantz, Kelly A; Pang, Yi

    2013-09-01

    We describe an unusual case of unilateral optic nerve hypoplasia (ONH) in a patient with contralateral anisometropic/strabismic amblyopia. A seven-year-old boy presented with visual acuities of 6/12 R and 6/18 L and eccentric fixation in the left eye. Cycloplegic retinoscopy was R +1.50/-0.50 × 180 and L +5.25 DS. Funduscopy revealed optic nerve hypoplasia of the right eye. The patient fixated with his better-seeing right eye, despite the optic nerve hypoplasia. His reduced vision may be attributed to optic nerve hypoplasia in the right eye and amblyopia in the left. Although optic nerve hypoplasia can occur with ipsilateral amblyopia, we believe this is the first reported case of unilateral optic nerve hypoplasia in the fellow eye of an amblyopic patient.

  17. Optic Nerve Lymphoma. Report of Two Cases and Review of the Literature

    Science.gov (United States)

    Kim, Jennifer L.; Mendoza, Pia; Rashid, Alia; Hayek, Brent; Grossniklaus, Hans E.

    2014-01-01

    Lymphoma may involve the optic nerve as isolated optic nerve lymphoma or in association with CNS or systemic lymphoma. We present two biopsy-proven non-Hodgkin lymphomas of the optic nerve and compare our findings with previously reported cases. We discuss the mechanism of metastasis, classification of optic nerve involvement, clinical features, radiologic findings, optic nerve biopsy indications and techniques, histologic features, and treatments. We propose a classification system of optic nerve lymphoma: isolated optic nerve involvement, optic nerve involvement with CNS disease, optic nerve involvement with systemic disease, and optic nerve involvement with primary intraocular lymphoma. Although it is an uncommon cause of infiltrative optic neuropathy, optic nerve metastasis should be considered in patients with a history of lymphoma. The recommended approach to a patient with presumed optic nerve lymphoma includes neuroimaging, and cerebrospinal fluid evaluation as part of the initial work-up, then judicious use of optic nerve biopsy, depending on the clinical situation. PMID:25595061

  18. Electronmicroscopical evaluation of short-term nerve regeneration through a thin-walled biodegradable poly(DLLA-epsilon-CL) nerve guide filled with modified denatured muscle tissue

    NARCIS (Netherlands)

    Meek, MF; Robinson, PH; Stokroos, [No Value; Blaauw, EH; Kors, G; den Dunnen, WFA

    2001-01-01

    The aim of this study was to evaluate short-term peripheral nerve regeneration across a 15-mm gap in the sciatic nerve of the rat, using a thin-walled biodegradable poly(DL-lactide-epsilon -caprolactone) nerve guide filled with modified denatured muscle tissue (MDMT). The evaluation was performed us

  19. Electronmicroscopical evaluation of short-term nerve regeneration through a thin-walled biodegradable poly(DLLA-epsilon-CL) nerve guide filled with modified denatured muscle tissue

    NARCIS (Netherlands)

    Meek, MF; Robinson, PH; Stokroos, [No Value; Blaauw, EH; Kors, G; den Dunnen, WFA

    2001-01-01

    The aim of this study was to evaluate short-term peripheral nerve regeneration across a 15-mm gap in the sciatic nerve of the rat, using a thin-walled biodegradable poly(DL-lactide-epsilon -caprolactone) nerve guide filled with modified denatured muscle tissue (MDMT). The evaluation was performed us

  20. Whisking recovery after automated mechanical stimulation during facial nerve regeneration.

    NARCIS (Netherlands)

    Kleiss, I.J.; Knox, C.J.; Malo, J.S.; Marres, H.A.M.; Hadlock, T.A.; Heaton, J.T.

    2014-01-01

    IMPORTANCE Recovery from facial nerve transection is typically poor, but daily mechanical stimulation of the face in rats has been reported to remarkably enhance functional recovery after facial nerve transection and suture repair. This phenomenon needs additional investigation because of its import

  1. Mechanical Loading for Peripheral Nerve Stabilization and Regeneration

    Science.gov (United States)

    2012-10-01

    this outcome is not unheard of for nerve (or spinal cord) injury, it was nonetheless unanticipated given the large number of short-time point surgeries...tip of the curvature to the point which was 180° of turn from the starting point. Evaluation of no-slip gripping of nerve was performed in situ

  2. Quantitative STIR MRI as prognostic imaging biomarker for nerve regeneration

    NARCIS (Netherlands)

    Viddeleer, Alain Robert

    2016-01-01

    A transection of a forearm nerve e.g., because of an accident, has tremendous impact on a patient's daily life, as a number of hand muscles is paralyzed and part of the hand will suffer from sensory loss. Despite advances in surgery many patients will have remaining loss of function. If nerve regene

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

    Science.gov (United States)

    2012-10-01

    hydrogel scaffolds. Tissue Eng Part A 2011:17(11-12):1499-505 Lin YC, Ram adan M, Van Dyke, M, Kokai LE, Philips BJ, Rubin JP, Marra KG. Keratin gel f...Ram adan M, Van Dyke, M, Kokai LE, Philips BJ, Rubin JP, Marra KG. Keratin gel f iller for peripheral nerve repair in a rodent sciatic nerve injury

  4. A Silk Fibroin/Collagen Nerve Scaffold Seeded with a Co-Culture of Schwann Cells and Adipose-Derived Stem Cells for Sciatic Nerve Regeneration.

    Directory of Open Access Journals (Sweden)

    Yunqiang Xu

    Full Text Available As a promising alternative to autologous nerve grafts, tissue-engineered nerve grafts have been extensively studied as a way to bridge peripheral nerve defects and guide nerve regeneration. The main difference between autogenous nerve grafts and tissue-engineered nerve grafts is the regenerative microenvironment formed by the grafts. If an appropriate regenerative microenvironment is provided, the repair of a peripheral nerve is feasible. In this study, to mimic the body's natural regenerative microenvironment closely, we co-cultured Schwann cells (SCs and adipose-derived stem cells (ADSCs as seed cells and introduced them into a silk fibroin (SF/collagen scaffold to construct a tissue-engineered nerve conduit (TENC. Twelve weeks after the three different grafts (plain SF/collagen scaffold, TENC, and autograft were transplanted to bridge 1-cm long sciatic nerve defects in rats, a series of electrophysiological examinations and morphological analyses were performed to evaluate the effect of the tissue-engineered nerve grafts on peripheral nerve regeneration. The regenerative outcomes showed that the effect of treatment with TENCs was similar to that with autologous nerve grafts but superior to that with plain SF/collagen scaffolds. Meanwhile, no experimental animals had inflammation around the grafts. Based on this evidence, our findings suggest that the TENC we developed could improve the regenerative microenvironment and accelerate nerve regeneration compared to plain SF/collagen and may serve as a promising strategy for peripheral nerve repair.

  5. A Silk Fibroin/Collagen Nerve Scaffold Seeded with a Co-Culture of Schwann Cells and Adipose-Derived Stem Cells for Sciatic Nerve Regeneration.

    Science.gov (United States)

    Xu, Yunqiang; Zhang, Zhenhui; Chen, Xuyi; Li, Ruixin; Li, Dong; Feng, Shiqing

    2016-01-01

    As a promising alternative to autologous nerve grafts, tissue-engineered nerve grafts have been extensively studied as a way to bridge peripheral nerve defects and guide nerve regeneration. The main difference between autogenous nerve grafts and tissue-engineered nerve grafts is the regenerative microenvironment formed by the grafts. If an appropriate regenerative microenvironment is provided, the repair of a peripheral nerve is feasible. In this study, to mimic the body's natural regenerative microenvironment closely, we co-cultured Schwann cells (SCs) and adipose-derived stem cells (ADSCs) as seed cells and introduced them into a silk fibroin (SF)/collagen scaffold to construct a tissue-engineered nerve conduit (TENC). Twelve weeks after the three different grafts (plain SF/collagen scaffold, TENC, and autograft) were transplanted to bridge 1-cm long sciatic nerve defects in rats, a series of electrophysiological examinations and morphological analyses were performed to evaluate the effect of the tissue-engineered nerve grafts on peripheral nerve regeneration. The regenerative outcomes showed that the effect of treatment with TENCs was similar to that with autologous nerve grafts but superior to that with plain SF/collagen scaffolds. Meanwhile, no experimental animals had inflammation around the grafts. Based on this evidence, our findings suggest that the TENC we developed could improve the regenerative microenvironment and accelerate nerve regeneration compared to plain SF/collagen and may serve as a promising strategy for peripheral nerve repair.

  6. Differential expression of GAP-43 and neurofilament during peripheral nerve regeneration through bio-artificial conduits.

    Science.gov (United States)

    Carriel, Víctor; Garzón, Ingrid; Campos, Antonio; Cornelissen, Maria; Alaminos, Miguel

    2017-02-01

    Nerve conduits are promising alternatives for repairing nerve gaps; they provide a close microenvironment that supports nerve regeneration. In this sense, histological analysis of axonal growth is a determinant to achieve successful nerve regeneration. To evaluate this process, the most-used immunohistochemical markers are neurofilament (NF), β-III tubulin and, infrequently, GAP-43. However, GAP-43 expression in long-term nerve regeneration models is still poorly understood. In this study we analysed GAP-43 expression and its correlation with NF and S-100, using three tissue-engineering approaches with different regeneration profiles. A 10 mm gap was created in the sciatic nerve of 12 rats and repaired using collagen conduits or collagen conduits filled with fibrin-agarose hydrogels or with hydrogels containing autologous adipose-derived mesenchymal stem cells (ADMSCs). After 12 weeks the conduits were harvested for histological analysis. Our results confirm the long-term expression of GAP-43 in all groups. The expression of GAP-43 and NF was significantly higher in the group with ADMSCs. Interestingly, GAP-43 was observed in immature, newly formed axons and NF in thicker and mature axons. These proteins were not co-expressed, demonstrating their differential expression in newly formed nerve fascicles. Our descriptive and quantitative histological analysis of GAP-43 and NFL allowed us to determine, with high accuracy, the heterogenic population of axons at different stages of maturation in three tissue-engineering approaches. Finally, to perform a complete assessment of axonal regeneration, the quantitative immunohistochemical evaluation of both GAP-43 and NF could be a useful quality control in tissue engineering. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014 John Wiley & Sons, Ltd.

  7. An unusual radiological presentation of optic nerve sheath meningiom

    Directory of Open Access Journals (Sweden)

    Chameen Samarawickrama

    2016-04-01

    Full Text Available Our report describes an unusual radiological presentation of optic nerve sheath meningioma. The classic radiological appearance of optic nerve thickening with enhancement and calcification within the tumor was not seen; instead, an elongating gadolinium enhancing band-like area adjacent to the superomedial aspect of the left optic nerve sheath was identified. The diagnosis was confirmed on histopathology. Our report adds to the spectrum of presentations of this relatively common clinical entity.

  8. Influence of calcium alginate on peripheral nerve regeneration: in vivo study.

    Science.gov (United States)

    Szarek, Dariusz; Marycz, Krzysztof; Bednarz, Paulina; Tabakow, Paweł; Jarmundowicz, Włodzimierz; Laska, Jadwiga

    2013-01-01

    Recently, we described the influence of sodium alginate on the inflammatory infiltrate during neuroregeneration in tube nerve grafts. It was noticeable that there was the coexistence of inflammatory cells, including neutrophils, plasma cells, and macrophages with Schwann cells and axons. This may indicate a beneficial interaction between alginates and the infiltrate and the additional beneficial effect of the cells on the neuroregeneration process in the inflammatory infiltrates. In this study, we have performed in vivo evaluation of our novel tubular implant prepared by a polyurethane/polylactide blend filled with alginate fibers. The influence of filling the lumen of the tubes with sodium and calcium alginates on the regeneration process of the rat sciatic nerve was investigated. The neuroregeneration process was assessed by detailed histomorphometric studies, axon counting, and calculating the regenerative indexes. It was observed that calcium alginate had a supportive effect on nerve regeneration similar to nerve autotransplant.

  9. Effects of Extracellular ATP and Its Receptors on Peripheral Nerve Regeneration in SD Rats

    Institute of Scientific and Technical Information of China (English)

    王栓科; 张致英; 洪光祥; 王同光; 王发斌; 康皓

    2003-01-01

    To explore the effect of the extracellular ATP and its receptors on axon regeneration in the sciatic nerve defect in rats, 0. 5 cm defect of the sciatic nerve was made and repaired with long arm silicon tube like a "Y" type. The single arm of the silicon tube was sutured to proximal of the sciatic nerve. 10μl 1 mmol/L ATP in physiological saline was injected into the left chamber of the silicon tube (experimental group) and physiological saline injected into another silicon tube as a control group. In another model 1 mmol/L 10 μl ATP and 1 mmol/L 10μl ATP+0.2 mg/ml suramin were injected respectively into two arms of the silicon tube. After 4 and 8 weeks the specimens were obtained from the silicon tube for examining the axon regeneration histologically and image analysis. All the regeneration axons grew into the silicon tube containing the ATP, but there was no axon regeneration in the silicon tube containing the ATP+Suramin or physiological saline. It was demonstrated that extracellular ATP had a powerful attraction to the regenerated axon of peripheral nerve. The suramin inhibited the axon induction of the extracellular ATP completely via the ATP receptors.

  10. Electrical stimulation does not enhance nerve regeneration if delayed after sciatic nerve injury: the role of fibrosis

    Directory of Open Access Journals (Sweden)

    Na Han

    2015-01-01

    Full Text Available Electrical stimulation has been shown to accelerate and enhance nerve regeneration in sensory and motor neurons after injury, but there is little evidence that focuses on the varying degrees of fibrosis in the delayed repair of peripheral nerve tissue. In this study, a rat model of sciatic nerve transection injury was repaired with a biodegradable conduit at 1 day, 1 week, 1 month and 2 months after injury, when the rats were divided into two subgroups. In the experimental group, rats were treated with electrical stimuli of frequency of 20 Hz, pulse width 100 ms and direct current voltage of 3 V; while rats in the control group received no electrical stimulation after the conduit operation. Histological results showed that stained collagen fibers comprised less than 20% of the total operated area in the two groups after delayed repair at both 1 day and 1 week but after longer delays, the collagen fiber area increased with the time after injury. Immunohistochemical staining revealed that the expression level of transforming growth factor β (an indicator of tissue fibrosis decreased at both 1 day and 1 week after delayed repair but increased at both 1 and 2 months after delayed repair. These findings indicate that if the biodegradable conduit repair combined with electrical stimulation is delayed, it results in a poor outcome following sciatic nerve injury. One month after injury, tissue degeneration and distal fibrosis are apparent and are probably the main reason why electrical stimulation fails to promote nerve regeneration after delayed repair.

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

    Science.gov (United States)

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

    2015-01-01

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

  12. Hemangioblastoma of the optic nerve--case report.

    Science.gov (United States)

    Higashida, Tetsuhiro; Sakata, Katsumi; Kanno, Hiroshi; Kawasaki, Takashi; Tanabe, Yutaka; Yamamoto, Isao

    2007-05-01

    A 64-year-old man presented with a rare sporadic hemangioblastoma arising in the left optic nerve manifesting as left visual disturbance gradually progressive over 5 years. Magnetic resonance imaging revealed a well-enhanced mass in the left optic nerve. Partial resection of the tumor was performed via the frontoorbital approach. The histological diagnosis was optic nerve hemangioblastoma. Hemangioblastoma must be considered in the differential diagnosis of optic nerve tumors even in the absence of other lesions associated with von Hippel-Lindau disease.

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

    Science.gov (United States)

    Ceci, Maria Laura; Mardones-Krsulovic, Camila; Sánchez, Mario; Valdivia, Leonardo E; Allende, Miguel L

    2014-10-17

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

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

    Directory of Open Access Journals (Sweden)

    Lin Wang

    2015-01-01

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

  15. Effects of tacrolimus (FK506) on sciatic nerve regeneration in rats

    Institute of Scientific and Technical Information of China (English)

    Weiguo Zhang; Decheng Lü; Shouyu Wang; Chongyang Fu

    2009-01-01

    BACKGROUND: Tacrolimus (FK506) protects peripheral nerves located in damaged regions by inhibiting T lymphocyte proliferation and activation.OBJECTIVE: To evaluate the effect of FK506 on promoting regeneration of rat sciatic nerve. DESIGN, TIME AND SETTING: A randomized, controlled, animal study was performed at the Laboratory of the Department of Orthopedic Surgery, Dalian Medical University, China, from September 2007 to September 2008.MATERIALS: A total of 60 adult, male, Sprague-Dawley rats were equally and randomly divided into model, local administration and systemic administration groups. All rats received a neurotomy of bilateral sciatic nerves to establish models of nerve regeneration chambers. The powder and injection of FK506 were supplied by Fujisawa Pharmaceutical, Japan.METHODS: The regeneration chambers of the model group were infused with 0.2 mL saline. The systemic group were injected with 0.2 mL saline, followed by daily subcutaneous injections of FK506 (1 mg/kg), for 14 days. The local administration group was infused with 0.2 mL FK506 (1 μg/mL).MAIN OUTCOME MEASURES: Local immune response was observed using hematoxylin-eosin staining. Myelinated nerve fiber number, myelin sheath and nerve fiber thickness were observed using toluidine blue staining. Wet weight of gastrocnemius was evaluated. Compound muscle action potential amplitude, latency, and conduction time were recorded, and motor nerve conduction velocity was calculated using electrophysiology.RESULTS: The total number of myeiinated nerve fibers in the local and systemic administration groups was significantly higher than in the model group. The density of myelinated nerve fibers, myelin sheath thickness and mean axon diameter were significantly increased in the systemic administration group compared with the model group (P < 0.05). Lymphocyte infiltration was decreased in the local and systemic administration groups compared with the model group. The wet weight of rat gastrocnemius in

  16. Effect of bleeding on nerve regeneration and epineural scar formation in rat sciatic nerves: an experimental study.

    Science.gov (United States)

    Servet, Erkan; Bekler, Halil; Kılınçoğlu, Volkan; Özler, Turhan; Özkut, Afşar

    2016-01-01

    Epineural scar formation is one of the most significant negative factors affecting surgical repair after peripheral nerve injury. The scar tissue mechanically hinders axonal regeneration and causes adhesions between nerves and surrounding tissues. A hemostatic agent Ankaferd Blood Stopper (ABS; İmmun Gıda İlaç Kozmetik San. ve Tic. Ltd. Şti., Istanbul, Turkey) has not been previously used. Decreasing the postoperative bleeding and adhesions between nerve and surrounding tissues will prevent the formation of scar tissue, as well as corresponding compressive neuropathy and/or deceleration of axonal regeneration. The purpose of this experimental study was to investigate the effects of bleeding on nerve healing and scar tissue after repair of peripheral nerve injuries. The right sciatic nerve of 30 Sprague-Dawley male rats (weighing 260-330 g) was cut 1.5 cm proximal to the trifurcation and repaired primarily with 8/0 sutures using epineural technique. The rats were then divided into 3 groups. Saline was applied in Group 1 (n=10), ABS in Group 2 (n=10), and heparin in Group 3 (n=10) for 5 minutes to the repair site and surrounding tissues. In each group, electrophysiological measurements were performed with electromyography (EMG) at postoperative week 12. Magnetic resonance diffusion tensor imaging was used at week 12. Macroscopical and histopathological evaluations were conducted after sacrificing the rats at week 24 with total excision of the repaired sciatic nerves and surrounding tissues. The ABS and saline groups showed better healing than the heparin group. The ABS and saline groups were better in the histopathologic evaluations, but there was no statistically significant difference between the 2 groups. Statistically significant differences were not found between the 3 groups. Significant results may be obtained with larger studies.

  17. Intraorbital neuromuscular choristoma adjacent to the optic nerve

    Directory of Open Access Journals (Sweden)

    Arie Perry, M.D.

    2017-03-01

    Full Text Available Neuromuscular choristoma is a rare tumor that incorporates mature skeletal muscle within fascicles of peripheral nerve. The etiology is poorly understood, yet most present in large nerves of children, with a tight link to post-operative fibromatosis recently appreciated. Herein, we report an exceptional intra-orbital example in a 53-year-old man with optic nerve compression.

  18. Role of Netrin-1 Signaling in Nerve Regeneration

    National Research Council Canada - National Science Library

    Dun, Xin-Peng; Parkinson, David

    2017-01-01

    .... 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...

  19. Mechanical Loading for Peripheral Nerve Stabilization and Regeneration

    Science.gov (United States)

    2013-04-01

    phenomenon is often equated to a phantom limb phenomenon in humans; therefore, it may not be a response to pain , in animals. Therefore, in addition, bitter...motor function, sensory loss, and chronic pain with inappropriate autonomic responses. Consequently, strategies for enhancing nervous function are of...peripheral nerve damage is often poor, particularly for severed nerves. The result can be impaired motor function, sensory loss, and chronic pain with

  20. A comparative study of gland cells implicated in the nerve dependence of salamander limb regeneration.

    Science.gov (United States)

    Kumar, Anoop; Nevill, Graham; Brockes, Jeremy P; Forge, Andrew

    2010-07-01

    Limb regeneration in salamanders proceeds by formation of the blastema, a mound of proliferating mesenchymal cells surrounded by a wound epithelium. Regeneration by the blastema depends on the presence of regenerating nerves and in earlier work it was shown that axons upregulate the expression of newt anterior gradient (nAG) protein first in Schwann cells of the nerve sheath and second in dermal glands underlying the wound epidermis. The expression of nAG protein after plasmid electroporation was shown to rescue a denervated newt blastema and allow regeneration to the digit stage. We have examined the dermal glands by scanning and transmission electron microscopy combined with immunogold labelling of the nAG protein. It is expressed in secretory granules of ductless glands, which apparently discharge by a holocrine mechanism. No external ducts were observed in the wound epithelium of the newt and axolotl. The larval skin of the axolotl has dermal glands but these are absent under the wound epithelium. The nerve sheath was stained post-amputation in innervated but not denervated blastemas with an antibody to axolotl anterior gradient protein. This antibody reacted with axolotl Leydig cells in the wound epithelium and normal epidermis. Staining was markedly decreased in the wound epithelium after denervation but not in the epidermis. Therefore, in both newt and axolotl the regenerating axons induce nAG protein in the nerve sheath and subsequently the protein is expressed by gland cells, under (newt) or within (axolotl) the wound epithelium, which discharge by a holocrine mechanism. These findings serve to unify the nerve dependence of limb regeneration.

  1. Stem cells and related factors involved in facial nerve function regeneration

    Directory of Open Access Journals (Sweden)

    Kamil H. Nelke

    2015-09-01

    Full Text Available The facial nerve (VII is one of the most important cranial nerves for head and neck surgeons. Its function is closely related to facial expressions that are individual for every person. After its injury or palsy, its functions can be either impaired or absent. Because of the presence of motor, sensory and parasympathetic fibers, the biology of its repair and function restoration depends on many factors. In order to achieve good outcome, many different therapies can be performed in order to restore as much of the nerve function as possible. When rehabilitation and physiotherapy are not sufficient, additional surgical procedures and therapies are taken into serious consideration. The final outcome of many of them is discussable, depending on nerve damage etiology. Stem cells in facial nerve repair are used, but long-term outcomes and results are still not fully known. In order to understand this therapeutic approach, clinicians and surgeons should understand the immunobiology of nerve repair and regeneration. In this review, potential stem cell usage in facial nerve regeneration procedures is discussed.

  2. Effect of mutated defensin NP-1 on sciatic nerve regeneration after transection--A pivot study.

    Science.gov (United States)

    Xu, Chungui; Bai, Lili; Chen, Yuhong; Fan, Chengming; Hu, Zanmin; Xu, Hailin; Jiang, Baoguo

    2016-03-23

    Defensins are small cationic peptides that constitute the first line of defense against pathogens and are involved in immune regulation. In this study, their role in peripheral nerve regeneration was investigated. Rat sciatic nerves were transected and the two nerve stumps were bridged by a chitin conduit with a gap of 5mm between the stumps. The animals were injected intramuscularly with mutated rabbit neutrophil peptide 1 (defensin mNP-1), the positive control nerve growth factor (NGF) or the negative control saline, for 7 consecutive days after repair. After 6 weeks, the sciatic functional index (SFI), MNCV (motor nerve conductive velocity) and morphological parameters including myelinated fiber amounts, fiber diameter, axon diameter, myelin thickness and G-ratio were measured. Compared to the SFI of saline group, the NGF and mNP-1 groups had an increase of 18.3% and 18.8%, respectively. The numbers of myelinated fibers in the distal nerve of NGF and mNP-1 groups were 1.45- and 1.32-fold higher than in the saline group. The MNCVs of NGF and mNP-1 groups were 7.3 and 4.4 times of that of saline group. Fiber diameter, axon diameter, myelin thickness and G-ratio in the NGF and mNP-1 groups were also significantly higher than those of saline group. Our results demonstrate that, like NGF, the defensin mNP-1 can promote regeneration after a peripheral nerve cut.

  3. Effect of skilled and unskilled training on nerve regeneration and functional recovery

    Directory of Open Access Journals (Sweden)

    A.S. Pagnussat

    2012-08-01

    Full Text Available The most disabling aspect of human peripheral nerve injuries, the majority of which affect the upper limbs, is the loss of skilled hand movements. Activity-induced morphological and electrophysiological remodeling of the neuromuscular junction has been shown to influence nerve repair and functional recovery. In the current study, we determined the effects of two different treatments on the functional and morphological recovery after median and ulnar nerve injury. Adult Wistar male rats weighing 280 to 330 g at the time of surgery (N = 8-10 animals/group were submitted to nerve crush and 1 week later began a 3-week course of motor rehabilitation involving either "skilled" (reaching for small food pellets or "unskilled" (walking on a motorized treadmill training. During this period, functional recovery was monitored weekly using staircase and cylinder tests. Histological and morphometric nerve analyses were used to assess nerve regeneration at the end of treatment. The functional evaluation demonstrated benefits of both tasks, but found no difference between them (P > 0.05. The unskilled training, however, induced a greater degree of nerve regeneration as evidenced by histological measurement (P < 0.05. These data provide evidence that both of the forelimb training tasks used in this study can accelerate functional recovery following brachial plexus injury.

