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https://www.readbyqxmd.com/read/29157398/new-advances-in-disease-modifying-therapies-for-relapsing-and-progressive-forms-of-multiple-sclerosis
#1
REVIEW
Angela Vidal-Jordana
Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system in which inflammation, demyelination, and axonal loss occurs from early stages of the disease. It mainly affects people between 20 and 40 years old, with a female predominance. Treatment options have been increasingly growing in the past years and newer drugs, some with novel mechanisms of action, are being developed for treating patients with MS. There is an increasing interest in developing new drugs that will promote neuroprotection and/or myelin repair through different mechanisms of action that may target the most degenerative component of the disease...
February 2018: Neurologic Clinics
https://www.readbyqxmd.com/read/29157392/multiple-sclerosis-mechanisms-of-disease-and-strategies-for-myelin-and-axonal-repair
#2
REVIEW
Hernan Nicolas Lemus, Arthur E Warrington, Moses Rodriguez
Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system with a variety of presentations and unclear pathogenesis. Multiple sclerosis has been associated with the term autoimmunity as a surrogate for pathogenesis. Multiple sclerosis is an organ-specific disease with immune-mediated myelin destruction. Understanding the complex etiology of multiple sclerosis and the importance of axon integrity is critical for clinicians who treat the disease. This review discusses the immune and autoimmune aspects of multiple sclerosis based on the current published data and novel evidence of strategies that promote remyelination and protect axons...
February 2018: Neurologic Clinics
https://www.readbyqxmd.com/read/29154141/novel-genes-associated-with-amyotrophic-lateral-sclerosis-diagnostic-and-clinical-implications
#3
REVIEW
Ruth Chia, Adriano Chiò, Bryan J Traynor
BACKGROUND: The disease course of amyotrophic lateral sclerosis (ALS) is rapid and, because its pathophysiology is unclear, few effective treatments are available. Genetic research aims to understand the underlying mechanisms of ALS and identify potential therapeutic targets. The first gene associated with ALS was SOD1, identified in 1993 and, by early 2014, more than 20 genes had been identified as causative of, or highly associated with, ALS. These genetic discoveries have identified key disease pathways that are therapeutically testable and could potentially lead to the development of better treatments for people with ALS...
November 16, 2017: Lancet Neurology
https://www.readbyqxmd.com/read/29146953/achievements-and-obstacles-of-remyelinating-therapies-in-multiple-sclerosis
#4
REVIEW
Martin Stangel, Tanja Kuhlmann, Paul M Matthews, Trevor J Kilpatrick
Remyelination in the CNS is the natural process of damage repair in demyelinating diseases such as multiple sclerosis (MS). However, remyelination becomes inadequate in many people with MS, which results in axonal degeneration and clinical disability. Enhancement of remyelination is a logical therapeutic goal; nevertheless, all currently licensed therapies for MS are immunomodulatory and do not support remyelination directly. Several molecular pathways have been identified as potential therapeutic targets to induce remyelination, and some of these have now been assessed in proof-of-concept clinical trials...
November 17, 2017: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/29130658/-vein-nerve-conduit-supported-by-vascular-stent-in-the-regeneration-of-peripheral-nerve-in-rabbits
#5
Wei-Kun Meng, Zhong Huang, Zhen Tan, Liang Li, Qiang Guo, Zhen Zhang, Cheng-Xi Wu, Lei Liu, Fu-Guo Huang, Guang-Lin Wang
OBJECTIVE: To evaluate the effectiveness of autologous vein nerve conduit supported by vascular stent in repairing a 10 mm gap peroneal nerve in white New Zealand rabbits. METHODS: 30 New Zealand rabbits were randomly divided into three groups: autologous nerve group (group A),conventional autologous vein nerve conduit group (group B),autologous vein nerve conduit supported by vascular stent group (group C). 10 mm common peroneal nerve was cut off. In groups A,the peroneal nerve was turned 180 ° before suturing...
