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https://www.readbyqxmd.com/read/28059646/irreversible-changes-occurring-in-long-term-denervated-schwann-cells-affect-delayed-nerve-repair
#1
Giulia Ronchi, Michele Cillino, Giovanna Gambarotta, Benedetta Elena Fornasari, Stefania Raimondo, Pierfrancesco Pugliese, Pierluigi Tos, Adriana Cordova, Francesco Moschella, Stefano Geuna
OBJECTIVE Multiple factors may affect functional recovery after peripheral nerve injury, among them the lesion site and the interval between the injury and the surgical repair. When the nerve segment distal to the lesion site undergoes chronic degeneration, the ensuing regeneration (when allowed) is often poor. The aims of the current study were as follows: 1) to examine the expression changes of the neuregulin 1/ErbB system during long-term nerve degeneration; and 2) to investigate whether a chronically denervated distal nerve stump can sustain nerve regeneration of freshly axotomized axons...
January 6, 2017: Journal of Neurosurgery
https://www.readbyqxmd.com/read/28057929/a-novel-role-for-the-dna-repair-gene-rad51-in-netrin-1-signalling
#2
K A Glendining, D Markie, R J M Gardner, E A Franz, S P Robertson, C L Jasoni
Mutations in RAD51 have recently been linked to human Congenital Mirror Movements (CMM), a developmental disorder of the motor system. The only gene previously linked to CMM encodes the Netrin-1 receptor DCC, which is important for formation of corticospinal and callosal axon tracts. Thus, we hypothesised that Rad51 has a novel role in Netrin-1-mediated axon development. In mouse primary motor cortex neurons, Rad51 protein was redistributed distally down the axon in response to Netrin-1, further suggesting a functional link between the two...
January 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28045825/the-effect-of-carnitine-on-peripheral-nerve-regeneration
#3
Kemal Karaca, Fevzi Solmaz
INTRODUCTION: Proximal and distal axons of the nerve body are subject to varying degrees of traumatic degeneration after an incision. The histologic structure of rat peripheral nerves cannot be distinguished from the human. Studies on systemic carnitine treatment following peripheral nerve injury and its positive results are available in the literature. There are no reported results of local administration. METHODS: The authors used 50 rats. A total of 5 groups were created by randomly assigning the rats...
December 30, 2016: Journal of Craniofacial Surgery
https://www.readbyqxmd.com/read/28039763/spatial-and-temporal-arrangement-of-neuronal-intrinsic-and-extrinsic-mechanisms-controlling-axon-regeneration
#4
REVIEW
Andrea Tedeschi, Frank Bradke
Axon regeneration and neuronal tissue repair varies across animal lineages as well as in the mammalian central and peripheral nervous systems. While the peripheral nervous system retains the ability to self-repair, the majority of axons in the adult mammalian central nervous system (CNS) fail to reactivate intrinsic growth programs after injury. Recent findings, however, suggest that long-distance axon regeneration, neuronal circuit assembly and recovery of functions in the adult mammalian CNS are possible...
December 28, 2016: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/28036084/preferential-enhancement-of-sensory-and-motor-axon-regeneration-by-combining-extracellular-matrix-components-with-neurotrophic-factors
#5
Daniel Santos, Francisco González-Pérez, Guido Giudetti, Silvestro Micera, Esther Udina, Jaume Del Valle, Xavier Navarro
After peripheral nerve injury, motor and sensory axons are able to regenerate but inaccuracy of target reinnervation leads to poor functional recovery. Extracellular matrix (ECM) components and neurotrophic factors (NTFs) exert their effect on different neuronal populations creating a suitable environment to promote axonal growth. Here, we assessed in vitro and in vivo the selective effects of combining different ECM components with NTFs on motor and sensory axons regeneration and target reinnervation. Organotypic cultures with collagen, laminin and nerve growth factor (NGF)/neurotrophin-3 (NT3) or collagen, fibronectin and brain-derived neurotrophic factor (BDNF) selectively enhanced sensory neurite outgrowth of DRG neurons and motor neurite outgrowth from spinal cord slices respectively...
