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https://www.readbyqxmd.com/read/28642362/regulation-of-rhoa-by-stat3-coordinates-glial-scar-formation
#1
Francois Renault-Mihara, Masahiko Mukaino, Munehisa Shinozaki, Hiromi Kumamaru, Satoshi Kawase, Matthieu Baudoux, Toshiki Ishibashi, Soya Kawabata, Yuichiro Nishiyama, Keiko Sugai, Kaori Yasutake, Seiji Okada, Masaya Nakamura, Hideyuki Okano
Understanding how the transcription factor signal transducer and activator of transcription-3 (STAT3) controls glial scar formation may have important clinical implications. We show that astrocytic STAT3 is associated with greater amounts of secreted MMP2, a crucial protease in scar formation. Moreover, we report that STAT3 inhibits the small GTPase RhoA and thereby controls actomyosin tonus, adhesion turnover, and migration of reactive astrocytes, as well as corralling of leukocytes in vitro. The inhibition of RhoA by STAT3 involves ezrin, the phosphorylation of which is reduced in STAT3-CKO astrocytes...
June 22, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28624361/low-intensity-rtms-has-sex-dependent-effects-on-the-local-response-of-glia-following-a-penetrating-cortical-stab-injury
#2
Darren Clarke, Marissa A Penrose, Alan R Harvey, Jennifer Rodger, Kristyn A Bates
Repetitive transcranial magnetic stimulation (rTMS), a non-invasive form of brain stimulation, has shown experimental and clinical efficacy in a range of neuromodulatory models, even when delivered at low intensity (i.e. subthreshold for action potential generation). After central nervous system (CNS) injury, studies suggest that reactive astrocytes and microglia can have detrimental but also beneficial effects; thus modulating glial activity, for example through application of rTMS, could potentially be a useful therapeutic tool following neurotrauma...
June 15, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28621171/boundary-cap-neural-crest-stem-cell-transplants-contribute-mts1-s100a4-expressing-cells-in-the-glial-scar
#3
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/28593744/thermosensitive-heparin-poloxamer-hydrogels-enhance-the-effects-of-gdnf-on-neuronal-circuit-remodelling-and-neuroprotection-after-spinal-cord-injury
#4
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/28571719/blockade-of-chondroitin-sulfate-proteoglycans-induced-axonal-growth-inhibition-by-lotus
#5
Yuji Kurihara, Yu Saito, Kohtaro Takei
Chondroitin sulfate proteoglycans (CSPGs) are axon growth inhibitors in the glial scar, and restrict axon regeneration following damage to the adult mammalian central nervous system. CSPGs have recently been identified as functional ligands for Nogo receptor-1 (NgR1), which is the common receptor for Nogo proteins, myelin-associated glycoprotein (MAG), oligodendrocyte myelin glycoprotein (OMgp) and B lymphocyte stimulator (BLyS). We have previously reported that through its binding to NgR1, lateral olfactory tract usher substance (LOTUS) suppresses Nogo, MAG, OMgp, and BLyS-induced axon growth inhibition...
May 30, 2017: Neuroscience
https://www.readbyqxmd.com/read/28562227/a-combinatorial-approach-to-induce-sensory-axon-regeneration-into-the-dorsal-root-avulsed-spinal-cord
#6
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/28554011/physical-chitosan-microhydrogels-as-scaffolds-for-spinal-cord-injury-restoration-and-axon-regeneration
#7
Jamila Chedly, Sylvia Soares, Alexandra Montembault, Ysander von Boxberg, Michèle Veron-Ravaille, Christine Mouffle, Marie-Noelle Benassy, Jacques Taxi, Laurent David, Fatiha Nothias
Recovery from traumatic spinal cord injury (SCI) usually fails due to a cascade of cellular and molecular events that compromise neural tissue reconstitution by giving rise to glial scarring and cavity formation. We designed a scaffold material for SCI treatment containing only chitosan and water as fragmented physical hydrogel suspension (Chitosan-FPHS), with defined degree of acetylation (DA), polymer concentration, and mean fragment size. Implantation of Chitosan-FPHS alone into rat spinal cord immediately after a bilateral dorsal hemisection promoted reconstitution of spinal tissue and vasculature, and diminished fibrous glial scarring: with astrocyte processes primarily oriented towards the lesion, the border between lesion site and intact tissue became permissive for regrowth of numerous axons into, and for some even beyond the lesion site...
