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spinal cord regeneration

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https://www.readbyqxmd.com/read/28630630/roles-of-mesenchymal-stem-cells-in-spinal-cord-injury
#1
REVIEW
Jing Qu, Huanxiang Zhang
Spinal cord injury (SCI) represents one of the most complicated and heterogeneous pathological processes of central nervous system (CNS) impairments, which is still beyond functional regeneration. Transplantation of mesenchymal stem cells (MSCs) has been shown to promote the repair of the injured spinal cord tissues in animal models, and therefore, there is much interest in the clinical use of these cells. However, many questions which are essential to improve the therapy effects remain unanswered. For instance, the functional roles and related molecular regulatory mechanisms of MSCs in vivo are not yet completely determined...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28628111/interaction-of-reactive-astrocytes-with-type-i-collagen-induces-astrocytic-scar-formation-through-the-integrin-n-cadherin-pathway-after-spinal-cord-injury
#2
Masamitsu Hara, Kazu Kobayakawa, Yasuyuki Ohkawa, Hiromi Kumamaru, Kazuya Yokota, Takeyuki Saito, Ken Kijima, Shingo Yoshizaki, Katsumi Harimaya, Yasuharu Nakashima, Seiji Okada
Central nervous system (CNS) injury transforms naive astrocytes into reactive astrocytes, which eventually become scar-forming astrocytes that can impair axonal regeneration and functional recovery. This sequential phenotypic change, known as reactive astrogliosis, has long been considered unidirectional and irreversible. However, we report here that reactive astrocytes isolated from injured spinal cord reverted in retrograde to naive astrocytes when transplanted into a naive spinal cord, whereas they formed astrocytic scars when transplanted into injured spinal cord, indicating the environment-dependent plasticity of reactive astrogliosis...
June 19, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28626748/the-multiple-roles-of-fgf-signaling-in-the-developing-spinal-cord
#3
REVIEW
Ruth Diez Del Corral, Aixa V Morales
During vertebrate embryonic development, the spinal cord is formed by the neural derivatives of a neuromesodermal population that is specified at early stages of development and which develops in concert with the caudal regression of the primitive streak. Several processes related to spinal cord specification and maturation are coupled to this caudal extension including neurogenesis, ventral patterning and neural crest specification and all of them seem to be crucially regulated by Fibroblast Growth Factor (FGF) signaling, which is prominently active in the neuromesodermal region and transiently in its derivatives...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28626016/the-mtor-substrate-s6-kinase-1-s6k1-is-a-negative-regulator-of-axon-regeneration-and-a-potential-drug-target-for-central-nervous-system-injury
#4
Hassan Al-Ali, Ying Ding, Tatiana Slepak, Wei Wu, Yan Sun, Yania Martinez, Xiao-Ming Xu, V P Lemmon, J L Bixby
The mammalian target of Rapamycin (mTOR) positively regulates axon growth in the mammalian central nervous system (CNS). Though axon regeneration and functional recovery from CNS injuries are typically limited, knockdown or deletion of PTEN, a negative regulator of mTOR, increases mTOR activity and induces robust axon growth and regeneration. It has been suggested that inhibition of S6 Kinase 1 (S6K1, gene symbol: RPS6KB1), a prominent mTOR target, would blunt mTOR's positive effect on axon growth. In contrast to this expectation, we demonstrate that inhibition of S6K1 in CNS neurons promotes neurite outgrowth in vitro by 2-3 fold...
June 16, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28621171/boundary-cap-neural-crest-stem-cell-transplants-contribute-mts1-s100a4-expressing-cells-in-the-glial-scar
#5
Carl Trolle, Patrik Ivert, Jan Hoeber, Iris Rocamonde-Lago, Svitlana Vasylovska, Eugen Lukanidin, Elena N Kozlova
AIM: During development, boundary cap neural crest stem cells (bNCSCs) assist sensory axon growth into the spinal cord. Here we repositioned them to test if they assist regeneration of sensory axons in adult mice after dorsal root avulsion injury. MATERIALS & METHODS: Avulsed mice received bNCSC or human neural progenitor (hNP) cell transplants and their contributions to glial scar formation and sensory axon regeneration were analyzed with immunohistochemistry and transganglionic tracing...
June 16, 2017: Regenerative Medicine
https://www.readbyqxmd.com/read/28616030/time-lapse-changes-of-in-vivo-injured-neuronal-substructures-in-the-central-nervous-system-after-low-energy-two-photon-nanosurgery
#6
Zhikai Zhao, Shuangxi Chen, Yunhao Luo, Jing Li, Smaranda Badea, Chaoran Ren, Wutian Wu
There is currently very little research regarding the dynamics of the subcellular degenerative events that occur in the central nervous system in response to injury. To date, multi-photon excitation has been primarily used for imaging applications; however, it has been recently used to selectively disrupt neural structures in living animals. However, understanding the complicated processes and the essential underlying molecular pathways involved in these dynamic events is necessary for studying the underlying process that promotes neuronal regeneration...