  4. Morphometry of Axons in Optic Nerves of Siamese's Twins

    Institute of Scientific and Technical Information of China (English)

    Xinzu Gu; Zhenping Zhang; Qi Lin; Jiongji Liang; Wenyu Lu; Xiulan Ye; A A Sadun

    2002-01-01

    Purpose: To observe the development of optic nerve, we examined four optic nerves from Siameses Twins by absolute counts of axons.Methods: Mean axon diameter, mean axon density, totally axonal population and optic nerve area were noted for each optic nerve. The mean axon diameter and the mean axon density were compared between paraxial (inner sectors)and cortical (outer sectors)areas of the nerves.Results: More myelinated axons were seen in the inner sectors as compared to the outer sectors(average 11 axons/1 000 μm2 in inner sectors and 34 axons/l 000 μm2 in outer sectors( P=0. 036) . The myelinated fibers were also smaller(63 microns) in the outer sectors as compared to the inner sectors(72 microns) ( P = 0. 001 ). The average cross sectors area for the four 40 week stage optical nerves of Siamese Twins was 3.32 × 103 as compared to 1 million axons for 32-week-old normals.Conclusion: Our finding of fewer axonal number and small myelinated fibers in the Siamese Twins suggests hypoplasia. Myelination was more abnormal in the paraxial optic nerve than that in the peripheral sectors, suggesting anomalous development of optic nerve peripherally and delayed developnent centrally. Axonal density is higher in inner sectors than that in outer sectors, suggesting delayed development of the outer nerve sector.

  5. Regeneration patterns influence hindlimb automutilation after sciatic nerve repair using stem cells in rats.

    Science.gov (United States)

    Haselbach, Daniel; Raffoul, Wassim; Larcher, Lorenz; Tremp, Mathias; Kalbermatten, Daniel F; di Summa, Pietro G

    2016-11-10

    Hindlimb autophagy is common after rat sciatic total axotomy and is considered as a sign of neuropathic pain. We applied adult stem cells in a fibrin conduit in a total sciatic axotomy model to improve nerve regeneration, investigating whether a correlation could be detected between stem cells effects on regeneration and limb autophagy. After sciatic nerve section, a 1-cm sciatic gap was crossed using fibrin conduits. Experimental groups included empty fibrin conduits, fibrin conduits seeded with primary Schwann cells, and fibrin conduits seeded with Schwann cell-like differentiated mesenchymal or adipose-derived stem cells (dMSCs and dASCs). Controls were represented by autografts and by sham rats (tot n=34). At 16 weeks post-implantation, regeneration pattern was analysed on histological sections and related to eventual autophagy. Hindlimbs were evaluated and scored according to autophagy Wall's scale and X-Rays radiological evaluation. All regenerative cell lines significantly improved myelination at the mid conduit level, compared to the empty tubes. However, dMSC could not significantly improve myelination at the distal stump, showing a more chaotic regeneration compared to both other cells groups and controls. Autophagy was correlated to this regeneration patterns, with higher autophagy scores in the empty and dMSC group. Hindlimb autophagy can be used as index of neuropathic pain due to nerve lesion or on-going immature regeneration. dMSC group was characterized by a less targeted regeneration comparing to dASC and primary Schwann cells, which confirmed their effectiveness in regeneration and potential in future clinical applications. Copyright © 2016. Published by Elsevier Ireland Ltd.

  6. Extracellular matrix components in peripheral nerve repair:how to affect neural cellular response and nerve regeneration?

    Institute of Scientific and Technical Information of China (English)

    Alba C de Luca; Stephanie P Lacour; Wassim Raffoul; Pietro G di Summa

    2014-01-01

    Peripheral nerve injury is a serious problem affecting signiifcantly patients’ life. Autografts are the“gold standard” used to repair the injury gap, however, only 50% of patients fully recover from the trauma. Artiifcial conduits are a valid alternative to repairing peripheral nerve. They aim at conifning the nerve environment throughout the regeneration process, and providing guidance to axon outgrowth. Biocompatible materials have been carefully designed to reduce inlfamma-tion and scar tissue formation, but modiifcations of the inner lumen are still required in order to optimise the scaffolds. Biomicking the native neural tissue with extracellular matrix ifllers or coatings showed great promises in repairing longer gaps and extending cell survival. In addition, extracellular matrix molecules provide a platform to further bind growth factors that can be released in the system over time. Alternatively, conduit ifllers can be used for cell transplantation at the injury site, reducing the lag time required for endogenous Schwann cells to proliferate and take part in the regeneration process. This review provides an overview on the importance of ex-tracellular matrix molecules in peripheral nerve repair.

  7. Fingolimod induces the transition to a nerve regeneration promoting Schwann cell phenotype.

    Science.gov (United States)

    Heinen, André; Beyer, Felix; Tzekova, Nevena; Hartung, Hans-Peter; Küry, Patrick

    2015-09-01

    Successful regeneration of injured peripheral nerves is mainly attributed to the plastic behavior of Schwann cells. Upon loss of axons, these cells trans-differentiate into regeneration promoting repair cells which provide trophic support to regrowing axons. Among others, activation of cJun was revealed to be involved in this process, initiating the stereotypic pattern of Schwann cell phenotype alterations during Wallerian degeneration. Nevertheless, the ability of Schwann cells to adapt and therefore the nerve's potential to regenerate can be limited in particular after long term denervation or in neuropathies leading to incomplete regeneration only and thus emphasizing the need for novel therapeutic approaches. Here we stimulated primary neonatal and adult rat Schwann cells with Fingolimod/FTY720P and investigated its impact on the regeneration promoting phenotype. FTY720P activated a number of de-differentiation markers including cJun and interfered with maturation marker and myelin expression. Functionally, FTY720P treated Schwann cells upregulated growth factor expression and these cells enhanced dorsal root ganglion neurite outgrowth on inhibitory substrates. Our results therefore provide strong evidence that FTY720P application supports the generation of a repair promoting cellular phenotype and suggest that Fingolimod could be used as treatment for peripheral nerve injuries and diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Intermediate filaments of zebrafish retinal and optic nerve astrocytes and Müller glia: differential distribution of cytokeratin and GFAP

    Directory of Open Access Journals (Sweden)

    Mosier Amanda L

    2010-03-01

    Full Text Available Abstract Background Optic nerve regeneration (ONR following injury is a model for central nervous system regeneration. In zebrafish, ONR is rapid - neurites cross the lesion and enter the optic tectum within 7 days; in mammals regeneration does not take place unless astrocytic reactivity is suppressed. Glial fibrillary acidic protein (GFAP is used as a marker for retinal and optic nerve astrocytes in both fish and mammals, even though it has long been known that astrocytes of optic nerves in many fish, including zebrafish, express cytokeratins and not GFAP. We used immunofluorescence to localize GFAP and cytokeratin in wild-type zebrafish and transgenic zebrafish expressing green fluorescent protein (GFP under control of a GFAP promoter to determine the pattern of expression of intermediate filaments in retina and optic nerve. Findings GFAP labeling and GFAP gene expression as indicated by GFP fluorescence was found only in the Müller glial cells of the retina. Within Müller cells, GFP fluorescence filled the entire cell while GFAP labelling was more restricted in distribution. No GFAP expression was observed in optic nerves. Cytokeratin labeling of astrocytes was observed throughout the optic nerve and less intensely in cells in the retinal inner plexiform layer. The retinal inner limiting membrane was strongly labeled by anti-cytokeratin. Conclusions Studies of astrocyte function during ONR in zebrafish cannot solely rely on GFAP as an astrocyte marker or indicator of reactivity. Future studies of ONR in zebrafish should include evaluation of changes in cytokeratin expression and localization in the optic nerve.

  9. Long-term result of guided nerve regeneration with an inert microporous polytetrafluoroethylene conduit

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Objective: To evaluate the long-term outcome of Polytetrafluoroethylene (PTFE) conduit in nerve repair and to provide more evidence in view of its potential application to achieve a satisfactory functional recovery in clinical settings. Methods: Thirty-six Wistar rats had their right sciatic nerve transected and were repaired with either conventional microsuture technique (Control group, n=18) or a PTFE conduit with a gap of 5 mm left between the nerve stumps (PTFE group, n=18). At 6 and 9 months after the operation, electrophysiological assessment and measurement of gastrocnemius muscle weight were conducted and morphology of the regenerated nerves were studied with image analysis. Results: At 6 months postoperatively, the nerve conduction velocity recovered to 60.86% and 54.36% (P>0.05), and the gastrocnemius muscle weight recovered to 50.89% and 46.11% (P>0.05) in the Control group and the PTFE group respectively. At 9 months postoperatively, the recovery rate was 65.99% and 58.79% for NCV (P>0.05), and 52.56% and 47.89% for gastrocnemius muscle weight (P>0.05) in the Control group and the PTFE group respectively. Regenerated nerve fibers in the PTFE group had a regular round shape with no fragmentation, wrinkling or splitting of the myelin sheath. Image analysis revealed that the ratio of the myelin area to the total fiber area was larger at 9 months than at 6 months in both groups (P<0.01). Conclusions: Microporous PTFE conduit may be an alternative for nerve repair allowing of guided nerve regeneration and functional recovery with no obvious adverse effect at long-term.

  10. A rare case of bilateral optic nerve sheath meningioma

    Directory of Open Access Journals (Sweden)

    Somen Misra

    2014-01-01

    Full Text Available A 60-year-old female presented with gradual, painless, progressive diminution of vision, and progressive proptosis of left eye since 7 years. Ophthalmological examination revealed mild proptosis and total optic atrophy in the left eye. Magnetic resonance imaging (MRI and computed tomography (CT brain with orbit showed bilateral optic nerve sheath meningioma (ONSM involving the intracranial, intracanalicular, intraorbital part of the optic nerve extending up to optic chiasma and left cavernous sinus.

  11. 3D multi-channel bi-functionalized silk electrospun conduits for peripheral nerve regeneration.

    Science.gov (United States)

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

    2015-01-01

    Despite technological advances over the past 25 years, a complete recovery from peripheral nerve injuries remains unsatisfactory today. The autograft is still considered the "gold standard" in clinical practice; however, postoperative complications and limited availability of nerve tissue have motivated the development of alternative approaches. Among them, the development of biomimetic nerve graft substitutes is one of the most promising strategies. In this study, multichanneled silk electrospun conduits bi-functionalized with Nerve Growth Factor (NGF) and Ciliary Neurotropic Factor (CNTF) were fabricated to enhance peripheral nerve regeneration. These bioactive guides consisting of longitudinally oriented channels and aligned nanofibers were designed in order to mimic the fascicular architecture and fibrous extracellular matrix found in native nerve. The simple use of the electrospinning technique followed by a manual manipulation to manufacture these conduits provides tailoring of channel number and diameter size to create perineurium-like structures. Functionalization of the silk fibroin nanofiber did not affect its secondary structure and chemical property. ELISA assays showed the absence of growth factors passive release from the functionalized fibers avoiding the topical accumulation of proteins. In addition, our biomimetic multichanneled functionalized nerve guides displayed a mechanical behavior comparable to that of rat sciatic nerve with an ultimate peak stress of 4.0 ± 0.6 MPa and a corresponding elongation at failure of 156.8 ± 46.7%. Taken together, our results demonstrate for the first time our ability to design and characterize a bi-functionalized nerve conduit consisting of electrospun nanofibers with multichannel oriented and nanofibers aligned for peripheral regeneration. Our bioactive silk tubes thus represent a new and promising technique towards the creation of a biocompatible nerve guidance conduit. Copyright © 2014 Elsevier Ltd. All

  12. Sustained Growth Factor Delivery Promotes Axonal Regeneration in Long Gap Peripheral Nerve Repair

    Science.gov (United States)

    Kokai, Lauren E.; Bourbeau, Dennis; Weber, Douglas; McAtee, Jedidiah

    2011-01-01

    The aim of this study was to evaluate the long-term effect of localized growth factor delivery on sciatic nerve regeneration in a critical-size (>1 cm) peripheral nerve defect. Previous work has demonstrated that bioactive proteins can be encapsulated within double-walled, poly(lactic-co-glycolic acid)/poly(lactide) microspheres and embedded within walls of biodegradable polymer nerve guides composed of poly(caprolactone). Within this study, nerve guides containing glial cell line-derived neurotrophic factor (GDNF) were used to bridge a 1.5-cm defect in the male Lewis rat for a 16-week period. Nerve repair was evaluated through functional assessment of joint angle range of motion using video gait kinematics, gastrocnemius twitch force, and gastrocnemius wet weight. Histological evaluation of nerve repair included assessment of Schwann cell and neurofilament location with immunohistochemistry, evaluation of tissue integration and organization throughout the lumen of the regenerated nerve with Masson's trichrome stain, and quantification of axon fiber density and g-ratio. Results from this study showed that the measured gastrocnemius twitch force in animals treated with GDNF was significantly higher than negative controls and was not significantly different from the isograft-positive control group. Histological assessment of explanted conduits after 16 weeks showed improved tissue integration within GDNF releasing nerve guides compared to negative controls. Nerve fibers were present across the entire length of GDNF releasing guides, whereas nerve fibers were not detectable beyond the middle region of negative control guides. Therefore, our results support the use of GDNF for improved functional recovery above negative controls following large axonal defects in the peripheral nervous system. PMID:21189072

  13. Schwann cells originating from skin-derived precursors promote peripheral nerve regeneration in rats

    Institute of Scientific and Technical Information of China (English)

    Ping Zhang; Xiaocheng Lu; Jianghai Chen; Zhenbing Chen

    2014-01-01

    Artiifcial guidance channels containing Schwann cells can promote the regeneration of injured peripheral nerve over long distances. However, primary Schwann cells are not suitable for autotransplantation. Under speciifc conditions, skin-derived progenitors can be induced to dif-ferentiate into Schwann cells. Therefore, adult rat dorsal skin (dermis)-derived progenitors were isolated and induced to differentiate with DMEM/F12 containing B27, neuregulin 1, and for-skolin. Immunolfuorescence staining and reverse transcription polymerase chain reaction (RT-PCR) conifrmed that the resultant cells were indeed Schwann cells. Artiifcial guidance channels containing skin-derived progenitors, Schwann cells originating from skin-derived progenitors, or primary Schwann cells were used to bridge 5 mm sciatic nerve defects. Schwann cells originating from skin-derived progenitors signiifcantly promoted sciatic nerve axonal regeneration. The sig-niifcant recovery of injured rat sciatic nerve function after the transplantation of Schwann cells originating from skin-derived progenitors was conifrmed by electromyogram. The therapeutic effect of Schwann cells originating from skin-derived progenitors was better than that of skin-de-rived progenitors. These findings indicate that Schwann cells originating from skin-derived precursors can promote peripheral nerve regeneration in rats.

  14. Development of biomaterial scaffold for nerve tissue engineering: Biomaterial mediated neural regeneration

    Directory of Open Access Journals (Sweden)

    Sethuraman Swaminathan

    2009-11-01

    Full Text Available Abstract Neural tissue repair and regeneration strategies have received a great deal of attention because it directly affects the quality of the patient's life. There are many scientific challenges to regenerate nerve while using conventional autologous nerve grafts and from the newly developed therapeutic strategies for the reconstruction of damaged nerves. Recent advancements in nerve regeneration have involved the application of tissue engineering principles and this has evolved a new perspective to neural therapy. The success of neural tissue engineering is mainly based on the regulation of cell behavior and tissue progression through the development of a synthetic scaffold that is analogous to the natural extracellular matrix and can support three-dimensional cell cultures. As the natural extracellular matrix provides an ideal environment for topographical, electrical and chemical cues to the adhesion and proliferation of neural cells, there exists a need to develop a synthetic scaffold that would be biocompatible, immunologically inert, conducting, biodegradable, and infection-resistant biomaterial to support neurite outgrowth. This review outlines the rationale for effective neural tissue engineering through the use of suitable biomaterials and scaffolding techniques for fabrication of a construct that would allow the neurons to adhere, proliferate and eventually form nerves.

  15. Cutaneous lesions sensory impairment recovery and nerve regeneration in leprosy patients

    Directory of Open Access Journals (Sweden)

    Ximena Illarramendi

    2012-12-01

    Full Text Available It is important to understand the mechanisms that enable peripheral neurons to regenerate after nerve injury in order to identify methods of improving this regeneration. Therefore, we studied nerve regeneration and sensory impairment recovery in the cutaneous lesions of leprosy patients (LPs before and after treatment with multidrug therapy (MDT. The skin lesion sensory test results were compared to the histopathological and immunohistochemical protein gene product (PGP 9.5 and the p75 nerve growth factor receptors (NGFr findings. The cutaneous neural occupation ratio (CNOR was evaluated for both neural markers. Thermal and pain sensations were the most frequently affected functions at the first visit and the most frequently recovered functions after MDT. The presence of a high cutaneous nerve damage index did not prevent the recovery of any type of sensory function. The CNOR was calculated for each biopsy, according to the presence of PGP and NGFr-immunostained fibres and it was not significantly different before or after the MDT. We observed a variable influence of MDT in the recovery from sensory impairment in the cutaneous lesions of LPs. Nociception and cold thermosensation were the most recovered sensations. The recovery of sensation in the skin lesions appeared to be associated with subsiding inflammation rather than with the regenerative activity of nerve fibres.

  16. Development of biomaterial scaffold for nerve tissue engineering: Biomaterial mediated neural regeneration.

    Science.gov (United States)

    Subramanian, Anuradha; Krishnan, Uma Maheswari; Sethuraman, Swaminathan

    2009-11-25

    Neural tissue repair and regeneration strategies have received a great deal of attention because it directly affects the quality of the patient's life. There are many scientific challenges to regenerate nerve while using conventional autologous nerve grafts and from the newly developed therapeutic strategies for the reconstruction of damaged nerves. Recent advancements in nerve regeneration have involved the application of tissue engineering principles and this has evolved a new perspective to neural therapy. The success of neural tissue engineering is mainly based on the regulation of cell behavior and tissue progression through the development of a synthetic scaffold that is analogous to the natural extracellular matrix and can support three-dimensional cell cultures. As the natural extracellular matrix provides an ideal environment for topographical, electrical and chemical cues to the adhesion and proliferation of neural cells, there exists a need to develop a synthetic scaffold that would be biocompatible, immunologically inert, conducting, biodegradable, and infection-resistant biomaterial to support neurite outgrowth. This review outlines the rationale for effective neural tissue engineering through the use of suitable biomaterials and scaffolding techniques for fabrication of a construct that would allow the neurons to adhere, proliferate and eventually form nerves.

  17. Electrospun micro- and nanofiber tubes for functional nervous regeneration in sciatic nerve transections

    Directory of Open Access Journals (Sweden)

    Amadio Stefano

    2008-04-01

    Full Text Available Abstract Background Although many nerve prostheses have been proposed in recent years, in the case of consistent loss of nervous tissue peripheral nerve injury is still a traumatic pathology that may impair patient's movements by interrupting his motor-sensory pathways. In the last few decades tissue engineering has opened the door to new approaches;: however most of them make use of rigid channel guides that may cause cell loss due to the lack of physiological local stresses exerted over the nervous tissue during patient's movement. Electrospinning technique makes it possible to spin microfiber and nanofiber flexible tubular scaffolds composed of a number of natural and synthetic components, showing high porosity and remarkable surface/volume ratio. Results In this study we used electrospun tubes made of biodegradable polymers (a blend of PLGA/PCL to regenerate a 10-mm nerve gap in a rat sciatic nerve in vivo. Experimental groups comprise lesioned animals (control group and lesioned animals subjected to guide conduits implantated at the severed nerve stumps, where the tubular scaffolds are filled with saline solution. Four months after surgery, sciatic nerves failed to reconnect the two stumps of transected nerves in the control animal group. In most of the treated animals the electrospun tubes induced nervous regeneration and functional reconnection of the two severed sciatic nerve tracts. Myelination and collagen IV deposition have been detected in concurrence with regenerated fibers. No significant inflammatory response has been found. Neural tracers revealed the re-establishment of functional neuronal connections and evoked potential results showed the reinnervation of the target muscles in the majority of the treated animals. Conclusion Corroborating previous works, this study indicates that electrospun tubes, with no additional biological coating or drug loading treatment, are promising scaffolds for functional nervous regeneration. They

  18. Optical coherence tomography of the prostate nerves

    Science.gov (United States)

    Chitchian, Shahab

    Preservation of the cavernous nerves during prostate cancer surgery is critical in preserving a man's ability to have spontaneous erections following surgery. These microscopic nerves course along the surface of the prostate within a few millimeters of the prostate capsule, and they vary in size and location from one patient to another, making preservation of the nerves difficult during dissection and removal of a cancerous prostate gland. These observations may explain in part the wide variability in reported sexual potency rates (9--86%) following prostate cancer surgery. Any technology capable of providing improved identification, imaging, and visualization of the cavernous nerves during prostate cancer surgery would be of great assistance in improving sexual function after surgery, and result in direct patient benefit. Optical coherence tomography (OCT) is a noninvasive optical imaging technique capable of performing high-resolution cross-sectional in vivo and in situ imaging of microstructures in biological tissues. OCT imaging of the cavernous nerves in the rat and human prostate has recently been demonstrated. However, improvements in the OCT system and the quality of the images for identification of the cavernous nerves is necessary before clinical use. The following chapters describe complementary approaches to improving identification and imaging of the cavernous nerves during OCT of the prostate gland. After the introduction to OCT imaging of the prostate gland, the optimal wavelength for deep imaging of the prostate is studied in Chapter 2. An oblique-incidence single point measurement technique using a normal-detector scanning system was implemented to determine the absorption and reduced scattering coefficients, mua and m's , of fresh canine prostate tissue, ex vivo, from the diffuse reflectance profile of near-IR light as a function of source-detector distance. The effective attenuation coefficient, mueff, and the Optical Penetration Depth (OPD) were

  19. A NEW PLLA PCL COPOLYMER FOR NERVE REGENERATION

    NARCIS (Netherlands)

    DENDUNNEN, WFA; SCHAKENRAAD, JM; ZONDERVAN, GJ; PENNINGS, AJ; VANDERLEI, B; ROBINSON, PH

    1993-01-01

    The aim of this study is to evaluate the functional and cell biological applicability of a two-ply nerve guide constructed of a PLLA/PCL (i.e. poly-L-lactide and poly-epsilon-caprolactone) copolymer. To do so, we performed a cytotoxicity test, a subcutaneous biodegradation test and an in situ implan

  20. G-CSF prevents caspase 3 activation in Schwann cells after sciatic nerve transection, but does not improve nerve regeneration.

    Science.gov (United States)

    Frost, Hanna K; Kodama, Akira; Ekström, Per; Dahlin, Lars B

    2016-10-15

    Exogenous granulocyte-colony stimulating factor (G-CSF) has emerged as a drug candidate for improving the outcome after peripheral nerve injuries. We raised the question if exogenous G-CSF can improve nerve regeneration following a clinically relevant model - nerve transection and repair - in healthy and diabetic rats. In short-term experiments, distance of axonal regeneration and extent of injury-induced Schwann cell death was quantified by staining for neurofilaments and cleaved caspase 3, respectively, seven days after repair. There was no difference in axonal outgrowth between G-CSF-treated and non-treated rats, regardless if healthy Wistar or diabetic Goto-Kakizaki (GK) rats were examined. However, G-CSF treatment caused a significant 13% decrease of cleaved caspase 3-positive Schwann cells at the lesion site in healthy rats, but only a trend in diabetic rats. In the distal nerve segments of healthy rats a similar trend was observed. In long-term experiments of healthy rats, regeneration outcome was evaluated at 90days after repair by presence of neurofilaments, wet weight of gastrocnemius muscle, and perception of touch (von Frey monofilament testing weekly). The presence of neurofilaments distal to the suture line was similar in G-CSF-treated and non-treated rats. The weight ratio of ipsi-over contralateral gastrocnemius muscles, and perception of touch at any time point, were likewise not affected by G-CSF treatment. In addition, the inflammatory response in short- and long-term experiments was studied by analyzing ED1 stainable macrophages in healthy rats, but in neither case was any attenuation seen at the injury site or distal to it. G-CSF can prevent caspase 3 activation in Schwann cells in the short-term, but does not detectably affect the inflammatory response, nor improve early or late axonal outgrowth or functional recovery.

  1. ECHOGRAPHIC PICTURE OF OPTIC NERVE GLIOMA IN NEUROFIBROMATOSIS TYPE-1

    Directory of Open Access Journals (Sweden)

    Biljana Kuzmanović

    2002-12-01

    Full Text Available Background. Authors want to present echographic picture of orbital part of low-grade pilocytic astrocytoma involving the optic nerve and/or chiasm and optic tract (optic pathway glioma or visual pathway glioma.Methods. 4 children with neurofibromatosis type-1 complicated with optic pathway glioma diagnosed earlier with magnetic resonance were examined by ultrasound. Standardised A-scan technique was used for optic nerve width measurement. The 30° test and B-scan (axial, transverse and longitudinal sections of both eyes and orbits were performed as well.Results. The optic nerve diameter in our cases ranged from 4.48 to 8.5 mm. Two children had the left side optic pathway glioma, one boy had the right side optic pathway glioma and in one tumour was bilateral. The transversal section of the nerve revealed dark oval and in more perpendicular sections round void of the nerve. As the beam is swept towards the orbital apex void becomes more fusiform. The nerve and its sheaths are markedly widened. An abnormal increase in reflectivity and irregularity of the spike’s pattern is exhibited as well. No calcification along the sheaths is noticed. The transverse section of the tumour demonstrated an »inverse doughnut« sign. The outer whiter outline of the widened sheaths surrounds an inner darker circle. The longitudinal section revealed the optic nerve head continuing into the widened optic nerve. The 30° test was negative. The differential diagnosis of meningeoma, optic neuritis and orbital cysticercosis should be considered.Conclusions. Ultrasound as a cheap, safe, easily repeatable imaging method should become a method of choice for screening optic nerve tumours in neurofibromatosis type-1, especially in children, as well as for follow-up after treatment.

