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spinal cord regeneration

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https://www.readbyqxmd.com/read/29458076/bone-marrow-mesenchymal-stem-cells-bmscs-improved-functional-recovery-of-spinal-cord-injury-partly-by-promoting-axonal-regeneration
#1
REVIEW
Liya Lin, Hefeng Lin, Shi Bai, Lianshun Zheng, Xiaoming Zhang
Spinal cord injury (SCI) disrupts the spinal cord and results in the loss of sensory and motor function below the lesion site. The treatment of SCI became a challenge because the injured neurons fail to axon regenerate and repair after injury. Promoting axonal regeneration plays a key role in the treatment strategies for SCI. It would meet the goal of reconstruction the injured spinal cord and improving the functional recovery. Bone marrow mesenchymal stem cells (BMSCs) are attractive therapeutic potential cell sources for SCI, and it could rebuild the injured spinal cord through neuroprotection, neural regeneration and remyelinating...
February 16, 2018: Neurochemistry International
https://www.readbyqxmd.com/read/29453976/cell-type-specific-expression-of-constitutively-active-rheb-promotes-regeneration-of-bulbospinal-respiratory-axons-following-cervical-sci
#2
Mark W Urban, Biswarup Ghosh, Laura R Strojny, Cole G Block, Sara M Blazejewski, Megan C Wright, George M Smith, Angelo C Lepore
Damage to respiratory neural circuitry and consequent loss of diaphragm function is a major cause of morbidity and mortality in individuals suffering from traumatic cervical spinal cord injury (SCI). Repair of CNS axons after SCI remains a therapeutic challenge, despite current efforts. SCI disrupts inspiratory signals originating in the rostral ventral respiratory group (rVRG) of the medulla from their phrenic motor neuron (PhMN) targets, resulting in loss of diaphragm function. Using a rat model of cervical hemisection SCI, we aimed to restore rVRG-PhMN-diaphragm circuitry by stimulating regeneration of injured rVRG axons via targeted induction of Rheb (ras homolog enriched in brain), a signaling molecule that regulates neuronal-intrinsic axon growth potential...
February 14, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29451438/reinnervation-of-the-rectum-with-transfer-of-the-genital-branch-of-the-genitofemoral-nerve-to-the-pelvic-nerve-in-rats
#3
Chuanjiang Dong, Ping Zhu, Zonglan Xie, Zheqi Fan, Ziqiang Dong
OBJECTIVE The purpose of this study was to determine the feasibility of rectum reinnervation with transfer of a primarily genitofemoral nerve to the pelvic nerve in the rat. METHODS Thirty-six male rats were randomly divided into 3 groups: rats in the nerve transfer group (n = 12) were subjected to rectal denervation and then bilateral genitofemoral nerve-pelvic nerve transfer; rats in the nerve resection group (n = 12) underwent rectum denervation without nerve transfer; and rats in the control group (n = 12) underwent sham surgery...
February 16, 2018: Journal of Neurosurgery. Spine
https://www.readbyqxmd.com/read/29451216/does-combined-therapy-of-curcumin-and-epigallocatechin-gallate-have-a-synergistic-neuroprotective-effect-against-spinal-cord-injury
#4
Jiri Ruzicka, Lucia Machova Urdzikova, Barbora Svobodova, Anubhav G Amin, Kristyna Karova, Jana Dubisova, Kristyna Zaviskova, Sarka Kubinova, Meic Schmidt, Meena Jhanwar-Uniyal, Pavla Jendelova
Systematic inflammatory response after spinal cord injury (SCI) is one of the factors leading to lesion development and a profound degree of functional loss. Anti-inflammatory compounds, such as curcumin and epigallocatechin gallate (EGCG) are known for their neuroprotective effects. In this study, we investigated the effect of combined therapy of curcumin and EGCG in a rat model of acute SCI induced by balloon compression. Immediately after SCI, rats received curcumin, EGCG, curcumin + EGCG or saline [daily intraperitoneal doses (curcumin, 6 mg/kg; EGCG 17 mg/kg)] and weekly intramuscular doses (curcumin, 60 mg/kg; EGCG 17 mg/kg)] for 28 days...
