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spinal cord regeneration

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https://www.readbyqxmd.com/read/28088077/rhoa-knockdown-by-cationic-amphiphilic-copolymer-sirhoa-polyplexes-enhances-axonal-regeneration-in-rat-spinal-cord-injury-model
#1
So-Jung Gwak, Christian Macks, Da Un Jeong, Mark Kindy, Michael Lynn, Ken Webb, Jeoung Soo Lee
Spinal cord injury (SCI) results in permanent loss of motor and sensory function due to developmentally-related and injured-induced changes in the extrinsic microenvironment and intrinsic neuronal biochemistry that limit plasticity and axonal regeneration. Our long term goal is to develop cationic, amphiphilic copolymers (poly (lactide-co-glycolide)-g-polyethylenimine, PgP) for combinatorial delivery of therapeutic nucleic acids (TNAs) and drugs targeting these different barriers. In this study, we evaluated the ability of PgP to deliver siRNA targeting RhoA, a critical signaling pathway activated by multiple extracellular inhibitors of axonal regeneration...
January 3, 2017: Biomaterials
https://www.readbyqxmd.com/read/28075461/resistance-of-interleukin-6-to-the-extracellular-inhibitory-environment-promotes-axonal-regeneration-and-functional-recovery-following-spinal-cord-injury
#2
Gang Yang, Wen-Yuan Tang
Interleukin-6 (IL)-6 was originally discovered as a factor that contributes to the secondary pathological and inflammatory response in the central nervous system (CNS) following injury. However, accumulating evidence suggests that IL-6 is also involved in functional and structural recovery following CNS injury by promoting axonal sprou-ting. This suggests a potential dual role of IL-6 in CNS injury. However, the definitive function of IL-6 in neural injury and the corresponding underlying mechanisms are still topics of controversy...
January 5, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28073086/human-neural-progenitors-derived-from-integration-free-ipscs-for-sci-therapy
#3
Ying Liu, Yiyan Zheng, Shenglan Li, Haipeng Xue, Karl Schmitt, Georgene W Hergenroeder, Jiaqian Wu, Yuanyuan Zhang, Dong H Kim, Qilin Cao
As a potentially unlimited autologous cell source, patient induced pluripotent stem cells (iPSCs) provide great capability for tissue regeneration, particularly in spinal cord injury (SCI). However, despite significant progress made in translation of iPSC-derived neural progenitor cells (NPCs) to clinical settings, a few hurdles remain. Among them, non-invasive approach to obtain source cells in a timely manner, safer integration-free delivery of reprogramming factors, and purification of NPCs before transplantation are top priorities to overcome...
January 5, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28069919/calpain-mediated-proteolysis-of-talin-and-fak-regulates-adhesion-dynamics-necessary-for-axon-guidance
#4
Patrick C Kerstein, Kevin M Patel, Timothy M Gomez
: Guidance of axons to their proper synaptic target sites requires spatially and temporally precise modulation of biochemical signals within growth cones. Ionic calcium (Ca(2+)) is an essential signal for axon guidance that mediates opposing affects on growth cone motility. The diverse effects of Ca(2+) arise from the precise localization of Ca(2+) signals into microdomains containing specific Ca(2+) effectors. For example, differences in the mechanical and chemical composition of the underlying substrata elicit local Ca(2+) signals within growth cone filopodia that regulate axon guidance through activation of the protease calpain...
January 9, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28069497/a-modified-collagen-scaffold-facilitates-endogenous-neurogenesis-for-acute-spinal-cord-injury-repair
#5
Caixia Fan, Xing Li, Zhifeng Xiao, Yannan Zhao, Hui Liang, Bin Wang, Sufang Han, Xiaoran Li, Bai Xu, Nuo Wang, Sumei Liu, Weiwei Xue, Jianwu Dai
Due to irreversible neuronal loss and glial scar deposition, spinal cord injury (SCI) ultimately results in permanent neurological dysfunction. Neuronal regeneration of neural stem cells (NSCs) residing in the spinal cord could be an ideal strategy for replenishing the lost neurons and restore function. However, many myelin-associated inhibitors in the SCI microenvironment limit the ability of spinal cord NSCs to regenerate into neurons. Here, a linearly ordered collagen scaffold was used to prevent scar deposition, guide nerve regeneration and carry drugs to neutralize the inhibitory molecules...
