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https://www.readbyqxmd.com/read/28338622/phosphodiesterase-inhibitors-as-a-therapeutic-approach-to-neuroprotection-and-repair
#1
REVIEW
Eric P Knott, Mazen Assi, Sudheendra N R Rao, Mousumi Ghosh, Damien D Pearse
A wide diversity of perturbations of the central nervous system (CNS) result in structural damage to the neuroarchitecture and cellular defects, which in turn are accompanied by neurological dysfunction and abortive endogenous neurorepair. Altering intracellular signaling pathways involved in inflammation and immune regulation, neural cell death, axon plasticity and remyelination has shown therapeutic benefit in experimental models of neurological disease and trauma. The second messengers, cyclic adenosine monophosphate (cyclic AMP) and cyclic guanosine monophosphate (cyclic GMP), are two such intracellular signaling targets, the elevation of which has produced beneficial cellular effects within a range of CNS pathologies...
March 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28328634/bridging-the-gap-engineered-porcine-derived-urinary-bladder-matrix-conduits-as-a-novel-scaffold-for-peripheral-nerve-regeneration
#2
Lyly Nguyen, Ashkan Afshari, Nathaniel D Kelm, Alonda C Pollins, R Bruce Shack, Mark D Does, Wesley P Thayer
PURPOSE: This study aims to compare engineered nerve conduits constructed from porcine-derived urinary bladder matrix (UBM) with the criterion-standard nerve autografts, for segmental loss peripheral nerve repairs. METHODS: Forty-eight Sprague-Dawley rats were divided into 2 groups. All underwent a 10-mm sciatic nerve gap injury. This was repaired using either (1) reverse autograft-the 10-mm cut segment was oriented 180 degrees and used to coapt the proximal and distal stumps or (2) UBM conduit-the 10-mm nerve gap was bridged with UBM conduit...
March 21, 2017: Annals of Plastic Surgery
https://www.readbyqxmd.com/read/28320842/stat3-controls-the-long-term-survival-and-phenotype-of-repair-schwann-cells-during-nerve-regeneration
#3
Cristina Benito, Catherine M Davis, Jose A Gomez-Sanchez, Mark Turmaine, Dies Meijer, Valeria Poli, Rhona Mirsky, Kristjan R Jessen
After nerve injury, Schwann cells convert to a phenotype specialised to promote repair. But during the slow process of axonal regrowth, these repair Schwann cells gradually lose their regeneration-supportive features and eventually die. Although this is a key reason for the frequent regeneration failures in humans, the transcriptional mechanisms that control long-term survival and phenotype of repair cells have not been studied, and the molecular signalling underlying their decline is obscure. We show, in mice, that Schwann cell STAT3 has a dual role...
March 20, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28300644/the-connective-tissue-phenotype-of-glaucomatous-cupping-in-the-monkey-eye-clinical-and-research-implications
#4
REVIEW
Hongli Yang, Juan Reynaud, Howard Lockwood, Galen Williams, Christy Hardin, Luke Reyes, Cheri Stowell, Stuart K Gardiner, Claude F Burgoyne
In a series of previous publications we have proposed a framework for conceptualizing the optic nerve head (ONH) as a biomechanical structure. That framework proposes important roles for intraocular pressure (IOP), IOP-related stress and strain, cerebrospinal fluid pressure (CSFp), systemic and ocular determinants of blood flow, inflammation, auto-immunity, genetics, and other non-IOP related risk factors in the physiology of ONH aging and the pathophysiology of glaucomatous damage to the ONH. The present report summarizes 20 years of technique development and study results pertinent to the characterization of ONH connective tissue deformation and remodeling in the unilateral monkey experimental glaucoma (EG) model...
March 12, 2017: Progress in Retinal and Eye Research
https://www.readbyqxmd.com/read/28300134/white-matter-repair-after-extracellular-vesicles-administration-in-an-experimental-animal-model-of-subcortical-stroke
#5
Laura Otero-Ortega, Fernando Laso-García, María Del Carmen Gómez-de Frutos, Berta Rodríguez-Frutos, Jorge Pascual-Guerra, Blanca Fuentes, Exuperio Díez-Tejedor, María Gutiérrez-Fernández
Mesenchymal stem cells have previously been shown to mediate brain repair after stroke; they secrete 50-100 nm complexes called extracellular vesicles (EVs), which could be responsible for provoking neurovascular repair and functional recovery. EVs have been observed by electron microscopy and NanoSight, and they contain associated proteins such as CD81 and Alix. This purified, homogeneous population of EVs was administered intravenously after subcortical stroke in rats. To evaluate the EVs effects, we studied the biodistribution, proteomics analysis, functional evaluation, lesion size, fiber tract integrity, axonal sprouting and white matter repair markers...