May 19, 2017: Biomaterials
https://www.readbyqxmd.com/read/28544974/cetuximab-modified-collagen-scaffold-directs-neurogenesis-of-injury-activated-endogenous-neural-stem-cells-for-acute-spinal-cord-injury-repair
#8
Xing Li, Yannan Zhao, Shixiang Cheng, Sufang Han, Muya Shu, Bing Chen, Xuyi Chen, Fengwu Tang, Nuo Wang, Yue Tu, Bin Wang, Zhifeng Xiao, Sai Zhang, Jianwu Dai
Studies have shown that endogenous neural stem cells (NSCs) activated by spinal cord injury (SCI) primarily generate astrocytes to form glial scar. The NSCs do not differentiate into neurons because of the adverse microenvironment. In this study, we defined the activation timeline of endogenous NSCs in rats with severe SCI. These injury-activated NSCs then migrated into the lesion site. Cetuximab, an EGFR signaling antagonist, significantly increased neurogenesis in the lesion site. Meanwhile, implanting cetuximab modified linear ordered collagen scaffolds (LOCS) into SCI lesion sites in dogs resulted in neuronal regeneration, including neuronal differentiation, maturation, myelination, and synapse formation...
May 18, 2017: Biomaterials
https://www.readbyqxmd.com/read/28536635/the-regulatory-mechanisms-of-ng2-cspg4-expression
#9
REVIEW
Emmanuel Ampofo, Beate M Schmitt, Michael D Menger, Matthias W Laschke
Neuron-glial antigen 2 (NG2), also known as chondroitin sulphate proteoglycan 4 (CSPG4), is a surface type I transmembrane core proteoglycan that is crucially involved in cell survival, migration and angiogenesis. NG2 is frequently used as a marker for the identification and characterization of certain cell types, but little is known about the mechanisms regulating its expression. In this review, we provide evidence that the regulation of NG2 expression underlies inflammation and hypoxia and is mediated by methyltransferases, transcription factors, including Sp1, paired box (Pax) 3 and Egr-1, and the microRNA miR129-2...
2017: Cellular & Molecular Biology Letters
https://www.readbyqxmd.com/read/28512291/characterization-of-mechanically-matched-hydrogel-coatings-to-improve-the-biocompatibility-of-neural-implants
#10
Kevin C Spencer, Jay C Sy, Khalil B Ramadi, Ann M Graybiel, Robert Langer, Michael J Cima
Glial scar is a significant barrier to neural implant function. Micromotion between the implant and tissue is suspected to be a key driver of glial scar formation around neural implants. This study explores the ability of soft hydrogel coatings to modulate glial scar formation by reducing local strain. PEG hydrogels with controllable thickness and elastic moduli were formed on the surface of neural probes. These coatings significantly reduced the local strain resulting from micromotion around the implants. Coated implants were found to significantly reduce scarring in vivo, compared to hard implants of identical diameter...
May 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28501777/mir-140-bdnf-axis-regulates-normal-human-astrocyte-proliferation-and-lps-induced-il-6-and-tnf-%C3%AE-secretion
#11
Zhiming Tu, Yawei Li, Yuliang Dai, Lei Li, Guohua Lv, Ivan Chen, Bing Wang
Reactive astrocyte proliferation after spinal cord injury (SCI) contributes to glial scar formation that impedes axonal regeneration. The mechanisms underlying astrocyte proliferation upon injury remain partially understood. MicroRNAs (miRNAs) function as a major class of post-transcriptional gene expression regulators that participate in many biological processes. In this study, we focused on the functional role of miR-140 in normal human astrocyte (NHA) cell proliferation. Ectopic miR-140 expression significantly inhibited NHA cell viability and proliferation; miR-140 inhibition exerted the opposite function...