September 2017: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/29128308/oxidative-stress-and-dna-damage-after-cerebral-ischemia-potential-therapeutic-targets-to-preserve-the-genome-and-improve-stroke-recovery
#6
REVIEW
Peiying Li, R Anne Stetler, Rehana K Leak, Yejie Shi, Yan Li, Weifeng Yu, Michael V L Bennett, Jun Chen
The past two decades have witnessed remarkable advances in oxidative stress research, particularly in the context of ischemic brain injury. Oxidative stress in ischemic tissues compromises the integrity of the genome, resulting in DNA lesions, cell death in neurons, glial cells, and vascular cells, and impairments in neurological recovery after stroke. As DNA is particularly vulnerable to oxidative attack, cells have evolved the ability to induce multiple DNA repair mechanisms, including base excision repair (BER), nucleotide excision repair (NER) and non-homogenous endpoint jointing (NHEJ)...
November 8, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29124786/schwann-cell-precursors-in-health-and-disease
#7
REVIEW
Jorge B Aquino, Romina Sierra
Schwann cell precursors (SCPs) are frequently regarded as neural crest-derived cells (NCDCs) found in contact with axons during nerve formation. Nevertheless, cells with SCPs properties can be found up to the adulthood. They are well characterized with regard to both gene expression profile and cellular behavior -for instance, proliferation, migratory capabilities and survival requirements-. They differ in origin regarding their anatomic location: even though most of them are derived from migratory NCCs, there is also contribution of the boundary cap neural crest cells (bNCCs) to the skin and other tissues...
November 10, 2017: Glia
https://www.readbyqxmd.com/read/29123469/suppression-of-inflammatory-demyelinaton-and-axon-degeneration-through-inhibiting-kv3-channels
#8
Peter Jukkola, Yuanzheng Gu, Amy E Lovett-Racke, Chen Gu
The development of neuroprotective and repair strategies for treating progressive multiple sclerosis (MS) requires new insights into axonal injury. 4-aminopyridine (4-AP), a blocker of voltage-gated K(+) (Kv) channels, is used in symptomatic treatment of progressive MS, but the underlying mechanism remains unclear. Here we report that deleting Kv3.1-the channel with the highest 4-AP sensitivity-reduces clinical signs in experimental autoimmune encephalomyelitis (EAE), a mouse model for MS. In Kv3.1 knockout (KO) mice, EAE lesions in sensory and motor tracts of spinal cord were markedly reduced, and radial astroglia were activated with increased expression of brain derived neurotrophic factor (BDNF)...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29123467/the-role-of-sdf-1-cxcr4-cxcr7-in-neuronal-regeneration-after-cerebral-ischemia
#9
REVIEW
Xi Cheng, Huibin Wang, Xiuchun Zhang, Shanshan Zhao, Zhike Zhou, Xiaopeng Mu, Chuansheng Zhao, Weiyu Teng
Stromal cell-derived factor-1 is a chemoattractant produced by bone marrow stromal cell lines. It is recognized as a critical factor in the immune and central nervous systems (CNSs) as well as exerting a role in cancer. SDF-1 activates two G protein-coupled receptors, CXCR4 and CXCR7; these are expressed in both developing and mature CNSs and participate in multiple physiological and pathological events, e.g., inflammatory response, neurogenesis, angiogenesis, hematopoiesis, cancer metastasis, and HIV infection...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29109239/graded-elevation-of-c-jun-in-schwann-cells-in-vivo-gene-dosage-determines-effects-on-development-re-myelination-tumorigenesis-and-hypomyelination
#10
Shaline V Fazal, Jose A Gomez-Sanchez, Laura J Wagstaff, Nicolo Musner, Georg Otto, Martin Janz, Rhona Mirsky, Kristjan R Jessen
Schwann cell c-Jun is implicated in adaptive and maladaptive functions in peripheral nerves. In injured nerves, this transcription factor promotes the repair Schwann cell phenotype and regeneration, and it promotes Schwann cell mediated neurotrophic support in models of peripheral neuropathies. However, c-Jun is associated with tumour formation in some systems, it potentially supresses myelin genes, and has been implicated in demyelinating neuropathies. To clarify these issues, and determine how c-Jun levels determine its function, we have generated, c-Jun OE/+ and c-Jun OE/OE mice, with graded expression of c-Jun in Schwann cells, and examined these lines during development, in adulthood and after injury using RNA sequencing analysis, quantitative electron microscopic morphometry, Western blotting and functional tests...