March 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28296347/gdnf-schwann-cells-in-hydrogel-scaffolds-promote-regional-axon-regeneration-remyelination-and-functional-improvement-after-spinal-cord-transection-in-rats
#6
Bingkun K Chen, Nicolas N Madigan, Jeffrey S Hakim, Mahrokh Dadsetan, Siobhan S McMahon, Michael J Yaszemski, Anthony J Windebank
Positively-charged oligo[poly(ethylene glycol)fumarate] (OPF(+) ) is a biodegradable hydrogel used for spinal cord injury repair. We compared scaffolds containing primary Schwann cells (SCs) to scaffolds delivering SCs genetically modified to secrete high concentrations of glial cell-derived neurotrophic factor (GDNF). Multichannel OPF(+) scaffolds loaded with SCs or GDNF-SCs were implanted into transected rat spinal cords for 4 weeks. GDNF-SCs promoted regeneration of more axons into OPF(+) scaffolds (2773...
March 10, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28293524/effect-of-axonal-trauma-on-nerve-regeneration-in-side-to-side-neurorrhaphy-an-experimental-study
#7
Henrikki Rönkkö, Harry Göransson, Hanna-Stiina Taskinen, Pasi Paavilainen, Tero Vahlberg, Matias Röyttä
BACKGROUND: Side-to-side (STS) neurorrhaphy can be performed distally to ensure timely end-organ innervation. It leaves the distal end of the injured nerve intact for further reconstruction. Despite encouraging clinical results, only few experimental studies have been published to enhance the regeneration results of the procedure. We examined the influence of different size epineural windows and degree of axonal injury of STS repair on nerve regeneration and donor nerve morbidity. METHODS: Three clinically relevant repair techniques of the transected common peroneal nerve (CPN) were compared...
December 2016: Plastic and Reconstructive Surgery. Global Open
https://www.readbyqxmd.com/read/28283540/extrinsic-repair-of-injured-dendrites-as-a-paradigm-for-regeneration-by-fusion-in-caenorhabditis-elegans
#8
Meital Oren-Suissa, Tamar Gattegno, Veronika Kravtsov, Benjamin Podbilewicz
Injury triggers regeneration of axons and dendrites. Research identified factors required for axonal regeneration outside the CNS, but little is known about regeneration triggered by dendrotomy. Here we study neuronal plasticity triggered by dendrotomy and determine the fate of complex PVD arbors following laser surgery of dendrites. We find that severed primary dendrites grow towards each other and reconnect via branch fusion. Simultaneously, terminal branches lose self-avoidance and grow towards each other, meeting and fusing at the tips via an AFF-1-mediated process...
March 10, 2017: Genetics
https://www.readbyqxmd.com/read/28283336/tissue-engineering-with-peripheral-blood-derived-mesenchymal-stem-cells-promotes-the-regeneration-of-injured-peripheral-nerves
#9
Mengjie Pan, Xianghai Wang, Yijing Chen, Shangtao Cao, Jinkun Wen, Guofeng Wu, Yuanyuan Li, Lixia Li, Changhui Qian, Zhenqi Qin, Zhenlin Li, Dandan Tan, Zhihao Fan, Wutian Wu, Jiasong Guo
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...
March 7, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28279353/small-molecule-stabilization-of-14-3-3-protein-protein-interactions-stimulates-axon-regeneration
#10
Andrew Kaplan, Barbara Morquette, Antje Kroner, SooYuen Leong, Carolin Madwar, Ricardo Sanz, Sara L Banerjee, Jack Antel, Nicolas Bisson, Samuel David, Alyson E Fournier
Damaged central nervous system (CNS) neurons have a poor ability to spontaneously regenerate, causing persistent functional deficits after injury. Therapies that stimulate axon growth are needed to repair CNS damage. 14-3-3 adaptors are hub proteins that are attractive targets to manipulate cell signaling. We identify a positive role for 14-3-3s in axon growth and uncover a developmental regulation of the phosphorylation and function of 14-3-3s. We show that fusicoccin-A (FC-A), a small-molecule stabilizer of 14-3-3 protein-protein interactions, stimulates axon growth in vitro and regeneration in vivo...
