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axon regeneration

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https://www.readbyqxmd.com/read/28646336/nogo-a-antibodies-enhance-axonal-repair-and-remyelination-in-neuro-inflammatory-and-demyelinating-pathology
#1
Benjamin V Ineichen, Sandra Kapitza, Christiane Bleul, Nicolas Good, Patricia S Plattner, Maryam S Seyedsadr, Julia Kaiser, Marc P Schneider, Björn Zörner, Roland Martin, Michael Linnebank, Martin E Schwab
Two hallmarks of chronic multiple sclerosis lesions are the absence of significant spontaneous remyelination and primary as well as secondary neurodegeneration. Both characteristics may be influenced by the presence of inhibitory factors preventing myelin and neuronal repair. We investigated the potential of antibodies against Nogo-A, a well-known inhibitory protein for neuronal growth and plasticity, to enhance neuronal regeneration and remyelination in two animal models of multiple sclerosis. We induced a targeted experimental autoimmune encephalomyelitis (EAE) lesion in the dorsal funiculus of the cervical spinal cord of adult rats resulting in a large drop of skilled forelimb motor functions...
June 23, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28645526/injury-induced-gp130-cytokine-signaling-in-peripheral-ganglia-is-reduced-in-diabetes-mellitus
#2
Jon P Niemi, Angela R Filous, Alicia DeFrancesco, Jane A Lindborg, Nisha A Malhotra, Gina N Wilson, Bowen Zhou, Samuel D Crish, Richard E Zigmond
Neuropathy is a major diabetic complication. While the mechanism of this neuropathy is not well-understood, it is believed to result in part from deficient nerve regeneration. Work from our laboratory established that gp130 family of cytokines are induced in animals after axonal injury and are involved in the induction of regeneration-associated genes (RAGs) and in the conditioning lesion response. Here, we examine whether a reduction of cytokine signaling occurs in diabetes. Streptozotocin (STZ) was used to destroy pancreatic β cells, leading to chronic hyperglycemia...
June 20, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28645295/identification-of-the-flotillin-1-2-heterocomplex-as-a-target-of-autoantibodies-in-bona-fide-multiple-sclerosis
#3
S Hahn, G Trendelenburg, M Scharf, Y Denno, S Brakopp, B Teegen, C Probst, K P Wandinger, M Buttmann, A Haarmann, F Szabados, M Vom Dahl, T Kümpfel, P Eichhorn, H Gold, F Paul, S Jarius, N Melzer, W Stöcker, L Komorowski
BACKGROUND: Autoantibodies, in particular those against aquaporin-4 and myelin-oligodendrocyte glycoprotein (MOG), aid as biomarkers in the differential diagnosis of demyelination. Here, we report on discovery of autoantibodies against flotillin in patients with multiple sclerosis (MS). METHODS: The target antigen was identified by histo-immunoprecipitation using the patients' sera and cryosections of rat or pig cerebellum combined with mass spectrometrical analysis...
June 23, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28643358/maximizing-functional-axon-repair-in-the-injured-cns-lessons-from-neuronal-development
#4
Andrew Kaplan, Mardja Bueno, Luyang Hua, Alyson E Fournier
The failure of damaged axons to regrow underlies disability in central nervous system injury and disease. Therapies that stimulate axon repair will be critical to restore function. Extensive axon regeneration can be induced by manipulation of oncogenes and tumor suppressors, however it has been difficult to translate this into functional recovery in models of spinal cord injury. The current challenge is to maximize the functional integration of regenerating axons to recover motor and sensory behaviours. Insights into axonal growth and wiring during nervous system development are helping guide new approaches to boost regeneration and functional connectivity after injury in the mature nervous system...
June 23, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28642578/human-endothelial-cells-secrete-neurotropic-factors-to-direct-axonal-growth-of-peripheral-nerves
#5
Jonathan M Grasman, David L Kaplan
Understanding how nerves spontaneously innervate tissues or regenerate small injuries is critical to enhance material-based interventions to regenerate large scale, traumatic injuries. During embryogenesis, neural and vascular tissues form interconnected, complex networks as a result of signaling between these tissue types. Here, we report that human endothelial cells (HUVECs) secrete brain-derived neurotrophic factor (BDNF), which significantly stimulated axonal growth from chicken or rat dorsal root ganglia (DRGs)...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28641110/sox11-expression-promotes-regeneration-of-some-retinal-ganglion-cell-types-but-kills-others
#6
Michael W Norsworthy, Fengfeng Bei, Riki Kawaguchi, Qing Wang, Nicholas M Tran, Yi Li, Benedikt Brommer, Yiming Zhang, Chen Wang, Joshua R Sanes, Giovanni Coppola, Zhigang He
At least 30 types of retinal ganglion cells (RGCs) send distinct messages through the optic nerve to the brain. Available strategies of promoting axon regeneration act on only some of these types. Here we tested the hypothesis that overexpressing developmentally important transcription factors in adult RGCs could reprogram them to a "youthful" growth-competent state and promote regeneration of other types. From a screen of transcription factors, we identified Sox11 as one that could induce substantial axon regeneration...