May 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28616017/inhibition-and-enhancement-of-neural-regeneration-by-chondroitin-sulfate-proteoglycans
#7
REVIEW
Heikki Rauvala, Mikhail Paveliev, Juha Kuja-Panula, Natalia Kulesskaya
The current dogma in neural regeneration research implies that chondroitin sulfate proteoglycans (CSPGs) inhibit plasticity and regeneration in the adult central nervous system (CNS). We argue that the role of the CSPGs can be reversed from inhibition to activation by developmentally expressed CSPG-binding factors. Heparin-binding growth-associated molecule (HB-GAM; also designated as pleiotrophin) has been studied as a candidate molecule that might modulate the role of CSPG matrices in plasticity and regeneration...
May 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28613324/a-fusion-of-minicircle-dna-and-nanoparticle-delivery-technologies-facilitates-therapeutic-genetic-engineering-of-autologous-canine-olfactory-mucosal-cells
#8
Alexander M Delaney, Christopher F Adams, Alinda R Fernandes, Arwa F Al-Shakli, Jon Sen, Darren R Carwardine, Nicolas Granger, Divya M Chari
Olfactory ensheathing cells (OECs) promote axonal regeneration and improve locomotor function when transplanted into the injured spinal cord. A recent clinical trial demonstrated improved motor function in domestic dogs with spinal injury following autologous OEC transplantation. Their utility in canines offers promise for human translation, as dogs are comparable to humans in terms of clinical management and genetic/environmental variation. Moreover, the autologous, minimally invasive derivation of OECs makes them viable for human spinal injury investigation...
June 14, 2017: Nanoscale
https://www.readbyqxmd.com/read/28599613/immunohistochemical-analysis-of-canine-and-feline-muscle-disorders-using-formalin-fixed-paraffin-embedded-tissues
#9
Takanori Shiga, Kazuyuki Uchida, James K Chambers, Hiroyuki Nakayama
Histochemical techniques used in examination of muscle biopsies typically require frozen sections. Given that most of the specimens submitted to a veterinary laboratory for diagnosis are formalin-fixed, the choice of staining methods is limited. We aimed to further advance the diagnostic capabilities of pathologists presented with formalin-fixed muscle samples and to describe the differences in immunohistopathologic findings between neurogenic and myogenic muscle disorders. Based on hematoxylin and eosin staining, we defined in dogs the histologic lesions in 4 neurogenic disorders (degenerative myelopathy and polyneuropathy) and 2 myogenic disorders (dystrophin-deficient muscular dystrophy)...
June 1, 2017: Journal of Veterinary Diagnostic Investigation
https://www.readbyqxmd.com/read/28598857/sdf-1-overexpression-by-mesenchymal-stem-cells-enhances-gap-43-positive-axonal-growth-following-spinal-cord-injury
#10
Andrew Nathaniel Stewart, Jessica Jane Matyas, Ryan Matthew Welchko, Alison Delanie Goldsmith, Sarah Elizabeth Zeiler, Ute Hochgeschwender, Ming Lu, Zhenhong Nan, Julien Rossignol, Gary Leo Dunbar
PURPOSE: Utilizing genetic overexpression of trophic molecules in cell populations has been a promising strategy to develop cell replacement therapies for spinal cord injury (SCI). Over-expressing the chemokine, stromal derived factor-1 (SDF-1α), which has chemotactic effects on many cells of the nervous system, offers a promising strategy to promote axonal regrowth following SCI. The purpose of this study was to explore the effects of human SDF-1α, when overexpressed by mesenchymal stem cells (MSCs), on axonal growth and motor behavior in a contusive rat model of SCI...
June 6, 2017: Restorative Neurology and Neuroscience
https://www.readbyqxmd.com/read/28593744/thermosensitive-heparin-poloxamer-hydrogels-enhance-the-effects-of-gdnf-on-neuronal-circuit-remodelling-and-neuroprotection-after-spinal-cord-injury
#11
Ying-Zheng Zhao, Xi Jiang, Qian Lin, He-Lin Xu, Ya-Dong Huang, Cui-Tao Lu, Jun Cai
Traumatic spinal cord injury (SCI) results in paraplegia or quadriplegia, and currently, therapeutic interventions for axonal regeneration after SCI are not clinically available. Animal studies have revealed that glial cell-derived neurotrophic factor (GDNF) plays multiple beneficial roles in neuroprotection, glial scarring remodelling, axon regeneration and remyelination in SCI. However, the poor physicochemical stability of GDNF, as well as its limited ability to cross the blood-spinal cord barrier, hampers the development of GDNF as an effective therapeutic intervention in clinical practice...
