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https://www.readbyqxmd.com/read/28735026/regulated-viral-bdnf-delivery-in-combination-with-schwann-cells-promotes-axonal-regeneration-through-capillary-alginate-hydrogels-after-spinal-cord-injury
#1
Shengwen Liu, Beatrice Sandner, Thomas Schackel, LaShae Nicholson, Abdelwahed Chtarto, Liliane Tenenbaum, Radhika Puttagunta, Rainer Müller, Norbert Weidner, Armin Blesch
Grafting of cell-seeded alginate capillary hydrogels into a spinal cord lesion site provides an axonal bridge while physically directing regenerating axonal growth in a linear pattern. However, without an additional growth stimulus, bridging axons fail to extend into the distal host spinal cord. Here we examined whether a combinatory strategy would support regeneration of descending axons across a cervical (C5) lateral hemisection lesion in the rat spinal cord. Following spinal cord transections, Schwann cell (SC)-seeded alginate hydrogels were grafted to the lesion site and AAV5 expressing brain-derived neurotrophic factor (BDNF) under control of a tetracycline-regulated promoter was injected caudally...
July 19, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28726548/wnt-yap-interactions-during-neural-tissue-patterning-of-human-induced-pluripotent-stem-cells
#2
Julie Bejoy, Liqing Song, Yi Zhou, Yan Li
Human induced pluripotent stem cells (hiPSCs) have special ability to self-assemble into neural spheroids or mini-brain like structures. During the self-assembly process, Wnt signaling plays an important role in regional patterning and establishing positional identity of hiPSC-derived neural progenitors. Recently, the role of Wnt signaling in regulating Yes-associated protein (YAP) expression (nuclear or cytoplasmic), the pivotal regulator during organ growth and tissue generation, has attracted increasing interests...
July 20, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28726160/complete-canine-spinal-cord-transection-model-a-large-animal-model-for-the-translational-research-of-spinal-cord-regeneration
#3
Sufang Han, Xing Li, Zhifeng Xiao, Jianwu Dai
No abstract text is available yet for this article.
July 18, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/28722682/activation-of-the-nrf2-are-signaling-pathway-by-probucol-contributes-to-inhibiting-inflammation-and-neuronal-apoptosis-after-spinal-cord-injury
#4
Zipeng Zhou, Chang Liu, Shurui Chen, Haosen Zhao, Kang Zhou, Wei Wang, Yajiang Yuan, Zhuo Li, Yue Guo, Zhaoliang Shen, Xifan Mei
The nuclear erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway plays an essential role in the cellular antioxidant and anti-inflammatory responses. Spinal cord injury (SCI) results in a massive release of inflammatory factors and free radicals, which seriously compromise nerve recovery and axon regeneration. In this study, we examined the efficacy of probucol on anti-inflammatory responses and functional recovery after SCI by activating the Nrf2/ARE signaling pathway. We also investigated the mechanism by which inflammation is inhibited in this process...
July 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28714852/the-small-molecule-mimetic-agonist-trimebutine-of-adhesion-molecule-l1-contributes-to-functional-recovery-after-spinal-cord-injury-in-mice
#5
Junping Xu, Chengliang Hu, Qiong Jiang, Hongchao Pan, Huifan Shen, Melitta Schachner
Curing spinal cord injury (SCI) in mammals is a daunting task because of the lack of permissive mechanisms and strong inhibitory responses at and around the lesion. The neural cell adhesion molecule L1CAM (L1) has been shown to favor axonal regrowth and enhance neuronal survival and synaptic plasticity, and thus constitutes a viable target to promote regeneration after SCI. Since delivery of full-length L1 or its extracellular domain could encounter difficulties in translation to therapy in humans, we have identified several small organic compounds that bind to L1 and stimulate neuronal survival, neuronal migration, and neurite outgrowth in an L1-dependent manner...