  2. Unilateral Optic Nerve Hypoplasia with Contralateral Optic Pathway Hypoplasia: A Case Report.

    Science.gov (United States)

    Nishi, Tomo; Yukawa, Eiichi; Taoka, Toshiaki; Ogata, Nahoko

    2013-01-01

    Optic nerve hypoplasia is diagnosed by the ophthalmoscopic appearance of the fundus of the eye and by standard magnetic resonance imaging of the brain. The ability to study eyes with optic nerve hypoplasia by magnetic resonance diffusion tensor imaging has improved the evaluation of the optic pathways. The authors report a case of unilateral optic nerve hypoplasia with hypoplasia of the contralateral optic pathway. The entire visual pathway of this patient was examined by magnetic resonance and magnetic resonance diffusion tensor imaging. The images show a decrease of the volume of the optic radiation contralateral to the optic nerve abnormality and also pre- and post-chiasmal abnormalities.

  3. Adipose Tissue Graft Improves Early but not Late Stages of Nerve Regeneration.

    Science.gov (United States)

    Bloancă, Vlad; Ceauşu, Amalia Raluca; Jitariu, Andreea Adriana; Barmayoun, Ariana; Moş, Raluca; Crăiniceanu, Zorin; Bratu, Tiberiu

    2017-01-01

    The aim of the study was to assess the effect of autologous fat graft on nerve regeneration by means of immunohistochemistry. The rat sciatic nerve was used; complete transection followed by primary neurorrhaphy was performed on both hind legs, on the left side a processed fat graft was applied, surrounding the nerve. Nerve biopsies were collected and immunohistochemical procedures were performed for glial fibrillary acidic protein (GFAP) and for neurofilament-associated protein(NFAP). At 4 weeks, GFAP-positive cells were observed in the connective tissue formed between the two nerve endings on the left side only. At 10 weeks, GFAP-positive structures were present and exhibited a tendency to become linear on both sides, with an increased density on the left. NFAP-positive expression was present in the left treated limb with a disorganized pattern. Adipose tissue led to the stimulation of GFAP-positive Schwann cells, which could have a positive impact on nerve regeneration in the clinical setting. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  4. MRI of optic nerve lesion in multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Fujii, Koichi; Uehara, Masako; Ashikaga, Ryuuichirou; Inoue, Masaaki; Yamamoto, Takashi; Hamada, Tatsumi; Ishida, Osamu; Nakao, Yuzou; Miyakoshi, Keizou (Kinki Univ., Osakasayama, Osaka (Japan). School of Medicine)

    1992-12-01

    We evaluated the ability of MRI using short TI inversion recovery (STIR) to detect optic nerve lesions in multiple sclerosis (MS). Eleven patients with MS were studied with MRI at 0.5 T. STIR images revealed high signal lesions in all of 14 nerves in 11 patients with previous and recurrent attack of optic neuritis. In addition, two of seven asymptomatic nerves also showed high intensity on STIR images. The high signal lesions on STIR images seemed to reflect demyelination in the nerves with some attacks and to show occult lesions in the nerves without any attack. STIR method was concluded to be a potentially useful procedure in detection of optic nerve lesions in MS. (author).

  5. Biosynthesis of membrane cholesterol during peripheral nerve development, degeneration and regeneration.

    Science.gov (United States)

    Yao, J K

    1988-09-01

    Biosynthesis of peripheral nerve cholesterol was investigated by the in vivo and in vitro incorporation of [1-14C]-acetate into sciatic endoneurium of normal rats during development, degeneration and regeneration. Labeled sterols were rapidly formed (less than 10 min) within the endoneurial portion of sciatic nerve after [1-14C]acetate administration by intraneural injection. The majority of labeled sterols were initially found in lanosterol and desmosterol. After six hr, the 14C-labeling in both precursors was decreased to minimum, whereas cholesterol became the major labeled product of sterol. As myelination proceeded, the incorporation of [1-14C]acetate into endoneurial cholesterol decreased rapidly and reached a minimum after six mo. In mature adult nerve, an increased proportion of biosynthesis of lanosterol and desmosterol also was demonstrated. The in vitro incorporation of [1-14C]acetate into cholesterol was inhibited during Wallerian degeneration. Instead, cholesteryl esters were labeled as the major sterol product. Such inhibition, however, was not observed in the adult Trembler nerve (Brain Res. 325, 21-27, 1985), which is presumed to be due to a primary metabolic disorder of Schwann cells. The cholesterol biosynthesis was gradually resumed in degenerated nerve by either regeneration of crush-injured nerve or reattachment of the transected nerve. These results suggest that cholesterol biosynthesis in peripheral nerve relies on the axon to provide necessary substrates. De novo synthesis appears to be one of the major sources of endoneurial cholesterol that forms and maintains peripheral nerve myelin.

  6. Mechanical tension promotes skin nerve regeneration by upregulating nerve growth factor expression

    Institute of Scientific and Technical Information of China (English)

    Hu Xiao; Dechang Wang; Ran Huo; Yibing Wang; Yongqiang Feng; Qiang Li

    2013-01-01

    This study aimed to explore the role of mechanical tension in hypertrophic scars and the change in nerve density using hematoxylin-eosin staining and S100 immunohistochemistry, and to observe the expression of nerve growth factor by western blot analysis. The results demonstrated that mechanical tension contributed to the formation of a hyperplastic scar in the back skin of rats, in conjunction with increases in both nerve density and nerve growth factor expression in the scar tissue. These experimental findings indicate that the cutaneous nervous system plays a role in hypertrophic scar formation caused by mechanical tension.

  7. Nerve regeneration in chitosan conduits and in autologous nerve grafts in healthy and in type 2 diabetic Goto-Kakizaki rats.

    Science.gov (United States)

    Stenberg, Lena; Kodama, Akira; Lindwall-Blom, Charlotta; Dahlin, Lars B

    2016-02-01

    Knowledge about nerve regeneration after nerve injury and reconstruction in appropriate diabetic animal models is incomplete. Short-term nerve regeneration after reconstruction of a 10-mm sciatic nerve defect with either a hollow chitosan conduit or an autologous nerve graft was investigated in healthy Wistar and diabetic Goto-Kakizaki (GK) rats. After 21 days, axonal outgrowth, the presence of activated and apoptotic Schwann cells and the thickness of the formed matrix in the conduits were measured. In general, nerve regeneration was superior in autologous nerve grafts. In chitosan conduits, a matrix, which was thicker in diabetic rats, was formed and was positively correlated with length of axonal outgrowth. Axonal outgrowth in conduits and in nerve grafts extended further in diabetic rats than in healthy rats. There was a higher percentage of activating transcription factor 3 (ATF3)-immunostained cells in nerve segments from healthy rats than in diabetic rats after autologous nerve graft reconstruction. In chitosan conduits, more cleaved caspase 3-stained Schwann cells were generally observed in the matrix from the diabetic rats than in healthy rats. However, there were fewer apoptotic cells in the distal segment in diabetic rats reconstructed with a chitosan conduit. Preoperative glucose levels were positively correlated with axonal outgrowth after both reconstruction methods. Axonal regeneration was better in autologous nerve grafts than in hollow chitosan conduits and was enhanced in diabetic GK rats compared to healthy rats after reconstruction. This study provides insights into the nerve regeneration process in a clinically relevant diabetic animal model. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

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

    Science.gov (United States)

    2015-09-01

    2 AD______________ AWARD NUMBER: W81XWH-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: Li, Zhongyu CONTRACTING ORGANIZATION: Wake Forest...DATE September 2015 2. REPORT TYPE Annual Report 3. DATES COVERED 1 Sep 2014 - 31 Aug 2015 4. TITLE AND SUBTITLE Acceleration of Regeneration of Large

  9. Magnetic resonance imaging in optic nerve lesions with multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Kojima, Shigeyuki; Hirayama, Keizo; Kakisu, Yonetsugu; Adachi, Emiko (Chiba Univ. (Japan). School of Medicine)

    1990-12-01

    Magnetic resonance imaging (MRI) of the optic nerve was performed in 10 patients with multiple sclerosis (MS) using short inversion time inversion recovery (STIR) pulse sequences, and the results were compared with the visual evoked potentials (VEP). The 10 patients had optic neuritis in the chronic or remitting phase together with additional symptoms or signs allowing a diagnosis of clinically definite or probable MS. Sixteen optic nerves were clinically affected and 4 were unaffected. MRI was performed using a 0.5 tesla supeconducting unit, and multiple continuous 5 mm coronal and axial STIR images were obtained. A lesion was judged to be present if a focal or diffuse area of increased signal intensity was detectd in the optic nerve. In VEP, a delay in peak latency or no P 100 component was judged to be abnormal. With regard to the clinically affected optic nerves, MRI revealed a region of increased signal intensity in 14/16 (88%) and the VEP was abnormal in 16/16 (100%). In the clinically unaffected optic nerves, MRI revealed an increased signal intensity in 2/4 (50%). One of these nerves had an abnormal VEP and the other had a VEP latency at the upper limit of normal. The VEP was abnormal in 1/4 (25%). In the clinically affected optic nerves, the degree of loss of visual acuity was not associated with the longitudinal extent of the lesions shown by MRI. The mean length was 17.5 mm in optic nerves with a slight disturbance of visual acuity and 15.0 mm in nerves with severe visual loss. MRI using STIR pulse sequences was found to be almost as sensitive as VEP in detecting both clinically affected and unaffected optic nerve lesions in patients with MS, and was useful in visualizing the location or size of the lesions. (author).

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

    Science.gov (United States)

    2014-10-01

    tests to determine purity (size exclusion chromatography for molecular weight, amino acids analysis, ELISA for protein identification, and gel rheology ...labeled hydrogel will be used in a fate and distribution study in a rat model. The hydrogel gel has been successfully labeled and adequate labeled...distribution study. Labeled keratin gel will be placed inside nerve conduits. The ends of the conduits will be closed, and the conduits will be

  11. Endoscopic optic nerve decompression for nontraumatic compressive optic neuropathy

    Directory of Open Access Journals (Sweden)

    Cheng-long REN

    2015-11-01

    Full Text Available Objective To describe the preliminary experience with endoscopic optic nerve decompression (EOND for nontraumatic compressive optic neuropathies (NCONs. Methods The clinical data of 10 patients, male 5 and female 5, with a mean age of 44.3±5.1 years, who underwent EOND for visual loss (n=5 or visual deterioration (n=5 due to tumor compression in General Hospital of Armed Police Forces of China in the period from April 2013 to April 2014 were analyzed retrospectively. Preoperative and 6-month-postoperative clinical and imaging data of these patients were reviewed and analyzed. Results Among 5 patients who lost light perception (including 2 patients with bilateral optic nerve compression before operation, 4 of them showed visual improvement to different degrees on the 7th day after operation (with improvement of bilateral visual acuity. The other 5 patients with visual impairment before operation recovered their visual acuity to different extent after the operation. All of the patients had no obvious post-operative complications. Conclusion EOND is a safe, effective, and minimally invasive surgical technique affording recovery of visual function to NCON patients. DOI: 10.11855/j.issn.0577-7402.2015.11.12

  12. All-optical WDM Regeneration of DPSK Signals using Optical Fourier Transformation and Phase Sensitive Amplification

    DEFF Research Database (Denmark)

    Guan, Pengyu; Røge, Kasper Meldgaard; Kjøller, Niels-Kristian;

    2015-01-01

    We propose a novel all-optical WDM regeneration scheme for DPSK signals based on optical Fourier transformation and phase sensitive amplification. Phase regeneration of a WDM signal consisting of 4x10-Gbit/s phase noise degraded DPSK channels is demonstrated for the first time.......We propose a novel all-optical WDM regeneration scheme for DPSK signals based on optical Fourier transformation and phase sensitive amplification. Phase regeneration of a WDM signal consisting of 4x10-Gbit/s phase noise degraded DPSK channels is demonstrated for the first time....

  13. RAGE Deficiency Improves Postinjury Sciatic Nerve Regeneration in Type 1 Diabetic Mice

    Science.gov (United States)

    Juranek, Judyta K.; Geddis, Matthew S.; Song, Fei; Zhang, Jinghua; Garcia, Jose; Rosario, Rosa; Yan, Shi Fang; Brannagan, Thomas H.; Schmidt, Ann Marie

    2013-01-01

    Peripheral neuropathy and insensate limbs and digits cause significant morbidity in diabetic individuals. Previous studies showed that deletion of the receptor for advanced end-glycation products (RAGE) in mice was protective in long-term diabetic neuropathy. Here, we tested the hypothesis that RAGE suppresses effective axonal regeneration in superimposed acute peripheral nerve injury attributable to tissue-damaging inflammatory responses. We report that deletion of RAGE, particularly in diabetic mice, resulted in significantly higher myelinated fiber densities and conduction velocities consequent to acute sciatic nerve crush compared with wild-type control animals. Consistent with key roles for RAGE-dependent inflammation, reconstitution of diabetic wild-type mice with RAGE-null versus wild-type bone marrow resulted in significantly improved axonal regeneration and restoration of function. Diabetic RAGE-null mice displayed higher numbers of invading macrophages in the nerve segments postcrush compared with wild-type animals, and these macrophages in diabetic RAGE-null mice displayed greater M2 polarization. In vitro, treatment of wild-type bone marrow–derived macrophages with advanced glycation end products (AGEs), which accumulate in diabetic nerve tissue, increased M1 and decreased M2 gene expression in a RAGE-dependent manner. Blockade of RAGE may be beneficial in the acute complications of diabetic neuropathy, at least in part, via upregulation of regeneration signals. PMID:23172920

  14. Micro-Nanostructured Polyaniline Assembled in Cellulose Matrix via Interfacial Polymerization for Applications in Nerve Regeneration.

    Science.gov (United States)

    Xu, Dingfeng; Fan, Lin; Gao, Lingfeng; Xiong, Yan; Wang, Yanfeng; Ye, Qifa; Yu, Aixi; Dai, Honglian; Yin, Yixia; Cai, Jie; Zhang, Lina

    2016-07-13

    Conducting polymers have emerged as frontrunners to be alternatives for nerve regeneration, showing a possibility of the application of polyaniline (PANI) as the nerve guidance conduit. In the present work, the cellulose hydrogel was used as template to in situ synthesize PANI via the limited interfacial polymerization method, leading to one conductive side in the polymer. PANI sub-micrometer dendritic particles with mean diameter of ∼300 nm consisting of the PANI nanofibers and nanoparticles were uniformly assembled into the cellulose matrix. The hydrophobic PANI nanoparticles were immobilized in the hydrophilic cellulose via the phytic acid as "bridge" at presence of water through hydrogen bonding interaction. The PANI/cellulose composite hydrogels exhibited good mechanical properties and biocompatibility as well as excellent guiding capacity for the sciatic nerve regeneration of adult Sprague-Dawley rats without any extra treatment. On the basis of the fact that the pure cellulose hydrogel was an inert material for the neural repair, PANI played an indispensable role on the peripheral nerve regeneration. The hierarchical micro-nanostructure and electrical conductivity of PANI could remarkably induce the adhesion and guiding extension of neurons, showing its great potential in biomedical materials.

  15. Inhibition of Rho-kinase differentially affects axon regeneration of peripheral motor and sensory nerves.

    Science.gov (United States)

    Joshi, Abhijeet R; Bobylev, Ilja; Zhang, Gang; Sheikh, Kazim A; Lehmann, Helmar C

    2015-01-01

    The small GTPase RhoA and its down-stream effector Rho-kinase (ROCK) are important effector molecules of the neuronal cytoskeleton. Modulation of the RhoA/ROCK pathway has been shown to promote axonal regeneration, however in vitro and animal studies are inconsistent regarding the extent of axonal outgrowth induced by pharmacological inhibition of ROCK. We hypothesized that injury to sensory and motor nerves result in diverse activation levels of RhoA, which may impact the response of those nerve fiber modalities to ROCK inhibition. We therefore examined the effects of Y-27632, a chemical ROCK inhibitor, on the axonal outgrowth of peripheral sensory and motor neurons grown in the presence of growth-inhibiting chondroitin sulfate proteoglycans (CSPGs). In addition we examined the effects of three different doses of Y-27632 on nerve regeneration of motor and sensory nerves in animal models of peripheral nerve crush. In vitro, sensory neurons were less responsive to Y-27632 compared to motor neurons in a non-growth permissive environment. These differences were associated with altered expression and activation of RhoA in sensory and motor axons. In vivo, systemic treatment with high doses of Y-27632 significantly enhanced the regeneration of motor axons over short distances, while the regeneration of sensory fibers remained largely unchanged. Our results support the concept that in a growth non-permissive environment, the regenerative capacity of sensory and motor axons is differentially affected by the RhoA/ROCK pathway, with motor neurons being more responsive compared to sensory. Future treatments, that are aimed to modulate RhoA activity, should consider this functional diversity.

  16. The effect of 810 nm low-power Ga-Al-As laser treatment on the regeneration of a damaged optic nerve%810nm低能量镓铝砷激光对大鼠视神经钳夹伤后的再生作用

    Institute of Scientific and Technical Information of China (English)

    林阳阳; 苑秀华; 周方倩; 王中莉; 刘苗苗; 林振原

    2011-01-01

    Objective To determine whether or not 810 nm low power Ga-Al-As laser treatment can stimulate the regeneration of damaged optic nerves by measuring the expression of growth associated protein 43 ( GAP-43 )and flash-visual evoked potential (F-VEP). Methods Eighty-eight Wistar rats weighing (180-220) g were randomly divided into a laser therapy group with 40 rats,an injury group with 32 rats,and a normal control group with 16 rats.Each group was subdivided into 1st,3rd,6th and 9th week subgroups.A standardized crushing of the optic nerve was applied to make the model.After this,the laser therapy group was treated for 3 minutes daily at 60 mW applied transcutaneously to a 5 mm diameter spot on the injured optic nerve.The injury and normal control groups received the same treatment with no laser output.The expression of GAP-43 was detected by immunohistochemistry and RT-PCR after 1,3,6 and 9 weeks of treatment.F-VEP was measured pre-injury,immediately after injury and 1,3,6 and 9 weeks post injury. Results After the optic nerve was injured,obvious changes in F-VEP were detected,including significantly prolonged latencies of N1,P1 and N2 waves.The latency increased immediately after the optic nerve injured,and then recovered,but after 1 and 3 weeks the latency was still prolonged.There was significant recovery from the 3rd to the 9th week.In the laser therapy group,the peak latencies of the N1,P1 and N2 waves were also prolonged,but the changes were less than those in the injury group.Expression of GAP-43 was hardly detectable in normal retinas and optic nerves.GAP-43 had its highest expression level at 1 week post-injury,and then decreased.At the 1st,3rd and 6th week post-injury,the expression of GAP-43 in the laser therapy group was significantly higher than in the injury group.GAP-43 mRNA content in the retina showed the same tendency as GAP-43 protein. Conclusion A 810 nm low power Ga-Al-As laser can promote neural repair and axonal regeneration after optic nerve

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

    Science.gov (United States)

    Sharma, Anup Dutt

    Peripheral nerve regeneration is a complex biological process responsible for regrowth of neural tissue following a nerve injury. The main objective of this project was to enhance peripheral nerve regeneration using interdisciplinary approaches involving polymeric scaffolds, stem cell therapy, drug delivery and high content screening. Biocompatible and biodegradable polymeric materials such as poly (lactic acid) were used for engineering conduits with micropatterns capable of providing mechanical support and orientation to the regenerating axons and polyanhydrides for fabricating nano/microparticles for localized delivery of neurotrophic growth factors and cytokines at the site of injury. Transdifferentiated bone marrow stromal cells or mesenchymal stem cells (MSCs) were used as cellular replacements for lost native Schwann cells (SCs) at the injured nerve tissue. MSCs that have been transdifferentiated into an SC-like phenotype were tested as a substitute for the myelinating SCs. Also, genetically modified MSCs were engineered to hypersecrete brain- derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) to secrete therapeutic factors which Schwann cell secrete. To further enhance the regeneration, nerve growth factor (NGF) and interleukin-4 (IL4) releasing polyanhydrides nano/microparticles were fabricated and characterized in vitro for their efficacy. Synergistic use of these proposed techniques was used for fabricating a multifunctional nerve regeneration conduit which can be used as an efficient tool for enhancing peripheral nerve regeneration.

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

    Science.gov (United States)

    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.

  19. 3D-engineering of Cellularized Conduits for Peripheral Nerve Regeneration

    Science.gov (United States)

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

    2016-01-01

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

  20. Neuron-Specific Deletion of the Nf2 Tumor Suppressor Impairs Functional Nerve Regeneration

    Science.gov (United States)

    Schulz, Alexander; Büttner, Robert; Toledo, Andrea; Baader, Stephan L.; von Maltzahn, Julia; Irintchev, Andrey; Bauer, Reinhard; Morrison, Helen

    2016-01-01

    In contrast to axons of the central nervous system (CNS), axons of the peripheral nervous system (PNS) show better, but still incomplete and often slow regeneration following injury. The tumor suppressor protein merlin, mutated in the hereditary tumor syndrome Neurofibromatosis type 2 (NF2), has recently been shown to have RhoA regulatory functions in PNS neurons—in addition to its well-characterized, growth-inhibitory activity in Schwann cells. Here we report that the conditional knockout of merlin in PNS neurons leads to impaired functional recovery of mice following sciatic nerve crush injury, in a gene-dosage dependent manner. Gross anatomical or electrophysiological alterations of sciatic nerves could not be detected. However, correlating with attenuated RhoA activation due to merlin deletion, ultrastructural analysis of nerve samples indicated enhanced sprouting of axons with reduced caliber size and increased myelination compared to wildtype animals. We conclude that deletion of the tumor suppressor merlin in the neuronal compartment of peripheral nerves results in compromised functional regeneration after injury. This mechanism could explain the clinical observation that NF2 patients suffer from higher incidences of slowly recovering facial nerve paralysis after vestibular schwannoma surgery. PMID:27467574

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

    Directory of Open Access Journals (Sweden)

    Christopher S Crowe

    2015-09-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-05-01

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

  3. Clonal analysis reveals nerve-dependent and independent roles on mammalian hind limb tissue maintenance and regeneration.

    Science.gov (United States)

    Rinkevich, Yuval; Montoro, Daniel T; Muhonen, Ethan; Walmsley, Graham G; Lo, David; Hasegawa, Masakazu; Januszyk, Michael; Connolly, Andrew J; Weissman, Irving L; Longaker, Michael T

    2014-07-08

    The requirement and influence of the peripheral nervous system on tissue replacement in mammalian appendages remain largely undefined. To explore this question, we have performed genetic lineage tracing and clonal analysis of individual cells of mouse hind limb tissues devoid of nerve supply during regeneration of the digit tip, normal maintenance, and cutaneous wound healing. We show that cellular turnover, replacement, and cellular differentiation from presumed tissue stem/progenitor cells within hind limb tissues remain largely intact independent of nerve and nerve-derived factors. However, regenerated digit tips in the absence of nerves displayed patterning defects in bone and nail matrix. These nerve-dependent phenotypes mimic clinical observations of patients with nerve damage resulting from spinal cord injury and are of significant interest for translational medicine aimed at understanding the effects of nerves on etiologies of human injury.

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

    Science.gov (United States)

    2014-10-01

    Products 21 7. Participants & Other Collaborating Organizations 22 8. Special Reporting Requirements 23 9. Appendices 24 3... Corning Inc) were also added to the nerve conduit. Figure 2 illustrates the nerve conduit in which the drug (NGF) stored in the orifice between...7525 DLG 7E, Evonik). The PLGA was dissolved in acetone and ethanol and conduits were then formed and emulsified in water. 15µm diffusion holes

  5. Evaluation of the Optic Nerve Head in Glaucoma.

    Science.gov (United States)

    Gandhi, Monica; Dubey, Suneeta

    2013-01-01

    Glaucoma is an optic neuropathy leading to changes in the intrapaillary and parapaillary regions of the optic disk. Despite technological advances, clinical identification of optic nerve head characteristics remains the first step in diagnosis. Careful examination of the disk parameters including size, shape, neuroretinal rim shape and pallor; size of the optic cup in relation to the area of the disk; configuration and depth of the optic cup; ratios of cup-to-disk diameter and cup-to-disk area; presence and location of splinter-shaped hemorrhages; occurrence, size, configuration, and location of parapapillary chorioretinal atrophy; and visibility of the retinal nerve fiber layer (RNFL) is important to differentiate between the glaucomatous and nonglaucomatous optic neuropathy. How to cite this article: Gandhi M, Dubey S. Evaluation of the Optic Nerve Head in Glaucoma. J Current Glau Prac 2013;7(3):106-114.

  6. Poly(amidoamine Hydrogels as Scaffolds for Cell Culturing and Conduits for Peripheral Nerve Regeneration

    Directory of Open Access Journals (Sweden)

    Fabio Fenili

    2011-01-01

    Full Text Available Biodegradable and biocompatible poly(amidoamine-(PAA- based hydrogels have been considered for different tissue engineering applications. First-generation AGMA1 hydrogels, amphoteric but prevailing cationic hydrogels containing carboxylic and guanidine groups as side substituents, show satisfactory results in terms of adhesion and proliferation properties towards different cell lines. Unfortunately, these hydrogels are very swellable materials, breakable on handling, and have been found inadequate for other applications. To overcome this problem, second-generation AGMA1 hydrogels have been prepared adopting a new synthetic method. These new hydrogels exhibit good biological properties in vitro with satisfactory mechanical characteristics. They are obtained in different forms and shapes and successfully tested in vivo for the regeneration of peripheral nerves. This paper reports on our recent efforts in the use of first-and second-generation PAA hydrogels as substrates for cell culturing and tubular scaffold for peripheral nerve regeneration.

  7. The synthesis and characterization of a novel biodegradable and electroactive polyphosphazene for nerve regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Qingsong, E-mail: zhangqingsong@whut.edu.cn [Biomedical Materials and Engineering Research Center, Wuhan University of Technology, Wuhan 430070 (China); Yan Yuhua; Li Shipu; Feng Tao [Biomedical Materials and Engineering Research Center, Wuhan University of Technology, Wuhan 430070 (China)

    2010-01-01

    Conductive polymers have been of great interest to the biopharmaceutical industry because of their cell adhesion and proliferation. In this paper, a novel electrically-conductive and biodegradable polyphosphazene polymer containing parent aniline pentamer (PAP) and glycine ethyl ester (GEE) as side chains was synthesized through a nucleophilic substitution reaction for its potential application in nerve regeneration. The electrical conductivity of the polymer was {approx} 2 x 10{sup -5} S/cm in the semiconducting region upon preliminarily protonic-doped experiment. Degradation studies carried out in phosphate-buffered saline at 37 deg. C showed a mass loss of {approx} 50% after 70 days. In vitro cytotoxicity to the RSC96 Schwann cells was evaluated using the cell viability assay. The polymer exhibited no cytotoxicity, indicating that such a polyphosphazene polymer has potential as scaffold material in tissue engineering for peripheral nerve regeneration or other biomedical devices that require electroactivity.

