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axonal repair

Ravinder Bamba, Thanapong Waitayawinyu, Ratnam Nookala, David Colton Riley, Richard B Boyer, Kevin W Sexton, Chinnakart Boonyasirikool, Sunyarn Niempoog, Nathaniel D Kelm, Mark D Does, Richard D Dortch, Robert Bruce Shack, Wesley P Thayer
BACKGROUND: Peripheral nerve injury can have a devastating impact on our military and veteran population. Current strategies for peripheral nerve repair include techniques such as nerve tubes, nerve grafts, tissue matrices, and nerve growth guides to enhance the number of regenerating axons. Even with such advanced techniques, it takes months to regain function. In animal models, polyethylene glycol (PEG) therapy has shown to improve both physiologic and behavioral outcomes after nerve transection by fusion of a portion of the proximal axons to the distal axon stumps...
November 2016: Journal of Trauma and Acute Care Surgery
Johanna Flygt, Fredrik Clausen, Niklas Marklund
BACKGROUND: Injury to the white matter may lead to impaired neuronal signaling and is commonly observed following traumatic brain injury (TBI). Although endogenous repair of TBI-induced white matter pathology is limited, oligodendrocyte progenitor cells (OPCs) may be stimulated to proliferate and regenerate functionally myelinating oligodendrocytes. Even though OPCs are present throughout the adult brain, little is known about their proliferative activity following axonal injury caused by TBI...
October 17, 2016: Restorative Neurology and Neuroscience
Mingyong Gao, Paul Lu, Dan Lynam, Bridget Bednark, W Marie Campana, Jeff Sakamoto, Mark Tuszynski
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...
October 20, 2016: Journal of Neural Engineering
Robert C A M van Waardenburg
Tyrosyl-DNA phosphodiesterase I (TDP1), like most DNA repair associated proteins, is not essential for cell viability. However, dysfunctioning TDP1 or ATM (ataxia telangiectasia mutated) results in autosomal recessive neuropathology with similar phenotypes, including cerebellar atrophy. Dual inactivation of TDP1 and ATM causes synthetic lethality. A TDP1H(493)R catalytic mutant is associated with spinocerebellar ataxia with axonal neuropathy (SCAN1), and stabilizes the TDP1 catalytic obligatory enzyme-DNA covalent complex...
2016: Journal of Neurology & Neuromedicine
Mehmet Emin Önger, Burcu Delibaş, Aysın Pınar Türkmen, Erkan Erener, Berrin Zuhal Altunkaynak, Süleyman Kaplan
Nerve injuries result in functional loss in the innervated organ or body parts, and recovery is difficult unless surgical treatment has been done. Different surgical treatments have been suggested for nerve repair. Tissue engineering related to growth factors has arisen as an alternative approach for triggering and improving nerve regeneration. Therefore, the aim of this review is to provide a comprehensive analysis related to growth factors as tools for optimizing the regeneration process. Studies and reviews on the use of growth factors for nerve regeneration were compiled over the course of the review...
October 17, 2016: Drug Discoveries & Therapeutics
Marco Bacigaluppi, Gianluca Luigi Russo, Luca Peruzzotti-Jametti, Silvia Rossi, Stefano Sandrone, Erica Butti, Roberta De Ceglia, Andrea Bergamaschi, Caterina Motta, Mattia Gallizioli, Valeria Studer, Emanuela Colombo, Cinthia Farina, Giancarlo Comi, Letterio Salvatore Politi, Luca Muzio, Claudia Villani, Roberto William Invernizzi, Dirk Matthias Hermann, Diego Centonze, Gianvito Martino
: Ischemic stroke is the leading cause of disability, but effective therapies are currently widely lacking. Recovery from stroke is very much dependent on the possibility to develop treatments able to both halt the neurodegenerative process as well as to foster adaptive tissue plasticity. Here we show that ischemic mice treated with neural precursor cell (NPC) transplantation had on neurophysiological analysis, early after treatment, reduced presynaptic release of glutamate within the ipsilesional corticospinal tract (CST), and an enhanced NMDA-mediated excitatory transmission in the contralesional CST...
October 12, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Jaime Eugenín-von Bernhardi, Leda Dimou
NG2-glia are a mysterious and ubiquitous glial population with a highly branched morphology. Initial studies suggested that their unique function is the generation and maintenance of oligodendrocytes in the central nervous system (CNS), important for proper myelination and therefore for axonal support and fast conduction velocity. Over the last years this simplistic notion has been dramatically changed: the wide and homogeneous distribution of NG2-glia within all areas of the developing CNS that is maintained during the whole lifespan, their potential to also differentiate into other cell types in a spatiotemporal manner, their active capability of maintaining their population and their dynamic behavior in altered conditions have raised the question: are NG2-glia simple progenitor cells or do they play further major roles in the normal function of the CNS? In this chapter, we will discuss some important features of NG2-glia like their homeostatic distribution in the CNS and their potential to differentiate into diverse cell types...
