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https://www.readbyqxmd.com/read/28646336/nogo-a-antibodies-enhance-axonal-repair-and-remyelination-in-neuro-inflammatory-and-demyelinating-pathology
#1
Benjamin V Ineichen, Sandra Kapitza, Christiane Bleul, Nicolas Good, Patricia S Plattner, Maryam S Seyedsadr, Julia Kaiser, Marc P Schneider, Björn Zörner, Roland Martin, Michael Linnebank, Martin E Schwab
Two hallmarks of chronic multiple sclerosis lesions are the absence of significant spontaneous remyelination and primary as well as secondary neurodegeneration. Both characteristics may be influenced by the presence of inhibitory factors preventing myelin and neuronal repair. We investigated the potential of antibodies against Nogo-A, a well-known inhibitory protein for neuronal growth and plasticity, to enhance neuronal regeneration and remyelination in two animal models of multiple sclerosis. We induced a targeted experimental autoimmune encephalomyelitis (EAE) lesion in the dorsal funiculus of the cervical spinal cord of adult rats resulting in a large drop of skilled forelimb motor functions...
June 23, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28638124/expression-of-the-human-herpesvirus-6a-latency-associated-transcript-u94a-disrupts-human-oligodendrocyte-progenitor-migration
#2
Andrew Campbell, Jessica M Hogestyn, Christopher J Folts, Brittany Lopez, Christoph Pröschel, David Mock, Margot Mayer-Pröschel
Progression of demyelinating diseases is caused by an imbalance of two opposing processes: persistent destruction of myelin and myelin repair by differentiating oligodendrocyte progenitor cells (OPCs). Repair that cannot keep pace with destruction results in progressive loss of myelin. Viral infections have long been suspected to be involved in these processes but their specific role remains elusive. Here we describe a novel mechanism by which HHV-6A, a member of the human herpesvirus family, may contribute to inadequate myelin repair after injury...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28629798/proteomic-analysis-of-mesenchymal-to-schwann-cell-transdifferentiation
#3
Anup D Sharma, Jayme Wiederin, Metin Uz, Pawel Ciborowski, Surya K Mallapragada, Howard E Gendelman, Donald S Sakaguchi
While transplantation of Schwann cells facilitates axon regeneration, remyelination and repair after peripheral nerve injury clinical use is limited by cell bioavailability. We posit that such limitation in cell access can be overcome by the use of autologous bone-marrow derived mesenchymal stem cells (MSCs). As MSCs can transdifferentiate to Schwann cell-phenotypes and accelerate nerve regeneration we undertook proteomic evaluation of the cells to uncover the protein contents that affects Schwann cell formulation...
June 16, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28629387/an-updated-assessment-of-microglia-depletion-current-concepts-and-future-directions
#4
REVIEW
Jinming Han, Robert A Harris, Xing-Mei Zhang
Microglia are the principal resident immune cells in the central nervous system and are believed to be versatile players in both inflammatory and physiological contexts. On the one hand, in order to safeguard the microenvironment microglia can be rapidly activated by contact with microbial products or cell debris, thereby exerting the functions of innate immunity via phagocytosis and secretion of cytokines and chemokines. Conversely, microglia can also assist in brain development, synaptic plasticity and neural repair through the production of neurotrophic factors and clearance of myelin debris...
June 19, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28624802/heparin-based-coacervate-of-bfgf-facilitates-peripheral-nerve-regeneration-by-inhibiting-endoplasmic-reticulum-stress-following-sciatic-nerve-injury
#5
Rui Li, Shuang Zou, Yanqing Wu, Yiyang Li, Sinan Khor, Yuqin Mao, Huacheng He, Ke Xu, Hongyu Zhang, Xiaokun Li, Jian Wang, Huai Jiang, Qike Jin, Qingsong Ye, Zhouguang Wang, Jian Xiao
Creating a microenvironment at the injury site that favors axonal regrowth and remyelinationis pivotal to the success of therapeutic reinnervation. The mature myelin sheath of the peripheral nervous system depends on active participation of Schwann cells to form new cytoskeletal components and tremendous amounts of relevant neurotrophic factors. In this study, we utilized a new biomaterial for growth factor delivery consisting of a biocompatible polycation, poly(ethylene argininylaspartatediglyceride) and heparin...
