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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/29155769/a-simple-approach-to-induce-experimental-autoimmune-neuritis-in-c57bl-6-mice-for-functional-and-neuropathological-assessments
#3
David G Gonsalvez, Jessica L Fletcher, Sang Won Yoo, Rhiannon J Wood, Simon S Murray, Junhua Xiao
Experimental autoimmune neuritis (EAN) is a well-appreciated experimental model of autoimmune peripheral demyelinating diseases. EAN disease is induced by immunizing mice with neurogenic peptides to direct an inflammatory attack toward components of the peripheral nervous system (PNS). Recent advances have enabled the induction of EAN in the relatively resistant C57BL/6 mouse line using myelin protein zero (P0)106-125 or P0180-199 peptides delivered in adjuvant combined with the injection of pertussis toxin...
November 9, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29141977/vitamins-associated-with-brain-aging-mild-cognitive-impairment-and-alzheimer-disease-biomarkers-epidemiological-and-experimental-evidence-plausible-mechanisms-and-knowledge-gaps
#4
REVIEW
Michael Fenech
The key to preventing brain aging, mild cognitive impairment (MCI), and Alzheimer disease (AD) via vitamin intake is first to understand molecular mechanisms, then to deduce relevant biomarkers, and subsequently to test the level of evidence for the impact of vitamins in the relevant pathways and their modulation of dementia risk. This narrative review infers information on mechanisms from gene and metabolic defects associated with MCI and AD, and assesses the role of vitamins using recent results from animal and human studies...
November 2017: Advances in Nutrition
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/29125428/schwann-cells-and-mesenchymal-stem-cells-in-laminin-or-fibronectin-aligned-matrices-and-regeneration-across-a-critical-size-defect-of-15-mm-in-the-rat-sciatic-nerve
#6
Francisco Gonzalez-Perez, Joaquim Hernández, Claudia Heimann, James B Phillips, Esther Udina, Xavier Navarro
OBJECTIVE Artificial nerve guides are being developed to substitute for autograft repair after peripheral nerve injuries. However, the use of conduits is limited by the length of the gap that needs to be bridged, with the success of regeneration highly compromised in long gaps. Addition of aligned proregenerative cells and extracellular matrix (ECM) components inside the conduit can be a good strategy to achieve artificial grafts that recreate the natural environment offered by a nerve graft. The purpose of this study was to functionalize chitosan devices with different cell types to support regeneration in limiting gaps in the rat peripheral nerve...
November 10, 2017: Journal of Neurosurgery. Spine
https://www.readbyqxmd.com/read/29123469/suppression-of-inflammatory-demyelinaton-and-axon-degeneration-through-inhibiting-kv3-channels
#7
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/29109239/graded-elevation-of-c-jun-in-schwann-cells-in-vivo-gene-dosage-determines-effects-on-development-re-myelination-tumorigenesis-and-hypomyelination
#8
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/29099679/photobiomodulation-in-neuroscience-a-summary-of-personal-experience
#9
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/29095924/distinct-ng2-proteoglycan-dependent-roles-of-resident-microglia-and-bone-marrow-derived-macrophages-during-myelin-damage-and-repair
#10
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/29090002/adipose-derived-mesenchymal-stem-cells-accelerate-nerve-regeneration-and-functional-recovery-in-a-rat-model-of-recurrent-laryngeal-nerve-injury
#11
Yun Li, Wen Xu, Li-Yu Cheng
Medialization thyroplasty or injection laryngoplasty for unilateral vocal fold paralysis cannot restore mobility of the vocal fold. Recent studies have shown that transplantation of mesenchymal stem cells is effective in the repair of nerve injuries. This study investigated whether adipose-derived stem cell transplantation could repair recurrent laryngeal nerve injury. Rat models of recurrent laryngeal nerve injury were established by crushing with micro forceps. Adipose-derived mesenchymal stem cells (ADSCs; 8 × 10(5)) or differentiated Schwann-like adipose-derived mesenchymal stem cells (dADSCs; 8 × 10(5)) or extracellular matrix were injected at the site of injury...
September 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/29090001/phenotypic-changes-of-schwann-cells-on-the-proximal-stump-of-injured-peripheral-nerve-during-repair-using-small-gap-conduit-tube
#12
Shi-Jun Zhang, Wen-Liang Wu, Kai-Yun Yang, Yun-Zhen Chen, Hai-Chun Liu
Dedifferentiation of Schwann cells is an important feature of the response to peripheral nerve injury and specific negative myelination regulators are considered to have a major role in this process. However, most experiments have focused on the distal nerve stump, where the Notch signaling pathway is strongly associated with Schwann cell dedifferentiation and repair of the nerve. We observed the phenotypic changes of Schwann cells and changes of active Notch signaling on the proximal stump during peripheral nerve repair using small gap conduit tubulization...