  8. Relationship Between Optic Nerve Appearance and Retinal Nerve Fiber Layer Thickness as Explored with Spectral Domain Optical Coherence Tomography

    Science.gov (United States)

    Aleman, Tomas S.; Huang, Jiayan; Garrity, Sean T.; Carter, Stuart B.; Aleman, Wendy D.; Ying, Gui-shuang; Tamhankar, Madhura A.

    2014-01-01

    Purpose To study the relationship between the appearance of the optic nerve and the retinal nerve fiber layer (RNFL) thickness determined by spectral domain optical coherence tomography (OCT). Methods Records from patients with spectral domain-OCT imaging in a neuro-ophthalmology practice were reviewed. Eyes with glaucoma/glaucoma suspicion, macular/optic nerve edema, pseudophakia, and with refractive errors > 6D were excluded. Optic nerve appearance by slit lamp biomicroscopy was related to the RNFL thickness by spectral domain-OCT and to visual field results. Results Ninety-one patients (176 eyes; mean age: 49 ± 15 years) were included. Eighty-three eyes (47%) showed optic nerve pallor; 89 eyes (50.6%) showed RNFL thinning (sectoral or average peripapillary). Average peripapillary RNFL thickness in eyes with pallor (mean ± SD = 76 ± 17 μm) was thinner compared to eyes without pallor (91 ± 14 μm, P < 0.001). Optic nerve pallor predicted RNFL thinning with a sensitivity of 69% and a specificity of 75%. Optic nerve appearance predicted RNFL thinning (with a sensitivity and specificity of 81%) when RNFL had thinned by ∼ 40%. Most patients with pallor had RNFL thinning with (66%) or without (25%) visual field loss; the remainder had normal RNFL and fields (5%) or with visual field abnormalities (4%). Conclusions Optic nerve pallor as a predictor of RNFL thinning showed fair sensitivity and specificity, although it is optimally sensitive/specific only when substantial RNFL loss has occurred. Translational Relevance Finding an acceptable relationship between the optic nerve appearance by ophthalmoscopy and spectral domain-OCT RNFL measures will help the clinician's interpretation of the information provided by this technology, which is gaining momentum in neuro-ophthalmic research. PMID:25374773

  9. Further Development of Scaffolds for Regeneration of Nerves

    Science.gov (United States)

    Sakamoto, Jeffrey; Tuszynski, Mark

    2009-01-01

    Progress has been made in continuing research on scaffolds for the guided growth of nerves to replace damaged ones. The scaffolds contain pores that are approximately cylindrical and parallel, with nearly uniform widths ranging from tens to hundreds of microns. At the earlier stage of development, experimental scaffolds had been made from agarose hydrogel. Such a scaffold was made in a multistep process in which poly(methyl methacrylate) [PMMA] fibers were used as templates for the pores. The process included placement of a bundle of the PMMA fibers in a tube, filling the interstices in the tube with a hot agarose solution, cooling to turn the solution into a gel, and then immersion in acetone to dissolve the PMMA fibers. The scaffolds were typically limited to about 25 pores per scaffold, square cross sections of no more than about 1.5 by 1.5 mm, and lengths of no more than about 2 mm.

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

    Directory of Open Access Journals (Sweden)

    Wei GJ

    2013-08-01

    Full Text Available Guo-Jun Wei,1 Meng Yao,1 Yan-Song Wang,1 Chang-Wei Zhou,1 De-Yu Wan,1 Peng-Zhen Lei,1 Jian Wen,1 Hong-Wei Lei,2 Da-Ming Dong1 1Department of Orthopaedics, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China; 2Department of Rheumatology, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China Background: Peripheral nerve injury is a common trauma, but presents a significant challenge to the clinic. Silk-based materials have recently become an important biomaterial for tissue engineering applications due to silk’s biocompatibility and impressive mechanical and degradative properties. In the present study, a silk fibroin peptide (SF16 was designed and used as a component of the hydrogel scaffold for the repair of peripheral nerve injury. Methods: The SF16 peptide’s structure was characterized using spectrophotometry and atomic force microscopy, and the SF16 hydrogel was analyzed using scanning electron microscopy. The effects of the SF16 hydrogel on the viability and growth of live cells was first assessed in vitro, on PC12 cells. The in vivo test model involved the repair of a nerve gap with tubular nerve guides, through which it was possible to identify if the SF16 hydrogel would have the potential to enhance nerve regeneration. In this model physiological saline was set as the negative control, and collagen as the positive control. Walking track analysis and electrophysiological methods were used to evaluate the functional recovery of the nerve at 4 and 8 weeks after surgery. Results: Analysis of the SF16 peptide’s characteristics indicated that it consisted of a well-defined secondary structure and exhibited self-assembly. Results of scanning electron microscopy showed that the peptide based hydrogel may represent a porous scaffold that is viable for repair of peripheral nerve injury. Analysis of cell culture also supported that the hydrogel was an effective

  11. Combining peripheral nerve grafts and chondroitinase promotes functional axonal regeneration in the chronically injured spinal cord.

    Science.gov (United States)

    Tom, Veronica J; Sandrow-Feinberg, Harra R; Miller, Kassi; Santi, Lauren; Connors, Theresa; Lemay, Michel A; Houlé, John D

    2009-11-25

    Because there currently is no treatment for spinal cord injury, most patients are living with long-standing injuries. Therefore, strategies aimed at promoting restoration of function to the chronically injured spinal cord have high therapeutic value. For successful regeneration, long-injured axons must overcome their poor intrinsic growth potential as well as the inhibitory environment of the glial scar established around the lesion site. Acutely injured axons that regenerate into growth-permissive peripheral nerve grafts (PNGs) reenter host tissue to mediate functional recovery if the distal graft-host interface is treated with chondroitinase ABC (ChABC) to cleave inhibitory chondroitin sulfate proteoglycans in the scar matrix. To determine whether a similar strategy is effective for a chronic injury, we combined grafting of a peripheral nerve into a highly relevant, chronic, cervical contusion site with ChABC treatment of the glial scar and glial cell line-derived neurotrophic factor (GDNF) stimulation of long-injured axons. We tested this combination in two grafting paradigms: (1) a peripheral nerve that was grafted to span a chronic injury site or (2) a PNG that bridged a chronic contusion site with a second, more distal injury site. Unlike GDNF-PBS treatment, GDNF-ChABC treatment facilitated axons to exit the PNG into host tissue and promoted some functional recovery. Electrical stimulation of axons in the peripheral nerve bridge induced c-Fos expression in host neurons, indicative of synaptic contact by regenerating fibers. Thus, our data demonstrate, for the first time, that administering ChABC to a distal graft interface allows for functional axonal regeneration by chronically injured neurons.

  12. Recurrent laryngeal nerve regeneration using an oriented collagen scaffold containing Schwann cells.

    Science.gov (United States)

    Chitose, Shun-Ichi; Sato, Kiminori; Fukahori, Mioko; Sueyoshi, Shintaro; Kurita, Takashi; Umeno, Hirohito

    2017-07-01

    Regeneration of the recurrent laryngeal nerve (RLN), which innervates the intrinsic laryngeal muscles such that they can perform complex functions, is particularly difficult to achieve. Synkinesis after RLN neogenesis leads to uncoordinated movement of laryngeal muscles. Recently, some basic research studies have used cultured Schwann cells (SCs) to repair peripheral nerve injuries. This study aimed to regenerate the RLN using an oriented collagen scaffold containing cultured SCs. Preliminary animal experiment. A 10-mm-long autologous canine cervical ansa was harvested. The nerve tissue was scattered and subcultured on oriented collagen sheets in reduced serum medium. After verifying that the smaller cultivated cells with high nucleus-cytoplasm ratios were SCs, collagen sheets with longitudinally oriented cells were rolled and inserted into a 20-mm collagen conduit. The fabricated scaffolds containing SCs were autotransplanted to a 20-mm deficient RLN, and vocal fold movements and histological characteristics were observed. Scaffolds containing cultured SCs were successfully fabricated. Immunocytochemical examination revealed that these isolated and cultured cells, identified as SCs, expressed S-100 protein and GFAP but not vimentin. The orientation of SCs matched that of the oriented collagen sheet. Two months after successful transplantation, laryngeal endoscopy revealed coordinated movement of the bilateral vocal folds by external stimulation under light general anesthesia. Hematoxylin and eosin staining showed that the regenerated RLN lacked epineurium surrounding the nerve fibers and was interspersed with collagen fibers. Myelin protein zero was expressed around many axons. Partial regeneration of RLN was achieved through the use of oriented collagen scaffolding. NA Laryngoscope, 127:1622-1627, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  13. Assessment of in vivo behavior of polymer tube nerve grafts simultaneously with the peripheral nerve regeneration process using scanning electron microscopy technique.

    Science.gov (United States)

    Szarek, Dariusz; Marycz, Krzysztof; Laska, Jadwiga; Bednarz, Paulina; Jarmundowicz, Włodzimierz

    2013-01-01

    In this study, scanning electron microscopy (SEM) has been applied for instantaneous assessment of processes occurring at the site of regenerating nerve. The technique proved to be especially useful when an artificial implant should have been observed but have not yet been extensively investigated before for assessment of nerve tissue. For in vivo studies, evaluation of implant's morphology and its neuroregenerative properties is of great importance when new prototype is developed. However, the usually applied histological techniques require separate and differently prepared samples, and therefore, the results are never a 100% comparable. In our research, we found SEM as a technique providing detailed data both on an implant behavior and the nerve regeneration process inside the implant. Observations were carried out during 12-week period on rat sciatic nerve injury model reconstructed with nerve autografts and different tube nerve grafts. Samples were analyzed with haematoxylin-eosin (HE), immunocytochemical staining for neurofillament and S-100 protein, SEM, TEM, and the results were compared. SEM studies enabled to obtain characteristic pictures of the regeneration process similarly to TEM and histological studies. Schwann cell transformation and communication as well as axonal outgrowth were identified, newly created and matured axons could be recognized. Concurrent analysis of biomaterial changes in the implant (degradation, collapsing of the tube wall, migration of alginate gel) was possible. This study provides the groundwork for further use of the described technique in the nerve regeneration studies.

  14. Stretch-induced nerve injury: a proposed technique for the study of nerve regeneration and evaluation of the influence of gabapentin on this model

    Directory of Open Access Journals (Sweden)

    J.A. Machado

    2013-11-01

    Full Text Available The rat models currently employed for studies of nerve regeneration present distinct disadvantages. We propose a new technique of stretch-induced nerve injury, used here to evaluate the influence of gabapentin (GBP on nerve regeneration. Male Wistar rats (300 g; n=36 underwent surgery and exposure of the median nerve in the right forelimbs, either with or without nerve injury. The technique was performed using distal and proximal clamps separated by a distance of 2 cm and a sliding distance of 3 mm. The nerve was compressed and stretched for 5 s until the bands of Fontana disappeared. The animals were evaluated in relation to functional, biochemical and histological parameters. Stretching of the median nerve led to complete loss of motor function up to 12 days after the lesion (P<0.001, compared to non-injured nerves, as assessed in the grasping test. Grasping force in the nerve-injured animals did not return to control values up to 30 days after surgery (P<0.05. Nerve injury also caused an increase in the time of sensory recovery, as well as in the electrical and mechanical stimulation tests. Treatment of the animals with GBP promoted an improvement in the morphometric analysis of median nerve cross-sections compared with the operated vehicle group, as observed in the area of myelinated fibers or connective tissue (P<0.001, in the density of myelinated fibers/mm2 (P<0.05 and in the degeneration fragments (P<0.01. Stretch-induced nerve injury seems to be a simple and relevant model for evaluating nerve regeneration.

  15. Effect of white adipose tissue flap and insulin-like growth factor-1 on nerve regeneration in rats.

    Science.gov (United States)

    Kilic, Ayhan; Ojo, Bukola; Rajfer, Rebecca A; Konopka, Geoffrey; Hagg, Daniel; Jang, Eugene; Akelina, Yelena; Mao, Jeremy J; Rosenwasser, Melvin P; Tang, Peter

    2013-07-01

    Adipose tissue-derived stem cells and insulin-like growth factor-1 (IGF-1) have shown potential to enhance peripheral nerve regeneration. The purpose of this study was to investigate the effect of an in vivo biologic scaffold, consisting of white adipose tissue flap (WATF) and/or IGF-1 on nerve regeneration in a crush injury model. Forty rats all underwent a sciatic nerve crush injury and then received: a pedicled WATF, a controlled local release of IGF-1, both treatments, or no treatment at the injury site. Outcomes were the normalized maximum isometric tetanic force (ITF) of the tibialis anterior muscle and histomorphometric measurements. At 4 weeks, groups with WATF had a statistically significant improvement in maximum ITF recovery, as compared to those without (P nerve regeneration in this model. Utilizing the WATF may have a beneficial therapeutic role in peripheral nerve injuries. Copyright © 2013 Wiley Periodicals, Inc.

  16. Microelectronic neural bridge for signal regeneration and function rebuilding over two separate nerves

    Energy Technology Data Exchange (ETDEWEB)

    Shen Xiaoyan; Wang Zhigong; Xie Shushan; Huang Zonghao [Institute of RF- and OE-ICs, Southeast University, Nanjing 210096 (China); Lue Xiaoying, E-mail: zgwang@seu.edu.cn [Key Laboratory of Bioelectronics, Southeast University, Nanjing 210096 (China)

    2011-06-15

    According to the feature of neural signals, a micro-electronic neural bridge (MENB) has been designed. It consists of two electrode arrays for neural signal detection and functional electrical stimulation (FES), and a microelectronic circuit for signal amplifying, processing, and FES driving. The core of the system is realized in 0.5-{mu}m CMOS technology and used in animal experiments. A special experimental strategy has been designed to demonstrate the feasibility of the system. With the help of the MENB, the withdrawal reflex function of the left/right leg of one spinal toad has been rebuilt in the corresponding leg of another spinal toad. According to the coherence analysis between the source and regenerated neural signals, the controlled spinal toad's sciatic nerve signal is delayed by 0.72 ms in relation to the sciatic nerve signal of the source spinal toad and the cross-correlation function reaches a value of 0.73. This shows that the regenerated signal is correlated with the source sciatic signal significantly and the neural activities involved in reflex function have been regenerated. The experiment demonstrates that the MENB is useful in rebuilding the neural function between nerves of different bodies. (semiconductor integrated circuits)

  17. Neuroprotection trek--the next generation: neuromodulation II. Applications--epilepsy, nerve regeneration, neurotrophins

    Science.gov (United States)

    Andrews, Russell J.

    2003-01-01

    Three examples of neuroprotective applications of electrical stimulation-neuromodulation-are considered: (1) the diagnosis and treatment of epilepsy, (2) the augmentation of peripheral nerve regeneration after transection, and (3) the interaction between electrical stimulation and neurotrophins (notably brain derived neurotrophic factor [BDNF]) in various neuroprotective situations. The research cited demonstrates clear benefit from appropriate electrical stimulation in the treatment of (1) certain patients with medication-refractory epilepsy, and (2) the functional regeneration of peripheral nerves after transection and surgical repair. Furthermore, neuromodulation of peripheral nerve regeneration has been associated with an increase in the neurotrophin BDNF. The roles of BDNF and other neurotrophins in several disorders of the nervous system are discussed in the context of neuromodulation and its augmentation of neurotrophins. Neuromodulation-at least in part through its effect on BDNF and other neurotrophins-will likely play a major role in the treatment (and possibly prevention) of disorders of the nervous system for which neuroproteive pharmacologic agents have traditionally been sought.

  18. Microelectronic neural bridge for signal regeneration and function rebuilding over two separate nerves*

    Institute of Scientific and Technical Information of China (English)

    Shen Xiaoyan; Wang Zhigong; Lü Xiaoying; Xie Shushan; Huang Zonghao

    2011-01-01

    According to the feature of neural signals, a micro-electronic neural bridge (MENB) has been designed.It consists of two electrode arrays for neural signal detection and functional electrical stimulation (FES), and a microelectronic circuit for signal amplifying, processing, and FES driving. The core of the system is realized in 0.5-μm CMOS technology and used in animal experiments. A special experimental strategy has been designed to demonstrate the feasibility of the system. With the help of the MENB, the withdrawal reflex function of the left/right leg of one spinal toad has been rebuilt in the corresponding leg of another spinal toad. According to the coherence analysis between the source and regenerated neural signals, the controlled spinal toad's sciatic nerve signal is delayed by 0.72 ms in relation to the sciatic nerve signal of the source spinal toad and the cross-correlation function reaches a value of 0.73. This shows that the regenerated signal is correlated with the source sciatic signal significantly and the neural activities involved in reflex function have been regenerated. The experiment demonstrates that the MENB is useful in rebuilding the neural function between nerves of different bodies.

  19. Regeneration of long-distance peripheral nerve defects after delayed reconstruction in healthy and diabetic rats is supported by immunomodulatory chitosan nerve guides.

    Science.gov (United States)

    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

  20. Alignment and composition of laminin-polycaprolactone nanofiber blends enhance peripheral nerve regeneration.

    Science.gov (United States)

    Neal, Rebekah A; Tholpady, Sunil S; Foley, Patricia L; Swami, Nathan; Ogle, Roy C; Botchwey, Edward A

    2012-02-01

    Peripheral nerve transection occurs commonly in traumatic injury, causing deficits distal to the injury site. Conduits for repair currently on the market are hollow tubes; however, they often fail due to slow regeneration over long gaps. To facilitate increased regeneration speed and functional recovery, the ideal conduit should provide biochemically relevant signals and physical guidance cues, thus playing an active role in regeneration. To that end, laminin and laminin-polycaprolactone (PCL) blend nanofibers were fabricated to mimic peripheral nerve basement membrane. In vitro assays established 10% (wt) laminin content is sufficient to retain neurite-promoting effects of laminin. In addition, modified collector plate design to introduce an insulating gap enabled the fabrication of aligned nanofibers. The effects of laminin content and fiber orientation were evaluated in rat tibial nerve defect model. The lumens of conduits were filled with nanofiber meshes of varying laminin content and alignment to assess changes in motor and sensory recovery. Retrograde nerve conduction speed at 6 weeks was significantly faster in animals receiving aligned nanofiber conduits than in those receiving random nanofiber conduits. Animals receiving nanofiber-filled conduits showed some conduction in both anterograde and retrograde directions, whereas in animals receiving hollow conduits, no impulse conduction was detected. Aligned PCL nanofibers significantly improved motor function; aligned laminin blend nanofibers yielded the best sensory function recovery. In both cases, nanofiber-filled conduits resulted in better functional recovery than hollow conduits. These studies provide a firm foundation for the use of natural-synthetic blend electrospun nanofibers to enhance existing hollow nerve guidance conduits.

  1. Electrical stimulation combined with exercise increase axonal regeneration after peripheral nerve injury.

    Science.gov (United States)

    Asensio-Pinilla, Elena; Udina, Esther; Jaramillo, Jessica; Navarro, Xavier

    2009-09-01

    Although injured peripheral axons are able to regenerate, functional recovery is usually poor after nerve transection. In this study we aim to elucidate the role of neuronal activity, induced by nerve electrical stimulation and by exercise, in promoting axonal regeneration and modulating plasticity in the spinal cord after nerve injury. Four groups of adult rats were subjected to sciatic nerve transection and suture repair. Two groups received electrical stimulation (3 V, 0.1 ms at 20 Hz) for 1 h, immediately after injury (ESa) or during 4 weeks (1 h daily; ESc). A third group (ES+TR) received 1 h electrical stimulation and was submitted to treadmill running during 4 weeks (5 m/min, 2 h daily). A fourth group performed only exercise (TR), whereas an untreated group served as control (C). Nerve conduction, H reflex and algesimetry tests were performed at 1, 3, 5, 7 and 9 weeks after surgery, to assess muscle reinnervation and changes in excitability of spinal cord circuitry. Histological analysis was made at the end of the follow-up. Groups that received acute ES and/or were forced to exercise in the treadmill showed higher levels of muscle reinnervation and increased numbers of regenerated myelinated axons when compared to control animals or animals that received chronic ES. Combining ESa with treadmill training significantly improved muscle reinnervation during the initial phase. The facilitation of the monosynaptic H reflex in the injured limb was reduced in all treated groups, suggesting that the maintenance of activity helps to prevent the development of hyperreflexia.

  2. VGLUT1 synapses and P-boutons on regenerating motoneurons after nerve crush.

    Science.gov (United States)

    Schultz, Adam J; Rotterman, Travis M; Dwarakanath, Anirudh; Alvarez, Francisco J

    2017-09-01

    Stretch-sensitive Ia afferent monosynaptic connections with motoneurons form the stretch reflex circuit. After nerve transection, Ia afferent synapses and stretch reflexes are permanently lost, even after regeneration and reinnervation of muscle by motor and sensory afferents is completed in the periphery. This loss greatly affects full recovery of motor function. However, after nerve crush, reflex muscle forces during stretch do recover after muscle reinnervation and reportedly exceed 140% baseline values. This difference might be explained by structural preservation after crush of Ia afferent synapses on regenerating motoneurons and decreased presynaptic inhibitory control. We tested these possibilities in rats after crushing the tibial nerve (TN), and using Vesicular GLUtamate Transporter 1 (VGLUT1) and the 65 kDa isoform of glutamic acid-decarboxylase (GAD65) as markers of, respectively, Ia afferent synapses and presynaptic inhibition (P-boutons) on retrogradely labeled motoneurons. We analyzed motoneurons during regeneration (21 days post crush) and after they reinnervate muscle (3 months). The results demonstrate a significant loss of VGLUT1 terminals on dendrites and cell bodies at both 21 days and 3 months post-crush. However, in both cellular compartments, the reductions were small compared to those observed after TN full transection. In addition, we found a significant decrease in the number of GAD65 P-boutons per VGLUT1 terminal and their coverage of VGLUT1 boutons. The results support the hypothesis that better preservation of Ia afferent synapses and a change in presynaptic inhibition could contribute to maintain or even increase the stretch reflex after nerve crush and by difference to nerve transection. © 2017 Wiley Periodicals, Inc.

  3. Fibrin glue repair leads to enhanced axonal elongation during early peripheral nerve regeneration in an in vivo mouse model

    Institute of Scientific and Technical Information of China (English)

    Georgios Koulaxouzidis; Gernot Reim; Christian Witzel

    2015-01-01

    Microsurgical suturing is the gold standard of nerve coaptation. Although literature on the usefulness of ifbrin glue as an alternative is becoming increasingly available, it remains contradic-tory. Furthermore, no data exist on how both repair methods might inlfuence the morphological aspects (arborization; branching) of early peripheral nerve regeneration. We used the sciatic nerve transplantation model in thy-1 yellow lfuorescent protein mice (YFP;n = 10). Pieces of nerve (1cm) were grafted from YFP-negative mice (n = 10) into those expressing YFP. We per-formed microsuture coaptations on one side and used ifbrin glue for repair on the contralateral side. Seven days after grafting, the regeneration distance, the percentage of regenerating and ar-borizing axons, the number of branches per axon, the coaptation failure rate, the gap size at the repair site and the time needed for surgical repair were all investigated. Fibrin glue repair resulted in regenerating axons travelling further into the distal nerve. It also increased the percentage of arborizing axons. No coaptation failure was detected. Gap sizes were comparable in both groups. Fibrin glue signiifcantly reduced surgical repair time. The increase in regeneration distance, even after the short period of time, is in line with the results of others that showed faster axonal regen-eration after ifbrin glue repair. The increase in arborizing axons could be another explanation for better functional and electrophysiological results after ifbrin glue repair. Fibrin glue nerve coap-tation seems to be a promising alternative to microsuture repair.

  4. Intrinsic facilitation of adult peripheral nerve regeneration by the Sonic hedgehog morphogen.

    Science.gov (United States)

    Martinez, Jose A; Kobayashi, Masaki; Krishnan, Anand; Webber, Christine; Christie, Kimberly; Guo, GuiFang; Singh, Vandana; Zochodne, Douglas W

    2015-09-01

    Intrinsic molecular determinants of neurodevelopmental outcomes assume new, albeit related roles during adult neural regeneration. Here we studied and identified a facilitatory role for Sonic hedgehog protein (Shh), a morphogen that influences motor neuron floor plate architecture, during adult peripheral neuron regeneration. Shh and its receptors were expressed in adult dorsal root ganglia (DRG) neurons, axons and glia and trended toward higher levels following axotomy injury. Knockdown of Shh in adult sensory neurons resulted in decreased outgrowth and branching in vitro, identifying a role for Shh in facilitating outgrowth. The findings argued for an intrinsic action to support neuron regeneration. Support of advancement and turning however, were not identified in adult sensory neuron growth cones in response to local extrinsic gradients of Shh. That intrinsic Shh supported the regrowth of peripheral nerves after injury was confirmed by the analysis of axon regrowth from the proximal stumps of transected sciatic nerves. By exposing regenerating axons to local infusions of Shh siRNA in vivo within a conduit bridging the transected proximal and distal stumps, we achieved local knockdown of Shh. In response, there was attenuated axonal and Schwann cell outgrowth beyond the transection zone. Unlike its role during neurodevelopment, Shh facilitates but does not confer regenerative outgrowth properties to adult neurons alone. Exploring the differing properties of morphogens and related proteins in the adult nervous system identifies new and important roles for them.

  5. Regulation of dorso‐ventral polarity by the nerve cord during annelid regeneration: A review of experimental evidence

    Science.gov (United States)

    Boilly‐Marer, Yolande; Bely, Alexandra E.