July 14, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28709993/intracellular-calcium-release-through-ip3r-or-ryr-contributes-to-secondary-axonal-degeneration
#6
Ben C Orem, Nicolas Pelisch, Joshua Williams, Jacqueline M Nally, David P Stirling
Severed CNS axons often retract or dieback away from the injury site and fail to regenerate. The precise mechanisms underlying acute axonal dieback and secondary axonal degeneration remain poorly understood. Here we investigate the role of Ca(2+) store mediated intra-axonal Ca(2+) release in acute axonal dieback and secondary axonal degeneration. To differentiate between primary (directly transected) and "bystander" axonal injury (axons spared by the initial injury but then succumb to secondary degeneration) in real-time we use our previously published highly focal laser-induced spinal cord injury (LiSCI) ex vivo model...
July 12, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28698718/the-holy-grail-of-orthopedic-surgery-mesenchymal-stem-cells-their-current-uses-and-potential-applications
#7
REVIEW
Roberto Berebichez-Fridman, Ricardo Gómez-García, Julio Granados-Montiel, Enrique Berebichez-Fastlicht, Anell Olivos-Meza, Julio Granados, Cristina Velasquillo, Clemente Ibarra
Only select tissues and organs are able to spontaneously regenerate after disease or trauma, and this regenerative capacity diminishes over time. Human stem cell research explores therapeutic regenerative approaches to treat various conditions. Mesenchymal stem cells (MSCs) are derived from adult stem cells; they are multipotent and exert anti-inflammatory and immunomodulatory effects. They can differentiate into multiple cell types of the mesenchyme, for example, endothelial cells, osteoblasts, chondrocytes, fibroblasts, tenocytes, vascular smooth muscle cells, and sarcomere muscular cells...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28695279/epigenetic-regulation-of-neural-stem-cell-differentiation-towards-spinal-cord-regeneration
#8
REVIEW
Tomonori Kameda, Takuya Imamura, Kinichi Nakashima
Severe spinal cord injury (SCI) leads to almost complete neural cell loss at the injured site, causing the irreversible disruption of neuronal circuits. The transplantation of neural stem or precursor cells (NS/PCs) has been regarded as potentially effective for SCI treatment because NS/PCs can compensate for the injured sites by differentiating into neurons and glial cells (astrocytes and oligodendrocytes). An understanding of the molecular mechanisms that regulate the proliferation, fate specification and maturation of NS/PCs and their progeny would facilitate the establishment of better therapeutic strategies for regeneration after SCI...
July 10, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28694236/fibrin-functionalization-with-synthetic-adhesive-ligands-interacting-with-%C3%AE-6%C3%AE-1-integrin-receptor-enhance-neurite-outgrowth-of-embryonic-stem-cell-derived-neural-stem-progenitors
#9
Joana Silva, Ana R Bento, Daniela Barros, Tiago L Laundos, Susana R Sousa, Pedro Quelhas, Mónica M Sousa, Ana P Pêgo, Isabel F Amaral
To enhance fibrin hydrogel affinity towards pluripotent stem cell-derived neural stem/progenitor cells (NSPCs) and its capacity to support NSPC migration and neurite extension, we explored the tethering of synthetic peptides engaging integrin α6β1, a cell receptor enriched in NSPCs. Six α6β1 integrin ligands were tested for their ability to support integrin α6β1-mediated adhesion of embryonic stem cell-derived NSPCs (ES-NSPs) and sustain ES-NSPC viability, migration, and neuronal differentiation. Due to their better performance, peptides T1, HYD1, and A5G81 were immobilized into fibrin and functionalized gels characterized in terms of peptide binding efficiency, structure and viscoelastic properties...