June 21, 2017: Neuron
https://www.readbyqxmd.com/read/28638701/reinnervation-of-denervated-muscle-by-implantation-of-nerve-muscle-endplate-band-graft-to-the-native-motor-zone-of-the-target-muscle
#7
Liancai Mu, Stanislaw Sobotka, Jingming Chen, Themba Nyirenda
INTRODUCTION: Motor endplate reinnervation is critical for restoring motor function of the denervated muscle. We developed a novel surgical technique called nerve-muscle-endplate band grafting (NMEG) for muscle reinnervation. METHODS: Experimentally denervated sternomastoid muscle in the rat was reinnervated by transferring a NMEG from the ipsilateral sternohyoid muscle to the native motor zone (NMZ) of the target muscle. A NMEG pedicle contained a block of muscle (~ 6 × 6 × 3 mm), a nerve branch with axon terminals, and a motor endplate band with numerous neuromuscular junctions...
June 2017: Brain and Behavior
https://www.readbyqxmd.com/read/28632904/ngf-and-fgf-2-promote-reinnervation-by-nerve-muscle-endplate-grafting
#8
Liancai Mu, Stanislaw Sobotka, Jingming Chen, Themba Nyirenda
INTRODUCTION: This study was designed to test whether exogenous application of nerve growth factor (NGF) and basic fibroblast growth factor (FGF-2) to muscles reinnervated with nerve-muscle-endplate band grafting (NMEG) could promote specific outcomes. METHODS: The right sternomastoid muscle in adult rats was experimentally denervated and immediately reinnervated by implanting a NMEG pedicle from the ipsilateral sternohyoid muscle. A fibrin sealant containing NGF and FGF-2 was focally applied to the implantation site...
June 20, 2017: Muscle & Nerve
https://www.readbyqxmd.com/read/28632137/electrospun-silk-polyaniline-conduits-for-functional-nerve-regeneration-in-rat-sciatic-nerve-injury-model
#9
Suradip Das, Manav Sharma, Dhiren Saharia, Kushal Sarma, Elizabeth Muir, Utpal Bora
The present study describes the fabrication of polyaniline-silk fibroin nanocomposite based nerve conduits and its subsequent implantation in a rat sciatic nerve injury model for peripheral nerve regeneration. This is the first in vivo study of polyaniline based nerve conduit describing the safety and efficacy of the conduits in treating peripheral nerve injuries. The nanocomposite was synthesised by electrospinning a mixture of silk fibroin protein and polyaniline wherein the silk nanofibers were observed to be uniformly coated with polyaniline nanoparticles...
June 20, 2017: Biomedical Materials
https://www.readbyqxmd.com/read/28630356/developmental-downregulation-of-lis1-expression-limits-axonal-extension-and-allows-axon-pruning
#10
Kanako Kumamoto, Tokuichi Iguchi, Ryuichi Ishida, Takuya Uemura, Makoto Sato, Shinji Hirotsune
The robust axonal growth and regenerative capacities of young neurons decrease substantially with age. This developmental downregulation of axonal growth may facilitate axonal pruning and neural circuit formation but limits functional recovery following nerve damage. While external factors influencing axonal growth have been extensively investigated, relatively little is known about the intrinsic molecular changes underlying the age-dependent reduction in regeneration capacity. We report that developmental downregulation of LIS1 is responsible for the decreased axonal extension capacity of mature dorsal root ganglion (DRG) neurons...