    2017-01-01

    Abstract An important goal for understanding regeneration is determining how polarity is conferred to the regenerate. Here we review findings in two groups of polychaete annelids that implicate the ventral nerve cord in assigning dorso‐ventral polarity, and specifically ventral identity, to the regenerate. In nereids, surgical manipulations indicate that parapodia develop where dorsal and ventral body wall territories contact. Without a nerve cord at the wound site, the regenerate differentiates no evident polarity (with no parapodia) and only dorsal identity, while with two nerve cords the regenerate develops a twinned dorso‐ventral axis (with four parapodia per segment instead of the normal two). In sabellids, a striking natural dorso‐ventral inversion in parapodial morphology occurs along the body axis and this inversion is morphologically correlated with the position of the nerve cord. Parapodial inversion also occurs in segments in which the nerve cord has been removed, even without any segment amputation. Together, these data strongly support a role for the nerve cord in annelid dorso‐ventral pattern regulation, with the nerve cord conferring ventral identity. PMID:28616245

  6. Experimental considerations concerning the use of stem cells and tissue engineering for facial nerve regeneration: a systematic review.

    Science.gov (United States)

    Euler de Souza Lucena, Eudes; Guzen, Fausto Pierdoná; Lopes de Paiva Cavalcanti, José Rodolfo; Galvão Barboza, Carlos Augusto; Silva do Nascimento Júnior, Expedito; Cavalcante, Jeferson de Sousa

    2014-05-01

    Peripheral nerve trauma results in functional loss in the innervated organ, and recovery without surgical intervention is rare. Many surgical techniques can be used for repair in experimental models. The authors investigated the source and delivery method of stem cells in experimental outcomes, seeking to clarify whether stem cells must be differentiated in the injured facial nerve and improve the regenerative process. The following key terms were used: nervous regeneration, nerve regeneration, facial nerve regeneration, stem cells, embryonic stem cells, fetal stem cells, adult stem cells, facial nerve, facial nerve trauma, and facial nerve traumatism. The search was restricted to experimental studies that applied stem cell therapy and tissue engineering for nerve repair. Eight studies meeting the inclusion criteria were reviewed. Different sources of stem and precursor cells were explored (bone marrow mesenchymal stem cells, adipose-derived stem cells, dental pulp cells, and neural stem cells) for their potential application in the scenario of facial nerve injuries. Different material conduits (vases, collagen, and polyglycolic acid) were used as bridges. Immunochemistry and electrophysiology are the principal methods for analyzing regenerative effects. Although recent studies have shown that stem cells can act as a promising bridge for nerve repair, considerable optimization of these therapies will be required for their potential to be realized in a clinical setting. Based on these studies, the use of stem cells derived from different sources presents promising results related to facial nerve regeneration and produces effective functional results. The use of tubes also optimizes nerve repair, thus promoting greater myelination and axonal growth of peripheral nerves. Copyright © 2014 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  7. Antioxidative mechanism of Lycium barbarum polysaccharides promotes repair and regeneration following cavernous nerve injury

    Institute of Scientific and Technical Information of China (English)

    Zhan-kui Zhao; Hong-lian Yu; Bo Liu; Hui Wang; Qiong Luo; Xie-gang Ding

    2016-01-01

    Polysaccharides extracted from Lycium barbarum exhibit antioxidant properties. We hypothesized that these polysaccharides resist oxida-tive stress-induced neuronal damage following cavernous nerve injury. In this study, rat models were intragastrically administered Lycium barbarum polysaccharides for 2 weeks at 1, 7, and 14 days after cavernous nerve injury. Serum superoxide dismutase and glutathione peroxidase activities signiifcantly increased at 1 and 2 weeks post-injury. Serum malondialdehyde levels decreased at 2 and 4 weeks. At 12 weeks, peak intracavernous pressure, the number of myelinated axons and nicotinamide adenine dinucleotide phosphate-diaphorase-pos-itive nerve ifbers, levels of phospho-endothelial nitric oxide synthase protein and 3-nitrotyrosine were higher in rats administered at 1 day post-injury compared with rats administered at 7 and 14 days post-injury. These ifndings suggest that application of Lycium barbarum polysaccharides following cavernous nerve crush injury effectively promotes nerve regeneration and erectile functional recovery. This neu-roregenerative effect was most effective in rats orally administered Lycium barbarum polysaccharides at 1 day after cavernous nerve crush injury.

  8. Discrepancies in quantitative assessment of normal and regenerated peripheral nerve fibers between light and electron microscopy.

    Science.gov (United States)

    Ronchi, Giulia; Jager, Sara Buskbjerg; Vaegter, Christian Bjerggaard; Raimondo, Stefania; Giacobini-Robecchi, Maria Giuseppina; Geuna, Stefano

    2014-09-01

    Quantitative estimation of myelinated nerve fiber number, together with fiber size parameters, is one of the most important tools for nerve regeneration research. In this study we used a design-based stereological method to evaluate the regenerative process in two experimental paradigms: crush injury and autograft repair. Samples were embedded in resin and morphometric counting and measurements were performed using both light and electron microscopes. Results show a significant difference in myelinated fiber number estimation between light and electron microscopes, especially after autograft repair; light microscope significantly underestimates the number of fibers because of the large number of very small axons that can be detected only in electron microscope. The analysis of the size parameters also shows a higher number of small fibers in electron microscopic analysis, especially in regenerated nerves. This comparative study shows that the integration of data obtained in light microscope with those obtained in electron microscope is necessary in revealing very small myelinated fibers that cannot be detected otherwise. Moreover, the difference in the estimation of total number of myelinated fibers between light and electron microscopes must be considered in data analysis to ensure accurate interpretation of the results. © 2014 Peripheral Nerve Society.

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

    Science.gov (United States)

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

    2017-04-01

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

  10. Senescence in adipose-derived stem cells and its implications in nerve regeneration

    Institute of Scientific and Technical Information of China (English)

    Cristina Mantovani; Giorgio Terenghi; Valerio Magnaghi

    2014-01-01

    Adult mesenchymal stem cells, specifically adipose-derived stem cells have self-renewal and multiple differentiation potentials and have shown to be the ideal candidate for therapeutic applications in regenerative medicine, particularly in peripheral nerve regeneration. Adipose-de-rived stem cells are easily harvested, although they may show the effects of aging, hence their potential in nerve repair may be limited by cellular senescence or donor age. Cellular senescence is a complex process whereby stem cells grow old as consequence of intrinsic events (e.g., DNA damage) or environmental cues (e.g., stressful stimuli or diseases), which determine a permanent growth arrest. Several mechanisms are implicated in stem cell senescence, although no one is exclusive of the others. In this review we report some of the most important factors modulating the senescence process, which can inlfuence adipose-derived stem cell morphology and function, and compromise their clinical application for peripheral nerve regenerative cell therapy.

  11. Macrophage-Induced Blood Vessels Guide Schwann Cell-Mediated Regeneration of Peripheral Nerves.

    Science.gov (United States)

    Cattin, Anne-Laure; Burden, Jemima J; Van Emmenis, Lucie; Mackenzie, Francesca E; Hoving, Julian J A; Garcia Calavia, Noelia; Guo, Yanping; McLaughlin, Maeve; Rosenberg, Laura H; Quereda, Victor; Jamecna, Denisa; Napoli, Ilaria; Parrinello, Simona; Enver, Tariq; Ruhrberg, Christiana; Lloyd, Alison C

    2015-08-27

    The peripheral nervous system has remarkable regenerative capacities in that it can repair a fully cut nerve. This requires Schwann cells to migrate collectively to guide regrowing axons across a 'bridge' of new tissue, which forms to reconnect a severed nerve. Here we show that blood vessels direct the migrating cords of Schwann cells. This multicellular process is initiated by hypoxia, selectively sensed by macrophages within the bridge, which via VEGF-A secretion induce a polarized vasculature that relieves the hypoxia. Schwann cells then use the blood vessels as "tracks" to cross the bridge taking regrowing axons with them. Importantly, disrupting the organization of the newly formed blood vessels in vivo, either by inhibiting the angiogenic signal or by re-orienting them, compromises Schwann cell directionality resulting in defective nerve repair. This study provides important insights into how the choreography of multiple cell-types is required for the regeneration of an adult tissue.

  12. Analytic methods in assessment of optic nerve cupping.

    Science.gov (United States)

    Jindra, L F; Kuběna, T; Gaudino, R N

    2014-06-01

    The intent of this paper is to provide a systems-based analysis of the methods used to evaluate optic nerve cupping, identify potential flaws in these systems, and propose alternatives better to assess this anatomic quantity. Estimation of optic nerve cupping requires an analytic understanding of both the psychophysical as well as the mathematical bases inherent in this measure. When the (decimal-based) cup-to-disc ratio is used to quantitate optic nerve cupping, a one-dimensional, linear estimate is produced, which in turn is derived from two- or three-dimensional, non-linear physical quantities of area or volume, respectively. When extrapolating from volume, to area, to linear measures, due to the psychophysical constraints which limit this task, such a data-compressed estimate of optic nerve cupping may neither accurately reflect, nor correctly represent, the true amount of cupping actually present in the optic nerve head. This type of one-dimensional metric (when comparing calculations from two- or three-dimensional measures over a range of optic nerve cupping), appears to introduce errors which, while most pronounced earlier on in the disease progression, often overestimate the amount of relative cupping (percent cupping) present in a pathological process like glaucoma. The same systemic errors can also lead to overestimation of the progression in cupping, especially in optic nerves with low cup-to disc values. To provide clinically meaningful estimates of optic nerve cupping, the practitioner needs to be aware of psychophysical and mathematical limitations inherent in using a linear cup-to-disc ratio to estimate the amount of cupping observed in a physical structure like the optic disc. The resultant flaws introduced by observer extrapolation from three, to two, to one dimensions (volume, area, and linear); transposition from non-linear to linear quantities; and optical illusions, caused by factors like disc topology, morphology, and ametropia, can all

  13. Axonal regeneration and remyelination evaluation of chitosan/gelatin-based nerve guide combined with transforming growth factor-β1 and Schwann cells.

    Science.gov (United States)

    Nie, Xin; Deng, Manjing; Yang, Maojin; Liu, Luchuan; Zhang, Yongjie; Wen, Xiujie

    2014-01-01

    Despite efforts in peripheral nerve injury and regeneration, it is difficult to achieve a functional recovery following extended peripheral nerve lesions. Even if artificial nerve conduit, cell components and growth factors can enhance nerve regeneration, integration in peripheral nerve repair and regeneration remains yet to be explored. For this study, we used chitosan/gelatin nerve graft constructed with collagenous matrices as a vehicle for Schwann cells and transforming growth factor-β1 to bridge a 10-mm gap of the sciatic nerve and explored the feasibility of improving regeneration and reinnervation in rats. The nerve regeneration was assessed with functional recovery, electrophysiological test, retrograde labeling, and immunohistochemistry analysis during the post-operative period of 16 weeks. The results showed that the internal sides of the conduits were compact enough to prevent the connective tissues from ingrowth. Nerve conduction velocity, average regenerated myelin area, and myelinated axon count were similar to those treated with autograft (p > 0.05) but significantly higher than those bridged with chitosan/gelatin nerve graft alone (p regeneration and remyelination. A designed graft incorporating all of the tissue-engineering strategies for peripheral nerve regeneration may provide great progress in tissue engineering for nerve repair.

  14. Coincidental Optic Nerve Meningioma and Thyroid Eye Disease.

    Science.gov (United States)

    Garg, Aakriti; Patel, Payal; Lignelli, Angela; Baron, Edward; Kazim, Michael

    2015-01-01

    A 57-year-old woman with diabetes mellitus, hypertension, obesity, and Graves disease presented with clinical evidence of thyroid eye disease (TED) and optic neuropathy. She was referred when a tapered dose of steroids prompted worsening of her TED. CT and MRI were consistent with TED and bilateral optic nerve meningioma. To the authors' knowledge, this is the first reported case of concurrent TED and unsuspected bilateral optic nerve meningioma. When investigating the etiology of TED-associated optic neuropathy, careful attention to orbital imaging is required because coexisting pathology may exist.

  15. Morphometric analysis of the fascicular organisation of the optic nerve

    Directory of Open Access Journals (Sweden)

    Radunović Miroslav

    2015-01-01

    Full Text Available Background/Aim. The optic nerve is anatomically observed in four segments: intrabulbar, orbital, canalicular, and cranial. According to the literature, the surface of the transversal cut of the nerve is different through it. The aim of this study was to evaluate the fascicular organisation of the optic nerve, throughout its three segments from the eye. Methods. Five pairs of optic nerves, obtained from the autopsies were examined. Using Heidenhain's (azan staining, the cuts were prepared for microscopy. Morphometric analysis was performed using the stereological methods for morphometric cytology - the Weible’s testing system M42. The following measures were established: the surface of the transverse cut of the nerve, the entire surface of fasciculi, the entire surface of connective tissue and blood vessels, the number of fasciculi, the surface of a single fasciculus. Results. The surface of the transverse cut of the nerve was found to grow from the orbital to the cranial segment, as well as the entire surface of fasciculi. While their number is significantly lower in the cranial segment, the number of fasciculi varied slightly between the orbital and the canalicular segment. The surface of a single fasciculus grows from the bulb to the chiasma. There is probable a cause to believe that this may be due to fusion of the “small” fasciculi in the orbitocranial direction. Conclusion. There are significant differences among the examined parameters of the different parts of the optic nerve.

  16. An animal model of peripheral nerve regeneration after the application of a collagen-polyvinyl alcohol scaffold and mesenchymal stem cells.

    Science.gov (United States)

    Marinescu, Silviu Adrian; Zărnescu, Otilia; Mihai, Ioana Ruxandra; Giuglea, Carmen; Sinescu, Ruxandra Diana

    2014-01-01

    Extensive nerve injuries often leading to nerve gaps can benefit, besides the gold standard represented by autologous nerve grafts, by the inciting field of tissue engineering. To enhance the role of biomaterials in nerve regeneration, the nerve conduits are associated with Schwann or Schwann-like cells. In this study, we evaluated rat sciatic nerve regeneration, by using a biodegradable nerve guide composed of Collagen (COL) and Polyvinyl Alcohol (PVA), associated with mesenchymal stem cells (MSC). After the exposure of the rat sciatic nerve, a nerve gap was created by excising 1 cm of the nerve. Three experimental groups were used for nerve gap bridging: autografts, nerve conduits filled with medium culture and nerve conduits filled with MSC. The methods of sensory and motor assessment consisted of the functional evaluation of sciatic nerve recovery - toe-spread, pinprick tests and gastrocnemius muscle index (GMI). The histological and immunocytochemical analysis of the probes that were harvested from the repair site was performed at 12 weeks. Successful nerve regeneration was noted in all three groups at the end of the 12th week. The functional and immunocytochemical results suggested that COL-PVA tubes supported with mesenchymal stem cells could be considered similar to autologous nerve grafts in peripheral nerve regeneration, without the drawbacks of the last ones. The functional results were better for the autografts and the ultrastructural data were better for the nerve conduits, but there were not noticed any statistical differences.

  17. Nerve root degeneration and regeneration by intrathecal phenol in rats: a morphologic approach.

    Science.gov (United States)

    Romero-Figueroa, Socorro; Aldrete, J Antonio; Martínez-Cruz, Angelina; Orozco, Sandra; Castillo, Sebastian; Castillo-Henkel, Carlos; Guízar-Sahagún, Gabriel

    2006-12-01

    Intrathecal injection of phenol (ITP) has been used to control intractable pain and spasticity. Direct caustic nerve damage has been postulated as the mechanism of analgesia. Sensation is commonly recovered, suggesting that a spontaneous regeneration process takes place. There is, however, a lack of mechanistic information on ITP therapy. To define morphologically the neurolysis and regeneration phenomena produced by ITP, anesthetized rats were subjected to laminectomy at L5; 5 microl of 22% phenol in saline solution or vehicle (control) was injected. Light and electron microscopy studies of nerve roots were performed at 2, 14, and 60 days after injection. Rats given ITP showed at the early stage a variable amount of roots with signs of infarction characterized by loss of axon-myelin units and thrombosis of intra-root vessels. At 14 days, abundance of macrophages removing debris, open vessels, and nerve sprouts was identified in damaged roots. At this time, non-myelinating glial fibrillary acidic protein-positive Schwann cells were observed in both damaged and apparently undamaged roots. At 60 days, abundance of 2',3'-cyclic nucleotide 3'-phosphodiesterase-positive Schwann cells myelinating newly formed axons was observed in damaged roots. Control rats did not show signs of neural or vascular pathology. Attempting to prevent thrombosis, another group of rats received heparin before ITP; these anti-coagulated rats developed radicular thrombosis, neurolysis, and hemorrhage. In conclusion, neurolysis produced by ITP is associated with acute ischemia (not prevented by heparin) and is followed by vascular, nerve, and myelin regeneration. Our results help understand the lack of efficacy of and some complications by ITP clinical therapy.

  18. Sleeve bridging of the rhesus monkey ulnar nerve with muscular branches of the pronator teres:multiple ampliifcation of axonal regeneration

    Institute of Scientific and Technical Information of China (English)

    Yu-hui Kou; Pei-xun Zhang; Yan-hua Wang; Bo Chen; Na Han; Feng Xue; Hong-bo Zhang; Xiao-feng Yin; Bao-guo Jiang

    2015-01-01

    Multiple-bud regeneration,i.e., multiple amplification, has been shown to exist in peripheral nerve regeneration. Multiple buds grow towards the distal nerve stump during proximal nerve ifber regeneration. Our previous studies have veriifed the limit and validity of multiple ampli-ifcation of peripheral nerve regeneration using small gap sleeve bridging of small donor nerves to repair large receptor nerves in rodents. The present study sought to observe multiple ampli-ifcation of myelinated nerve ifber regeneration in the primate peripheral nerve. Rhesus monkey models of distal ulnar nerve defects were established and repaired using muscular branches of the right forearm pronator teres. Proximal muscular branches of the pronator teres were su-tured into the distal ulnar nerve using the small gap sleeve bridging method. At 6 months after suture, two-ifnger lfexion and mild wrist lfexion were restored in the ulnar-sided injured limbs of rhesus monkey. Neurophysiological examination showed that motor nerve conduction veloc-ity reached 22.63 ± 6.34 m/s on the affected side of rhesus monkey. Osmium tetroxide staining demonstrated that the number of myelinated nerve fibers was 1,657 ± 652 in the branches of pronator teres of donor, and 2,661 ± 843 in the repaired ulnar nerve. The rate of multiple ampliifcation of regenerating myelinated nerve ifbers was 1.61. These data showed that when muscular branches of the pronator teres were used to repair ulnar nerve in primates, effective regeneration was observed in regenerating nerve ifbers, and functions of the injured ulnar nerve were restored to a certain extent. Moreover, multiple ampliifcation was subsequently detected in ulnar nerve axons.

  19. Evaluation of inferior alveolar nerve regeneration by bifocal distraction osteogenesis with retrograde transportation of horseradish peroxidase in dogs.

    Directory of Open Access Journals (Sweden)

    Yosuke Shogen

    Full Text Available BACKGROUND: Bifocal distraction osteogenesis has been shown to be a reliable method for reconstructing segmental mandibular defects. However, there are few reports regarding the occurrence of inferior alveolar nerve regeneration during the process of distraction. Previously, we reported inferior alveolar nerve regeneration after distraction, and evaluated the regenerated nerve using histological and electrophysiological methods. In the present study, we investigated axons regenerated by bifocal distraction osteogenesis using retrograde transportation of horseradish peroxidase in the mandibles of dogs to determine their type and function. METHODS AND FINDINGS: Using a bifocal distraction osteogenesis method, we produced a 10-mm mandibular defect, including a nerve defect, in 11 dogs and distracted using a transport disk at a rate of 1 mm/day. The regenerated inferior alveolar nerve was evaluated by retrograde transportation of HRP in all dogs at 3 and 6 months after the first operation. At 3 and 6 months, HRP-labeled neurons were observed in the trigeminal ganglion. The number of HRP-labeled neurons in each section increased, while the cell body diameter of HRP-labeled neurons was reduced over time. CONCLUSIONS: We found that the inferior alveolar nerve after bifocal distraction osteogenesis successfully recovered until peripheral tissue began to function. Although our research is still at the stage of animal experiments, it is considered that it will be possible to apply this method in the future to humans who have the mandibular defects.

  20. Regenerating mammalian nerve fibres: changes in action potential waveform and firing characteristics following blockage of potassium conductance.

    Science.gov (United States)

    Kocsis, J D; Waxman, S G; Hildebrand, C; Ruiz, J A

    1982-12-22

    Extracellular application of potassium channel blocking agents is known to increase the amplitude and duration of the compound action potential in non-myelinated and demyelinated axons, but not in mature mammalian myelinated fibres. In the present study we used intra-axonal and whole nerve recording techniques to study the effects of the potassium channel blocking agent 4-aminopyridine (4-AP) on regenerating rat nerve fibres. Our results indicate that early regenerating (premyelinated) axons show considerable broadening of the action potential after 4-AP application and late regenerating (myelinated) axons give rise to burst activity following a single stimulus after 4-AP application. 4-AP did not affect spike waveform or firing properties of normal mature sciatic nerve fibres. These results demonstrate the importance of potassium conductance in stabilizing firing properties of myelinated regenerating axons.

  1. Using NGF heparin-poloxamer thermosensitive hydrogels to enhance the nerve regeneration for spinal cord injury.

    Science.gov (United States)

    Zhao, Ying-Zheng; Jiang, Xi; Xiao, Jian; Lin, Qian; Yu, Wen-Ze; Tian, Fu-Rong; Mao, Kai-Li; Yang, Wei; Wong, Ho Lun; Lu, Cui-Tao

    2016-01-01

    Nerve growth factor (NGF) has potential in spinal cord injury (SCI) therapy, but limited by the poor physicochemical stability and low ability to cross the blood spinal cord barrier. Novel heparin-poloxamer (HP) thermo-sensitive hydrogel was constructed to enhance the NGF regeneration on SCI. NGF-HP thermo-sensitive hydrogel was prepared and related characteristics including gelation temperature, rheological behavior and micromorphology were measured. Local NGF delivery to the injured spinal cord was achieved by in situ injection in the injured space. The cellular uptake of NGF-HP hydrogel was evaluated with PC12 cells in vitro. Pathologic characteristics and neuron regeneration effects on the SCI rats were studied to evaluate the enhanced therapy of NGF-HP hydrogel. Endoplasmic reticulum (ER) stress-induced apoptosis was analyzed to explore the related mechanism in SCI regeneration. NGF-HP hydrogel showed good morphology and stable bioactivity of NGF in vitro. NGF-HP hydrogel combined treatment significantly enhanced the efficiency of NGF cellular uptake (Pregeneration. Spinal cord injury (SCI) is a devastating condition that can lead to sudden loss of sensory and autonomic function. Current treatment includes decompression surgery, injury stabilization, secondary complications prevention and rehabilitation. However, neurological recovery is limited. Nerve growth factor (NGF) has potential in SCI therapy, but limited by the poor physicochemical stability and low ability to cross the blood spinal cord barrier. Hydrogels have good affinity and compatibility to biological tissue. In this study, we developed a novel heparin-poloxamer (HP) thermo-sensitive hydrogel to enhance the spinal cord regeneration of NGF. From SCI rat experiment, HP hydrogel combined with orthotopic injection technique showed best neuroprotective effects among experimental groups. This novel combined technique will provide an effective strategy for SCI regeneration. Copyright © 2015 Acta

  2. Impulse magnetic stimulation facilitates synaptic regeneration in rats following sciatic nerve injury

    Institute of Scientific and Technical Information of China (English)

    Sergey A. Zhivolupov; Miroslav M. Odinak; Nariman A. Rashidov; Ludmila S. Onischenko; Igor N. Samartsev; Anton A. Jurin

    2012-01-01

    The current studies describing magnetic stimulation for treatment of nervous system diseases mainly focus on transcranial magnetic stimulation and rarely focus on spinal cord magnetic stimula-tion. Spinal cord magnetic stimulation has been confirmed to promote neural plasticity after injuries of spinal cord, brain and peripheral nerve. To evaluate the effects of impulse magnetic stimulation of the spinal cord on peripheral nerve regneration, we compressed a 3 mm segment located in the middle third of the hip using a sterilized artery forceps to induce ischemia. Then, all animals un-derwent impulse magnetic stimulation of the lumbar portion of spinal crod and spinal nerve roots daily for 1 month. Electron microscopy results showed that in and below the injuryed segment, the inflammation and demyelination of neural tissue were alleviated, apoptotic cells were reduced, and injured Schwann cells and myelin fibers were repaired. These findings suggest that high-frequency impulse magnetic stimulation of spinal cord and corresponding spinal nerve roots promotes synaptic regeneration following sciatic nerve injury.

  3. Effect of Zofenopril on regeneration of sciatic nerve crush injury in a rat model

    Directory of Open Access Journals (Sweden)

    Kalender Ali

    2009-06-01

    Full Text Available Abstract Background Zofenopril is an antioxidant agent which has been shown to have beneficial effects in hypertension and heart failure. The aim of this study was to test the effects of Zofenopril on nerve regeneration and scarring in a rat model of peripheral nerve crush injury. Methods Twenty-one adult Sprague-Dawley rats underwent a surgical procedure involving right sciatic nerve crush injury. 15 mg/kg Zofenopril was administered orally to seven rats in group Z for seven days. Seven rats in group S received saline orally for seven days. Seven rats in the control group C received no drug after crush injury. Fourteenth and 42nd days after injury, functional and electromyography assessments of nerves were performed. Functional recovery was analyzed using a walking track assessment, and quantified using the sciatic functional index (SFI. After these evaluations, all rats were sacrificed and microscopic evaluations were performed. Results The Sciatic functional Index (SFI in group Z on 14th day is different significantly from group S and group C (p = 0.037. But on 42nd day there was no difference between groups (p = 0.278. The statistical analyses of electromyelographic (EMG studies showed that the latency in group Z is significantly different from group S (p = 0.006 and group C (p = 0.045. But on 42nd day there was no difference between groups like SFI (p = 0.147. The amplitude was evaluated better in group Z than others (p Conclusion Our results demonstrate that Zofenopril promotes the regeneration of peripheral nerve injuries in rat models.