January 2018: Neural Regeneration Research
https://www.readbyqxmd.com/read/29451203/a-growing-field-the-regulation-of-axonal-regeneration-by-wnt-signaling
#5
REVIEW
Armando L Garcia, Adanna Udeh, Karthik Kalahasty, Abigail S Hackam
The canonical Wnt/β-catenin pathway is a highly conserved signaling cascade that plays critical roles during embryogenesis. Wnt ligands regulate axonal extension, growth cone guidance and synaptogenesis throughout the developing central nervous system (CNS). Recently, studies in mammalian and fish model systems have demonstrated that Wnt/β-catenin signaling also promotes axonal regeneration in the adult optic nerve and spinal cord after injury, raising the possibility that Wnt could be developed as a therapeutic strategy...
January 2018: Neural Regeneration Research
https://www.readbyqxmd.com/read/29447138/inflammation-in-the-pathophysiology-of-neuropathic-pain
#6
Claudia Sommer, Mathias Leinders, Nurcan Üçeyler
Peripheral nerve injuries and diseases often lead to pain persisting beyond the resolution of damage, indicating an active disease-promoting process, which may result in chronic pain. This is regarded as a maladaptive mechanism resulting from neuroinflammation that originally serves to promote regeneration and healing. Knowledge on these physiological and pathophysiological processes has accumulated over the last few decades and has started to yield potential therapeutic targets. Key players are macrophages, T-lymphocytes, cytokines, and chemokines...
March 2018: Pain
https://www.readbyqxmd.com/read/29442452/the-neuroprotective-effect-of-n-acetylcysteine-in-spinal-cord-injured-rats
#7
Edyta Olakowska, Wiesław Marcol, Adam Właszczuk, Izabella Woszczycka-Korczyńska, Joanna Lewin-Kowalik
BACKGROUND: Spinal cord injury (SCI) is an important cause of impairment of sensory and motor nerve function. It has been shown that free-radical species play an important role in the pathogenesis of acute tissue trauma after SCI. There are no proven pharmacological therapies that provide neuroprotection and stimulate axonal growth after trauma. OBJECTIVES: The aim of this study was to investigate the neuroprotective effect of N-acetylcysteine (NAC) on the regeneration of spinal cord injuries in rats...
December 2017: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
https://www.readbyqxmd.com/read/29436581/the-pi3k-akt-foxo3a-pathway-regulates-regeneration-following-spinal-cord-injury-in-adult-rats-through-tnf-%C3%AE-and-p27kip1-expression
#8
Honghui Lu, Li-Hai Zhang, Lin Yang, Pei-Fu Tang
The aim of the present study was to elucidate the expression and role of the phosphatidylinositol 3‑kinase (PI3K)/Akt/forkhead box O3 (FOXO3a) pathway in the regeneration of the spinal cord following spinal cord injury (SCI), and its regulatory effect on tumor necrosis factor (TNF)-α and cyclin-dependent kinase inhibitor 1B (p27kip1) expression. Firstly, in a Sprague-Dawley rat model of SCI, western blot analysis revealed that the protein levels of PI3K, phosphorylated Akt and FOXO3a were markedly inhibited compared with those in the sham control group...
February 6, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29428230/fibrotic-scarring-following-lesions-to-the-central-nervous-system
#9
REVIEW
David Oliveira Dias, Christian Göritz
Following lesions to the central nervous system, scar tissue forms at the lesion site. Injury often severs axons and scar tissue is thought to block axonal regeneration, resulting in permanent functional deficits. While scar-forming astrocytes have been extensively studied, much less attention has been given to the fibrotic, non-glial component of the scar. We here review recent progress in understanding fibrotic scar formation following different lesions to the brain and spinal cord. We specifically highlight recent evidence for pericyte-derived fibrotic scar tissue formation, discussing the origin, recruitment, function and therapeutic relevance of fibrotic scarring...
February 8, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/29427106/the-neuropathology-of-spinocerebellar-ataxia-type-3-machado-joseph-disease
#10
Arnulf H Koeppen
Spinocerebellar ataxia type 3 (SCA-3)/Machado-Joseph disease (MJD), the most common autosomal dominant ataxia, affects many regions of the brain and spinal cord. Similar to SCA-1, SCA-2, SCA-6, SCA-7, and SCA-17, the mutation consists of a pathogenic translated cytosine-adenine-guanine (CAG) trinucleotide repeat expansion. Almost invariably, the substantia nigra and the dentate nucleus of the cerebellum bear the brunt of the disease, and these lesions account for the Parkinsonian and ataxic phenotypes. Lesions of motor nuclei in the brain stem cause the complex disturbance of ocular motility and weakness of the tongue...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29424673/nerve-fascicle-transfer-using-a-part-of-the-c-7-nerve-for-spinal-accessory-nerve-injury
#11
Xuan Ye, Yun-Dong Shen, Jun-Tao Feng, Wen-Dong Xu
OBJECTIVE Spinal accessory nerve (SAN) injury results in a series of shoulder dysfunctions and continuous pain. However, current treatments are limited by the lack of donor nerves as well as by undesirable nerve regeneration. Here, the authors report a modified nerve transfer technique in which they employ a nerve fascicle from the posterior division (PD) of the ipsilateral C-7 nerve to repair SAN injury. The technique, first performed in cadavers, was then undertaken in 2 patients. METHODS Six fresh cadavers (12 sides of the SAN and ipsilateral C-7) were studied to observe the anatomical relationship between the SAN and C-7 nerve...