May 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28622711/curcumin-accelerates-the-repair-of-sciatic-nerve-injury-in-rats-through-reducing-schwann-cells-apoptosis-and-promoting-myelinization
#6
Zhiwei Zhao, Xiaoling Li, Qing Li
BACKGROUND: Schwann cells (SCs) play an indispensable role in the repair and regeneration of injured peripheral nerve. Curcumin can reduce SCs apoptosis, and promote the regeneration and functional recovery of injured peripheral nerves. However, the corresponding mechanisms are not clear. OBJECTIVE: The article was aimed to explore the effect and corresponding mechanisms of curcumin on the repair of sciatic nerve injury in rats. METHODS: After surgery induced sciatic nerve injury, the model rats were divided into three groups and treated with curcumin, curcumin+PD98059 and curcumin+IGF-1 respectively for 4days...
June 12, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28606714/effect-of-physical-exercise-on-brain-and-lipid-metabolism-in-mouse-models-of-multiple-sclerosis
#7
REVIEW
Léo Houdebine, Cristina Anna Gallelli, Marialetizia Rastelli, Nirmal Kumar Sampathkumar, Julien Grenier
Multiple sclerosis (MS) is a central nervous demyelinating disease characterized by cyclic loss and repair of myelin sheaths associated with chronic inflammation and neuronal loss. This degenerative pathology is accompanied by modified levels of oxysterols (oxidative derivatives of cholesterol, implicated in cholesterol metabolism), highlighted in the brain, blood and cerebrospinal fluid of MS patients. The pathological accumulation of such derivatives is thought to participate in the onset and progression of the disease through their implication in inflammation, oxidative stress, demyelination and neurodegeneration...
June 9, 2017: Chemistry and Physics of Lipids
https://www.readbyqxmd.com/read/28604632/experimental-autoimmune-encephalomyelitis-eae-induced-elevated-expression-of-the-e1-isoform-of-methyl-cpg-binding-protein-2-mecp2e1-implications-in-multiple-sclerosis-ms-induced-neurological-disability-and-associated-myelin-damage
#8
Tina Khorshid Ahmad, Ting Zhou, Khaled AlTaweel, Claudia Cortes, Ryan Lillico, Ted Martin Lakowski, Kiana Gozda, Michael Peter Namaka
Multiple sclerosis (MS) is a chronic neurological disease characterized by the destruction of central nervous system (CNS) myelin. At present, there is no cure for MS due to the inability to repair damaged myelin. Although the neurotrophin brain derived neurotrophic factor (BDNF) has a beneficial role in myelin repair, these effects may be hampered by the over-expression of a transcriptional repressor isoform of methyl CpG binding protein 2 (MeCP2) called MeCP2E1. We hypothesize that following experimental autoimmune encephalomyelitis (EAE)-induced myelin damage, the immune system induction of the pathogenic MeCP2E1 isoform hampers the myelin repair process by repressing BDNF expression...
June 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28600955/parp-activity-and-inhibition-in-fetal-and-adult-oligodendrocyte-precursor-cells-effect-on-cell-survival-and-differentiation
#9
Vito A Baldassarro, Alessandra Marchesini, Luciana Giardino, Laura Calzà
Poly (ADP-ribose) polymerase (PARP) family members are ubiquitously expressed and play a key role in cellular processes, including DNA repair and cell death/survival balance. Accordingly, PARP inhibition is an emerging pharmacological strategy for cancer and neurodegenerative diseases. Consistent evidences support the critical involvement of PARP family members in cell differentiation and phenotype maturation. In this study we used an oligodendrocyte precursor cells (OPCs) enriched system derived from fetal and adult brain to investigate the role of PARP in OPCs proliferation, survival, and differentiation...
May 30, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28598297/the-neuronal-differentiation-microenvironment-is-essential-for-spinal-cord-injury-repair
#10
Yannan Zhao, Zhifeng Xiao, Bing Chen, Jianwu Dai
Spinal cord injury (SCI) often leads to substantial disability due to loss of motor function and sensation below the lesion. Neural stem cells (NSCs) are a promising strategy for SCI repair. However, NSCs rarely differentiate into neurons; they mostly differentiate into astrocytes because of the adverse microenvironment present after SCI. We have shown that myelin-associated inhibitors (MAIs) inhibited neuronal differentiation of NSCs. Given that MAIs activate epidermal growth factor receptor (EGFR) signaling, we used a collagen scaffold-tethered anti-EGFR antibody to attenuate the inhibitory effects of MAIs and create a neuronal differentiation microenvironment for SCI repair...