January 6, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28068836/electro-acupuncture-modulates-l1-adhesion-molecule-expression-after-mouse-spinal-cord-injury
#6
Zhe Wei, Yan Wang, Weijiang Zhao, Melitta Schachner
Spinal cord injury is a devastating neurological disease in desperate need of a cure. We have previously shown that overexpression of the adhesion molecule L1 contributes to locomotor recovery after injury and were therefore interested in how electro-acupuncture would influence the expression of this molecule. Here, we investigated the effects of electro-acupuncture at "Jiaji" points (EX-B2), newly established by us, in young adult mice to determine whether improved recovery via electro-acupuncture could be due to enhanced L1 expression...
January 9, 2017: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/28067245/effect-of-hierarchically-aligned-fibrin-hydrogel-in-regeneration-of-spinal-cord-injury-demonstrated-by-tractography-a-pilot-study
#7
Zhenxia Zhang, Shenglian Yao, Sheng Xie, Xiumei Wang, Feiyan Chang, Jie Luo, Jingming Wang, Jun Fu
Some studies have reported that scaffold or cell-based transplantation may improve functional recovery following SCI, but no imaging information regarding regeneration has been provided to date. This study used tractography to show the regenerating process induced by a new biomaterial-aligned fibrin hydrogel (AFG). A total of eight canines subjected to SCI procedures were assigned to the control or the AFG group. AFG was implanted into the SCI lesion immediately after injury in 5 canines. A follow-up was performed at 12 weeks to evaluate the therapeutic effect including the hindlimb functional recovery, anisotropy and continuity of fibers on tractography...
January 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28059863/spatiotemporal-expression-of-ski-after-rat-spinal-cord-injury
#8
Kaisheng Zhou, Wei Nan, Dongliang Feng, Zhigang Yi, Yandong Zhu, Zaiyun Long, Sen Li, Haihong Zhang, Yamin Wu
Ski is an evolutionarily conserved protein and widely participates in the regulation of various pathological and physiological processes such as wound healing, liver regeneration, development of the embryonic nervous system, muscle differentiation, and progression of many kinds of tumors. However, the distribution and function of Ski in central nervous system lesion and disease remain unclear. In this study, we investigated the spatiotemporal expression of Ski in a spinal cord injury (SCI) model in adult rats...
January 2, 2017: Neuroreport
https://www.readbyqxmd.com/read/28057043/rapid-healing-of-a-patient-with-dramatic-subacute-combined-degeneration-of-spinal-cord-a-case-report
#9
Florian C Roessler, Stephanie Wolff
BACKGROUND: Prevalence of cobalamin deficiency is high especially in older patients and an immediate therapy start is necessary to prevent irreversible neurological damages. Unfortunately, the diagnosis of cobalamin deficiency is difficult and at present, there is no consensus for diagnosis of this deficiency. Therefore, we aim to elucidate a meaningful diagnostic pathway by a case report with an initially misleading medical history. CASE PRESENTATION: A 57 year-old Caucasian man suffering from dramatic myelosis of the cervical posterior columns...
January 3, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/28056790/immunization-with-neural-derived-peptides-plus-scar-removal-induces-a-permissive-microenvironment-and-improves-locomotor-recovery-after-chronic-spinal-cord-injury
#10
Roxana Rodríguez-Barrera, Adrián Flores-Romero, Ana María Fernández-Presas, Elisa García-Vences, Raúl Silva-García, Mina Konigsberg, Liliana Blancas-Espinoza, Vinnitsa Buzoianu-Anguiano, Karla Soria-Zavala, Paola Suárez-Meade, Antonio Ibarra
BACKGROUND: Immunization with neural derived peptides (INDP) as well as scar removal-separately-have shown to induce morphological and functional improvement after spinal cord injury (SCI). In the present study, we compared the effect of INDP alone versus INDP with scar removal on motor recovery, regeneration-associated and cytokine gene expression, and axonal regeneration after chronic SCI. Scar removal was conducted through a single incision with a double-bladed scalpel along the stump, and scar renewal was halted by adding α,α'-dipyridyl...