June 19, 2017: Biology Open
https://www.readbyqxmd.com/read/28630333/boosting-cns-axon-regeneration-by-harnessing-antagonistic-effects-of-gsk3-activity
#11
Marco Leibinger, Anastasia Andreadaki, Renate Golla, Evgeny Levin, Alexander M Hilla, Heike Diekmann, Dietmar Fischer
Implications of GSK3 activity for axon regeneration are often inconsistent, if not controversial. Sustained GSK3 activity in GSK3(S/A) knock-in mice reportedly accelerates peripheral nerve regeneration via increased MAP1B phosphorylation and concomitantly reduces microtubule detyrosination. In contrast, the current study shows that lens injury-stimulated optic nerve regeneration was significantly compromised in these knock-in mice. Phosphorylation of MAP1B and CRMP2 was expectedly increased in retinal ganglion cell (RGC) axons upon enhanced GSK3 activity, but, surprisingly, no GSK3-mediated CRMP2 inhibition was detected in sciatic nerves, thus revealing a fundamental difference between central and peripheral axons...
June 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28629798/proteomic-analysis-of-mesenchymal-to-schwann-cell-transdifferentiation
#12
Anup D Sharma, Jayme Wiederin, Metin Uz, Pawel Ciborowski, Surya K Mallapragada, Howard E Gendelman, Donald S Sakaguchi
While transplantation of Schwann cells facilitates axon regeneration, remyelination and repair after peripheral nerve injury clinical use is limited by cell bioavailability. We posit that such limitation in cell access can be overcome by the use of autologous bone-marrow derived mesenchymal stem cells (MSCs). As MSCs can transdifferentiate to Schwann cell-phenotypes and accelerate nerve regeneration we undertook proteomic evaluation of the cells to uncover the protein contents that affects Schwann cell formulation...
June 16, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28628111/interaction-of-reactive-astrocytes-with-type-i-collagen-induces-astrocytic-scar-formation-through-the-integrin-n-cadherin-pathway-after-spinal-cord-injury
#13
Masamitsu Hara, Kazu Kobayakawa, Yasuyuki Ohkawa, Hiromi Kumamaru, Kazuya Yokota, Takeyuki Saito, Ken Kijima, Shingo Yoshizaki, Katsumi Harimaya, Yasuharu Nakashima, Seiji Okada
Central nervous system (CNS) injury transforms naive astrocytes into reactive astrocytes, which eventually become scar-forming astrocytes that can impair axonal regeneration and functional recovery. This sequential phenotypic change, known as reactive astrogliosis, has long been considered unidirectional and irreversible. However, we report here that reactive astrocytes isolated from injured spinal cord reverted in retrograde to naive astrocytes when transplanted into a naive spinal cord, whereas they formed astrocytic scars when transplanted into injured spinal cord, indicating the environment-dependent plasticity of reactive astrogliosis...
June 19, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28627942/diffusion-imaging-of-mild-traumatic-brain-injury-in-the-impact-accelerated-rodent-model-a-pilot-study
#14
Zora Kikinis, Marc Muehlmann, Ofer Pasternak, Sharon Peled, Praveen Kulkarni, Craig Ferris, Sylvain Bouix, Yogesh Rathi, Inga K Koerte, Steve Pieper, Alexander Yarmarkovich, Caryn L Porter, Bruce S Kristal, Martha E Shenton
PRIMARY OBJECTIVE: There is a need to understand pathologic processes of the brain following mild traumatic brain injury (mTBI). Previous studies report axonal injury and oedema in the first week after injury in a rodent model. This study aims to investigate the processes occurring 1 week after injury at the time of regeneration and degeneration using diffusion tensor imaging (DTI) in the impact acceleration rat mTBI model. RESEARCH DESIGN: Eighteen rats were subjected to impact acceleration injury, and three rats served as sham controls...
June 19, 2017: Brain Injury: [BI]
https://www.readbyqxmd.com/read/28626016/the-mtor-substrate-s6-kinase-1-s6k1-is-a-negative-regulator-of-axon-regeneration-and-a-potential-drug-target-for-central-nervous-system-injury
#15
Hassan Al-Ali, Ying Ding, Tatiana Slepak, Wei Wu, Yan Sun, Yania Martinez, Xiao-Ming Xu, V P Lemmon, J L Bixby
The mammalian target of Rapamycin (mTOR) positively regulates axon growth in the mammalian central nervous system (CNS). Though axon regeneration and functional recovery from CNS injuries are typically limited, knockdown or deletion of PTEN, a negative regulator of mTOR, increases mTOR activity and induces robust axon growth and regeneration. It has been suggested that inhibition of S6 Kinase 1 (S6K1, gene symbol: RPS6KB1), a prominent mTOR target, would blunt mTOR's positive effect on axon growth. In contrast to this expectation, we demonstrate that inhibition of S6K1 in CNS neurons promotes neurite outgrowth in vitro by 2-3 fold...
