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https://www.readbyqxmd.com/read/28105588/nogo-a-antibodies-for-progressive-multiple-sclerosis
#1
Benjamin V Ineichen, Patricia S Plattner, Nicolas Good, Roland Martin, Michael Linnebank, Martin E Schwab
Most of the current therapies, as well as many of the clinical trials, for multiple sclerosis (MS) target the inflammatory autoimmune processes, but less than 20% of all clinical trials investigate potential therapies for the chronic progressive disease stage of MS. The latter is responsible for the steadily increasing disability in many patients, and there is an urgent need for novel therapies that protect nervous system tissue and enhance axonal growth and/or remyelination. As outlined in this review, solid pre-clinical data suggest neutralization of the neurite outgrowth inhibitor Nogo-A as a potential new way to achieve both axonal and myelin repair...
January 19, 2017: CNS Drugs
https://www.readbyqxmd.com/read/28102835/spinal-cord-regeneration-in-xenopus-laevis
#2
Gabriela Edwards-Faret, Rosana Muñoz, Emilio E Méndez-Olivos, Dasfne Lee-Liu, Victor S Tapia, Juan Larraín
Here we present a protocol for the husbandry of Xenopus laevis tadpoles and froglets, and procedures to study spinal cord regeneration. This includes methods to induce spinal cord injury (SCI); DNA and morpholino electroporation for genetic studies; in vivo imaging for cell analysis; a swimming test to measure functional recovery; and a convenient model for screening for new compounds that promote neural regeneration. These protocols establish X. laevis as a unique model organism for understanding spinal cord regeneration by comparing regenerative and nonregenerative stages...
February 2017: Nature Protocols
https://www.readbyqxmd.com/read/28101532/overexpression-of-brain-derived-neurotrophic-factor-protects-large-retinal-ganglion-cells-after-optic-nerve-crush-in-mice
#3
Liang Feng, Zhen Puyang, Hui Chen, Peiji Liang, John B Troy, Xiaorong Liu
Brain-derived neurotrophic factor (BDNF), a neurotrophin essential for neuron survival and function, plays an important role in neuroprotection during neurodegenerative diseases. In this study, we examined whether a modest increase of retinal BDNF promotes retinal ganglion cell (RGC) survival after acute injury of the optic nerve in mice. We adopted an inducible Cre-recombinase transgenic system to up-regulate BDNF in the mouse retina and then examined RGC survival after optic nerve crush by in vivo imaging...
January 2017: ENeuro
https://www.readbyqxmd.com/read/28101526/rapamycin-resistant-mtor-activity-is-required-for-sensory-axon-regeneration-induced-by-a-conditioning-lesion
#4
Weitao Chen, Na Lu, Yue Ding, Yuan Wang, Leung Ting Chan, Xu Wang, Xin Gao, Songshan Jiang, Kai Liu
Neuronal mammalian target of rapamycin (mTOR) activity is a critical determinant of the intrinsic regenerative ability of mature neurons in the adult central nervous system (CNS). However, whether its action also applies to peripheral nervous system (PNS) neurons after injury remains elusive. To address this issue unambiguously, we used genetic approaches to determine the role of mTOR signaling in sensory axon regeneration in mice. We showed that deleting mTOR in dorsal root ganglion (DRG) neurons suppressed the axon regeneration induced by conditioning lesions...
November 2016: ENeuro
https://www.readbyqxmd.com/read/28095293/mapk-signaling-promotes-axonal-degeneration-by-speeding-the-turnover-of-the-axonal-maintenance-factor-nmnat2
#5
Lauren J Walker, Daniel W Summers, Yo Sasaki, E J Brace, Jeffrey Milbrandt, Aaron DiAntonio
Injury-induced (Wallerian) axonal degeneration is regulated via the opposing actions of pro-degenerative factors such as SARM1 and a MAPK signal and pro-survival factors, the most important of which is the NAD(+) biosynthetic enzyme NMNAT2 that inhibits activation of the SARM1 pathway. Here we investigate the mechanism by which MAPK signaling facilitates axonal degeneration. We show that MAPK signaling promotes the turnover of the axonal survival factor NMNAT2 in cultured mammalian neurons as well as the Drosophila ortholog dNMNAT in motoneurons...