July 7, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28691015/-mtor-signaling-pathway-a-potential-target-of-curcumin-in-the-treatment-of-spinal-cord-injury
#10
REVIEW
Jingquan Lin, Xue Huo, Xuehong Liu
The purpose of this review is to discuss the possibility of the treatment of spinal cord injury (SCI) with curcumin via regulating the mTOR signaling pathway, which may provide another strong support for curcumin to be a promising medicine applied to the treatment of SCI. Curcumin is termed as a multifunctional targeting therapy drug that regulates the mTOR signaling pathway in the treatment of numerous diseases. Previous research has already revealed that mTOR signaling pathway plays a vital role in prognosis, which involves the axon regeneration and autophagy...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28678209/nanofiber-scaffolds-as-drug-delivery-systems-to-bridge-spinal-cord-injury
#11
REVIEW
Angela Faccendini, Barbara Vigani, Silvia Rossi, Giuseppina Sandri, Maria Cristina Bonferoni, Carla Marcella Caramella, Franca Ferrari
The complex pathophysiology of spinal cord injury (SCI) may explain the current lack of an effective therapeutic approach for the regeneration of damaged neuronal cells and the recovery of motor functions. A primary mechanical injury in the spinal cord triggers a cascade of secondary events, which are involved in SCI instauration and progression. The aim of the present review is to provide an overview of the therapeutic neuro-protective and neuro-regenerative approaches, which involve the use of nanofibers as local drug delivery systems...
July 5, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28673884/serum-concentrations-of-fibrinogen-in-patients-with-spinal-cord-injury-and-its-relationship-with-neurological-function
#12
Jia-Ming Liu, Min Lan, Yang Zhou, Xuan-Yin Chen, Shan-Hu Huang, Zhi-Li Liu
BACKGROUND: Many studies have focused on the axons regeneration after spinal cord injury (SCI). And fibrinogen was reported to be an inhibitory factor for axons regeneration. However, most of these studies were based on animal experiments and in vitro trials. Few studies reported serum concentrations of fibrinogen in patients with SCI. OBJECTIVE: To investigate the circulating serum concentrations of fibrinogen in patients with SCI, and to determine the relationship between fibrinogen concentrations and patients' neurological function...
June 30, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28666378/mtor-signaling-pathway-differently-regulates-central-and-peripheral-axon-regeneration
#13
Ziwei Huang, Weihua Wang, Jinjin Ma, Bin Li, Jianquan Chen, Huilin Yang
Numerous studies have shown that the intrinsic axonal regenerative capacity of neurons differs between the peripheral and central nervous systems (CNSs). However, the molecular mechanisms controlling intrinsic axonal regenerative capacity are unclear. A better understanding of these mechanisms should aid in the development of effective therapeutic strategies for traumatic nervous system injury, including spinal cord injury. Here, we found that blocking mammalian target of rapamycin (mTOR) activity dramatically diminished axonal regrowth from embryonic cortical neurons...
June 28, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28661610/-durable-persistence-of-a-biocompatible-foreign-body-in-a-vertebral-channel-in-open-penetrating-trauma-of-a-spinal-cord-clinico-experimental-and-pathomorphological-peculiarities
#14
V I Tsymbalyuk, V V Medvedyev, V M Semenova, N Ya Grydina, Yu Ya Yaminskyi, Yu Yu Senchyk, N G Draguntsova, O A Rybachuk, S M Dychko, T I Petriv
Simulation model of open penetrating wound of a spinal cord (SC) with its durable com- pression by biocompatible foreign body, was tasted. Experimental animals - mature male rats (inbred line, descendent from a Wistar breed); the trauma simulation model - a left- sided transsection of the SC half on the Txi level; experimental groups: the main (a SC trau- ma + homotopic implantation of microporous hydrogel fragment - foreign body [n=10]), groups of comparison (the SC trauma [n=16]; the SC trauma + homotopic implantation of chemically identical analogue of hydrogel - NeuroGelTM [n=20])...
August 2016: Klinichna Khirurhiia
https://www.readbyqxmd.com/read/28659490/rhoa-inhibitor-treatment-at-acute-phase-of-spinal-cord-injury-may-induce-neurite-outgrowth-and-synaptogenesis
#15
Stephanie Devaux, Dasa Cizkova, Khalil Mallah, Melodie-Anne Karnoub, Zahra Laouby, Firas Kobeissy, Juraj Blasko, Serge Nataf, Laurent Pays, Celine Meriaux, Isabelle Fournier, Michel Salzet
The therapeutic use of RhoA inhibitors (RhoAi) has been experimentally tested in spinal cord injury (SCI). In order to decipher the underlying molecular mechanisms involved in such a process, an in vitro neuroproteomic-systems biology platform was developed in which the pan-proteomic profile of the dorsal root ganglia (DRG) cell line ND7/23 DRG was assessed in a large array of culture conditions using RhoAi and/or conditioned media obtained from SCI ex-vivo derived spinal cord slices. A fine mapping of the spatio-temporal molecular events of the RhoAi treatment in SCI was performed...