January 5, 2017: BMC Neuroscience
https://www.readbyqxmd.com/read/28036084/preferential-enhancement-of-sensory-and-motor-axon-regeneration-by-combining-extracellular-matrix-components-with-neurotrophic-factors
#11
Daniel Santos, Francisco González-Pérez, Guido Giudetti, Silvestro Micera, Esther Udina, Jaume Del Valle, Xavier Navarro
After peripheral nerve injury, motor and sensory axons are able to regenerate but inaccuracy of target reinnervation leads to poor functional recovery. Extracellular matrix (ECM) components and neurotrophic factors (NTFs) exert their effect on different neuronal populations creating a suitable environment to promote axonal growth. Here, we assessed in vitro and in vivo the selective effects of combining different ECM components with NTFs on motor and sensory axons regeneration and target reinnervation. Organotypic cultures with collagen, laminin and nerve growth factor (NGF)/neurotrophin-3 (NT3) or collagen, fibronectin and brain-derived neurotrophic factor (BDNF) selectively enhanced sensory neurite outgrowth of DRG neurons and motor neurite outgrowth from spinal cord slices respectively...
December 29, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28032120/inhibition-of-poly-adp-ribosylation-fails-to-increase-axonal-regeneration-or-improve-functional-recovery-after-adult-mammalian-cns-injury
#12
Xingxing Wang, Yuichi Sekine, Alexandra B Byrne, William B J Cafferty, Marc Hammarlund, Stephen M Strittmatter
After traumatic damage of the brain or spinal cord, many surviving neurons are disconnected, and recovery of function is limited by poor axon regeneration. Recent data have suggested that poly ADP-ribosylation plays a role in limiting axonal regrowth such that inhibition of poly (ADP-ribose) polymerase (PARP) may have therapeutic efficacy for neurological recovery after trauma. Here, we tested systemic administration of the PARP inhibitor, veliparib, and showed effective suppression of PARylation in the mouse CNS...
November 2016: ENeuro
https://www.readbyqxmd.com/read/28029610/impact-of-local-injection-of-brain-derived-neurotrophic-factor-expressing-mesenchymal-stromal-cells-mscs-combined-with-intravenous-msc-delivery-in-a-canine-model-of-chronic-spinal-cord-injury
#13
Seung Hoon Lee, Yongsun Kim, Daeun Rhew, Ahyoung Kim, Kwang Rae Jo, Yongseok Yoon, Kyeung Uk Choi, Taeseong Jung, Wan Hee Kim, Oh-Kyeong Kweon
BACKGROUND AIMS: The microenvironment of the chronically injured spinal cord does not allow for axonal regeneration due to glial scarring. To ameliorate this, several therapeutic strategies have been used. We investigated whether combined transplantation of chondroitinase ABC (chABC) and mesenchymal stromal cells (MSCs) genetically modified to secrete brain-derived neurotrophic factor (BDNF) with intravenous (IV) administration of MSCs can promote recovery of hindlimb function after chronic spinal cord injury (SCI)...
October 28, 2016: Cytotherapy
https://www.readbyqxmd.com/read/28025113/selecting-optimal-combinations-of-transcription-factors-to-promote-axon-regeneration-why-mechanisms-matter
#14
REVIEW
Ishwariya Venkatesh, Murray G Blackmore
Recovery from injuries to the central nervous system, including spinal cord injury, is constrained in part by the intrinsically low ability of many CNS neurons to mount an effective regenerative growth response. To improve outcomes, it is essential to understand and ultimately reverse these neuron-intrinsic constraints. Genetic manipulation of key transcription factors (TFs), which act to orchestrate production of multiple regeneration-associated genes, has emerged as a promising strategy. It is likely that no single TF will be sufficient to fully restore neuron-intrinsic growth potential, and that multiple, functionally interacting factors will be needed...
December 23, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/28009347/an-integrin-approach-to-axon-regeneration
#15
J W Fawcett
Axon regeneration in the CNS is blocked by inhibitory molecules in the environment and by a developmental loss of regenerative potential in CNS axons. Axon growth is a specialized form of cell migration, and for any cell to migrate there must be an adhesion molecule at the growth tip that recognizes a ligand in the environment, and which is linked to signaling and cytoskeletal mechanisms. The reasons for this loss of regenerative ability in CNS axons are several, but important contributors are the developmental loss of integrins that recognize ligands in the mature CNS environment, and selective trafficking of integrins and other molecules to exclude them from axons and direct them to dendrites...