November 6, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29104116/putative-roles-of-soluble-trophic-factors-in-facial-nerve-regeneration-target-reinnervation-and-recovery-of-vibrissal-whisking
#11
REVIEW
Habib Bendella, Svenja Rink, Maria Grosheva, Levent Sarikcioglu, Tessa Gordon, Doychin N Angelov
It is well-known that, after nerve transection and surgical repair, misdirected regrowth of regenerating motor axons may occur in three ways. The first way is that the axons enter into endoneurial tubes that they did not previously occupy, regenerate through incorrect fascicles and reinnervate muscles that they did not formerly supply. Consequently the activation of these muscles results in inappropriate movements. The second way is that, in contrast with the precise target-directed pathfinding by elongating motor nerves during embryonic development, several axons rather than a single axon grow out from each transected nerve fiber...
November 8, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/29099679/photobiomodulation-in-neuroscience-a-summary-of-personal-experience
#12
Shimon Rochkind
OBJECTIVE: This review summarizes personal experience with laser photobiomodulation and its potentials for the treatment of peripheral and central nerve system injuries. METHODS AND RESULTS: Laser photobiomodulation was shown to induce nerve cell activation, have a positive effect on metabolism of the nerve cells, and to stimulate nerve sprouting processes. Studies investigating the effects of laser photobiomodulation on injured peripheral nerves in rats reported immediate protective effects which increase the functional activity of the nerve, decrease or prevent scar tissue formation at the injured site, prevent or decrease degeneration in corresponding motor neurons of the spinal cord, and significantly increase axonal growth and myelinization...
November 2017: Photomedicine and Laser Surgery
https://www.readbyqxmd.com/read/29098916/a-novel-conduit-based-coaptation-device-for-primary-nerve-repair
#13
Ravinder Bamba, D Colton Riley, Nathaniel D Kelm, Nancy Cardwell, Alonda C Pollins, Ashkan Afshari, Lyly Ngyuen, Richard D Dortch, Wesley P Thayer
BACKGROUND: Conduit-based nerve repairs are commonly used for small nerve gaps, whereas primary repair may be performed if there is no tension on nerve endings. We hypothesize a conduit-based nerve coaptation device will improve nerve repair outcomes by avoiding sutures at the nerve repair site and utilizing the advantages of a conduit-based repair. METHODS: The left sciatic nerves of female Sprague-Dawley rats were transected and repaired using a novel conduit-based device...
November 3, 2017: International Journal of Neuroscience
https://www.readbyqxmd.com/read/29097315/mapping-of-thalamic-magnetic-susceptibility-in-multiple-sclerosis-indicates-decreasing-iron-with-disease-duration-a-proposed-mechanistic-relationship-between-inflammation-and-oligodendrocyte-vitality
#14
Ferdinand Schweser, Ana Luiza Raffaini Duarte Martins, Jesper Hagemeier, Fuchun Lin, Jannis Hanspach, Bianca Weinstock-Guttman, Simon Hametner, Niels P Bergsland, Michael G Dwyer, Robert Zivadinov
Recent advances in susceptibility MRI have dramatically improved the visualization of deep gray matter brain regions and the quantification of their magnetic properties in vivo, providing a novel tool to study the poorly understood iron homeostasis in the human brain. In this study, we used an advanced combination of the recent quantitative susceptibility mapping technique with dedicated analysis methods to study intra-thalamic tissue alterations in patients with clinically isolated syndrome (CIS) and multiple sclerosis (MS)...
October 30, 2017: NeuroImage
https://www.readbyqxmd.com/read/29095924/distinct-ng2-proteoglycan-dependent-roles-of-resident-microglia-and-bone-marrow-derived-macrophages-during-myelin-damage-and-repair
#15
Karolina Kucharova, William B Stallcup
We used a bone marrow transplantation approach to distinguish the activities of bone marrow-derived macrophages from the activities of central nervous system-resident microglia in phenomena associated with axon demyelination and remyelination. We transplanted wild type or germline NG2 null beta-actin-EGFP expressing bone marrow into irradiated wild type or NG2 null recipient mice, followed by analysis of lysolecithin-induced spinal cord demyelination and remyelination and quantification of Iba-1+/ F4/80+/ EGFP+ macrophages and Iba-1+/ F4/80+/ EGFP- microglia...