January 17, 2017: ELife
https://www.readbyqxmd.com/read/28095027/severe-and-extensive-traumatic-axonal-injury-following-minor-and-indirect-head-trauma
#6
Sung Ho Jang, Han Do Lee
OBJECTIVES: This study reports on a patient with mild traumatic brain injury (TBI) who showed severe and extensive traumatic axonal injury (TAI) of various neural tracts following minor and indirect head trauma, which was demonstrated by diffusion tensor tractography (DTT). CASE DESCRIPTION: A 26-year-old female patient suffered from indirect head trauma resulting from flexion-hyperextension injury after being hit from behind by a slowly moving car. At the time of head trauma, she felt tingling sensation on her four extremities; however, she did not experience loss of consciousness...
January 17, 2017: Brain Injury: [BI]
https://www.readbyqxmd.com/read/28093713/timing-of-future-remyelination-therapies-and-their-potential-to-stop-multiple-sclerosis-progression
#7
Burcu Zeydan, Moses Rodriguez, Orhun H Kantarci
Prior to the onset of demyelination in multiple sclerosis (MS), early oligodendrocyte injury, axonal degeneration and astroglial scarring occur. The irreversible progressive phase of MS begins when the axonal loss threshold is reached. Progressive disease onset has the highest impact on a poor prognosis in MS. Conversion to progressive disease is essentially an age-dependent process independent of disease duration and initial disease course. Although prevention of relapses has been the primary approach in the disease management, incomplete recovery from even the first relapse correlates with the long-term neurodegenerative phenotype of progressive MS onset...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28088900/synaptic-plasticity-dementia-and-alzheimer-disease
#8
Pietro Giusti, Stephen D Skaper, Laura Facci, Morena Zusso
Neuroplasticity is not only shaped by learning and memory but is also a mediator of responses to neuron attrition and injury (compensatory plasticity). As an ongoing process it reacts to neuronal cell activity and injury, death, and genesis, which encompasses the modulation of structural and functional processes of axons, dendrites, and synapses. The range of structural elements that comprise plasticity includes long-term potentiation (a cellular correlate of learning and memory), synaptic efficacy and remodelling, synaptogenesis, axonal sprouting and dendritic remodelling, and neurogenesis and recruitment...
January 13, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28088077/rhoa-knockdown-by-cationic-amphiphilic-copolymer-sirhoa-polyplexes-enhances-axonal-regeneration-in-rat-spinal-cord-injury-model
#9
So-Jung Gwak, Christian Macks, Da Un Jeong, Mark Kindy, Michael Lynn, Ken Webb, Jeoung Soo Lee
Spinal cord injury (SCI) results in permanent loss of motor and sensory function due to developmentally-related and injured-induced changes in the extrinsic microenvironment and intrinsic neuronal biochemistry that limit plasticity and axonal regeneration. Our long term goal is to develop cationic, amphiphilic copolymers (poly (lactide-co-glycolide)-g-polyethylenimine, PgP) for combinatorial delivery of therapeutic nucleic acids (TNAs) and drugs targeting these different barriers. In this study, we evaluated the ability of PgP to deliver siRNA targeting RhoA, a critical signaling pathway activated by multiple extracellular inhibitors of axonal regeneration...
January 3, 2017: Biomaterials
https://www.readbyqxmd.com/read/28081461/bdnf-gene-delivery-mediated-by-neuron-targeted-nanoparticles-is-neuroprotective-in-peripheral-nerve-injury
#10
Cátia D F Lopes, Nádia P Gonçalves, Carla P Gomes, Maria J Saraiva, Ana P Pêgo
Neuron-targeted gene delivery is a promising strategy to treat peripheral neuropathies. Here we propose the use of polymeric nanoparticles based on thiolated trimethyl chitosan (TMCSH) to mediate targeted gene delivery to peripheral neurons upon a peripheral and minimally invasive intramuscular administration. Nanoparticles were grafted with the non-toxic carboxylic fragment of the tetanus neurotoxin (HC) to allow neuron targeting and were explored to deliver a plasmid DNA encoding for the brain-derived neurotrophic factor (BDNF) in a peripheral nerve injury model...