  4. Blockade of transient receptor potential cation channel subfamily V member 1 promotes regeneration after sciatic nerve injury

    Institute of Scientific and Technical Information of China (English)

    Fei Ren; Hong Zhang; Chao Qi; Mei-ling Gao; Hong Wang; Xia-qing Li

    2015-01-01

    The transient receptor potential cation channel subfamily V member 1 (TRPV1) provides the sensation of pain (nociception). However, it remains unknown whether TRPV1 is activated after peripheral nerve injury, or whether activation of TRPV1 affects neural regeneration. In the present study, we established rat models of unilateral sciatic nerve crush injury, with or without pretreatment with AMG517 (300 mg/kg), a TRPV1 antagonist, injected subcutaneously into the ipsilateral paw 60 minutes before injury. At 1 and 2 weeks after injury, we performed immuno-lfuorescence staining of the sciatic nerve at the center of injury, at 0.3 cm proximal and distal to the injury site, and in the dorsal root ganglia. Our results showed that Wallerian degeneration occurred distal to the injury site, and neurite outgrowth and Schwann cell regeneration occurred proximal to the injury. The number of regenerating myelinated and unmyelinated nerve clus-ters was greater in the AMG517-pretreated rats than in the vehicle-treated group, most notably 2 weeks after injury. TRPV1 expression in the injured sciatic nerve and ipsilateral dorsal root ganglia was markedly greater than on the contralateral side. Pretreatment with AMG517 blocked this effect. These data indicate that TRPV1 is activated or overexpressed after sciatic nerve crush injury, and that blockade of TRPV1 may accelerate regeneration of the injured sciatic nerve.

  5. Outer Electrospun Polycaprolactone Shell Induces Massive Foreign Body Reaction and Impairs Axonal Regeneration through 3D Multichannel Chitosan Nerve Guides

    Science.gov (United States)

    Behrens, Peter; Wienecke, Soenke; Chakradeo, Tanmay; Glasmacher, Birgit

    2014-01-01

    We report on the performance of composite nerve grafts with an inner 3D multichannel porous chitosan core and an outer electrospun polycaprolactone shell. The inner chitosan core provided multiple guidance channels for regrowing axons. To analyze the in vivo properties of the bare chitosan cores, we separately implanted them into an epineural sheath. The effects of both graft types on structural and functional regeneration across a 10 mm rat sciatic nerve gap were compared to autologous nerve transplantation (ANT). The mechanical biomaterial properties and the immunological impact of the grafts were assessed with histological techniques before and after transplantation in vivo. Furthermore during a 13-week examination period functional tests and electrophysiological recordings were performed and supplemented by nerve morphometry. The sheathing of the chitosan core with a polycaprolactone shell induced massive foreign body reaction and impairment of nerve regeneration. Although the isolated novel chitosan core did allow regeneration of axons in a similar size distribution as the ANT, the ANT was superior in terms of functional regeneration. We conclude that an outer polycaprolactone shell should not be used for the purpose of bioartificial nerve grafting, while 3D multichannel porous chitosan cores could be candidate scaffolds for structured nerve grafts. PMID:24818158

  6. Substance P combined with epidermal stem cells promotes wound healing and nerve regeneration in diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    Fei-bin Zhu; Xiang-jing Fang; De-wu Liu; Ying Shao; Hong-yan Zhang; Yan Peng; Qing-ling Zhong; Yong-tie Li; De-ming Liu

    2016-01-01

    Exogenous substance P accelerates wound healing in diabetes, but the mechanism remains poorly understood. Here, we established a rat model by intraperitoneally injecting streptozotocin. Four wounds (1.8 cm diameter) were drilled using a self-made punch onto the back, bilateral to the vertebral column, and then treated using amniotic membrane with epidermal stem cells and/or substance P around and in the middle of the wounds. With the combined treatment the wound-healing rate was 100% at 14 days. With prolonged time, type I col-lagen content gradually increased, yet type III collagen content gradually diminished. Abundant protein gene product 9.5- and substance P-immunoreactive nerve ifbers regenerated. Partial nerve ifber endings extended to the epidermis. The therapeutic effects of combined substance P and epidermal stem cells were better than with amniotic membrane and either factor alone. Our results suggest that the com-bination of substance P and epidermal stem cells effectively contributes to nerve regeneration and wound healing in diabetic rats.

  7. Treatment of transected peripheral nerves with artemin improved motor neuron regeneration, but did not reduce nerve injury-induced pain behaviour.

    Science.gov (United States)

    Widenfalk, Johan; Wu, Weiping; Hao, Jingxia; Person, Jonas K E; Wiesenfeldt-Hallin, Zsuzsanna; Risling, Mårten

    2009-01-01

    Incomplete recovery of function and neuropathic pain are common problems after peripheral nerve injury. To develop new treatment strategies for peripheral nerve injuries we investigated whether the neurotrophic factor artemin could improve outcome after sciatic nerve injuries in rats. Artemin is a member of the glial cell line-derived neurotrophic factor (GDNF) family and exerts neuroprotective effects on sensory neurons as well as influencing behavioural thermal sensitivity. We additionally evaluated if fibrin sealant, which is sometimes used as a nerve glue, had any effects on neuropathic pain-related behaviour. After the sciatic nerve had been transected, 30 animals were randomised to one of three groups: treatment with a fibrin sealant that contained artemin in conjunction with sutures; fibrin sealant with no artemin (sham) in conjunction with sutures; or sutures alone (n=10 in each group). Motor function, sensory function, and autotomy were evaluated from 1 to 12 weeks after injury. Retrograde flourogold tracing 12 weeks after injury showed that the addition of artemin increased the number of regenerating motor neurons. However, it did not improve their performance, as measured by the Sciatic Function Index, compared with sham or suture alone. Animals treated with artemin had a non-significant increase in motor nerve conduction velocity compared with sham. However, artemin did not reverse nerve injury-induced pain behaviour such as cold or heat hypersensitivity. Fibrin sealant in itself did not ameliorate motor performance, or regeneration of motor neurons, or give rise to nerve injury-induced pain behaviour. The results indicate that artemin is of value as a treatment for peripheral nerve injuries, although the effects were limited. As the artemin high-affinity receptor GFRalpha-3 is present in Schwann cells and not in motor neurons, the effect on motor neuron axon regeneration may result from an indirect effect through Schwann cells in the injured nerve.

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

    Science.gov (United States)

    Yurie, Hirofumi; Ikeguchi, Ryosuke; Aoyama, Tomoki; Kaizawa, Yukitoshi; Tajino, Junichi; Ito, Akira; Ohta, Souichi; Oda, Hiroki; Takeuchi, Hisataka; Akieda, Shizuka; Tsuji, Manami; Nakayama, Koichi; Matsuda, Shuichi

    2017-01-01

    Background Although autologous nerve grafting is the gold standard treatment of peripheral nerve injuries, several alternative methods have been developed, including nerve conduits that use supportive cells. However, the seeding efficacy and viability of supportive cells injected in nerve grafts remain unclear. Here, we focused on a novel completely biological, tissue-engineered, scaffold-free conduit. Methods We developed six scaffold-free conduits from human normal dermal fibroblasts using a Bio 3D Printer. Twelve adult male rats with immune deficiency underwent mid-thigh-level transection of the right sciatic nerve. The resulting 5-mm nerve gap was bridged using 8-mm Bio 3D conduits (Bio 3D group, n = 6) and silicone tube (silicone group, n = 6). Several assessments were conducted to examine nerve regeneration eight weeks post-surgery. Results Kinematic analysis revealed that the toe angle to the metatarsal bone at the final segment of the swing phase was significantly higher in the Bio 3D group than the silicone group (-35.78 ± 10.68 versus -62.48 ± 6.15, respectively; p < 0.01). Electrophysiological studies revealed significantly higher compound muscle action potential in the Bio 3D group than the silicone group (53.60 ± 26.36% versus 2.93 ± 1.84%; p < 0.01). Histological and morphological studies revealed neural cell expression in all regions of the regenerated nerves and the presence of many well-myelinated axons in the Bio 3D group. The wet muscle weight of the tibialis anterior muscle was significantly higher in the Bio 3D group than the silicone group (0.544 ± 0.063 versus 0.396 ± 0.031, respectively; p < 0.01). Conclusions We confirmed that scaffold-free Bio 3D conduits composed entirely of fibroblast cells promote nerve regeneration in a rat sciatic nerve model. PMID:28192527

  9. 2R Regeneration in Concatenated Semiconductor Optical Amplifiers and Electroabsorbers

    DEFF Research Database (Denmark)

    Christiansen, Lotte Jin; Xu, Lin; Yvind, Kresten;

    2004-01-01

    We present a novel 2R regenerator with a large level separation and steep step a sharp, adjustable threshold based on concatenated semiconductor optical amplifiers and electroabsorbers. We demonstrate demonstrate improvements in both extinction-ratio and BER sensitivity atfor a 10 Gb/s NRZ signal....

  10. Polarization-Independent All-Optical Regenerator for DPSK Data

    Directory of Open Access Journals (Sweden)

    Valeria Vercesi

    2014-05-01

    Full Text Available We demonstrate polarization-independent simultaneous all-optical phase-preserving amplitude regeneration and wavelength conversion of NRZ differential phase shift keying (DPSK data by four-wave mixing (FWM in a semiconductor optical amplifier (SOA. The dependence upon polarization state of the signals is eliminated by using a co-polarized dual-pump architecture. Investigation on the regenerative capability vs. pumps detuning shows significant BER threshold margin improvement over 6 nm conversion range.

  11. [Up to date methods of optic nerve evaluation in patients with optic neuropathy of various etiology].

    Science.gov (United States)

    Sheremet, N L; Ronzina, I A; Galoian, N S; Kazarian, E E

    2011-01-01

    132 patients (188 eyes) with proven optic neuropathy of non-glaucomatous origin were examined using static perimetry, visual evoked potential (flash and pattern types), optic coherent tomography of papilla and thickness of peripapillary nerve fiber layer. Sensitivity/ specificity of methods for identification of optic nerve diseases in acute stage were 92/75%, 92/84%, 90/92% respectively. Combination of these three methods let us identify optic neuropathy in 100% of cases, including latent forms.

  12. Salidroside promotes peripheral nerve regeneration based on tissue engineering strategy using Schwann cells and PLGA: in vitro and in vivo

    Science.gov (United States)

    Liu, Hui; Lv, Peizhen; Zhu, Yongjia; Wu, Huayu; Zhang, Kun; Xu, Fuben; Zheng, Li; Zhao, Jinmin

    2017-01-01

    Salidriside (SDS), a phenylpropanoid glycoside derived from Rhodiola rosea L, has been shown to be neuroprotective in many studies, which may be promising in nerve recovery. In this study, the neuroprotective effects of SDS on engineered nerve constructed by Schwann cells (SCs) and Poly (lactic-co-glycolic acid) (PLGA) were studied in vitro. We further investigated the effect of combinational therapy of SDS and PLGA/SCs based tissue engineering on peripheral nerve regeneration based on the rat model of nerve injury by sciatic transection. The results showed that SDS dramatically enhanced the proliferation and function of SCs. The underlying mechanism may be that SDS affects SCs growth through the modulation of neurotrophic factors (BDNF, GDNF and CNTF). 12 weeks after implantation with a 12 mm gap of sciatic nerve injury, SDS-PLGA/SCs achieved satisfying outcomes of nerve regeneration, as evidenced by morphological and functional improvements upon therapy by SDS, PLGA/SCs or direct suture group assessed by sciatic function index, nerve conduction assay, HE staining and immunohistochemical analysis. Our results demonstrated the significant role of introducing SDS into neural tissue engineering to promote nerve regeneration.

  13. Glaucoma severity affects diffusion tensor imaging (DTI) parameters of the optic nerve and optic radiation

    Energy Technology Data Exchange (ETDEWEB)

    Sidek, S. [Department of Biomedical Imaging, University Malaya, Research Imaging Centre, Faculty of Medicine, University Malaya (Malaysia); Medical Imaging Unit, Faculty of Medicine, Universiti Teknologi MARA, Selangor (Malaysia); Ramli, N. [Department of Biomedical Imaging, University Malaya, Research Imaging Centre, Faculty of Medicine, University Malaya (Malaysia); Rahmat, K., E-mail: katt_xr2000@yahoo.com [Department of Biomedical Imaging, University Malaya, Research Imaging Centre, Faculty of Medicine, University Malaya (Malaysia); Ramli, N.M.; Abdulrahman, F. [Department of Ophthalmology, Faculty of Medicine, University Malaya, Kuala Lumpur (Malaysia); Tan, L.K. [Department of Biomedical Imaging, University Malaya, Research Imaging Centre, Faculty of Medicine, University Malaya (Malaysia)

    2014-08-15

    Objectives: To evaluate whether MR diffusion tensor imaging (DTI) of the optic nerve and optic radiation in glaucoma patients provides parameters to discriminate between mild and severe glaucoma and to determine whether DTI derived indices correlate with retinal nerve fibre layer (RNFL) thickness. Methods: 3-Tesla DTI was performed on 90 subjects (30 normal, 30 mild glaucoma and 30 severe glaucoma subjects) and the FA and MD of the optic nerve and optic radiation were measured. The categorisation into mild and severe glaucoma was done using the Hodapp–Parrish–Anderson (HPA) classification. RNFL thickness was also assessed on all subjects using OCT. Receiver operating characteristic (ROC) analysis and Spearman's correlation coefficient was carried out. Results: FA and MD values in the optic nerve and optic radiation decreased and increased respectively as the disease progressed. FA at the optic nerve had the highest sensitivity (87%) and specificity (80%). FA values displayed the strongest correlation with RNFL thickness in the optic nerve (r = 0.684, p ≤ 0.001) while MD at the optic radiation showed the weakest correlation with RNFL thickness (r = −0.360, p ≤ 0.001). Conclusions: The high sensitivity and specificity of DTI-derived FA values in the optic nerve and the strong correlation between DTI-FA and RNFL thickness suggest that these parameters could serve as indicators of disease severity.

  14. Peripheral Nerve Regeneration Following Crush Injury to Rat Peroneal Nerve by Aqueous Extract of Medicinal Mushroom Hericium erinaceus (Bull.: Fr) Pers. (Aphyllophoromycetideae)

    OpenAIRE

    Kah-Hui Wong; Murali Naidu; Pamela David; Mahmood Ameen Abdulla; Noorlidah Abdullah; Umah Rani Kuppusamy; Vikineswary Sabaratnam

    2011-01-01

    Nerve crush injury is a well-established axonotmetic model in experimental regeneration studies to investigate the impact of various pharmacological treatments. Hericium erinaceus is a temperate mushroom but is now being cultivated in tropical Malaysia. In this study, we investigated the activity of aqueous extract of H. erinaceus fresh fruiting bodies in promoting functional recovery following an axonotmetic peroneal nerve injury in adult female Sprague-Dawley rats by daily oral administrati...

  15. Optic Nerve Injury in a Patient with Chronic Allergic Conjunctivitis

    Directory of Open Access Journals (Sweden)

    Ribhi Hazin

    2014-01-01

    Full Text Available Manipulation of the optic nerve can lead to irreversible vision changes. We present a patient with a past medical history of skin allergy and allergic conjunctivitis (AC who presented with insidious unexplained unilateral vision loss. Physical exam revealed significant blepharospasm, mild lid edema, bulbar conjunctival hyperemia, afferent pupillary defect, and slight papillary hypertrophy. Slit lamp examination demonstrated superior and inferior conjunctival scarring as well as superior corneal scarring but no signs of external trauma or neurological damage were noted. Conjunctival cultures and cytologic evaluation demonstrated significant eosinophilic infiltration. Subsequent ophthalmoscopic examination revealed optic nerve atrophy. Upon further questioning, the patient admitted to vigorous itching of the affected eye for many months. Given the presenting symptoms, history, and negative ophthalmological workup, it was determined that the optic nerve atrophy was likely secondary to digital pressure from vigorous itching. Although AC can be a significant source of decreased vision via corneal ulceration, no reported cases have ever described AC-induced vision loss of this degree from vigorous itching and chronic pressure leading to optic nerve damage. Despite being self-limiting in nature, allergic conjunctivitis should be properly managed as extreme cases can result in mechanical compression of the optic nerve and compromise vision.

  16. Robust Optic Nerve Segmentation on Clinically Acquired CT.

    Science.gov (United States)

    Panda, Swetasudha; Asman, Andrew J; Delisi, Michael P; Mawn, Louise A; Galloway, Robert L; Landman, Bennett A

    2014-03-21

    The optic nerve is a sensitive central nervous system structure, which plays a critical role in many devastating pathological conditions. Several methods have been proposed in recent years to segment the optic nerve automatically, but progress toward full automation has been limited. Multi-atlas methods have been successful for brain segmentation, but their application to smaller anatomies remains relatively unexplored. Herein we evaluate a framework for robust and fully automated segmentation of the optic nerves, eye globes and muscles. We employ a robust registration procedure for accurate registrations, variable voxel resolution and image field-of-view. We demonstrate the efficacy of an optimal combination of SyN registration and a recently proposed label fusion algorithm (Non-local Spatial STAPLE) that accounts for small-scale errors in registration correspondence. On a dataset containing 30 highly varying computed tomography (CT) images of the human brain, the optimal registration and label fusion pipeline resulted in a median Dice similarity coefficient of 0.77, symmetric mean surface distance error of 0.55 mm, symmetric Hausdorff distance error of 3.33 mm for the optic nerves. Simultaneously, we demonstrate the robustness of the optimal algorithm by segmenting the optic nerve structure in 316 CT scans obtained from 182 subjects from a thyroid eye disease (TED) patient population.

  17. Identification of regeneration-associated genes after central and peripheral nerve injury in the adult rat

    Directory of Open Access Journals (Sweden)

    Brook Gary A

    2003-05-01

    Full Text Available Abstract Background It is well known that neurons of the peripheral nervous system have the capacity to regenerate a severed axon leading to functional recovery, whereas neurons of the central nervous system do not regenerate successfully after injury. The underlying molecular programs initiated by axotomized peripheral and central nervous system neurons are not yet fully understood. Results To gain insight into the molecular mechanisms underlying the process of regeneration in the nervous system, differential display polymerase chain reaction has been used to identify differentially expressed genes following axotomy of peripheral and central nerve fibers. For this purpose, axotomy induced changes of regenerating facial nucleus neurons, and non-regenerating red nucleus and Clarke's nucleus neurons have been analyzed in an intra-animal side-to-side comparison. One hundred and thirty five gene fragments have been isolated, of which 69 correspond to known genes encoding for a number of different functional classes of proteins such as transcription factors, signaling molecules, homeobox-genes, receptors and proteins involved in metabolism. Sixty gene fragments correspond to genomic mouse sequences without known function. In situ-hybridization has been used to confirm differential expression and to analyze the cellular localization of these gene fragments. Twenty one genes (~15% have been demonstrated to be differentially expressed. Conclusions The detailed analysis of differentially expressed genes in different lesion paradigms provides new insights into the molecular mechanisms underlying the process of regeneration and may lead to the identification of genes which play key roles in functional repair of central nervous tissues.

  18. All-optical signal processing and regeneration

    DEFF Research Database (Denmark)

    Wolfson, David

    2001-01-01

    for multi-channel operation. It is shown that the cascadability of GC-SOAs is superior at 2.5 Gbit/s compared to conventional SOAs for up to at least 16 wavelength channels, whereas the benefit is reduced at higher bit rates due to influence from relaxation oscillations in the GC-SOA. Furthermore, all......The trend in the industry today is that more and more complex functionalities are moving from the electrical domain and into the optical domain, demonstrating that all-optical networks are coming closer to realisation. In order for this progress to continue, there is a need for advanced optical...... amplifier (SOA)-based devices. The thesis starts out by giving a description of the motivations and driving forces for the current evolution of optical networks from point-to-point systems to all-otpical network topologies. The use of SOA-based devices for all-optical gating is investigated with the use...

  19. Microarray and cDNA sequence analysis of transcription during nerve-dependent limb regeneration

    Directory of Open Access Journals (Sweden)

    Bryant Susan V

    2009-01-01

    Full Text Available Abstract Background Microarray analysis and 454 cDNA sequencing were used to investigate a centuries-old problem in regenerative biology: the basis of nerve-dependent limb regeneration in salamanders. Innervated (NR and denervated (DL forelimbs of Mexican axolotls were amputated and transcripts were sampled after 0, 5, and 14 days of regeneration. Results Considerable similarity was observed between NR and DL transcriptional programs at 5 and 14 days post amputation (dpa. Genes with extracellular functions that are critical to wound healing were upregulated while muscle-specific genes were downregulated. Thus, many processes that are regulated during early limb regeneration do not depend upon nerve-derived factors. The majority of the transcriptional differences between NR and DL limbs were correlated with blastema formation; cell numbers increased in NR limbs after 5 dpa and this yielded distinct transcriptional signatures of cell proliferation in NR limbs at 14 dpa. These transcriptional signatures were not observed in DL limbs. Instead, gene expression changes within DL limbs suggest more diverse and protracted wound-healing responses. 454 cDNA sequencing complemented the microarray analysis by providing deeper sampling of transcriptional programs and associated biological processes. Assembly of new 454 cDNA sequences with existing expressed sequence tag (EST contigs from the Ambystoma EST database more than doubled (3935 to 9411 the number of non-redundant human-A. mexicanum orthologous sequences. Conclusion Many new candidate gene sequences were discovered for the first time and these will greatly enable future studies of wound healing, epigenetics, genome stability, and nerve-dependent blastema formation and outgrowth using the axolotl model.

  20. Calpain 3 Expression Pattern during Gastrocnemius Muscle Atrophy and Regeneration Following Sciatic Nerve Injury in Rats

    Directory of Open Access Journals (Sweden)

    Ronghua Wu

    2015-11-01

    Full Text Available Calpain 3 (CAPN3, also known as p94, is a skeletal muscle-specific member of the calpain family that is involved in muscular dystrophy; however, the roles of CAPN3 in muscular atrophy and regeneration are yet to be understood. In the present study, we attempted to explain the effect of CAPN3 in muscle atrophy by evaluating CAPN3 expression in rat gastrocnemius muscle following reversible sciatic nerve injury. After nerve injury, the wet weight ratio and cross sectional area (CSA of gastrocnemius muscle were decreased gradually from 1–14 days and then recovery from 14–28 days. The active form of CAPN3 (~62 kDa protein decreased slightly on day 3 and then increased from day 7 to 14 before a decrease from day 14 to 28. The result of linear correlation analysis showed that expression of the active CAPN3 protein level was negatively correlated with muscle wet weight ratio. CAPN3 knockdown by short interfering RNA (siRNA injection improved muscle recovery on days 7 and 14 after injury as compared to that observed with control siRNA treatment. Depletion of CAPN3 gene expression could promote myoblast differentiation in L6 cells. Based on these findings, we conclude that the expression pattern of the active CAPN3 protein is linked to muscle atrophy and regeneration following denervation: its upregulation during early stages may promote satellite cell renewal by inhibiting differentiation, whereas in later stages, CAPN3 expression may be downregulated to stimulate myogenic differentiation and enhance recovery. These results provide a novel mechanistic insight into the role of CAPN3 protein in muscle regeneration after peripheral nerve injury.

  1. A Multidisciplinary Approach to Educating Preschool Children with Optic Nerve Hypoplasia and Septo-Optic Nerve Dysplasia.

    Science.gov (United States)

    Bahar, Cheryl; Brody, Jill; McCann, Mary Ellen; Mendiola, Rosalinda; Slott, Gayle

    2003-01-01

    This article discusses the observations and experiences of a multidisciplinary team at the Blind Childrens Center in Los Angeles, which works specifically with children from birth to 5 years of age who have been diagnosed with optic nerve hypoplasia and may have septo-optic displasia. Strategies for educational interventions are explained.…

  2. Long echo time STIR sequence MRI of optic nerves in optic neuritis

    Energy Technology Data Exchange (ETDEWEB)

    Onofrj, M. [Dept. of Neurology, State Univ. of Chieti, Ospedale ex-Pediatrico (Italy); Tartaro, A. [Dept. of Radiology, State Univ. of Chieti (Italy); Thomas, A. [Dept. of Neurology, State Univ. of Chieti, Ospedale ex-Pediatrico (Italy); Gambi, D. [Dept. of Neurology, State Univ. of Chieti, Ospedale ex-Pediatrico (Italy); Fulgente, T. [Dept. of Neurology, State Univ. of Chieti, Ospedale ex-Pediatrico (Italy); Delli Pizzi, C. [Dept. of Radiology, State Univ. of Chieti (Italy); Bonomo, L. [Dept. of Radiology, State Univ. of Chieti (Italy)

    1996-01-01

    MRI of the optic nerves was obtained in 13 patients with acute optic neuritis and 13 with a previous optic neuritis (ON), assessed by clinical features, visual fields and visual evoked potentials. Results of the conventional short tau inversion recovery (STIR) sequence obtained with a short echo time (STE-STIR; 22 ms) were compared with those of a long echo time (LTE-STIR: 80 ms) sequence. The conventional STE-STIR sequence revealed lesions in the optic nerves in 78.5% of acute and 58.8% of previous ON. The LTE-STIR sequence showed abnormalities in 92.8% of acutely symptomatic nerves and 94.1% of nerves with previous ON. The optic nerve lesions appeared significantly longer with the LTE-STIR sequence than with the conventional STE-STIR sequences, in both acute and previous ON. (orig.)

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

    Science.gov (United States)

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

    2017-02-01

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

  4. Blunt Facial Trauma Causing Isolated Optic Nerve Hematoma

    Directory of Open Access Journals (Sweden)

    R. Parab

    2013-01-01

    Full Text Available Traumatic optic neuropathy is an uncommon, yet serious, result of facial trauma. The authors present a novel case of a 59-year-old gentleman who presented with an isolated blunt traumatic left optic nerve hematoma causing vision loss. There were no other injuries or fractures to report. This case highlights the importance of early recognition of this rare injury and reviews the current literature and management of traumatic optic neuropathy.