June 7, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28588362/folic-acid-modulates-matrix-metalloproteinase-2-expression-alleviates-neuropathic-pain-and-improves-functional-recovery-in-spinal-cord-injured-rats
#12
Gurwattan S Miranpuri, Sivan Vadakkadath Meethal, Emmanuel Sampene, Abhishek Chopra, Seah Buttar, Carrie Nacht, Neydis Moreno, Kush Patel, Lisa Liu, Anupama Singh, Chandra K Singh, Nithya Hariharan, Bermans Iskandar, Daniel K Resnick
BACKGROUND: The molecular underpinnings of spinal cord injury (SCI) associated with neuropathic pain (NP) are unknown. Recent studies have demonstrated that matrix metalloproteinases (MMPs) such as MMP2 play a critical role in inducing NP following SCI. Promoter methylation of MMPs is known to suppress their transcription and reduce NP. In this context, it has been shown in rodents that folic acid (FA), an FDA approved dietary supplement and key methyl donor in the central nervous system (CNS), increases axonal regeneration and repair of injured CNS in part via methylation...
May 2017: Annals of Neurosciences
https://www.readbyqxmd.com/read/28578430/expression-profiles-of-cholesterol-metabolism-related-genes-are-altered-during-development-of-experimental-autoimmune-encephalomyelitis-in-the-rat-spinal-cord
#13
Irena Lavrnja, Kosara Smiljanic, Danijela Savic, Aleksandra Mladenovic-Djordjevic, Katarina Tesovic, Selma Kanazir, Sanja Pekovic
Increased evidence suggests that dysregulation of cholesterol metabolism may be a key event contributing to progression of multiple sclerosis (MS). Using an experimental autoimmune encephalomyelitis (EAE) model of MS we revealed specific changes in the mRNA and protein expression of key molecules involved in the maintaining of cholesterol homeostasis in the rat spinal cord: 3-hydroxy-3-methylglutaryl-coenzyme-A reductase (HMGCR), apolipoprotein E (ApoE) and cholesterol 24-hydroxylase (CYP46A1) during the course of disease...
June 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28578005/isolation-characterization-and-differentiation-of-multipotent-neural-progenitor-cells-from-human-cerebrospinal-fluid-in-fetal-cystic-myelomeningocele
#14
Mario Marotta, Alejandra Fernández-Martín, Marc Oria, Cesar G Fontecha, Carles Giné, Vicente Martínez-Ibáñez, Elena Carreras, Michael A Belfort, Gloria Pelizzo, Jose L Peiró
Despite benefits of prenatal in utero repair of myelomeningocele, a severe type of spina bifida aperta, many of these patients will still suffer mild to severe impairment. One potential source of stem cells for new regenerative medicine-based therapeutic approaches for spinal cord injury repair is neural progenitor cells (NPCs) in cerebrospinal fluid (CSF). To this aim, we extracted CSF from the cyst surrounding the exposed neural placode during the surgical repair of myelomeningocele in 6 fetuses (20 to 26weeks of gestation)...
May 15, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28576065/-chitosan-g-glycidyl-methacrylate-xanthan-hydrogel-implant-in-wistar-rats-for-spinal-cord-regeneration
#15
E A Elizalde-Peña, I A Quintero-Ortega, D G Zárate-Triviño, A Nuño-Licona, J Gough, I C Sanchez, D I Medina, G Luna-Barcenas
This work reports the results of in vivo assays of an implant composed of the hydrogel Chitosan-g-Glycidyl Methacrylate-Xanthan [(CTS-g-GMA)-X] in Wistar rats. Degradation kinetics of hydrogels was assessed by lysozyme assays. Wistar rats were subjected to laminectomy by cutting the spinal cord with a scalpel. After the surgical procedure, hydrogels were implanted in the injured zone (level T8). Somatosensory evoked potentials (SEPs) obtained by electric stimulation onto periphery nerves were registered in the corresponding central nervous system (CNS) areas...
September 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28575969/li-activated-nanohydroxyapatite-doped-with-eu-3-ions-enhances-proliferative-activity-and-viability-of-human-stem-progenitor-cells-of-adipose-tissue-and-olfactory-ensheathing-cells-further-perspective-of-nhap-li-eu-3-application-in-theranostics
#16
Krzysztof Marycz, Paulina Sobierajska, Agnieszka Smieszek, Monika Maredziak, Katarzyna Wiglusz, Rafal J Wiglusz
Spinal cord injuries (SCI) often require simultaneous regeneration of nerve tissue and bone. Hydroxyapatites are described as bioresorbable materials with proper biocompatibility and osteoconductivity, therefore its application for spinal surgery is considered. In this paper, we present repeatable method for developing nanocrystalline calcium hydroxyapatites structurally modified with Li(+) ions (nHAP:Li(+)). Obtained biomaterials were profoundly characterized in terms of their physicochemical properties. Moreover, we have shown that nHAP:Li(+) doped with europium (Eu(3+)) may serve as a theranostic agent, what additionally extend its potential usage for SCI treatment...