March 2017: Biomaterials
https://www.readbyqxmd.com/read/28075461/resistance-of-interleukin-6-to-the-extracellular-inhibitory-environment-promotes-axonal-regeneration-and-functional-recovery-following-spinal-cord-injury
#11
Gang Yang, Wen-Yuan Tang
Interleukin-6 (IL)-6 was originally discovered as a factor that contributes to the secondary pathological and inflammatory response in the central nervous system (CNS) following injury. However, accumulating evidence suggests that IL-6 is also involved in functional and structural recovery following CNS injury by promoting axonal sprou-ting. This suggests a potential dual role of IL-6 in CNS injury. However, the definitive function of IL-6 in neural injury and the corresponding underlying mechanisms are still topics of controversy...
February 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28074457/the-acute-effects-of-thymoquinone-on-acute-peripheral-nerve-injury-an-experimental-study
#12
İsmail Gülşen, Hakan Ak, Mikail Kara, Abdulsemat Gökalp, Veysel Akyol, Ömer Faruk Koçak, Murat Çetin Rağbetli
BACKGROUND: The purpose of this study was to evaluate the acute effects of thymoquinone (TQ) on acute nerve injury. METHODS: A rat model of crush injury of the sciatic nerve was used. Animals were divided into 3 groups: control, trauma, and TQ treatment groups (n=6 per group). Seven days after injury, sciatic nerve specimens were obtained from the site of the injury and analyzed histologically and stereologically. Axon diameter, myelin thickness, and axon density were measured...
November 2016: Ulusal Travma Ve Acil Cerrahi Dergisi, Turkish Journal of Trauma & Emergency Surgery: TJTES
https://www.readbyqxmd.com/read/28072502/wallerian-degeneration-beyond-the-corticospinal-tracts-conventional-and-advanced-mri-findings
#13
REVIEW
Yin Jie Chen, Seyed Ali Nabavizadeh, Arastoo Vossough, Sunil Kumar, Laurie A Loevner, Suyash Mohan
Wallerian degeneration (WD) is defined as progressive anterograde disintegration of axons and accompanying demyelination after an injury to the proximal axon or cell body. Since the 1980s and 1990s, conventional magnetic resonance imaging (MRI) sequences have been shown to be sensitive to changes of WD in the subacute to chronic phases. More recently, advanced MRI techniques, such as diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI), have demonstrated some of earliest changes attributed to acute WD, typically on the order of days...
November 7, 2016: Journal of Neuroimaging: Official Journal of the American Society of Neuroimaging
https://www.readbyqxmd.com/read/28070857/a-small-organic-compound-mimicking-the-l1-cell-adhesion-molecule-promotes-functional-recovery-after-spinal-cord-injury-in-zebrafish
#14
Sudhanshu Sahu, Zhihua Zhang, Rong Li, Junkai Hu, Huifan Shen, Gabriele Loers, Yanqin Shen, Melitta Schachner
Tacrine is a small organic compound that was discovered to mimic the functions of the neural cell adhesion molecule L1 by promoting the cognate functions of L1 in vitro, such as neuronal survival, neuronal migration, neurite outgrowth, and myelination. Based on studies indicating that L1 enhances functional recovery in different central and peripheral nervous system disease paradigms of rodents, it deemed interesting to investigate the beneficial role of tacrine in the attractive zebrafish animal model, by evaluating functional recovery after spinal cord injury...
January 9, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28070856/mir-29c-prkci-regulates-axonal-growth-of-dorsal-root-ganglia-neurons-under-hyperglycemia
#15
Longfei Jia, Lei Wang, Michael Chopp, Chao Li, Yi Zhang, Alexandra Szalad, Zheng Gang Zhang
Diabetes initially induces distal axonal damage of peripheral nerves, but molecular mechanisms that mediate axonal injury are not fully understood. MircoRNAs (miRNAs) regulate axonal growth. We found that diabetic db/db mice exhibited substantial upregulation of miR-29c in dorsal root ganglia (DRG) neurons, sciatic nerve, and foot pad tissues. Bioinformatic analysis revealed PRKCI, a gene that encodes a member of the protein kinase C (PKC) iota, as a putative target for miR-29c. Western blot analysis showed that diabetic mice exhibited a considerable reduction of PRKCI protein levels in sciatic nerve tissues and DRG neurons...