  5. Optical coherence tomography of the rat cavernous nerves

    Science.gov (United States)

    Fried, Nathaniel M.; Rais-Bahrami, Soroush; Lagoda, Gwen A.; Chuang, Ying; Burnett, Arthur L.; Su, Li-Ming

    2007-02-01

    Improvements in identification, imaging, and visualization of the cavernous nerves during radical prostatectomy, which are responsible for erectile function, may improve nerve preservation and postoperative potency. Optical coherence tomography (OCT) is capable of real-time, high-resolution, cross-sectional, in vivo tissue imaging. The rat prostate serves as an excellent model for studying the use of OCT for imaging the cavernous nerves, as the rat cavernous nerve is a large, visible, and distinct bundle allowing for easy identification with OCT in addition to histologic confirmation. Imaging was performed with the Niris OCT system and a handheld 8 Fr probe, capable of acquiring real-time images with 11-μm axial and 25-μm lateral resolution in tissue. Open surgical exposure of the prostate was performed on a total of 6 male rats, and OCT images of the prostate, cavernous nerve, pelvic plexus ganglion, seminal vesicle, blood vessels, and periprostatic fat were acquired. Cavernous nerve electrical stimulation with simultaneous intracorporeal pressure measurements was performed to confirm proper identification of the cavernous nerves. The prostate and cavernous nerves were also processed for histologic analysis and further confirmation. Cross-sectional and longitudinal OCT images of the cavernous nerves were acquired and compared with histologic sections. The cavernous nerve and ganglion could be differentiated from the surrounding prostate gland, seminal vesicle, blood vessels, bladder, and fatty tissue. We report preliminary results of OCT images of the rat cavernous nerves with histologic correlation and erectile stimulation measurements, thus providing interpretation of prostate structures as they appear in OCT images.

  6. Quantitative contrast-enhanced MR imaging of the optic nerve

    Energy Technology Data Exchange (ETDEWEB)

    Simon, J.H. [Depts. of Radiology, Univ. of Colorado Health Sciences Center, Denver, CO (United States)]|[Iowa Univ., Iowa City, IA (United States); Rubinstein, D. [Depts. of Radiology, Univ. of Colorado Health Sciences Center, Denver, CO (United States)]|[Iowa Univ., Iowa City, IA (United States); Brown, M. [Depts. of Radiology, Univ. of Colorado Health Sciences Center, Denver, CO (United States)]|[Iowa Univ., Iowa City, IA (United States); Yuh, W. [Depts. of Radiology, Univ. of Colorado Health Sciences Center, Denver, CO (United States)]|[Iowa Univ., Iowa City, IA (United States); Birch-Iensen, M. [Depts. of Radiology, Univ. of Colorado Health Sciences Center, Denver, CO (United States)]|[Iowa Univ., Iowa City, IA (United States); Szumowski, J. [Depts. of Radiology, Univ. of Colorado Health Sciences Center, Denver, CO (United States)]|[Iowa Univ., Iowa City, IA (United States); Stears, J. [Depts. of Radiology, Univ. of Colorado Health Sciences Center, Denver, CO (United States)]|[Iowa Univ., Iowa City, IA (United States)

    1994-11-01

    During the acute stages of optic neuritis damage to the blood-optic nerve barrier can be detected using i.v. paramagnetic contrast-enhanced MR imaging. Quantification of the enhancement pattern of the optic nerve, intraorbital fat and muscle was determined in 15 normal subjects using 3 fat-suppression MR imaging methods: T1-weighted spin-echo and spoiled gradient-echo sequences preceded by a flat-frequency selective pulse (FATSAT+SE and FATSAT+SPGR, respectively) and a pulse sequence combining CHOPPER fat suppression with a fat-frequency selective preparation pulse (HYBRID). Pre- and postcontrast-enhanced studies were acquired for FATSAT+SE and FATSAT+SPGR. There was no significant enhancement of the optic nerve by either method (mean increase of 0.96% and 5.3%, respectively), while there was significant enhancement in muscle (mean 118.2% and 108.2%, respectively; p<0.005) and fat (mean increase of 13% and 37%, respectively; p<0.05). Postcontrast optic nerve/muscle signal intensity ratios (mean, SD) were 0.51 (0.07), 0.58 (0.05) and 0.75 (0.05) for FATSAT+SE, FATSAT+SPGR and HYBRID, respectively. These results suggest a practical methodology and range of values for normal signal intensity increases and ratios of tissue signal that can be used as objective measures of optic neuritis for natural history studies and treatment trials. (orig.).

  7. Stimulation of the human auditory nerve with optical radiation

    Science.gov (United States)

    Fishman, Andrew; Winkler, Piotr; Mierzwinski, Jozef; Beuth, Wojciech; Izzo Matic, Agnella; Siedlecki, Zygmunt; Teudt, Ingo; Maier, Hannes; Richter, Claus-Peter

    2009-02-01

    A novel, spatially selective method to stimulate cranial nerves has been proposed: contact free stimulation with optical radiation. The radiation source is an infrared pulsed laser. The Case Report is the first report ever that shows that optical stimulation of the auditory nerve is possible in the human. The ethical approach to conduct any measurements or tests in humans requires efficacy and safety studies in animals, which have been conducted in gerbils. This report represents the first step in a translational research project to initiate a paradigm shift in neural interfaces. A patient was selected who required surgical removal of a large meningioma angiomatum WHO I by a planned transcochlear approach. Prior to cochlear ablation by drilling and subsequent tumor resection, the cochlear nerve was stimulated with a pulsed infrared laser at low radiation energies. Stimulation with optical radiation evoked compound action potentials from the human auditory nerve. Stimulation of the auditory nerve with infrared laser pulses is possible in the human inner ear. The finding is an important step for translating results from animal experiments to human and furthers the development of a novel interface that uses optical radiation to stimulate neurons. Additional measurements are required to optimize the stimulation parameters.

  8. Optical stimulation of the facial nerve: a surgical tool?

    Science.gov (United States)

    Richter, Claus-Peter; Teudt, Ingo Ulrik; Nevel, Adam E.; Izzo, Agnella D.; Walsh, Joseph T., Jr.

    2008-02-01

    One sequela of skull base surgery is the iatrogenic damage to cranial nerves. Devices that stimulate nerves with electric current can assist in the nerve identification. Contemporary devices have two main limitations: (1) the physical contact of the stimulating electrode and (2) the spread of the current through the tissue. In contrast to electrical stimulation, pulsed infrared optical radiation can be used to safely and selectively stimulate neural tissue. Stimulation and screening of the nerve is possible without making physical contact. The gerbil facial nerve was irradiated with 250-μs-long pulses of 2.12 μm radiation delivered via a 600-μm-diameter optical fiber at a repetition rate of 2 Hz. Muscle action potentials were recorded with intradermal electrodes. Nerve samples were examined for possible tissue damage. Eight facial nerves were stimulated with radiant exposures between 0.71-1.77 J/cm2, resulting in compound muscle action potentials (CmAPs) that were simultaneously measured at the m. orbicularis oculi, m. levator nasolabialis, and m. orbicularis oris. Resulting CmAP amplitudes were 0.3-0.4 mV, 0.15-1.4 mV and 0.3-2.3 mV, respectively, depending on the radial location of the optical fiber and the radiant exposure. Individual nerve branches were also stimulated, resulting in CmAP amplitudes between 0.2 and 1.6 mV. Histology revealed tissue damage at radiant exposures of 2.2 J/cm2, but no apparent damage at radiant exposures of 2.0 J/cm2.

  9. Initial Pattern of Optic Nerve Enhancement in Korean Patients with Unilateral Optic Neuritis

    Science.gov (United States)

    Son, Dae Yong; Park, Kyung-Ah; Seok, Su Sie; Lee, Ju-Yeun

    2017-01-01

    Purpose The purpose of this study was to demonstrate whether the pattern of optic nerve enhancement in magnetic resonance imaging (MRI) can help to differentiate between idiopathic optic neuritis (ON), neuromyelitis optica (NMO), and multiple sclerosis (MS) in unilateral ON. Methods An MRI of the brain and orbits was obtained in patients with acute unilateral ON. Patients with ON were divided into three groups: NMO, MS, and idiopathic ON. The length and location of the abnormal optic nerve enhancement were compared for ON eyes with and without NMO or MS. The correlation between the pattern of optic nerve enhancement and the outcome of visual function was analyzed. Results Of the 36 patients with ON who underwent an MRI within 2 weeks of the onset, 19 were diagnosed with idiopathic ON, 9 with NMO, and 8 with MS. Enhancement of the optic nerve occurred in 21 patients (58.3%) and was limited to the orbital segment in 12 patients. Neither the length nor the location of the optic nerve enhancement was significantly correlated with visual functions other than contrast sensitivity or the diagnosis of idiopathic ON, MS, or NMO. Patients with greater extent of optic nerve sheath enhancement and more posterior segment involvement showed higher contrast sensitivity. Conclusions Our data revealed that the pattern of optic nerve enhancement was not associated with diagnosis of idiopathic ON, NMO, or MS in Korean patients with unilateral ON. We believe further studies that include different ethnic groups will lead to a more definitive answer on this subject. PMID:28243026

  10. Evaluation of biodegradable polymer conduits--poly(L-lactic acid)--for guiding sciatic nerve regeneration in mice.

    Science.gov (United States)

    Goulart, Camila Oliveira; Lopes, Fátima Rosalina Pereira; Monte, Zulmira Oliveira; Dantas, Severino Valentim; Souto, Allana; Oliveira, Júlia Teixeira; Almeida, Fernanda Martins; Tonda-Turo, Chiara; Pereira, Cristina Cardoso; Borges, Cristiano Piacsek; Martinez, Ana Maria Blanco

    2016-04-15

    Polymeric biomaterials are often used for stimulating nerve regeneration. Among different conduits, poly(lactide acid) - PLA polymer is considered to be a good substrate due to its biocompatibility and resorbable characteristics. This polymer is an aliphatic polyester which has been mostly used in biomedical application. It is an organic compound with low allergenic potential, low toxicity, high biocompatibility and predictable kinetics of degradation. In this study we fabricated and evaluated a PLA microporous hollow fiber as a conduit for its ability to bridge a nerve gap in a mouse sciatic nerve injury model. The PLA conduit was prepared from a polymer solution, throughout extrusion technique. The left sciatic nerve of C57BL/6 mouse was transected and the nerve stumps were placed into a resorbable PLA (PLA group) or a PCL conduit (PCL group), n=5 each group. We have also used another group in which the nerves were repaired by autograft (autograft group, n=5). Motor function was analyzed according to sciatic functional index (SFI). After 56days, the regenerated nerves were processed for light and electron microscopy and morphometric analyses were performed. A quantitative analysis of regenerated nerves showed significant increase in the number of myelinated fibers and blood vessels in animals that received PLA conduit. The PLA group exhibited better overall tissue organization compared to other groups. Presenting well-organized bundles, many regenerating clusters composed of preserved nerve fibers surrounded by layers of compacted perineurium-like cells. Also the SFI revealed a significant improvement in functional recovery. This work suggests that PLA conduits are suitable substrate for cell survival and it provides an effective strategy to be used to support axonal growth becoming a potential alternative to autograft.

  11. Microgravity-Driven Optic Nerve/Sheath Biomechanics Simulations

    Science.gov (United States)

    Ethier, C. R.; Feola, A.; Myers, J. G.; Nelson, E.; Raykin, J.; Samuels, B.

    2016-01-01

    Visual Impairment and Intracranial Pressure (VIIP) syndrome is a concern for long-duration space flight. Current thinking suggests that the ocular changes observed in VIIP syndrome are related to cephalad fluid shifts resulting in altered fluid pressures [1]. In particular, we hypothesize that increased intracranial pressure (ICP) drives connective tissue remodeling of the posterior eye and optic nerve sheath (ONS). We describe here finite element (FE) modeling designed to understand how altered pressures, particularly altered ICP, affect the tissues of the posterior eye and optic nerve sheath (ONS) in VIIP. METHODS: Additional description of the modeling methodology is provided in the companion IWS abstract by Feola et al. In brief, a geometric model of the posterior eye and optic nerve, including the ONS, was created and the effects of fluid pressures on tissue deformations were simulated. We considered three ICP scenarios: an elevated ICP assumed to occur in chronic microgravity, and ICP in the upright and supine positions on earth. Within each scenario we used Latin hypercube sampling (LHS) to consider a range of ICPs, ONH tissue mechanical properties, intraocular pressures (IOPs) and mean arterial pressures (MAPs). The outcome measures were biomechanical strains in the lamina cribrosa, optic nerve and retina; here we focus on peak values of these strains, since elevated strain alters cell phenotype and induce tissue remodeling. In 3D, the strain field can be decomposed into three orthogonal components, denoted as first, second and third principal strains. RESULTS AND CONCLUSIONS: For baseline material properties, increasing ICP from 0 to 20 mmHg significantly changed strains within the posterior eye and ONS (Fig. 1), indicating that elevated ICP affects ocular tissue biomechanics. Notably, strains in the lamina cribrosa and retina became less extreme as ICP increased; however, within the optic nerve, the occurrence of such extreme strains greatly increased as

  12. Optic nerve pH and PO2

    DEFF Research Database (Denmark)

    Pedersen, Daniella B; Stefánsson, Einar; Kiilgaard, Jens Folke

    2006-01-01

    Earlier studies have demonstrated that carbonic anhydrase inhibitors (CAIs) increase optic nerve oxygen tension (ONPO(2)) in pigs. We hypothesized that the mechanism of this effect was either a CO(2) increase or a pH decrease in tissue and blood. To test this hypothesis we investigated and compared...... how optic nerve pH (ONpH) and ONPO(2) are affected by: (1) carbonic anhydrase inhibition; (2) respiratory acidosis, and (3) metabolic acidosis. We measured ONpH with a glass pH electrode and ONPO(2) with a polarographic oxygen electrode. One of the electrodes was placed in the vitreous cavity 0.5 mm...

  13. Chemical shift selective magnetic resonance imaging of the optic nerve in patients with acute optic neuritis

    DEFF Research Database (Denmark)

    Larsson, H B; Thomsen, C; Frederiksen, J

    1988-01-01

    of the 16 patients, abnormalities were seen. In one patient with bilateral symptoms, signal hyperintensity and swelling of the right side of the chiasm were found. In another patient the optic nerve was found diffusely enlarged with only a marginally increased signal in the second echo. In the third patient......Optic neuritis is often the first manifestation of multiple sclerosis (MS). Sixteen patients with acute optic neuritis and one patient with benign intracranial hypertension (BIH) were investigated by magnetic resonance imaging, using a chemical shift selective double spin echo sequence. In 3...... an area of signal hyperintensity and swelling was seen in the left optic nerve. In the patient with BIH the subarachnoid space which surrounds the optic nerves was enlarged. Even using this refined pulse sequence, avoiding the major artefact in imaging the optic nerve, the chemical shift artefact, lesions...

  14. [The effect of cerebrolysin on the regeneration of the peripheral nerve depending on the scheme of paraneural administration].

    Science.gov (United States)

    Shchudlo, N A; Shchudlo, M M; Borisova, I V

    2013-01-01

    An experimental morphological study in 56 animals has been performed in order to analyze the effect of cerebrolysin on the dynamics and long-term results of peripheral nerve regeneration after the transection and microsurgical suturing depending on the scheme of the preparation of paraneural infusion. The regeneration process was evaluated after 2.5; 4; 6 and 12 months. There was a stimulating effect of the preparation on the regenerative growth and differentiation of nerve fiber axial cylinders, vascularization of the distal segment of regenerating nerve and the trophic condition of myelin-forming Schwann cells. When the preparation is used according to the prolonged scheme, the effect persists for up to 10.5 months after the end of paraneural injection course.

  15. Determining degree of optic nerve edema from color fundus photography

    Science.gov (United States)

    Agne, Jason; Wang, Jui-Kai; Kardon, Randy H.; Garvin, Mona K.

    2015-03-01

    Swelling of the optic nerve head (ONH) is subjectively assessed by clinicians using the Frisén scale. It is believed that a direct measurement of the ONH volume would serve as a better representation of the swelling. However, a direct measurement requires optic nerve imaging with spectral domain optical coherence tomography (SD-OCT) and 3D segmentation of the resulting images, which is not always available during clinical evaluation. Furthermore, telemedical imaging of the eye at remote locations is more feasible with non-mydriatic fundus cameras which are less costly than OCT imagers. Therefore, there is a critical need to develop a more quantitative analysis of optic nerve swelling on a continuous scale, similar to SD-OCT. Here, we select features from more commonly available 2D fundus images and use them to predict ONH volume. Twenty-six features were extracted from each of 48 color fundus images. The features include attributes of the blood vessels, optic nerve head, and peripapillary retina areas. These features were used in a regression analysis to predict ONH volume, as computed by a segmentation of the SD-OCT image. The results of the regression analysis yielded a mean square error of 2.43 mm3 and a correlation coefficient between computed and predicted volumes of R = 0:771, which suggests that ONH volume may be predicted from fundus features alone.

  16. Development of Electrically Conductive Oligo(polyethylene Glycol) Fumarate-Polypyrrole Hydrogels for Nerve Regeneration

    Science.gov (United States)

    Runge, M. Brett; Dadsetan, Mahrokh; Baltrusaitis, Jonas; Ruesink, Terry; Lu, Lichun; Windebank, Anthony J.; Yaszemski, Michael J.

    2014-01-01

    Electrically conductive hydrogel composites consisting of oligo(polyethylene glycol) fumarate (OPF) and polypyrrole (PPy) were developed for applications in nerve regeneration. OPF-PPy scaffolds were synthesized using three different anions: naphthalene-2-sulfonic acid sodium salt (NSA), dodecylbenzenesulfonic acid sodium salt (DBSA), and dioctyl sulfosuccinate sodium salt (DOSS). Scaffolds were characterized by ATR-FTIR, XPS, AFM, dynamic mechanical analysis, electrical resistivity measurements, and swelling experiments. OPF-PPy scaffolds were shown to consist of up to 25 mol% polypyrrole with a compressive modulus ranging from 265 to 323 kPa and a sheet resistance ranging from 6 to 30 × 103 Ohms/square. In vitro studies using PC12 cells showed OPF-PPy materials had no cytotoxicity and PC12 cells showed distinctly better cell attachment and an increase in the percent of neurite bearing cells on OPF-PPy materials compared to OPF. The neurite lengths of PC12 cells were significantly higher on OPF-PPyNSA and OPF-PPyDBSA. These results show that electrically conductive OPF-PPy hydrogels are promising candidates for future applications in nerve regeneration. PMID:20942380

  17. Peripheral Nerve Regeneration Following Crush Injury to Rat Peroneal Nerve by Aqueous Extract of Medicinal Mushroom Hericium erinaceus (Bull.: Fr Pers. (Aphyllophoromycetideae

    Directory of Open Access Journals (Sweden)

    Kah-Hui Wong

    2011-01-01

    Full Text Available Nerve crush injury is a well-established axonotmetic model in experimental regeneration studies to investigate the impact of various pharmacological treatments. Hericium erinaceus is a temperate mushroom but is now being cultivated in tropical Malaysia. In this study, we investigated the activity of aqueous extract of H. erinaceus fresh fruiting bodies in promoting functional recovery following an axonotmetic peroneal nerve injury in adult female Sprague-Dawley rats by daily oral administration. The aim was to investigate the possible use of this mushroom in the treatment of injured nerve. Functional recovery was assessed in behavioral experiment by walking track analysis. Peroneal functional index (PFI was determined before surgery and after surgery as rats showed signs of recovery. Histological examinations were performed on peroneal nerve by immunofluorescence staining and neuromuscular junction by combined silver-cholinesterase stain. Analysis of PFI indicated that return of hind limb function occurred earlier in rats of aqueous extract or mecobalamin (positive control group compared to negative control group. Regeneration of axons and reinnervation of motor endplates in extensor digitorum longus muscle in rats of aqueous extract or mecobalamin group developed better than in negative control group. These data suggest that daily oral administration of aqueous extract of H. erinaceus fresh fruiting bodies could promote the regeneration of injured rat peroneal nerve in the early stage of recovery.

  18. Peripheral Nerve Regeneration Following Crush Injury to Rat Peroneal Nerve by Aqueous Extract of Medicinal Mushroom Hericium erinaceus (Bull.: Fr) Pers. (Aphyllophoromycetideae).

    Science.gov (United States)

    Wong, Kah-Hui; Naidu, Murali; David, Pamela; Abdulla, Mahmood Ameen; Abdullah, Noorlidah; Kuppusamy, Umah Rani; Sabaratnam, Vikineswary

    2011-01-01

    Nerve crush injury is a well-established axonotmetic model in experimental regeneration studies to investigate the impact of various pharmacological treatments. Hericium erinaceus is a temperate mushroom but is now being cultivated in tropical Malaysia. In this study, we investigated the activity of aqueous extract of H. erinaceus fresh fruiting bodies in promoting functional recovery following an axonotmetic peroneal nerve injury in adult female Sprague-Dawley rats by daily oral administration. The aim was to investigate the possible use of this mushroom in the treatment of injured nerve. Functional recovery was assessed in behavioral experiment by walking track analysis. Peroneal functional index (PFI) was determined before surgery and after surgery as rats showed signs of recovery. Histological examinations were performed on peroneal nerve by immunofluorescence staining and neuromuscular junction by combined silver-cholinesterase stain. Analysis of PFI indicated that return of hind limb function occurred earlier in rats of aqueous extract or mecobalamin (positive control) group compared to negative control group. Regeneration of axons and reinnervation of motor endplates in extensor digitorum longus muscle in rats of aqueous extract or mecobalamin group developed better than in negative control group. These data suggest that daily oral administration of aqueous extract of H. erinaceus fresh fruiting bodies could promote the regeneration of injured rat peroneal nerve in the early stage of recovery.

  19. [Effect of embryonic anlage allografts of the rat spinal cord on growth of regenerating fibers of the recipient nerve].

    Science.gov (United States)

    Petrova, E S; Isaeva, E N

    2014-01-01

    A comparative study of the effect of tissue and suspension allografts of an embryonic spinal cord on regeneration of nerve fibers of impaired (by application of a ligature) sciatic nerve in rats was conducted. It was demonstrated that unlike tissue grafts that reach a large volume 21 and 60 days after transplantation, suspension grafts do not inhibit the growth of axons of the recipient to the periphery. It was established that introduction of a suspension of dissociated cells of the spinal cord embryonic anlages (but not fragments of these anlages) into the impaired sciatic nerve in rats results in an increase in the amount of myelinated regenerating nerve fibers of the recipient 60 days after the operation.

  20. Visualization analysis of research frontiers and trends in nerve regeneration and osseoperception in the repair of tooth loss.

    Science.gov (United States)

    Zhang, Xiaoge; Tang, Tian; Zhao, Zhihe; Zheng, Leilei; Ding, Yin

    2014-11-15

    This study analyzed 85 articles indexed by the Web of Science concerning nerve regeneration and osseoperception during tooth loss repair. Using the Web of Science database and Citespace III software, a document co-citation network map was drawn by document co-citation analysis and word frequency analysis methods. Combined with emergent node secondary literature retrieval, subject headings with apparent changing word frequency trends were retrieved so as to identify research frontiers and development trends. Research frontiers and hotspots for neuronal calcium sensor protein were quantitatively explored to forecast future research developments in nerve regeneration and osseoperception during repair of tooth loss.

  1. Visualization analysis of research frontiers and trends in nerve regeneration and osseoperception in the repair of tooth loss

    Institute of Scientific and Technical Information of China (English)

    Xiaoge Zhang; Tian Tang; Zhihe Zhao; Leilei Zheng; Yin Ding

    2014-01-01

    This study analyzed 85 articles indexed by the Web of Science concerning nerve regeneration and osseoperception during tooth loss repair. Using the Web of Science database and Citespace III software, a document co-citation network map was drawn by document co-citation analysis and word frequency analysis methods. Combined with emergent node secondary literature retrieval, subject headings with apparent changing word frequency trends were retrieved so as to identify research frontiers and development trends. Research frontiers and hotspots for neuronal calcium sensor protein were quantitatively explored to forecast future research developments in nerve regeneration and osseoperception during repair of tooth loss.

  2. BDNF gene delivery within and beyond templated agarose multi-channel guidance scaffolds enhances peripheral nerve regeneration

    Science.gov (United States)

    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.

  3. Effects of Valproic Acid on Axonal Regeneration and Recovery of Motor Function after Peripheral Nerve Injury in the Rat

    Directory of Open Access Journals (Sweden)

    Ting Rao

    2014-03-01

    Full Text Available Background:   Valproic acid (VPA is used to be an effective anti-epileptic drug and mood stabilizer. It has recently been demonstrated that VPA could promote neurite outgrowth, activate the extracellular signal regulated kinase pathway, and increases bcl-2 and growth cone-associated protein 43 levels in spinal cord. In the present research we demonstrate the effect of VPA on peripheral nerve regeneration and recovery of motor function following sciatic nerve transaction in rats. Methods:   The rats in VPA group and control group were administered with valproic acid (300mg/kg and sodium chloride respectively after operation. Each animal was observed sciatic nerve index (SFI at 2-week intervals and studied electrophysiology at 4-week intervals for 12 weeks. Histological and morphometrical analyses were performed 12 weeks after operation. Using the digital image-analysis system, thickness of the myelin sheath was measured, and total numbers of regenerated axons were counted. Results:   There was a significant difference in SFI, electrophysiological index (motor-nerve conduct velocity, and morphometrical results (regenerated axon number and thickness of myelin sheath in nerve regeneration between the VPA group and controls (   P

  4. Combination of fibrin-agarose hydrogels and adipose-derived mesenchymal stem cells for peripheral nerve regeneration

    Science.gov (United States)

    Carriel, Víctor; Garrido-Gómez, Juan; Hernández-Cortés, Pedro; Garzón, Ingrid; García-García, Salomé; Sáez-Moreno, José Antonio; Sánchez-Quevedo, María del Carmen; Campos, Antonio; Alaminos, Miguel

    2013-04-01

    Objective. The objective was to study the effectiveness of a commercially available collagen conduit filled with fibrin-agarose hydrogels alone or with fibrin-agarose hydrogels containing autologous adipose-derived mesenchymal stem cells (ADMSCs) in a rat sciatic nerve injury model. Approach. A 10 mm gap was created in the sciatic nerve of 48 rats and repaired using saline-filled collagen conduits or collagen conduits filled with fibrin-agarose hydrogels alone (acellular conduits) or with hydrogels containing ADMSCs (ADMSC conduits). Nerve regeneration was assessed in clinical, electrophysiological and histological studies. Main results. Clinical and electrophysiological outcomes were more favorable with ADMSC conduits than with the acellular or saline conduits, evidencing a significant recovery of sensory and motor functions. Histological analysis showed that ADMSC conduits produce more effective nerve regeneration by Schwann cells, with higher remyelination and properly oriented axonal growth that reached the distal areas of the grafted conduits, and with intensely positive expressions of S100, neurofilament and laminin. Extracellular matrix was also more abundant and better organized around regenerated nerve tissues with ADMSC conduits than those with acellular or saline conduits. Significance. Clinical, electrophysiological and histological improvements obtained with tissue-engineered ADMSC conduits may contribute to enhancing axonal regeneration by Schwann cells.