2017: PloS One
https://www.readbyqxmd.com/read/29093056/first-person-richard-eva
#16
(no author information available yet)
First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Richard Eva is the first author on 'EFA6 regulates selective polarised transport and axon regeneration from the axon initial segment', published in Journal of Cell Science. Richard is a research associate in the laboratory of Prof. James Fawcett, investigating the intrinsic mechanisms preventing brain and spinal cord axons from regenerating after injury in order to identify novel strategies for enhancing repair...
November 1, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/29090000/scaffoldless-tissue-engineered-nerve-conduit-promotes-peripheral-nerve-regeneration-and-functional-recovery-after-tibial-nerve-injury-in-rats
#17
Aaron M Adams, Keith W VanDusen, Tatiana Y Kostrominova, Jacob P Mertens, Lisa M Larkin
Damage to peripheral nerve tissue may cause loss of function in both the nerve and the targeted muscles it innervates. This study compared the repair capability of engineered nerve conduit (ENC), engineered fibroblast conduit (EFC), and autograft in a 10-mm tibial nerve gap. ENCs were fabricated utilizing primary fibroblasts and the nerve cells of rats on embryonic day 15 (E15). EFCs were fabricated utilizing primary fibroblasts only. Following a 12-week recovery, nerve repair was assessed by measuring contractile properties in the medial gastrocnemius muscle, distal motor nerve conduction velocity in the lateral gastrocnemius, and histology of muscle and nerve...
September 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/29080030/progenitors-in-the-ependyma-of-the-spinal-cord-a-potential-resource-for-self-repair-after-injury
#18
Nicolás Marichal, Cecilia Reali, María Inés Rehermann, Omar Trujillo-Cenóz, Raúl E Russo
Traumatic injury of the spinal cord leads to devastating conditions that affect ~2.5 million people worldwide. This is because the mammalian spinal cord reacts to injury with only limited endogenous repair. Functional restoration requires the replacement of lost cells, the growth and navigation of regenerating axons on a permissive scaffold and axon re-myelination. The manipulation of endogenous spinal stem cells is regarded as a potential strategy to restore function. For this type of therapy it is necessary to determine the molecular and functional mechanisms regulating the proliferation, migration and differentiation of adult spinal progenitors...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29073528/microglia-origins-homeostasis-and-roles-in-myelin-repair
#19
REVIEW
Amy F Lloyd, Claire L Davies, Veronique E Miron
Microglia are the resident macrophages of the central nervous system (CNS), implicated in developmental processes, homeostasis, and responses to injury. Derived from the yolk sac during development, microglia self-renew, self-regulate their numbers during homeostatic conditions, and show a robust proliferative capacity even in adulthood. Together with monocyte-derived macrophages (MDM), microglia coordinate the regeneration of CNS myelin around axons, termed remyelination. Gene expression analyses and experimental modelling have identified pro-remyelination roles for microglia/MDM in clearance of myelin debris, secretion of growth factors, and remodelling of the extracellular matrix...
October 23, 2017: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/29067656/imaging-analysis-of-the-neuromuscular-junction-in-dystrophic-muscle
#20
Stephen J P Pratt, Shama R Iyer, Sameer B Shah, Richard M Lovering
Duchenne muscular dystrophy (DMD), caused by the absence of the protein dystrophin, is characterized as a neuromuscular disease in which muscle weakness, increased susceptibility to muscle injury, and inadequate repair appear to underlie the pathology. Considerable attention has been dedicated to studying muscle fiber damage, but there is little information to determine if damage from contraction-induced injury also occurs at or near the nerve terminal axon. Interestingly, both human patients and the mouse model for DMD (the mdx mouse) present fragmented neuromuscular junction (NMJ) morphology...
2018: Methods in Molecular Biology
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