September 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/29081882/derivation-of-telencephalic-oligodendrocyte-progenitors-from-human-pluripotent-stem-cells
#13
Tamara Major, Ann Powers, Viviane Tabar
Oligodendrocytes are the main myelinating cell of the adult CNS and are vulnerable to injury in diverse disorders such as spinal cord injury, stroke, trauma, pharmacological and radiation toxicity, as well as neuroinflammation. Human pluripotent stem cells are attractive sources of oligodendrocyte lineage cells and provide a promising treatment strategy for exogenous myelin repair through transplantation. This unit describes a protocol for the step-wise differentiation of forebrain late oligodendrocyte progenitor cells (OPCs) from human pluripotent stem cells in defined chemical in vitro culture conditions...
November 8, 2017: Current Protocols in Stem Cell Biology
https://www.readbyqxmd.com/read/29080030/progenitors-in-the-ependyma-of-the-spinal-cord-a-potential-resource-for-self-repair-after-injury
#14
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
#15
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/29038005/prednisone-alleviates-demyelination-through-regulation-of-the-nlrp3-inflammasome-in-a-c57bl-6-mouse-model-of-cuprizone-induced-demyelination
#16
Hao Yu, Mingfeng Wu, Geng Lu, Tingting Cao, Nan Chen, Yijia Zhang, Higuo Jiang, Hongbin Fan, Ruiqin Yao
Myelin abnormalities, oligodendrocyte damage, and concomitant glia activation are common in demyelinating diseases of the central nervous system (CNS). Increasing evidence has demonstrated that the inflammatory response triggers demyelination and gliosis in demyelinating disorders. Numerous clinical interventions, including those used to treat multiple sclerosis (MS), have confirmed prednisone (PDN) as a powerful anti-inflammatory drug that reduces the inflammatory response and promotes tissue repair in multiple inflammation sites...
October 13, 2017: Brain Research
https://www.readbyqxmd.com/read/29029896/clemastine-fumarate-as-a-remyelinating-therapy-for-multiple-sclerosis-rebuild-a-randomised-controlled-double-blind-crossover-trial
#17
Ari J Green, Jeffrey M Gelfand, Bruce A Cree, Carolyn Bevan, W John Boscardin, Feng Mei, Justin Inman, Sam Arnow, Michael Devereux, Aya Abounasr, Hiroko Nobuta, Alyssa Zhu, Matt Friessen, Roy Gerona, Hans Christian von Büdingen, Roland G Henry, Stephen L Hauser, Jonah R Chan
BACKGROUND: Multiple sclerosis is a degenerative inflammatory disease of the CNS characterised by immune-mediated destruction of myelin and progressive neuroaxonal loss. Myelin in the CNS is a specialised extension of the oligodendrocyte plasma membrane and clemastine fumarate can stimulate differentiation of oligodendrocyte precursor cells in vitro, in animal models, and in human cells. We aimed to analyse the efficacy and safety of clemastine fumarate as a treatment for patients with multiple sclerosis...
October 10, 2017: Lancet
https://www.readbyqxmd.com/read/29024633/the-healthy-and-diseased-microenvironments-regulate-oligodendrocyte-properties-implications-for-regenerative-medicine
#18
REVIEW
Prisca S Leferink, Vivi M Heine
White matter disorders are characterized by deficient myelin or myelin loss, lead to a range of neurologic dysfunctions, and can result in early death. Oligodendrocytes, which are responsible for white matter formation, are the first targets for treatment. However, many studies indicate that failure of white matter repair goes beyond the intrinsic incapacity of oligodendrocytes to (re)generate myelin and that failed interactions with neighboring cells or factors in the diseased microenvironment can underlie white matter defects...
October 10, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28990762/multichanneled-nerve-guidance-conduit-with-spatial-gradients-of-neurotrophic-factors-and-oriented-nanotopography-for-repairing-the-peripheral-nervous-system
#19
Yo-Cheng Chang, Ming-Hong Chen, Shih-Yung Liao, Hsi-Chin Wu, Chen-Hsiang Kuan, Jui-Sheng Sun, Tzu-Wei Wang
Peripheral nerve injuries, causing sensory and motor impairment, affect a great number of patients annually. It is therefore important to incorporate different strategies to promote nerve healing. Among the treatment options, however, the efficacy of nerve conduits is often compromised by their lack of living cells, insufficient growth factors, and absence of the extracellular matrix (ECM)-like structure. To improve the functional recovery, we aimed to develop a natural biodegradable multichanneled scaffold characterized with aligned electrospun nanofibers and neurotrophic gradient (MC/AN/NG) to guide axon outgrowth...
October 17, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28983582/effects-of-tripterygium-glycoside-treatment-on-experimental-autoimmune-encephalomyelitis
#20
Jianmin Qiu, Xuelian You, Gang Wu
Experimental autoimmune encephalomyelitis (EAE) is an autoimmune disease mediated by CD4+ T cells. It is characterized by mononuclear cell infiltration around the small blood vessels in the central nervous system (CNS). Previous investigations have found that apoptosis is associated with the occurrence and development of autoimmune disease, and that mononuclear cell apoptosis and clearance from the CNS is one of the repair mechanisms of EAE. Tripterygium wilfordii glycoside (TWP) is an organic matter isolated from Tripterygium wilfordii, which has anti‑inflammatory and immunosuppressive effects...
December 2017: Molecular Medicine Reports
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