January 9, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28070672/opposing-effects-of-progranulin-deficiency-on-amyloid-and-tau-pathologies-via-microglial-tyrobp-network
#16
Hideyuki Takahashi, Zoe A Klein, Sarah M Bhagat, Adam C Kaufman, Mikhail A Kostylev, Tsuneya Ikezu, Stephen M Strittmatter
Progranulin (PGRN) is implicated in Alzheimer's disease (AD) as well as frontotemporal lobar degeneration. Genetic studies demonstrate an association of the common GRN rs5848 variant that results in reduced PGRN levels with increased risk for AD. However, the mechanisms by which PGRN reduction from the GRN AD risk variant or mutation exacerbates AD pathophysiology remain ill defined. Here, we show that the GRN AD risk variant has no significant effects on florbetapir positron emission tomographic amyloid imaging and cerebrospinal fluid (CSF) Aβ levels, whereas it is associated with increased CSF tau levels in human subjects of the Alzheimer's disease neuroimaging initiative studies...
January 9, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28069926/creatine-enhances-mitochondrial-mediated-oligodendrocyte-survival-following-demyelinating-injury
#17
Kelly A Chamberlain, Kristen S Chapey, Sonia E Nanescu, Jeffrey K Huang
: Chronic oligodendrocyte loss, which occurs in the demyelinating disorder multiple sclerosis (MS), contributes to axonal dysfunction and neurodegeneration. Current therapies are able to reduce MS severity, but do not prevent transition into the progressive phase of the disease, which is characterized by chronic neurodegeneration. Therefore, pharmacological compounds that promote oligodendrocyte survival could be beneficial for neuroprotection in MS. Here, we investigated the role of creatine, an organic acid involved in ATP buffering, in oligodendrocyte function...
January 9, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28069919/calpain-mediated-proteolysis-of-talin-and-fak-regulates-adhesion-dynamics-necessary-for-axon-guidance
#18
Patrick C Kerstein, Kevin M Patel, Timothy M Gomez
: Guidance of axons to their proper synaptic target sites requires spatially and temporally precise modulation of biochemical signals within growth cones. Ionic calcium (Ca(2+)) is an essential signal for axon guidance that mediates opposing affects on growth cone motility. The diverse effects of Ca(2+) arise from the precise localization of Ca(2+) signals into microdomains containing specific Ca(2+) effectors. For example, differences in the mechanical and chemical composition of the underlying substrata elicit local Ca(2+) signals within growth cone filopodia that regulate axon guidance through activation of the protease calpain...
January 9, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28067793/time-dependent-nerve-growth-factor-signaling-changes-in-the-rat-retina-during-optic-nerve-crush-induced-degeneration-of-retinal-ganglion-cells
#19
Louise A Mesentier-Louro, Sara De Nicolò, Pamela Rosso, Luigi A De Vitis, Valerio Castoldi, Letizia Leocani, Rosalia Mendez-Otero, Marcelo F Santiago, Paola Tirassa, Paolo Rama, Alessandro Lambiase
Nerve growth factor (NGF) is suggested to be neuroprotective after nerve injury; however, retinal ganglion cells (RGC) degenerate following optic-nerve crush (ONC), even in the presence of increased levels of endogenous NGF. To further investigate this apparently paradoxical condition, a time-course study was performed to evaluate the effects of unilateral ONC on NGF expression and signaling in the adult retina. Visually evoked potential and immunofluorescence staining were used to assess axonal damage and RGC loss...
January 5, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28067783/stem-cell-transplantation-for-peripheral-nerve-regeneration-current-options-and-opportunities
#20
REVIEW
Liangfu Jiang, Salazar Jones, Xiaofeng Jia
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...
January 5, 2017: International Journal of Molecular Sciences
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