March 8, 2017: Neuron
https://www.readbyqxmd.com/read/28270745/chaperone-proteins-in-the-central-nervous-system-and-peripheral-nervous-system-after-nerve-injury
#11
REVIEW
Shalina S Ousman, Ariana Frederick, Erin-Mai F Lim
Injury to axons of the central nervous system (CNS) and the peripheral nervous system (PNS) is accompanied by the upregulation and downregulation of numerous molecules that are involved in mediating nerve repair, or in augmentation of the original damage. Promoting the functions of beneficial factors while reducing the properties of injurious agents determines whether regeneration and functional recovery ensues. A number of chaperone proteins display reduced or increased expression following CNS and PNS damage (crush, transection, contusion) where their roles have generally been found to be protective...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28267791/dmyc-is-required-in-retinal-progenitors-to-prevent-jnk-mediated-retinal-glial-activation
#12
Lígia Tavares, Andreia Correia, Marília A Santos, João B Relvas, Paulo S Pereira
In the nervous system, glial cells provide crucial insulation and trophic support to neurons and are important for neuronal survival. In reaction to a wide variety of insults, glial cells respond with changes in cell morphology and metabolism to allow repair. Additionally, these cells can acquire migratory and proliferative potential. In particular, after axonal damage or pruning the clearance of axonal debris by glial cells is key for a healthy nervous system. Thus, bidirectional neuron-glial interactions are crucial in development, but little is known about the cellular sensors and signalling pathways involved...
March 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28266869/pig-induced-pluripotent-stem-cell-derived-neural-rosettes-parallel-human-differentiation-into-sensory-neural-subtypes
#13
Robin L Webb, Amalia Gallegos-Cárdenas, Colette N Miller, Nicholas J Solomotis, Hong-Xiang Liu, Franklin D West, Steven L Stice
The pig is the large animal model of choice for study of nerve regeneration and wound repair. Availability of porcine sensory neural cells would conceptually allow for analogous cell-based peripheral nerve regeneration in porcine injuries of similar severity and size to those found in humans. After recently reporting that porcine (or pig) induced pluripotent stem cells (piPSCs) differentiate into neural rosette (NR) structures similar to human NRs, here we demonstrate that pig NR cells could differentiate into neural crest cells and other peripheral nervous system-relevant cell types...
March 7, 2017: Cellular Reprogramming
https://www.readbyqxmd.com/read/28265351/elevated-axonal-membrane-permeability-and-its-correlation-with-motor-deficits-in-an-animal-model-of-multiple-sclerosis
#14
Gary Leung, Melissa Tully, Jonathan Tang, Shengxi Wu, Riyi Shi
BACKGROUND: It is increasingly clear that in addition to myelin disruption, axonal degeneration may also represent a key pathology in multiple sclerosis (MS). Hence, elucidating the mechanisms of axonal degeneration may not only enhance our understanding of the overall MS pathology, but also elucidate additional therapeutic targets. The objective of this study is assess the degree of axonal membrane disruption and its significance in motor deficits in EAE mice. METHODS: Experimental Autoimmune Encephalomyelitis was induced in mice by subcutaneous injection of myelin oligodendrocyte glycoprotein/complete Freud's adjuvant emulsion, followed by two intraperitoneal injections of pertussis toxin...
2017: Translational Neurodegeneration
https://www.readbyqxmd.com/read/28264978/deletion-of-the-fractalkine-receptor-cx3cr1-improves-endogenous-repair-axon-sprouting-and-synaptogenesis-after-spinal-cord-injury-in-mice
#15
Camila M Freria, Jodie C E Hall, Ping Wei, Zhen Guan, Dana M McTigue, Phillip G Popovich
Impaired signaling via CX3CR1, the fractalkine receptor, promotes recovery after traumatic spinal contusion injury in mice, a benefit achieved in part by reducing macrophage-mediated injury at the lesion epicenter. Here, we tested the hypothesis that CX3CR1-dependent changes in microglia and macrophage functions also will enhance neuroplasticity, at and several segments below the injury epicenter. New data show that in the presence of inflammatory stimuli, CX3CR1-deficient (CX3CR1(-/-)) microglia and macrophages adopt a reparative phenotype and increase expression of genes that encode neurotrophic and gliogenic proteins...