July 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28501505/sevoflurane-postconditioning-attenuates-reactive-astrogliosis-and-glial-scar-formation-after-ischemia-reperfusion-brain-injury
#12
Yong-Ming Zhu, Xue Gao, Yong Ni, Wei Li, Thomas A Kent, Shi-Gang Qiao, Chen Wang, Xiao-Xuan Xu, Hui-Ling Zhang
Cerebral ischemia leads to astrocyte's activation and glial scar formation. Glial scar can inhibit axonal regeneration during the recovery phase. It has demonstrated that sevoflurane has neuroprotective effects against ischemic stroke, but its effects on ischemia-induced formation of astrogliosis and glial scar are unknown. This study was designed to investigate the effect of sevoflurane postconditioning on astrogliosis and glial scar formation in ischemic stroke model both in vivo and in vitro. The results showed that 2...
May 10, 2017: Neuroscience
https://www.readbyqxmd.com/read/28486224/long-term-neuropathological-changes-associated-with-cerebral-palsy-in-a-nonhuman-primate-model-of-hypoxic-ischemic-encephalopathy
#13
Ryan M McAdams, Bobbi Fleiss, Christopher Traudt, Leslie Schwendimann, Jessica M Snyder, Robin L Haynes, Niranjana Natarajan, Pierre Gressens, Sandra E Juul
BACKGROUND: Cerebral palsy (CP) is the most common motor disability in childhood, with a worldwide prevalence of 1.5-4/1,000 live births. Hypoxic-ischemic encephalopathy (HIE) contributes to the burden of CP, but the long-term neuropathological findings of this association remain limited. METHODOLOGY: Thirty-four term Macaca nemestrina macaques were included in this long-term neuropathological study: 9 control animals delivered by cesarean section and 25 animals with perinatal asphyxia delivered by cesarean section after 15-18 min of umbilical cord occlusion (UCO)...
May 10, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28484372/potential-involvement-of-snail-members-in-neuronal-survival-and-astrocytic-migration-during-the-gecko-spinal-cord-regeneration
#14
Tingting Shen, Yingjie Wang, Qing Zhang, Xue Bai, Sumei Wei, Xuejie Zhang, Wenjuan Wang, Ying Yuan, Yan Liu, Mei Liu, Xiaosong Gu, Yongjun Wang
Certain regenerative vertebrates such as fish, amphibians and reptiles are capable of regenerating spinal cord after injury. Most neurons of spinal cord will survive from the injury and regrow axons to repair circuits with an absence of glial scar formation. However, the underlying mechanisms of neuronal anti-apoptosis and glia-related responses have not been fully clarified during the regenerative process. Gecko has becoming an inspiring model to address spinal cord regeneration in amniotes. In the present study, we investigated the regulatory roles of Snail family members, the important transcriptional factors involved in both triggering of the cell migration and cell survival, during the spontaneous spinal cord regeneration...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28477140/chondroitin-sulfate-impairs-neural-stem-cell-migration-through-rock-activation
#15
Layla T Galindo, Mayara T V V Mundim, Agnes S Pinto, Gabrielly M D Chiarantin, Maíra E S Almeida, Marcelo L Lamers, Alan R Horwitz, Marinilce F Santos, Marimelia Porcionatto
Brain injuries such as trauma and stroke lead to glial scar formation by reactive astrocytes which produce and secret axonal outgrowth inhibitors. Chondroitin sulfate proteoglycans (CSPG) constitute a well-known class of extracellular matrix molecules produced at the glial scar and cause growth cone collapse. The CSPG glycosaminoglycan side chains composed of chondroitin sulfate (CS) are responsible for its inhibitory activity on neurite outgrowth and are dependent on RhoA activation. Here, we hypothesize that CSPG also impairs neural stem cell migration inhibiting their penetration into an injury site...