September 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28562227/a-combinatorial-approach-to-induce-sensory-axon-regeneration-into-the-dorsal-root-avulsed-spinal-cord
#17
Jan Hoeber, Niclas König, Carl Trolle, Emilia Lekholm, Chunfang Zhou, Stanislava Pankratova, Elisabet Åkesson, Robert Fredriksson, Håkan Aldskogius, Elena N Kozlova
Spinal root injuries result in newly formed glial scar formation, which prevents regeneration of sensory axons causing permanent sensory loss. Previous studies showed that delivery of trophic factors or implantation of human neural progenitor cells supports sensory axon regeneration and partly restores sensory functions. In this study, we elucidate mechanisms underlying stem cell-mediated ingrowth of sensory axons after dorsal root avulsion (DRA). We show that human spinal cord neural stem/progenitor cells (hscNSPC), and also, mesoporous silica particles loaded with growth factor mimetics (MesoMIM), supported sensory axon regeneration...
May 31, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28559442/cxcl12%C3%AE-sdf-1-from-perisynaptic-schwann-cells-promotes-regeneration-of-injured-motor-axon%C3%A2-terminals
#18
Samuele Negro, Francesca Lessi, Elisa Duregotti, Paolo Aretini, Marco La Ferla, Sara Franceschi, Michele Menicagli, Elisanna Bergamin, Egle Radice, Marcus Thelen, Aram Megighian, Marco Pirazzini, Chiara M Mazzanti, Michela Rigoni, Cesare Montecucco
The neuromuscular junction has retained through evolution the capacity to regenerate after damage, but little is known on the inter-cellular signals involved in its functional recovery from trauma, autoimmune attacks, or neurotoxins. We report here that CXCL12α, also abbreviated as stromal-derived factor-1 (SDF-1), is produced specifically by perisynaptic Schwann cells following motor axon terminal degeneration induced by α-latrotoxin. CXCL12α acts via binding to the neuronal CXCR4 receptor. A CXCL12α-neutralizing antibody or a specific CXCR4 inhibitor strongly delays recovery from motor neuron degeneration in vivo Recombinant CXCL12α in vivo accelerates neurotransmission rescue upon damage and very effectively stimulates the axon growth of spinal cord motor neurons in vitro These findings indicate that the CXCL12α-CXCR4 axis plays an important role in the regeneration of the neuromuscular junction after motor axon injury...
May 30, 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28559136/intradiencephalon-injection-of-histamine-inhibited-the-recovery-of-locomotor-function-of-spinal-cord-injured-zebrafish
#19
Shu-Bing Huang, Hou-De Zhao, Lin-Fang Wang, Meng-Fei Sun, Ying-Li Zhu, Yi-Bo Wu, Yi-Da Xu, Shi-Xiao Peng, Chun Cui, Yan-Qin Shen
Human spinal cord injury (SCI) usually causes irreversible disability beneath the injured site due to poor neural regeneration. On the contrary, zebrafish show significant regenerative ability after SCI, thus is usually worked as an animal model for studying neuroregeneration. Most of the previous SCI studies focused on the local site of SCI, the supraspinal-derived signals were rarely mentioned. Here we showed that intradiencephalon injection of histamine (HA) inhibited the locomotor recovery in adult zebrafish post-SCI...
May 27, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28554806/blockade-of-atp-p2x7-receptor-enhances-ischiatic-nerve-regeneration-in-mice-following-a-crush-injury
#20
Tatianne Ribeiro, Júlia Teixeira Oliveira, Fernanda Martins Almeida, Marcelo Amorim Tomaz, Paulo A Melo, Suelen Adriani Marques, Geanne Matos de Andrade, Ana Maria Blanco Martinez
Preventing damage caused by nerve degeneration is a great challenge. There is a growing body of evidence implicating extracellular nucleotides and their P2 receptors in many pathophysiological mechanisms. In this work we aimed to investigate the effects of the administration of Brilliant Blue G (BBG) and Pyridoxalphosphate-6-azophenyl-2', 4'- disulphonic acid (PPADS), P2X7 and P2 non-selective receptor antagonists, respectively, on sciatic nerve regeneration. Four groups of mice that underwent nerve crush lesion were used: two control groups treated with vehicle (saline), a group treated with BBG and a group treated with PPADS during 28 days...
May 26, 2017: Brain Research
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