2016: Advances in Experimental Medicine and Biology
Michael S Fleming, Jian J Li, Daniel Ramos, Tong Li, David A Talmage, Shin-Ichi Abe, Silvia Arber, Wenqin Luo
: Axon-Schwann cell interactions are crucial for the development, function, and repair of the peripheral nervous system, but mechanisms underlying communication between axons and nonmyelinating Schwann cells are unclear. Here, we show that ER81 is functionally required in a subset of mouse RET(+) mechanosensory neurons for formation of Pacinian corpuscles, which are composed of a single myelinated axon and multiple layers of nonmyelinating Schwann cells, and Ret is required for the maintenance of Er81 expression...
October 5, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Yan Zhao, Yuan Zuo, Jianming Jiang, Huibo Yan, Xiliang Wang, Hunjun Huo, Yulong Xiao
Spinal cord injury (SCI) comprises nerve and motor function disorders that may be caused by a variety of damaging factors and is challenging to treat. The aim of the present study was to investigate the regenerative effects of neural stem cell (NSC) transplantation combined with intraperitoneal injection of erythropoietin (EPO) on cross-sectional SCI in rats. A model of SCI was induced in 40 adult Wistar rats via the complete transection of the 10th thoracic vertebra (T10). The rats were allocated at random into 4 groups: Control, NSC, EPO and NSC + EPO groups (n=10 per group)...
October 2016: Experimental and Therapeutic Medicine
Ying Wang, Hua Jia, Wen-Yuan Li, Li-Xin Guan, Lingxiao Deng, Yan-Cui Liu, Gui-Bo Liu
The present study aimed to evaluate the molecular mechanisms underlying combinatorial bone marrow stromal cell (BMSC) transplantation and chondroitinase ABC (Ch-ABC) therapy in a model of acellular nerve allograft (ANA) repair of the sciatic nerve gap in rats. Sprague Dawley rats (n=24) were used as nerve donors and Wistar rats (n=48) were randomly divided into the following groups: Group I, Dulbecco's modified Eagle's medium (DMEM) control group (ANA treated with DMEM only); Group II, Ch-ABC group (ANA treated with Ch-ABC only); Group III, BMSC group (ANA seeded with BMSCs only); Group IV, Ch-ABC + BMSCs group (Ch-ABC treated ANA then seeded with BMSCs)...
October 2016: Experimental and Therapeutic Medicine
Toni Luokkala, Jorma Ryhänen, Juha Näpänkangas, Teemu V Karjalainen
Background: The repair of a segmental peripheral nerve injury is a clinical challenge. Several studies have been performed to determine superior methods for overcoming nerve gaps. The purpose of this study was to investigate if the inside-out slided epineurium of the distal segment of an injured nerve can serve as a conduit to bridge a short nerve defect (10 mm). Methods: Nineteen sciatic nerves in Sprague-Dawley rats were transected, and a 10-mm gap was left between the ends. A section of distal epineurium was pulled inside out to bridge the gap...
September 2016: Hand: Official Journal of the American Association for Hand Surgery
Davide Lecca, Davide Marangon, Giusy T Coppolino, Aida Menéndez Méndez, Annamaria Finardi, Gloria Dalla Costa, Vittorio Martinelli, Roberto Furlan, Maria P Abbracchio
In the mature central nervous system (CNS), oligodendrocytes provide support and insulation to axons thanks to the production of a myelin sheath. During their maturation to myelinating cells, oligodendroglial precursors (OPCs) follow a very precise differentiation program, which is finely orchestrated by transcription factors, epigenetic factors and microRNAs (miRNAs), a class of small non-coding RNAs involved in post-transcriptional regulation. Any alterations in this program can potentially contribute to dysregulated myelination, impaired remyelination and neurodegenerative conditions, as it happens in multiple sclerosis (MS)...
October 4, 2016: Scientific Reports
Xiao Li, Qi Xu, Yuanyuan Wang, Fang Chen, Jiping He
Peripheral nerve injury requires a physical bridge across the lesion, which is limited by the insufficient supply of donor nerves. Here, we developed a new miniaturized bioreactor system for axon stretch growth. Dorsal root ganglia explants were first placed on two adjoining substrates and formed new synaptic connections. The axon bundles across the border between the top and bottom membranes were then stretched in a stepwise fashion by a microstepper motor system. After several days of stretch, the axon tracts could reach lengths that could develop into living nervous tissue constructs...