June 9, 2017: Organogenesis
https://www.readbyqxmd.com/read/28594400/the-role-of-oligodendrocyte-precursor-cells-expressing-the-gpr17-receptor-in-brain-remodeling-after-stroke
#11
Elisabetta Bonfanti, Paolo Gelosa, Marta Fumagalli, Leda Dimou, Francesca Viganò, Elena Tremoli, Mauro Cimino, Luigi Sironi, Maria P Abbracchio
Following stroke-induced neuronal damage, quiescent oligodendrocyte precursors (OPCs) are activated to proliferate and later to differentiate to myelin-producing cells. GPR17, a receptor transiently expressed on early OPCs, has emerged as a target to implement stroke repair through stimulation of OPC maturation. However, being GPR17 completely downregulated in myelin-producing oligodendrocytes, its actual role in determining the final fate of OPCs after cerebral ischemia is still uncertain. Here, to univocally define the spatiotemporal changes and final fate of GPR17-expressing OPCs, we induced ischemia by middle cerebral artery occlusion (MCAo) in reporter GPR17iCreER(T2):CAG-eGreen florescent protein (GFP) mice, in which, upon tamoxifen treatment, cells expressing GPR17 become green and traceable for their entire life...
June 8, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28588447/the-effects-of-epidermal-neural-crest-stem-cells-on-local-inflammation-microenvironment-in-the-defected-sciatic-nerve-of-rats
#12
Yue Li, Dongdong Yao, Jieyuan Zhang, Bin Liu, Lu Zhang, Hua Feng, Bingcang Li
Cell-based therapy is a promising strategy for the repair of peripheral nerve injuries (PNIs). epidermal neural crest stems cells (EPI-NCSCs) are thought to be important donor cells for repairing PNI in different animal models. Following PNI, inflammatory response is important to regulate the repair process. However, the effects of EPI-NCSCs on regulation of local inflammation microenviroment have not been investigated extensively. In the present study, these effects were studied by using 10 mm defected sciatic nerve, which was bridged with 15 mm artificial nerve composed of EPI-NCSCs, extracellular matrix (ECM) and poly (lactide-co-glycolide) (PLGA)...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28582448/acid-sphingomyelinase-deficiency-enhances-myelin-repair-after-acute-and-chronic-demyelination
#13
Marwan Chami, Ramona Halmer, Laura Schnoeder, Katrin Anne Becker, Carola Meier, Klaus Fassbender, Erich Gulbins, Silke Walter
The cuprizone animal model, also known as the toxic demyelination model, is a well-reproducible model of demyelination- and remyelination in mice, and has been useful in studying important aspect of human demyelinating diseases, including multiple sclerosis. In this study, we investigated the role of acid sphingomyelinase in demyelination and myelin repair by inducing acute and chronic demyelination with 5- or 12-week cuprizone treatment, followed by a 2-week cuprizone withdrawal phase to allow myelin repair...
2017: PloS One
https://www.readbyqxmd.com/read/28579877/the-application-of-graphene-oxidized-combining-with-decellularized-scaffold-to-repair-of-sciatic-nerve-injury-in-rats
#14
Qiaoling Wang, Jinlong Chen, Qingfei Niu, Xiumei Fu, Xiaohong Sun, Xiaojie Tong
This paper combined the decellularized scaffold of sciatic nerve of rats with graphene oxidized (GO), studied and facilitated the regeneration of sciatic nerve of rats, and provided the basis for the clinical application of nanomaterials. GO was prepared through improving Hammer's Method. Fourier Infrared Spectrum was used to scan and detect the functional groups in GO of sample by using the pellet method, the microcosmic morphological appearance of GO was observed by using the scanning electron microscope...
May 2017: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
https://www.readbyqxmd.com/read/28576706/rhigm22-enhances-remyelination-in-the-brain-of-the-cuprizone-mouse-model-of-demyelination
#15
Ariana P Mullin, Charlene Cui, Yu Wang, Jing Wang, Erika Troy, Anthony O Caggiano, Tom J Parry, Raymond W Colburn, Elias Pavlopoulos
Failure of oligodendrocyte precursor cells (OPCs) to differentiate and remyelinate axons is thought to be a major cause of the limited ability of the central nervous system to repair plaques of immune-mediated demyelination in multiple sclerosis (MS). Current therapies for MS aim to lessen the immune response in order to reduce the frequency and severity of attacks, but these existing therapies do not target remyelination or stimulate repair of the damaged tissue. Thus, the promotion of OPC differentiation and remyelination is potentially an important therapeutic goal...