February 9, 2018: Journal of Neurosurgery. Spine
https://www.readbyqxmd.com/read/29420729/combination-treatment-with-exogenous-gdnf-and-fetal-spinal-cord-cells-results-in-better-motoneuron-survival-and-functional-recovery-after-avulsion-injury-with-delayed-root-reimplantation
#12
Carolin Ruven, Smaranda-Ruxandra Badea, Wai-Man Wong, Wutian Wu
When spinal roots are torn off from the spinal cord, both the peripheral and central nervous system get damaged. As the motoneurons lose their axons, they start to die rapidly, whereas target muscles atrophy due to the denervation. In this kind of complicated injury, different processes need to be targeted in the search for the best treatment strategy. In this study, we tested glial cell-derived neurotrophic factor (GDNF) treatment and fetal lumbar cell transplantation for their effectiveness to prevent motoneuron death and muscle atrophy after the spinal root avulsion and delayed reimplantation...
February 6, 2018: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/29410176/transient-activation-of-wnt-%C3%AE-catenin-signaling-reporter-in-fibrotic-scar-formation-after-compression-spinal-cord-injury-in-adult-mice
#13
Takashi Yamagami, David E Pleasure, Kit S Lam, Chengji J Zhou
After traumatic spinal cord injury (SCI), a scar may form with a fibrotic core (fibrotic scar) and surrounding reactive astrocytes (glial scar) at the lesion site. The scar tissue is considered a major obstacle preventing regeneration both as a physical barrier and as a source for secretion of inhibitors of axonal regeneration. Understanding the mechanism of scar formation and how to control it may lead to effective SCI therapies. Using a compression-SCI model on adult transgenic mice, we demonstrate that the canonical Wnt/β-catenin signaling reporter TOPgal (TCF/Lef1-lacZ) positive cells appeared at the lesion site by 5 days, peaked on 7 days, and diminished by 14 days post injury...
February 2, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29408659/axonal-regeneration-of-different-tracts-following-transplants-of-human-glial-restricted-progenitors-into-the-injured-spinal-cord-in-rats
#14
Ying Jin, Jed S Shumsky, Itzhak Fischer
The goal of this study was to compare the efficacy of human glial restricted progenitors (hGRPs) in promoting axonal growth of different tracts. We examined the potential of hGRPs grafted into a cervical (C4) dorsal column lesion to test sensory axons, and into a C4 hemisection to test motor tracts. The hGRPs, thawed from frozen stocks, were suspended in a PureCol matrix and grafted acutely into a C4 dorsal column or hemisection lesion. Control rats received PureCol only. Five weeks after transplantation, all transplanted cells survived in rats with the dorsal column lesion but only about half of the grafts in the hemisection...
January 31, 2018: Brain Research
https://www.readbyqxmd.com/read/29395078/implantation-of-a-matrigel-loaded-agarose-scaffold-promotes-functional-regeneration-of-axons-after-spinal-cord-injury-in-rat
#15
Sungmin Han, Jee Youn Lee, Eun Young Heo, Il Keun Kwon, Tae Young Yune, Inchan Youn
An agarose scaffold can be useful for supporting and guiding injured axons after spinal cord injury (SCI), but the electrophysiological signal of regenerated axon in scaffolds has not yet been determined. The current study investigated whether a Matrigel-loaded agarose scaffold would enhance the regeneration of axons after SCI. Moreover, the functional connectivity of regenerated axons within the channels of the scaffold was evaluated by directly recording motor evoked potentials. Our data showed that the agarose scaffold containing Matrigel can support and enhance linearly organized axon regeneration after SCI...