October 3, 2016: Journal of Integrative Neuroscience
Jieun Jung, Jong-Wan Kim, Ho-Jin Moon, Jin Young Hong, Jung Keun Hyun
Neural stem cells (NSCs) have a high potency for differentiation to neurons and glial cells for replacement of damaged cells and paracrine effects for the regeneration and remyelination of host axons. Dental pulp is known to have a potential to differentiate into neural-like cells; therefore, dental pulp may be used as an autologous cell source for neural repair. In this study, we selectively expanded stem cells from human dental pulp in an initial culture using NSC media under xeno- and serum-free conditions...
2016: Stem Cells International
Cemal Firat, Ahmet Hamdi Aytekin, Mehmet Akif Durak, Yilmaz Geyik, Serkan Erbatur, Metin Dogan, Omer Elmas, Adile Ferda Dagli, Hamit Celik
AIM: Peripheral nerve defects generally occur due to mechanical, chemical, thermal and pathologic causes and the reconstruction is still a challenging problem. In the present study, we aimed to compare the effects of platelet rich plasma (PRP) that has high levels of growth factors and hyaluronic acid (HA) that is known to have positive effects on nerve regeneration by decreasing scar formation in a rat model where they were injected through allogeneic aorta graft in peripheral nerve defects using histopathologic and functional methods...
2016: Annali Italiani di Chirurgia
Da-Ming Cui, Tao Zeng, Jie Ren, Ke Wang, Yi Jin, Lin Zhou, Liang Gao
AIMS: Traumatic brain injury (TBI) is induced by complex primary and secondary mechanisms that give rise to cell death, inflammation, and neurological dysfunction. Understanding the mechanisms that drive neurological damage as well as those that promote repair can guide the development of therapeutic drugs for TBI. Kruppel-like factor 4 (KLF4) has been reported to negatively regulate axon regeneration of injured retinal ganglion cells (RGCs) through inhibition of JAK-STAT3 signaling. However, the role of KLF4 in TBI remains unreported...
September 27, 2016: CNS Neuroscience & Therapeutics
Erika J Olson, Bernhard C Lechtenberg, Chunxia Zhao, Elena Rubio de la Torre, Ilaria Lamberto, Stefan J Riedl, Philip E Dawson, Elena B Pasquale
EphA4 is a receptor tyrosine kinase with a critical role in repulsive axon guidance and synaptic function. However, aberrant EphA4 activity can inhibit neural repair after injury and exacerbate neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and Alzheimer's. We previously identified the cyclic peptide APY-d2 (APYCVYRβASWSC-nh2, containing a disulfide bond) as a potent and selective EphA4 antagonist. However, APY-d2 lacks sufficient plasma stability to be useful for EphA4 inhibition in vivo through peripheral administration...
September 8, 2016: ACS Medicinal Chemistry Letters
Zhan-Kui Zhao, Hong-Lian Yu, Bo Liu, Hui Wang, Qiong Luo, Xie-Gang Ding
Polysaccharides extracted from Lycium barbarum exhibit antioxidant properties. We hypothesized that these polysaccharides resist oxidative 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 significantly increased at 1 and 2 weeks post-injury. Serum malondialdehyde levels decreased at 2 and 4 weeks...
August 2016: Neural Regeneration Research
Li Gan, Lei Zhao, Yanteng Zhao, Ke Li, Zan Tong, Li Yi, Xiong Wang, Yinping Li, Weiqun Tian, Xiaohua He, Min Zhao, Yan Li, Yun Chen
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...
September 21, 2016: Journal of Neural Engineering
Mateus Vidigal de Castro, Roberta Barbizan, Rui Seabra Ferreira, Benedito Barraviera, Alexandre Leite Rodrigues de Oliveira
Axonal injuries at the interface between central and peripheral nervous system, such as ventral root avulsion (VRA), induce important degenerative processes, mostly resulting in neuronal and motor function loss. In the present work, we have compared two different fibrin sealants, one derived from human blood and another derived from animal blood and Crotalus durissus terrificus venom, as a promising treatment for this type of injury. Lewis rats were submitted to VRA (L4-L6) and had the avulsed roots reimplanted to the surface of the spinal cord, with the aid of fibrin sealant...
2016: Neural Plasticity
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