May 30, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28575206/heterozygote-galactocerebrosidase-galc-mutants-have-reduced-remyelination-and-impaired-myelin-debris-clearance-following-demyelinating-injury
#16
Nicole J Scott-Hewitt, Christopher J Folts, Jessica M Hogestyn, Gavin Piester, Margot Mayer-Pröschel, Mark D Noble
Genome-wide association studies (GWAS) are identifying multiple genetic risk factors for several diseases, but the functional role of these changes remains mostly unknown. Variants in the galactocerebrosidase (GALC) gene, for example, were identified as a risk factor for Multiple Sclerosis (MS); however, potential biological relevance of GALC variants to MS remains elusive. We found that heterozygote GALC mutant mice have reduced myelin debris clearance and diminished remyelination after a demyelinating insult...
May 31, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28571657/transplantation-of-bone-marrow-stromal-stem-cells-overexpressing-tropomyosin-receptor-kinase-a-for-peripheral-nerve-repair
#17
Meige Zheng, Junxiu Duan, Zhendan He, Zhiwei Wang, Shuhua Mu, Zhiwen Zeng, Junle Qu, Dong Wang, Jian Zhang
BACKGROUND AIMS: Previously we reported that overexpression of tropomyosin receptor kinase A (TrkA) could improve the survival and Schwann-like cell differentiation of bone marrow stromal stem cells (BMSCs) in nerve grafts for bridging rat sciatic nerve defects. The aim of this study was to investigate how TrkA affects the efficacy of BMSCs transplantation on peripheral nerve regeneration and functional recovery. METHODS: Rat BMSCs were infected with recombinant lentiviruses to construct TrkA-overexpressing BMSCs and TrkA-shRNA-expressing BMSCs, which were then seeded in acellular nerve allografts for bridging 10-mm rat sciatic nerve defects...
May 29, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28560006/fat-tissue-a-potential-schwann-cell-reservoir-isolation-and-identification-of-adipose-derived-schwann-cells
#18
Lulu Chen, Yuqing Jin, Xiaonan Yang, Zhangyin Liu, Yang Wang, Gangyang Wang, Zuoliang Qi, Zunli Shen
Schwann cells can be used to promote peripheral nerve repair. However, it is challenging to obtain abundant autologous Schwann cells without sacrificing nerve integrity. In this study, we isolated Schwann cells from murine inguinal adipose tissue and identified the cell phenotype and function in vivo and in vitro. Through H&E and immunofluorescence staining, we detected tiny nerve fibers and Schwann cells in adipose tissue. We evaluated the phenotype of spindle-shaped cells (Schwann cell-like cells, SCLCs) isolated from adipose tissue using immunofluorescence staining and real-time RT-PCR...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28556945/leukemia-lymphoma-related-factor-lrf-exhibits-stage-and-context-dependent-transcriptional-controls-in-the-oligodendrocyte-lineage-and-modulates-remyelination
#19
Nathan L Davidson, Fengshan Yu, Naruchorn Kijpaisalratana, Tuan Q Le, Laurel A Beer, Kryslaine L Radomski, Regina C Armstrong
Leukemia/lymphoma-related factor (LRF), a zinc-finger transcription factor encoded by Zbtb7a, is a protooncogene that regulates differentiation in diverse cell lineages, and in the CNS, its function is relatively unexplored. This study is the first to examine the role of LRF in CNS pathology. We first examined LRF expression in a murine viral model of spinal cord demyelination with clinically relevant lesion characteristics. LRF was rarely expressed in oligodendrocyte progenitors (OP) yet, was detected in nuclei of the majority of oligodendrocytes in healthy adult CNS and during remyelination...
May 30, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28555486/topically-administered-acetyl-l-carnitine-increases-sciatic-nerve-regeneration-and-improves-functional-recovery-after-tubulization-of-transected-short-nerve-gaps
#20
Rahim Mohammadi, Keyvan Amini
BACKGROUND: Peripheral nerve injuries repair is still among the most challenging and concern-raising tasks in neurosurgery. The effect of an acetyl-L-carnitin-loaded silicone tube as an in-situ delivery system in defects bridging was studied using a rat sciatic nerve regeneration model. METHODS: A 10-mm sciatic nerve defect was bridged using a silicone tube (SIL/ALC) filled with 10 µL acetyl-L-carnitine (100 ng/mL). In the control group (SIL), the tube was filled with the same volume of the phosphate-buffered solution...
August 2017: Journal of Neurosurgical Sciences
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