June 28, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28658046/induction-of-endogenous-neural-stem-cells-by-extracorporeal-shock-waves-after-spinal-cord-injury
#16
Dong-Chul Shin, Kee-Yong Ha, Young-Hoon Kim, Jang-Woon Kim, Yoo-Kyung Cho, Sang-Il Kim
STUDY DESIGN: Animal experimental study OBJECTIVES.: The purpose of this study is to investigate the effects of extracorporeal shock waves (ESWs) on endogenous neural stem cells (NSCs) proliferation after spinal cord injury (SCI). SUMMARY OF BACKGROUND DATA: Exogenous stem cell transplantation for SCI still has many limitations to be addressed such as ideal cell sources, timing of transplantation, and fate of the transplanted cells. Moreover, the efficacy is another issue due to a peculiar pathologic condition in the chronic phase of SCI...
June 27, 2017: Spine
https://www.readbyqxmd.com/read/28657487/delayed-spinal-cord-brachial-plexus-reconnection-after-c7-ventral-root-avulsion-the-effect-of-reinnervating-motoneurons-rescued-by-riluzole-treatment
#17
Balázs Gloviczki, Dénes G Török, Gábor Márton, László Gál, Tamás Bodzay, Sándor Pintér, Antal Nógrádi
Ventral root avulsion induces dramatic loss of the affected spinal cord motoneurons. The neuroprotective effect of riluzole has been previously proven on the injured motoneurons: the vast majority of them can be rescued even when they have no possibility to regenerate their axons. In this study the number of injured motoneurons rescued by riluzole treatment and their capacity to reinnervate the denervated forelimb muscles was investigated. Surgical reconnection with a peripheral nerve graft between the affected spinal cord segment and the C7 spinal nerve was established immediately or with 1- and 3-week delay after avulsion...
August 1, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28656221/effect-of-transplantation-of-olfactory-ensheathing-cell-conditioned-medium-induced-bone-marrow-stromal-cells-on-rats-with-spinal-cord-injury
#18
Linjie Feng, Hongquan Gan, Wenguo Zhao, Yingjie Liu
Spinal cord injury is a serious threat to human health and various techniques have been deployed to ameliorate or cure its effects. Stem cells transplantation is one of the promising methods. The primary aim of the present study was to investigate the effect of the transplantation of olfactory ensheathing cell (OEC) conditioned medium‑induced bone marrow stromal cells (BMSCs) on spinal cord injury. Rat spinal cord compression injury animal models were generated, and the rats divided into the following three groups: Group A, (control) Dulbecco's modified Eagle's medium‑treated group; group B, normal BMSC‑treated group; group C, OEC conditioned medium‑induced BMSC‑treated group...
August 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28654038/rewiring-neuronal-circuits-a-new-method-for-fast-neurite-extension-and-functional-neuronal-connection
#19
Margaret H Magdesian, Madeleine Anthonisen, G Monserratt Lopez-Ayon, Xue Ying Chua, Matthew Rigby, Peter Grütter
Brain and spinal cord injury may lead to permanent disability and death because it is still not possible to regenerate neurons over long distances and accurately reconnect them with an appropriate target. Here a procedure is described to rapidly initiate, elongate, and precisely connect new functional neuronal circuits over long distances. The extension rates achieved reach over 1.2 mm/h, 30-60 times faster than the in vivo rates of the fastest growing axons from the peripheral nervous system (0.02 to 0.04 mm/h)(28) and 10 times faster than previously reported for the same neuronal type at an earlier stage of development(4)...
June 13, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28646336/nogo-a-antibodies-enhance-axonal-repair-and-remyelination-in-neuro-inflammatory-and-demyelinating-pathology
#20
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
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