  5. Inflammatory stimulation preserves physiological properties of retinal ganglion cells after optic nerve injury

    Directory of Open Access Journals (Sweden)

    Henrike eStutzki

    2014-02-01

    Full Text Available Axonal injury in the optic nerve is associated with retinal ganglion cell (RGC degeneration and irreversible loss of vision. However, inflammatory stimulation (IS by intravitreal injection of Pam3Cys transforms RGCs into an active regenerative state enabling these neurons to survive injury and to regenerate axons into the injured optic nerve. Although morphological changes have been well studied, the functional correlates of RGCs transformed either into a de- or regenerating state at a sub-cellular level remain unclear. In the current study, we investigated the signal propagation in single intraretinal axons as well as characteristic activity features of RGCs in a naive, a degenerative or a regenerative state in ex vivo retinae one week after either optic nerve cut alone (ONC or additional inflammatory stimulation (ONC+IS. Recordings of single RGCs using high-density microelectrode arrays demonstrate that the mean intraretinal axonal conduction velocity significantly decreased within the first week after ONC. In contrast, when ONC was accompanied by regenerative Pam3Cys treatment the mean intraretinal velocity was undistinguishable from control RGCs, indicating a protective effect on the proximal axon. Spontaneous RGC activity decreased for the two most numerous RGC types (ON- and OFF-sustained cells within one post-operative week, but did not significantly increase in RGCs after inflammatory stimulation. The analysis of light-induced activity revealed that RGCs in ONC animals respond on average later and with fewer spikes than control RGCs. IS significantly improved the responsiveness of the two studied RGC types.These results show that the transformation into a regenerative state by IS preserves, at least transiently, the physiological functional properties of injured RGCs.

  6. Optic nerve histopathology in a case of Wolfram Syndrome

    DEFF Research Database (Denmark)

    Ross-Cisneros, Fred N; Pan, Billy X; Silva, Ruwan A

    2013-01-01

    Mitochondrial dysfunction in Wolfram Syndrome (WS) is controversial and optic neuropathy, a cardinal clinical manifestation, is poorly characterized. We here describe the histopathological features in postmortem retinas and optic nerves (ONs) from one patient with WS, testing the hypothesis...... that mitochondrial dysfunction underlies the pathology. Eyes and retrobulbar ONs were obtained at autopsy from a WS patient, and compared with those of a Leber hereditary optic neuropathy (LHON) patient and one healthy control. Retinas were stained with hematoxylin & eosin for general morphology and ONs were...... of axonal degeneration, involving primarily the papillomacular bundle, closely resembled LHON and other mitochondrial optic neuropathies, supporting that mitochondrial dysfunction underlies its pathogenesis....

  7. A subtractive cDNA library from an identified regenerating neuron is enriched in sequences up-regulated during nerve regeneration.

    Science.gov (United States)

    Korneev, S; Fedorov, A; Collins, R; Blackshaw, S E; Davies, J A

    1997-01-01

    We have constructed a subtractive cDNA library from regenerating Retzius cells of the leech, Hirudo medicinalis. It is highly enriched in sequences up-regulated during nerve regeneration. Sequence analysis of selected recombinants has identified both novel sequences and sequences homologous to molecules characterised in other species. Homologies include alpha-tubulin, a calmodulin-like protein, CAAT/enhancer-binding protein (C/EBP), protein 4.1 and synapsin. These types of proteins are exactly those predicted to be associated with axonal growth and their identification confirms the quality of the library. Most interesting, however, is the isolation of 5 previously uncharacterised cDNAs which appear to be up-regulated during regeneration. Their analysis is likely to provide new information on the molecular mechanisms of neuronal regeneration.

  8. Aspects of static and dynamic motor function in peripheral nerve regeneration: SSI and CatWalk gait analysis.

    Science.gov (United States)

    Bozkurt, A; Scheffel, J; Brook, G A; Joosten, E A; Suschek, C V; O'Dey, D M; Pallua, N; Deumens, R

    2011-05-16

    Assessment of the therapeutic potential of interventions to bridge-repair peripheral nerve defects heavily relies on the demonstration of improved functional outcome. In the present study we used CatWalk gait analysis (locomotor-test) and Static Sciatic Index (SSI) (static-toe-spread-test) to assess the behavioural benefits of autologous nerve transplantation (ANT) repair of 2-cm rat sciatic nerve defects (neurotmesis-lesion). A reproducible and standardised rat sciatic nerve crush lesion model (axonotmesis-lesion) was used to assess the extent of recovery supported by maximal axon regeneration (measured by SSI and CatWalk). Animals were behaviourally followed for a period of 10 weeks. SSI analysis showed that ANT induced a significant improvement in motor deficit from about -95 to -65, however, CatWalk analysis did not show any major indication of locomotor recovery. This discrepancy might suggest that improvements in static motor functions (such as toe spreading) could reflect an early indicator for the recovery of function. We also noted differences in axon regeneration including increased axon density, smaller axon diameters and thinner myelin sheaths in the distal region of the ANT in comparison to the equivalent region of crushed and normal nerves. This difference in axon regeneration may be related to the clearly improved toe spreading function. We conclude that SSI and CatWalk present different advantages and disadvantages for the assessment of motor recovery after bridge-repair of peripheral nerve defects. Copyright © 2010 Elsevier B.V. All rights reserved.

  9. Spontaneous resolution of optic nerve coloboma-associated retinal detachment.

    Science.gov (United States)

    Ying, Michelle S; Fuller, Jeff; Young, Joshua; Marcus, Dennis M

    2004-01-01

    We report a congenital neurosensory retinal detachment associated with an optic nerve coloboma with subsequent spontaneous reattachment. This represents the earliest reported case of such a clinical situation. An observation period is recommended for infants with this clinical course to allow for the opportunity of spontaneous reattachment.

  10. Bilateral iris, choroid, optic nerve colobomas and retinal detachment ...

    African Journals Online (AJOL)

    Rabah M. Shawky

    2013-12-05

    Dec 5, 2013 ... low posterior hair line, partial left simian crease, and short fingers. MRI brain shows ... The patient has mild mental retardation, now she can walk, dress, and feed ... and acoustic evidence of optic nerve head coloboma. B-scan.

  11. Optic nerve pH and PO2

    DEFF Research Database (Denmark)

    Pedersen, Daniella B; Stefánsson, Einar; Kiilgaard, Jens Folke;

    2006-01-01

    how optic nerve pH (ONpH) and ONPO(2) are affected by: (1) carbonic anhydrase inhibition; (2) respiratory acidosis, and (3) metabolic acidosis. We measured ONpH with a glass pH electrode and ONPO(2) with a polarographic oxygen electrode. One of the electrodes was placed in the vitreous cavity 0.5 mm...

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

    Science.gov (United States)

    Yurie, Hirofumi; Ikeguchi, Ryosuke; Aoyama, Tomoki; Kaizawa, Yukitoshi; Tajino, Junichi; Ito, Akira; Ohta, Souichi; Oda, Hiroki; Takeuchi, Hisataka; Akieda, Shizuka; Tsuji, Manami; Nakayama, Koichi; Matsuda, Shuichi

    2017-01-01

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

  13. Small gap anastomosis to repair peripheral nerve rupture using a nerve regeneration chamber constructed by scissoring and sleeve jointing autologous epineurium

    Institute of Scientific and Technical Information of China (English)

    Peiji Wang; Zhongliang Zhou; Qirong Dong

    2011-01-01

    A number of studies have shown how to eliminate the misorientated docking of the peripheral nerve bundle in the traditional epineurium or perineudum anastomosis, thus avoiding neuroma formation and axonal outgrowth from the coaptation sites, and seriously hindering neural function recovery. Based on the "peripheral nerve selective regeneration theory", this experiment was designed to investigate the feasibility and benefits of a new small gap anastomosis repairing peripheral nerve rupture, by scissoring and sleeve jointing an autologous epineurium. In the proximal stump of the nerve, a 1 mm-long epineurium was annularly separated and removed, while a 3 mm-long epineurium was longitudinally incised in the distal stump after the epineurium was dissociated from proximal to distal. The epineuria of the two stumps and the longitudinal incision were sutured, leaving a 2 mm gap between the two nerve stumps. Results show that the experimental rats quickly recovered autonomic activities, and there were minimal adhesions at the outer surface of the epineurial tube to the surrounding tissue. The morphologic changes to the sciatic nerve showed that connective tissue hyperplasia of the small gaps was significantly reduced, and nerve fibers were arranged orderly. No such changes were observed in the neurorrhaphy in situ group. Thus, the experiment confirmed that the new small gap anastomosis to repair peripheral nerve rupture by scissoring and sleeve jointing autologous epineurium is feasible, and that it is superior to epineurium neurorrhaphy in situ.

  14. Bone Marrow-Derived Cells as a Therapeutic Approach to Optic Nerve Diseases

    Directory of Open Access Journals (Sweden)

    Louise A. Mesentier-Louro

    2016-01-01

    Full Text Available Following optic nerve injury associated with acute or progressive diseases, retinal ganglion cells (RGCs of adult mammals degenerate and undergo apoptosis. These diseases have limited therapeutic options, due to the low inherent capacity of RGCs to regenerate and due to the inhibitory milieu of the central nervous system. Among the numerous treatment approaches investigated to stimulate neuronal survival and axonal extension, cell transplantation emerges as a promising option. This review focuses on cell therapies with bone marrow mononuclear cells and bone marrow-derived mesenchymal stem cells, which have shown positive therapeutic effects in animal models of optic neuropathies. Different aspects of available preclinical studies are analyzed, including cell distribution, potential doses, routes of administration, and mechanisms of action. Finally, published and ongoing clinical trials are summarized.

  15. Bone Marrow-Derived Cells as a Therapeutic Approach to Optic Nerve Diseases

    Science.gov (United States)

    Mesentier-Louro, Louise A.; Zaverucha-do-Valle, Camila; Rosado-de-Castro, Paulo H.; Silva-Junior, Almir J.; Pimentel-Coelho, Pedro M.; Mendez-Otero, Rosalia; Santiago, Marcelo F.

    2016-01-01

    Following optic nerve injury associated with acute or progressive diseases, retinal ganglion cells (RGCs) of adult mammals degenerate and undergo apoptosis. These diseases have limited therapeutic options, due to the low inherent capacity of RGCs to regenerate and due to the inhibitory milieu of the central nervous system. Among the numerous treatment approaches investigated to stimulate neuronal survival and axonal extension, cell transplantation emerges as a promising option. This review focuses on cell therapies with bone marrow mononuclear cells and bone marrow-derived mesenchymal stem cells, which have shown positive therapeutic effects in animal models of optic neuropathies. Different aspects of available preclinical studies are analyzed, including cell distribution, potential doses, routes of administration, and mechanisms of action. Finally, published and ongoing clinical trials are summarized. PMID:26649049

  16. Tissue engineering with peripheral blood-derived mesenchymal stem cells promotes the regeneration of injured peripheral nerves.

    Science.gov (United States)

    Pan, Mengjie; Wang, Xianghai; Chen, Yijing; Cao, Shangtao; Wen, Jinkun; Wu, Guofeng; Li, Yuanyuan; Li, Lixia; Qian, Changhui; Qin, Zhenqi; Li, Zhenlin; Tan, Dandan; Fan, Zhihao; Wu, Wutian; Guo, Jiasong

    2017-06-01

    Peripheral nerve injury repair can be enhanced by Schwann cell (SC) transplantation, but clinical applications are limited by the lack of a cell source. Thus, alternative systems for generating SCs are desired. Herein, we found the peripheral blood-derived mesenchymal stem cells (PBMSCs) could be induced into SC like cells with expressing SC-specific markers (S100, P75NTR and CNPase) and functional factors (NGF, NT-3, c-Fos, and Krox20). When the induced PBMSCs (iPBMSCs) were transplanted into crushed rat sciatic nerves, they functioned as SCs by wrapping the injured axons and expressing myelin specific marker of MBP. Furthermore, iPBMSCs seeded in an artificial nerve conduit to bridge a 10-mm defect in a sciatic nerve achieved significant nerve regeneration outcomes, including axonal regeneration and remyelination, nerve conduction recovery, and restoration of motor function, and attenuated myoatrophy and neuromuscular junction degeneration in the target muscle. Overall, the data from this study indicated that PBMSCs can transdifferentiate towards SC-like cells and have potential as grafting cells for nerve tissue engineering. Copyright © 2017. Published by Elsevier Inc.

  17. Streptozotocin-induced diabetes, and the optic nerve blood barrier.

    Science.gov (United States)

    Alemán, R; Mompeó, B; Castaño, I

    2016-04-01

    To study the features of the endoneurial micro-vessels of the optic nerve in streptozotocin-induced diabetic animals. Optic nerves from control and streptozotocin-induced diabetic animals were studied by light and transmission electron microscopy. Patency was determined by indirect immunofluorescence albumin detection. The expression of major histocompatibility complex class II molecules was performed by direct immunofluorescence. The endoneurial vessels were counted, and the endothelial cell, the basement membrane, and the surface of the transverse section of the nerve were measured. Vessels of diabetic rats showed vessel wall thickening, preservation of pericytes, an increase in endothelial cell transcytosis, and an increased number of perivascular macrophage cells. It may be concluded that the effects of hyperglycaemia on the inner vessels of the optic nerve are more similar to the cerebral diabetic vessels than to the retinal vessels in diabetic animals. Copyright © 2016 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

  18. Anatomical study of the nerve regeneration after selective neurectomy in the rabbit: clinical application for esthetic calf reduction.

    Science.gov (United States)

    Shin, Kang-Jae; Yoo, Ja-Young; Lee, Ju-Young; Gil, Young-Chun; Kim, Jeong-Nam; Koh, Ki-Seok; Song, Wu-Chul

    2015-12-01

    The purposes of this study were therefore to characterize the degeneration and regeneration of nerves to the calf muscles after selective neurectomy, both macroscopically and microscopically, and to determine the incidence of such regeneration in a rabbit model. Seventy four New Zealand white rabbits were used. Selective neurectomy to the triceps surae muscles was performed, and the muscles were subsequently harvested and weighed 1-4 months postneurectomy. The gastrocnemius muscles were stained with Sihler's solution to enable the macroscopic observation of any nerve regeneration that may have occurred subsequent to neurectomy. The change in triceps surae muscle weight was measured along the time course of the experiment. After neurectomy, nerve degeneration was followed by regeneration in all cases. The weight of the triceps surae muscle decreased dramatically between completion of the neurectomy and 1 month postneurectomy, but increased thereafter. The nerve branches were weakly stained with Sihler's solution until 2 months postneurectomy, and then strongly stained after 3 months. The number of myelinated axons was decreased at 2 month after neurectomy compared to nonneurectomized controls, but then gradually increased thereafter. Although there are currently no reports on the incidence of recovery after calf reduction, it may be a very common occurrence in the clinical field based on our findings. The findings of this study provide fundamental anatomical and surgical information to aid planning and practice in calf-reduction surgery.

  19. Experimental study on regeneration of ascending tract after spinal cord injury with predegenerated peripheral nerve graft and NGF infusion

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective:To explore the effects of predegenerated peripheral nerve graft (PPNG) combined with nerve growth factor (NGF) infusion on ascending sensory tract regeneration after spinal cord injury.Methods: Fifty female SD rats were randomly divided into 5 groups. Group A was treated with PPNG and NGF infusion, group B with PPNG, group C with NGF infusion, group D and group E were blank and normal control, respectively. Horseradish peroxidase-labled (HRP) tracing method was employed to evaluate the regeneration of injured nerves after 8 weeks. The extent of regeneration in and beyond the nerve graft was determined by counting the number of HRP-labeled fibers intersecting imaginary lines perpendicular to the axis of the graft and cord. For the sake of convenience, according to the relation of the PNG and spinal cord, 6 model zones were divided, including caudal of spinal cord, caudal transition zone, caudal zone in graft, rostral zone in graft, rostral transition zone and rostral of spinal cord. Results: On the transverse section of caudal zone in graft, rostral zone in graft, rostral transition zone, the fibers in group A were significantly higher than that in group B and C (P<0.05). Conclusion: PPNG combined with NGF may significantly promote the regeneration of ascending long tract after spinal cord injury. The regenerative fibers can penetrate the 2 graft-host interface scars.

  20. Evaluation of several techniques to modify denatured muscle tissue to obtain a scaffold for peripheral nerve regeneration

    NARCIS (Netherlands)

    Meek, MF; den Dunnen, WFA; Schakenraad, JM; Robinson, PH

    The aim of this study was to (1) evaluate the effect of several preparation techniques of denatured muscle tissue to obtain an open three-dimensional structure, and (2) test if this scaffold is suitable for peripheral nerve regeneration. Four samples (A-D) of muscle tissue specimens were evaluated

  1. Evaluation of several techniques to modify denatured muscle tissue to obtain a scaffold for peripheral nerve regeneration

    NARCIS (Netherlands)

    Meek, MF; den Dunnen, WFA; Schakenraad, JM; Robinson, PH

    1999-01-01

    The aim of this study was to (1) evaluate the effect of several preparation techniques of denatured muscle tissue to obtain an open three-dimensional structure, and (2) test if this scaffold is suitable for peripheral nerve regeneration. Four samples (A-D) of muscle tissue specimens were evaluated u

  2. Sox10 Expression in Goldfish Retina and Optic Nerve Head in Controls and after the Application of Two Different Lesion Paradigms

    Science.gov (United States)

    Parrilla, Marta; León-Lobera, Fernando; Lillo, Concepción; Arévalo, Rosario; Aijón, José; Lara, Juan Manuel; Velasco, Almudena

    2016-01-01

    The mammalian central nervous system (CNS) is unable to regenerate. In contrast, the CNS of fish, including the visual system, is able to regenerate after damage. Moreover, the fish visual system grows continuously throughout the life of the animal, and it is therefore an excellent model to analyze processes of myelination and re-myelination after an injury. Here we analyze Sox10+ oligodendrocytes in the goldfish retina and optic nerve in controls and after two kinds of injuries: cryolesion of the peripheral growing zone and crushing of the optic nerve. We also analyze changes in a major component of myelin, myelin basic protein (MBP), as a marker for myelinated axons. Our results show that Sox10+ oligodendrocytes are located in the retinal nerve fiber layer and along the whole length of the optic nerve. MBP was found to occupy a similar location, although its loose appearance in the retina differed from the highly organized MBP+ axon bundles in the optic nerve. After optic nerve crushing, the number of Sox10+ cells decreased in the crushed area and in the optic nerve head. Consistent with this, myelination was highly reduced in both areas. In contrast, after cryolesion we did not find changes in the Sox10+ population, although we did detect some MBP- degenerating areas. We show that these modifications in Sox10+ oligodendrocytes are consistent with their role in oligodendrocyte identity, maintenance and survival, and we propose the optic nerve head as an excellent area for research aimed at better understanding of de- and remyelination processes. PMID:27149509

  3. Sox10 Expression in Goldfish Retina and Optic Nerve Head in Controls and after the Application of Two Different Lesion Paradigms.

    Directory of Open Access Journals (Sweden)

    Marta Parrilla

    Full Text Available The mammalian central nervous system (CNS is unable to regenerate. In contrast, the CNS of fish, including the visual system, is able to regenerate after damage. Moreover, the fish visual system grows continuously throughout the life of the animal, and it is therefore an excellent model to analyze processes of myelination and re-myelination after an injury. Here we analyze Sox10+ oligodendrocytes in the goldfish retina and optic nerve in controls and after two kinds of injuries: cryolesion of the peripheral growing zone and crushing of the optic nerve. We also analyze changes in a major component of myelin, myelin basic protein (MBP, as a marker for myelinated axons. Our results show that Sox10+ oligodendrocytes are located in the retinal nerve fiber layer and along the whole length of the optic nerve. MBP was found to occupy a similar location, although its loose appearance in the retina differed from the highly organized MBP+ axon bundles in the optic nerve. After optic nerve crushing, the number of Sox10+ cells decreased in the crushed area and in the optic nerve head. Consistent with this, myelination was highly reduced in both areas. In contrast, after cryolesion we did not find changes in the Sox10+ population, although we did detect some MBP- degenerating areas. We show that these modifications in Sox10+ oligodendrocytes are consistent with their role in oligodendrocyte identity, maintenance and survival, and we propose the optic nerve head as an excellent area for research aimed at better understanding of de- and remyelination processes.

  4. Gene expression profiling studies in regenerating nerves in a mouse model for CMT1X: uninjured Cx32-knockout peripheral nerves display expression profile of injured wild type nerves.

    Science.gov (United States)

    Freidin, Mona; Asche-Godin, Samantha; Abrams, Charles K

    2015-01-01

    X-linked Charcot-Marie-Tooth disease (CMT1X) is an inherited peripheral neuropathy caused by mutations in GJB1, the human gene for Connexin32 (Cx32). This present study uses Ilumina Ref8-v2 BeadArray to examine the expression profiles of injured and uninjured sciatic nerves at 5, 7, and 14 days post-crush injury (dpi) from Wild Type (WT) and Cx32-knockout (Cx32KO) mice to identify the genes and signaling pathways that are dysregulated in the absence of Schwann cell Cx32. Given the assumption that loss of Schwann cell Cx32 disrupts the regeneration and maintenance of myelinated nerve leading to a demyelinating neuropathy in CMT1X, we initially hypothesized that nerve crush injury would result in significant increases in differential gene expression in Cx32KO mice relative to WT nerves. However, microarray analysis revealed a striking collapse in the number of differentially expressed genes at 5 and 7 dpi in Cx32KO nerves relative to WT, while uninjured and 14 dpi time points showed large numbers of differentially regulated genes. Further comparisons within each genotype showed limited changes in Cx32KO gene expression following crush injury when compared to uninjured Cx32KO nerves. By contrast, WT nerves exhibited robust changes in gene expression at 5 and 7 dpi with no significant differences in gene expression by 14dpi relative to uninjured WT nerve samples. Taken together, these data suggest that the gene expression profile in uninjured Cx32KO sciatic nerve strongly resembles that of a WT nerve following injury and that loss of Schwann cell Cx32 leads to a basal state of gene expression similar to that of an injured WT nerve. These findings support a role for Cx32 in non-myelinating and regenerating populations of Schwann cells in normal axonal maintenance in re-myelination, and regeneration of peripheral nerve following injury. Disruption of Schwann cell-axonal communication in CMT1X may cause dysregulation of signaling pathways that are essential for the

  5. Effect of silanization on chitosan porous scaffolds for peripheral nerve regeneration.

    Science.gov (United States)

    Li, Guicai; Zhang, Luzhong; Wang, Caiping; Zhao, Xueying; Zhu, Changlai; Zheng, Yanhong; Wang, Yaling; Zhao, Yahong; Yang, Yumin

    2014-01-30

    The aim of this study was to evaluate the feasibility of using 3-aminopropyltriethoxysilane (APTE) silanization treatment for modification and biocompatibility of lyophilized chitosan porous scaffolds. The process is beneficial for biomaterial development due to its low toxicity and simplicity. The silanization treatment with low APTE concentration showed no significant influence on the morphology of chitosan scaffolds, while a skin-like surface was observed for the silanized scaffolds treated with high APTE concentration. The porosity and surface amino densities were increased after silanization whereas the swelling ratio was reduced, and the degradation ratio in PBS and anti-acid degradation properties of the silanized chitosan scaffolds were significantly improved. The in vitro Schwann cells culture demonstrated that the silanized scaffolds with 8% APTE could obviously facilitate the attachment and proliferation of Schwann cells, indicating great potential for the application in peripheral nerve regeneration.

  6. Effects of NGF and TrkA on GAP-43+ nerve regeneration in rat autotransplanted splenic tissue

    Institute of Scientific and Technical Information of China (English)

    JIANG Deng-jin; GUO Guang-jin; WANG Lin; ZHANG Kun; ZHANG Tian-fei; ZUO Yan-fang

    2005-01-01

    Objective:To study the time-course of the regeneration of GAP-43+ nerve, and the effects of NGF and TrkA on this process. Methods: Adult Wistar rats underwent splenectomy and splenic autotransplantation, or sham-operation. On day 7, 14, 30, 60, 90, 120, and 180 after surgery, the density of GAP-43+ nerve fibers in spleen tissues were measured with the immunohistochemistry followed by computer image analysis. The expressions of GAP-43, NGF and TrkA were determined with in situ hybrdization, and their mRNA levels were detected with RT-PCR and image analysis qualification. Results: (1)The GAP-43+ nerve fibers began their regeneration on 30 d after operation and extended from greater omentum into splenic autotransplants. Density of the nerve fibers gradually became greater and almost normal 180 d after operation. (2) In splenic autografts, the mRNA expression of GAP-43, NGF and TrkA appeared on day 30 after the operation, gradually reached the peak on day 90. Conclusion: The renascent GAP-43+ nerve fibers may come from the greater omentum packaging the splenic autografts and NGF and TrkA can promote the nerval regeneration in the autotransplant spleen tissues.

  7. Immediate electrical stimulation enhances regeneration and reinnervation and modulates spinal plastic changes after sciatic nerve injury and repair.

    Science.gov (United States)

    Vivó, Meritxell; Puigdemasa, Antoni; Casals, Laura; Asensio, Elena; Udina, Esther; Navarro, Xavier

    2008-05-01

    We have studied whether electrical stimulation immediately after nerve injury may enhance axonal regeneration and modulate plas