June 16, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28625420/formation-and-remodeling-of-the-brain-extracellular-matrix-in-neural-plasticity-roles-of-chondroitin-sulfate-and-hyaluronan
#16
REVIEW
Shinji Miyata, Hiroshi Kitagawa
BACKGROUND: The extracellular matrix (ECM) of the brain is rich in glycosaminoglycans such as chondroitin sulfate (CS) and hyaluronan. These glycosaminoglycans are organized into either diffuse or condensed ECM. Diffuse ECM is distributed throughout the brain and fills perisynaptic spaces, whereas condensed ECM selectively surrounds parvalbumin-expressing inhibitory neurons (PV cells) in mesh-like structures called perineuronal nets (PNNs). The brain ECM acts as a non-specific physical barrier that modulates neural plasticity and axon regeneration...
June 15, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28624802/heparin-based-coacervate-of-bfgf-facilitates-peripheral-nerve-regeneration-by-inhibiting-endoplasmic-reticulum-stress-following-sciatic-nerve-injury
#17
Rui Li, Shuang Zou, Yanqing Wu, Yiyang Li, Sinan Khor, Yuqin Mao, Huacheng He, Ke Xu, Hongyu Zhang, Xiaokun Li, Jian Wang, Huai Jiang, Qike Jin, Qingsong Ye, Zhouguang Wang, Jian Xiao
Creating a microenvironment at the injury site that favors axonal regrowth and remyelinationis pivotal to the success of therapeutic reinnervation. The mature myelin sheath of the peripheral nervous system depends on active participation of Schwann cells to form new cytoskeletal components and tremendous amounts of relevant neurotrophic factors. In this study, we utilized a new biomaterial for growth factor delivery consisting of a biocompatible polycation, poly(ethylene argininylaspartatediglyceride) and heparin...
May 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28622711/curcumin-accelerates-the-repair-of-sciatic-nerve-injury-in-rats-through-reducing-schwann-cells-apoptosis-and-promoting-myelinization
#18
Zhiwei Zhao, Xiaoling Li, Qing Li
BACKGROUND: Schwann cells (SCs) play an indispensable role in the repair and regeneration of injured peripheral nerve. Curcumin can reduce SCs apoptosis, and promote the regeneration and functional recovery of injured peripheral nerves. However, the corresponding mechanisms are not clear. OBJECTIVE: The article was aimed to explore the effect and corresponding mechanisms of curcumin on the repair of sciatic nerve injury in rats. METHODS: After surgery induced sciatic nerve injury, the model rats were divided into three groups and treated with curcumin, curcumin+PD98059 and curcumin+IGF-1 respectively for 4days...
June 12, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28621199/sciatic-nerve-regeneration-by-transplantation-of-in-vitro-differentiated-nucleus-pulposus-progenitor-cells
#19
Takayuki Ishii, Daisuke Sakai, Jordy Schol, Tomoko Nakai, Kaori Suyama, Masahiko Watanabe
AIM: To assess the applicability of mouse intervertebral disc-derived nucleus pulposus (NP) progenitor cells as a cell source for sciatic nerve regeneration. MATERIALS & METHODS: P0-Cre/Floxed-EGFP-transgenic mouse-derived NP progenitor cells were differentiated to Schwann-like cells in conventional induction medium. Schwann-like cells were subsequently transplanted into a mouse model of sciatic nerve transection, and nerve regeneration assessed by immunohistochemistry, electron microscopy and functional walking track analysis and heat stimulus reflex...
June 16, 2017: Regenerative Medicine
https://www.readbyqxmd.com/read/28621171/boundary-cap-neural-crest-stem-cell-transplants-contribute-mts1-s100a4-expressing-cells-in-the-glial-scar
#20
Carl Trolle, Patrik Ivert, Jan Hoeber, Iris Rocamonde-Lago, Svitlana Vasylovska, Eugen Lukanidin, Elena N Kozlova
AIM: During development, boundary cap neural crest stem cells (bNCSCs) assist sensory axon growth into the spinal cord. Here we repositioned them to test if they assist regeneration of sensory axons in adult mice after dorsal root avulsion injury. MATERIALS & METHODS: Avulsed mice received bNCSC or human neural progenitor (hNP) cell transplants and their contributions to glial scar formation and sensory axon regeneration were analyzed with immunohistochemistry and transganglionic tracing...
June 16, 2017: Regenerative Medicine
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