May 5, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28473192/characterization-of-a-cerebral-palsy-like-model-in-rats-analysis-of-gait-pattern-and-of-brain-and-spinal-cord-motor-areas
#16
Adriana Souza Dos Santos, Wellington de Almeida, Bruno Popik, Bruno Marques Sbardelotto, Márcia Miranda Torrejais, Marcelo Alves de Souza, Lígia Aline Centenaro
In an attempt to propose an animal model that reproduces in rats the phenotype of cerebral palsy, this study evaluated the effects of maternal exposure to bacterial endotoxin associated with perinatal asphyxia and sensorimotor restriction on gait pattern, brain and spinal cord morphology. Two experimental groups were used: Control Group (CTG) - offspring of rats injected with saline during pregnancy and Cerebral Palsy Group (CPG) - offspring of rats injected with lipopolysaccharide during pregnancy, submitted to perinatal asphyxia and sensorimotor restriction for 30days...
August 2017: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/28469665/mechanisms-responsible-for-the-inhibitory-effects-of-epothilone-b-on-scar-formation-after-spinal-cord-injury
#17
Wei Zhao, Yong Chai, Yun Hou, Da-Wei Wang, Jian-Qiang Xing, Cheng Yang, Qing-Min Fang
Scar formation after spinal cord injury is regarded as an obstacle to axonal regeneration and functional recovery. Epothilone B provides moderate microtubule stabilization and is mainly used for anti-tumor therapy. It also reduces scar tissue formation and promotes axonal regeneration after spinal cord injury. The aim of the present study was to investigate the effect and mechanism of the microtubule-stabilizing reagent epothilone B in decreasing fibrotic scarring through its action on pericytes after spinal cord injury...
March 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28456012/neuregulin-1-positively-modulates-glial-response-and-improves-neurological-recovery-following-traumatic-spinal-cord-injury
#18
Arsalan Alizadeh, Scott M Dyck, Hardeep Kataria, Ghazaleh M Shahriary, Dung H Nguyen, Kallivalappil T Santhosh, Soheila Karimi-Abdolrezaee
Spinal cord injury (SCI) results in glial activation and neuroinflammation, which play pivotal roles in the secondary injury mechanisms with both pro- and antiregeneration effects. Presently, little is known about the endogenous molecular mechanisms that regulate glial functions in the injured spinal cord. We previously reported that the expression of neuregulin-1 (Nrg-1) is acutely and chronically declined following traumatic SCI. Here, we investigated the potential ramifications of Nrg-1 dysregulation on glial and immune cell reactivity following SCI...
April 29, 2017: Glia
https://www.readbyqxmd.com/read/28453954/local-delivery-of-chondroitinase-abc-with-or-without-stromal-cell-derived-factor-1%C3%AE-promotes-functional-repair-in-the-injured-rat-spinal-cord
#19
Malgosia M Pakulska, Charles H Tator, Molly S Shoichet
Traumatic spinal cord injury (SCI) is a devastating event for which functional recovery remains elusive. Due to the complex nature of SCI pathology, a combination treatment strategy will likely be required for success. We hypothesized that tissue and functional repair would be achieved in a rat model of impact-compression SCI by combining degradation of the glial scar, using chondroitinase ABC (ChABC), with recruitment of endogenous neural precursor cells (NPCs), using stromal cell-derived factor 1α (SDF)...
July 2017: Biomaterials
https://www.readbyqxmd.com/read/28447605/traumatic-spinal-cord-injury
#20
REVIEW
Christopher S Ahuja, Jefferson R Wilson, Satoshi Nori, Mark R N Kotter, Claudia Druschel, Armin Curt, Michael G Fehlings
Traumatic spinal cord injury (SCI) has devastating consequences for the physical, social and vocational well-being of patients. The demographic of SCIs is shifting such that an increasing proportion of older individuals are being affected. Pathophysiologically, the initial mechanical trauma (the primary injury) permeabilizes neurons and glia and initiates a secondary injury cascade that leads to progressive cell death and spinal cord damage over the subsequent weeks. Over time, the lesion remodels and is composed of cystic cavitations and a glial scar, both of which potently inhibit regeneration...
April 27, 2017: Nature Reviews. Disease Primers
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