December 29, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28035961/stem-cells-and-labeling-for-spinal-cord-injury
#6
REVIEW
Marina Gazdic, Vladislav Volarevic, Aleksandar Arsenijevic, Slaven Erceg, Victoria Moreno-Manzano, Nebojsa Arsenijevic, Miodrag Stojkovic
Spinal cord injury (SCI) is a devastating condition that usually results in sudden and long-lasting locomotor and sensory neuron degeneration below the lesion site. During the last two decades, the search for new therapies has been revolutionized with the improved knowledge of stem cell (SC) biology. SCs therapy offers several attractive strategies for spinal cord repair. The transplantation of SCs promotes remyelination, neurite outgrowth and axonal elongation, and activates resident or transplanted progenitor cells across the lesion cavity...
December 26, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28035702/refinements-of-nerve-repair-with-connector-assisted-coaptation
#7
REVIEW
Ivica Ducic, Bauback Safa, Erick DeVinney
Peripheral nerve repair can be very rewarding for both surgeon and patient when expected outcomes are achieved. In many cases, however, the results are suboptimal due to number of possible objective and technical reasons. Although we cannot influence patent's comorbidities, the extent or mechanism of the nerve injury, we may help optimize technical details when aiming towards improved outcomes. While the suture coaptation for primary nerve repair or nerve reconstruction with grafting served as the reconstructive standard for many decades, technical imperfections remain threats to reconstructive goals...
December 30, 2016: Microsurgery
https://www.readbyqxmd.com/read/28029073/exploring-optic-nerve-axon-regeneration
#8
Hong-Jiang Li, Zhao-Liang Sun, Xi-Tao Yang, Liang Zhu, Dong-Fu Feng
Traumatic optic nerve (ON) injury is a leading cause of irreversible visual impairment worldwide. To date, neither pharmacological nor surgical interventions are sufficient to halt or reverse the progression of visual loss. Axon regeneration is critical for functional recovery of vision following ON injury. After ON injury, retinal ganglion cells (RGCs) axons usually fail to regrow and instead die back, leading to the death of the RGCs and subsequently causing the functional loss of vision. However, the detailed molecular mechanisms underlying axon regeneration after ON injury remain poorly understood...
December 27, 2016: Current Neuropharmacology
https://www.readbyqxmd.com/read/28013092/overexpression-of-mitofusin2-decreased-the-reactive-astrocytes-proliferation-in-vitro-induced-by-oxygen-glucose-deprivation-reoxygenation
#9
Yulong Shi, Chengla Yi, Xiao Li, Jiangpeng Wang, Fangyuan Zhou, Xiaoqian Chen
Glia scar is a hallmark in late-stage of brain stroke disease, which hinder axonal regeneration and neuronal repair. Mitofusin2 (Mfn2) is a newly found cellular proliferation inhibitor. This study is to elucidate the role of Mfn2 in reactive astrocytes induced by oxygen-glucose deprivation/reoxygenation(OGD/R) model in vitro. Up-expression in EdU staining and protein level of GFAP, PCNA and CyclinD1, demonstrates the distinct activation and proliferation of astrocytes after the stimulation of OGD/R. Meanwhile, Mfn2 was proved to be down-regulated both in gene and protein levels...
December 22, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/28011153/wnt-signaling-promotes-axonal-regeneration-following-optic-nerve-injury-in-the-mouse
#10
Amit K Patel, Kevin K Park, Abigail S Hackam
Adult mammalian CNS axons generally do not regenerate, creating an obstacle to effective repair and recovery after neuronal injury. The canonical Wnt/β-catenin signaling pathway is an essential signal transduction cascade that regulates axon growth and neurite extension in the developing mammalian embryo. In this study, we investigated whether a Wnt/β-catenin signaling activator could be repurposed to induce regeneration in the adult CNS after axonal injury. We used a retinal ganglion cell (RGC) axon crush injury model in a transgenic Wnt reporter mouse, and intravitreal injections were used to deliver Wnt3a or saline to the RGC cell bodies within the retina...
December 21, 2016: Neuroscience
https://www.readbyqxmd.com/read/28009439/sudan-black-a-fast-easy-and-non-toxic-method-to-assess-myelin-repair-in-demyelinating-diseases
#11
Benjamin V Ineichen, Oliver Weinmann, Nicolas Good, Patricia Plattner, Carla Wicki, Elisabeth J Rushing, Michael Linnebank, Martin E Schwab
AIMS: The search for novel drugs that enhance myelin repair in entities such as multiple sclerosis has top priority in neurological research, not least because remyelination can hinder further neurodegeneration in neuro-inflammatory conditions. Recently, several new compounds with the potential to boost remyelination have been identified using high-throughput in vitro screening methods. However, assessing their potential to enhance remyelination in vivo using plastic embedded semi-thin sections or electron microscopy, even though being the gold standard for assessing remyelination, is toxic, extremely time-consuming, and expensive...