January 30, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29393906/the-effect-of-botulinum-neurotoxin-serotype-a-heavy-chain-on-the-growth-related-proteins-and-neurite-outgrowth-after-spinal-cord-injury-in-rats
#16
Ya-Fang Wang, Fu Liu, Jing Lan, Juan Bai, Xia-Qing Li
(1) Background: The botulinum toxin A (BoNT-A) heavy chain (HC) can stimulate the growth of primary motor neurites. (2) Methods: A recombinant BoNT/A HC was injected locally plus interval intrathecal catheter of BoNT/A HC to rats with ipsilateral semi-dissociated lumbar spinal cord injuries (SCIs). First, 2D gel with a silver nitrate stain was applied to detect the general pattern of protein expression. Growth associated protein 43 (GAP-43) and superior cervical ganglion 10 (SCG10) were chosen to represent the altered proteins, based on their molecular weight and pI, and were used to further detect their expression...
February 2, 2018: Toxins
https://www.readbyqxmd.com/read/29380749/injectable-hydrogels-of-optimized-acellular-nerve-for-injection-in-the-injured-spinal-cord
#17
Robert Chase Cornelison, Elisa Gonzalez-Rothi, Stacy L Porvasnik, Steven M Wellman, James H Park, David D Fuller, Christine E Schmidt
Spinal cord injury (SCI) affects a quarter million individuals in the United States, and there is currently no clinical treatment. Both fresh and acellular peripheral nerve grafts can induce spinal axon regeneration and support functional recovery in experimental injury models. Nonetheless, a scaffold that can be injected into a spinal contusion would be far less invasive to apply. We aimed to develop the first injectable acellular nerve graft for promoting repair after contusion SCI. Approach: We report a method to enzymatically solubilize optimized acellular (OA) nerve - a decellularized peripheral nerve graft developed in our laboratory and currently used clinically - to obtain an injectable solution that undergoes thermal gelation under physiological conditions...
January 30, 2018: Biomedical Materials
https://www.readbyqxmd.com/read/29373946/safety-and-efficacy-of-rose-bengal-derivatives-for-glial-scar-ablation-in-chronic-spinal-cord-injury
#18
Nandadevi Patil, Vincent Truong, Mackenzie Howard Holmberg, Nicolas D Stoflet, Mark Roderick McCoy, James R Dutton, Eric George Holmberg, Ann M Parr
There are currently no effective therapies available to ameliorate loss of function available for spinal cord injured patients. In addition, proposed treatments which demonstrated functional recovery in animal models of acute spinal cord injury (SCI) have almost invariably failed when applied to chronic injury models. Glial scar formation in chronic injury is a likely contributor to limitation on regeneration. We have successfully removed existing scar tissue in chronically contused rat spinal cord using a rose Bengal based photo ablation approach...
January 26, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29358338/quantitative-proteomics-after-spinal-cord-injury-in-a-regenerative-and-a-non-regenerative-stage-in-the-frog%C3%A2-xenopus-laevis
#19
Dasfne Lee-Liu, Liangliang Sun, Norman J Dovichi, Juan Larraín
The capacity to regenerate the spinal cord after an injury is a coveted trait that only a limited group of non-mammalian organisms can achieve. In Xenopus laevis, this capacity is only present during larval or tadpole stages, but is absent during postmetamorphic frog stages. This provides an excellent model for comparative studies between a regenerative and a non-regenerative stage to identify the cellular and molecular mechanisms that explain this difference in regenerative potential. Here, we used iTRAQ chemistry to obtain a quantitative proteome of the spinal cord 1 day after a transection injury in regenerative and non-regenerative stage animals, and used sham operated animals as controls...
January 22, 2018: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29353106/perineurium-like-sheath-derived-from-long-term-surviving-mesenchymal-stem-cells-confers-nerve-protection-to-the-injured-spinal-cord
#20
Yuan-Huan Ma, Xiang Zeng, Xue-Cheng Qiu, Qing-Shuai Wei, Ming-Tian Che, Ying Ding, Zhou Liu, Guo-Hui Wu, Jia-Hui Sun, Mao Pang, Li-Min Rong, Bin Liu, Zaid Aljuboori, Inbo Han, Eng-Ang Ling, Yuan-Shan Zeng
The functional multipotency enables mesenchymal stem cells (MSCs) promising translational potentials in treating spinal cord injury (SCI). Yet the fate of MSCs grafted into the injured spinal cord has not been fully elucidated even in preclinical studies, rendering concerns of their safety and genuine efficacy. Here we used a rat spinal cord transection model to evaluate the cell fate of allograft bone marrow derived MSCs. With the application of immunosuppressant, donor cells, delivered by biocompatible scaffold, survived up to 8 weeks post-grafting...
January 11, 2018: Biomaterials
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