March 6, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28264437/transplantation-of-embryonic-spinal-cord-derived-cells-helps-to-prevent-muscle-atrophy-after-peripheral-nerve-injury
#16
Carolin Ruven, Wen Li, Heng Li, Wai-Man Wong, Wutian Wu
Injuries to peripheral nerves are frequent in serious traumas and spinal cord injuries. In addition to surgical approaches, other interventions, such as cell transplantation, should be considered to keep the muscles in good condition until the axons regenerate. In this study, E14.5 rat embryonic spinal cord fetal cells and cultured neural progenitor cells from different spinal cord segments were injected into transected musculocutaneous nerve of 200-300 g female Sprague Dawley (SD) rats, and atrophy in biceps brachii was assessed...
February 27, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28263445/sustained-release-of-collagen-vi-potentiates-sciatic-nerve-regeneration-by-modulating-macrophage-phenotype
#17
Dan Lv, Lijuan Zhou, Xianyu Zheng, Yongcheng Hu
Although the peripheral nervous system has an intrinsic ability for repair and regeneration after injury, bridging long peripheral nerve defects remains a challenge. Functional nerve regeneration depends on interactions among axons, Schwann cells, fibroblasts and immune cells. Macrophages, as immune cells recruited early in this process, show polarization toward phenotypes that are detrimental or beneficial to tissue remodeling depending on the microenvironment of the scaffolds. In this study, we investigated the effects of macrophage phenotypes modulated by collagen VI on axonal regeneration and functional recovery by bridging a 15 mm long sciatic nerve defect in rats...
March 6, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28262732/transplantation-of-huc-mscs-seeded-collagen-scaffolds-reduces-scar-formation-and-promotes-functional-recovery-in-canines-with-chronic-spinal-cord-injury
#18
Xing Li, Jun Tan, Zhifeng Xiao, Yannan Zhao, Sufang Han, Dingyang Liu, Wen Yin, Jing Li, Juan Li, Siyi Wanggou, Bing Chen, Caiping Ren, Xingjun Jiang, Jianwu Dai
Spinal cord injury (SCI) can lead to locomotor deficits, and the repair of chronic SCI is considered one of the most challenging clinical problems. Although extensive studies have evaluated treatments for acute SCI in small animals, comparatively fewer studies have been conducted on large-animal SCI in the chronic phase, which is more clinically relevant. Here, we used a collagen-based biomaterial, named the NeuroRegen scaffold, loaded with human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in a canine chronic SCI model...
March 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28261764/a-biological-tube-technique-for-the-repair-of-peripheral-nerve-defects-using-stuffed-nerves
#19
Sercan Çapkın, Mustafa Akhisaroğlu, Bekir Uğur Ergür, Ali Abdülkadir Bacakoğlu
BACKGROUND: Presently described is research examining the "stuffed nerve" technique to repair peripheral nerve defects. METHODS: Twenty-one male Wistar Albino rats were divided into 3 groups of 7, and standard 10-mm defects were created in the sciatic nerve of all subjects. Rats were treated with autogenous nerve graft (Group 1), hollow vein graft (Group 2), or vein graft stuffed with shredded nerves (Group 3). After 12 weeks, electrophysiological and histomorphological analyses were performed to evaluate axonal regeneration...
January 2017: Ulusal Travma Ve Acil Cerrahi Dergisi, Turkish Journal of Trauma & Emergency Surgery: TJTES
https://www.readbyqxmd.com/read/28251686/e6020-a-synthetic-tlr4-agonist-accelerates-myelin-debris-clearance-schwann-cell-infiltration-and-remyelination-in-the-rat-spinal-cord
#20
Jamie S Church, Lindsay M Milich, Jessica K Lerch, Phillip G Popovich, Dana M McTigue
Oligodendrocyte progenitor cells (OPCs) are present throughout the adult brain and spinal cord and can replace oligodendrocytes lost to injury, aging, or disease. Their differentiation, however, is inhibited by myelin debris, making clearance of this debris an important step for cellular repair following demyelination. In models of peripheral nerve injury, TLR4 activation by lipopolysaccharide (LPS) promotes macrophage phagocytosis of debris. Here we tested whether the novel synthetic TLR4 agonist E6020, a Lipid A mimetic, promotes myelin debris clearance and remyelination in spinal cord white matter following lysolecithin-induced demyelination...
March 2, 2017: Glia
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