December 23, 2016: Neuropathology and Applied Neurobiology
https://www.readbyqxmd.com/read/28009275/the-mammalian-specific-protein-armcx1-regulates-mitochondrial-transport-during-axon-regeneration
#12
Romain Cartoni, Michael W Norsworthy, Fengfeng Bei, Chen Wang, Siwei Li, Yiling Zhang, Christopher V Gabel, Thomas L Schwarz, Zhigang He
Mitochondrial transport is crucial for neuronal and axonal physiology. However, whether and how it impacts neuronal injury responses, such as neuronal survival and axon regeneration, remain largely unknown. In an established mouse model with robust axon regeneration, we show that Armcx1, a mammalian-specific gene encoding a mitochondria-localized protein, is upregulated after axotomy in this high regeneration condition. Armcx1 overexpression enhances mitochondrial transport in adult retinal ganglion cells (RGCs)...
December 21, 2016: Neuron
https://www.readbyqxmd.com/read/28008990/experimental-immunological-demyelination-enhances-regeneration-in-autograft-repaired-long-peripheral-nerve-gaps
#13
Jun Ge, Shu Zhu, Yafeng Yang, Zhongyang Liu, Xueyu Hu, Liangliang Huang, Xin Quan, Meng Wang, Jinghui Huang, Yunqing Li, Zhuojing Luo
Peripheral nerve long gap defects are a clinical challenge in the regeneration field. Despite the wide variety of surgical techniques and therapies, autografting is the "gold standard" for peripheral nerve gap reconstruction. The pathological process of Wallerian degeneration from the time of acute injury to efficient regeneration requires several weeks. Regeneration time is critical for nerve reconstruction. Immunological demyelination induced by anti-galactocerebroside antibodies plus guinea pig complement was used to shorten the treatment time...
December 23, 2016: Scientific Reports
https://www.readbyqxmd.com/read/28006841/functional-and-structural-microanatomy-of-the-fetal-sciatic-nerve
#14
Maud Creze, Mazen Zaitouna, Timoh Krystel Nyango, Djibril Diallo, Cédric Lebacle, Marie-France Bellin, Denis Ducreux, Gérard Benoit, Thomas Bessede
INTRODUCTION: The ultrastructure of a nerve has implications for surgical nerve repair. The aim of our study was to characterize the fascicular vs. fibrillar anatomy and the autonomic vs. somatic nature of the fetal sciatic nerve (SN). METHODS: Immunohistochemistry for vesicular acetylcholine transporter, tyrosine hydroxylase, and peripheral myelin protein 22 was performed to identify cholinergic, adrenergic, and somatic axons, respectively in the human fetal SN...
December 22, 2016: Muscle & Nerve
https://www.readbyqxmd.com/read/28002403/xrcc1-mutation-is-associated-with-parp1-hyperactivation-and-cerebellar-ataxia
#15
Nicolas C Hoch, Hana Hanzlikova, Stuart L Rulten, Martine Tétreault, Emilia Komulainen, Limei Ju, Peter Hornyak, Zhihong Zeng, William Gittens, Stephanie A Rey, Kevin Staras, Grazia M S Mancini, Peter J McKinnon, Zhao-Qi Wang, Justin D Wagner, Grace Yoon, Keith W Caldecott
XRCC1 is a molecular scaffold protein that assembles multi-protein complexes involved in DNA single-strand break repair. Here we show that biallelic mutations in the human XRCC1 gene are associated with ocular motor apraxia, axonal neuropathy, and progressive cerebellar ataxia. Cells from a patient with mutations in XRCC1 exhibited not only reduced rates of single-strand break repair but also elevated levels of protein ADP-ribosylation. This latter phenotype is recapitulated in a related syndrome caused by mutations in the XRCC1 partner protein PNKP and implicates hyperactivation of poly(ADP-ribose) polymerase/s as a cause of cerebellar ataxia...
January 5, 2017: Nature
https://www.readbyqxmd.com/read/27989572/the-role-of-camp-and-its-downstream-targets-in-neurite-growth-in-the-adult-nervous-system
#16
REVIEW
Nicholas J Batty, Keith K Fenrich, Karim Fouad
Injured neurons in the adult mammalian central nervous system (CNS) have a very limited capacity for axonal regeneration and neurite outgrowth. This inability to grow new axons or to regrow injured axons is due to the presence of molecules that inhibit axonal growth, and age related changes in the neuron's innate growth capabilities. Available levels of cAMP are thought to have an important role in linking both of these factors. Elevated levels of cAMP in the developing nervous system are important for the guidance and stability of growth cones...