December 23, 2016: Eye
https://www.readbyqxmd.com/read/28007647/rewiring-the-spinal-cord-direct-and-indirect-strategies
#16
REVIEW
Maria Teresa Dell'Anno, Stephen M Strittmatter
Spinal cord injury is currently incurable. Treatment is limited to minimizing secondary complications and maximizing residual function by rehabilitation. Neurologic recovery is prevented by the poor intrinsic regenerative capacity of neurons in the adult central nervous system and by the presence of growth inhibitors in the adult brain and spinal cord. Here we identify three approaches to rewire the spinal cord after injury: axonal regeneration (direct endogenous reconnection), axonal sprouting (indirect endogenous reconnection) and neural stem cell transplantation (indirect exogenous reconnection)...
December 19, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/28003748/manipulation-of-schwann-cell-migration-across-the-astrocyte-boundary-by-polysialyltransferase-loaded-superparamagnetic-nanoparticles-under-magnetic-field
#17
Bing Xia, Liangliang Huang, Lei Zhu, Zhongyang Liu, Teng Ma, Shu Zhu, Jinghui Huang, Zhuojing Luo
Schwann cell (SC) transplantation is an attractive strategy for spinal cord injury (SCI). However, the efficacy of SC transplantation has been limited by the poor migratory ability of SCs in the astrocyte-rich central nervous system (CNS) environment and the inability to intermingle with the host astrocyte. In this study, we first magnetofected SCs by polysialyltransferase-functionalized superparamagnetic iron oxide nanoparticles (PST/SPIONs) to induce overexpression of polysialylation of neural cell adhesion molecule (PSA-NCAM) to enhance SC migration ability, before manipulating the direction of SC migration with the assistance of an applied magnetic field (MF)...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28001757/photobiomodulation-triple-treatment-in-peripheral-nerve-injury-nerve-and-muscle-response
#18
Mira M Mandelbaum-Livnat, Mara Almog, Moshe Nissan, Emmanuel Loeb, Yuval Shapira, Shimon Rochkind
BACKGROUND: Muscle preservation or decrease in muscle degeneration and progressive atrophy are major challenges in patients with severe peripheral nerve injury (PNI). Considerable interest exists in the potential therapeutic value of laser phototherapy (photobiomodulation) for restoring denervated muscle atrophy and for enhancing regeneration of severely injured peripheral nerves. As previously published, the laser phototherapy has a protective and immediate effect in PNI. Laser phototherapy in the early stages of muscle atrophy may preserve the denervated muscle by maintaining creatinine kinase (CK) activity and the amount of acetylcholine receptor (AChR)...
December 2016: Photomedicine and Laser Surgery
https://www.readbyqxmd.com/read/27989572/the-role-of-camp-and-its-downstream-targets-in-neurite-growth-in-the-adult-nervous-system
#19
REVIEW
Nicholas J Batty, Keith K Fenrich, Karim Fouad
Injured neurons in the adult mammalian central nervous system (CNS) have a very limited capacity for axonal regeneration and neurite outgrowth. This inability to grow new axons or to regrow injured axons is due to the presence of molecules that inhibit axonal growth, and age related changes in the neuron's innate growth capabilities. Available levels of cAMP are thought to have an important role in linking both of these factors. Elevated levels of cAMP in the developing nervous system are important for the guidance and stability of growth cones...
December 15, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27988344/combined-chondroitinase-and-klf7-expression-reduce-net-retraction-of-sensory-and-cst-axons-from-sites-of-spinal-injury
#20
Zimei Wang, Kristen Winsor, Christopher Nienhaus, Evan Hess, Murray G Blackmore
Axon regeneration in the central nervous system is limited both by inhibitory extracellular cues and by an intrinsically low capacity for axon growth in some CNS populations. Chondroitin sulfate proteoglycans (CSPGs) are well-studied inhibitors of axon growth in the CNS, and degradation of CSPGs by chondroitinase has been shown to improve the extension of injured axons. Alternatively, axon growth can be improved by targeting the neuron-intrinsic growth capacity through forced expression of regeneration-associated transcription factors...
December 14, 2016: Neurobiology of Disease
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