December 15, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27983992/single-injection-of-a-novel-nerve-growth-factor-coacervate-improves-structural-and-functional-regeneration-after-sciatic-nerve-injury-in-adult-rats
#17
Rui Li, Jiang Wu, Zhenkun Lin, Matthew R Nangle, Yi Li, Pingtao Cai, Dan Liu, Libin Ye, Zecong Xiao, Chaochao He, Jingjing Ye, Hongyu Zhang, Yingzheng Zhao, Jian Wang, Xiaokun Li, Yan He, Qingsong Ye, Jian Xiao
The prototypical neurotrophin, nerve growth factor (NGF), plays an important role in the development and maintenance of many neurons in both the central and peripheral nervous systems, and can promote functional recovery after peripheral nerve injury in adulthood. However, repair of peripheral nerve defects is hampered by the short half-life of NGF in vivo, and treatment with either NGF alone or NGF contained in synthetic nerve conduits is inferior to the use of nerve autografts, the current gold standard. We tested the reparative ability of a single local injection of a polyvalent coacervate containing polycation-poly(ethylene argininylaspartate diglyceride; PEAD), heparin, and NGF, in adult rats following sciatic nerve crush injury, using molecular, histological and behavioral approaches...
February 2017: Experimental Neurology
https://www.readbyqxmd.com/read/27978504/redox-guided-axonal-regrowth-requires-cyclic-gmp-dependent-protein-kinase-1-implication-for-neuropathic-pain
#18
Lucie Valek, Annett Häussler, Stefan Dröse, Philipp Eaton, Katrin Schröder, Irmgard Tegeder
Cyclic GMP-dependent protein kinase 1 (PKG1) mediates presynaptic nociceptive long-term potentiation (LTP) in the spinal cord and contributes to inflammatory pain in rodents but the present study revealed opposite effects in the context of neuropathic pain. We used a set of loss-of-function models for in vivo and in vitro studies to address this controversy: peripheral neuron specific deletion (SNS-PKG1(-/-)), inducible deletion in subsets of neurons (SLICK-PKG1(-/-)) and redox-dead PKG1 mutants. In contrast to inflammatory pain, SNS-PKG1(-/-) mice developed stronger neuropathic hyperalgesia associated with an impairment of nerve regeneration, suggesting specific repair functions of PKG1...
December 7, 2016: Redox Biology
https://www.readbyqxmd.com/read/27973754/transplantation-of-embryonic-spinal-cord-neurons-to-the-injured-distal-nerve-promotes-axonal-regeneration-after-delayed-nerve-repair
#19
Wenming Zhang, Xinyu Fang, Chaofan Zhang, Wen Li, Wai Man Wong, Yejun Xu, Wutian Wu, Jianhua Lin
Peripheral nerve injury (PNI) usually results in poor functional recovery. Nerve repair is the common clinical treatment for PNI but is always obstructed by the chronic degeneration of the distal stump and muscle. Cell transplantation can alleviate the muscle atrophy after PNI, but the subsequent recovery of the locomotive function is seldom described. In this study, we combined cell transplantation and nerve repair to investigate whether the transplantation of embryonic spinal cord cells could benefit the delayed nerve repair...
December 14, 2016: European Journal of Neuroscience
https://www.readbyqxmd.com/read/27973735/the-role-of-p38alpha-in-schwann-cells-in-regulating-peripheral-nerve-myelination-and-repair
#20
Sheridan L Roberts, Xin-Peng Dun, Gemma Dee, Bethany Gray, Thomas Mindos, David B Parkinson
Myelination in the peripheral nervous system (PNS) is controlled by both positive and negative regulators within Schwann cells to ensure timely onset and correct myelin thickness for saltatory conduction by neurons. Transcription factors such as Sox10, Oct6 and Krox20 form a positive regulatory network, whereas negative regulators such as cJun and Sox2 oppose myelination in Schwann cells. The role of the p38 mitogen activated protein kinase (MAPK) pathway has been studied in PNS myelination, but its precise function remains unclear, with both positive and negative effects of p38 activity reported upon both myelination and processes of nerve repair...
December 14, 2016: Journal of Neurochemistry
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