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Spinal cord injury cellular

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https://www.readbyqxmd.com/read/28819194/hdac3-inhibition-ameliorates-spinal-cord-injury-by-immunomodulation
#1
Tomoharu Kuboyama, Shalaka Wahane, Yong Huang, Xiang Zhou, Jamie K Wong, Andrew Koemeter-Cox, Michael Martini, Roland H Friedel, Hongyan Zou
Following spinal cord injury (SCI), the innate immune response of microglia and infiltrating macrophages clears up cellular debris and promotes tissue repair, but it also inflicts secondary injury from inflammatory responses. Immunomodulation aimed at maximizing the beneficial effects while minimizing the detrimental roles of the innate immunity may aid functional recovery after SCI. However, intracellular drivers of global reprogramming of the inflammatory gene networks in the innate immune cells are poorly understood...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28814499/therapeutic-stimulation-for-restoration-of-function-after-spinal-cord-injury
#2
REVIEW
Aiva Ievins, Chet T Moritz
Paralysis due to spinal cord injury can severely limit motor function and independence. This review summarizes different approaches to electrical stimulation of the spinal cord designed to restore motor function, with a brief discussion of their origins and the current understanding of their mechanisms of action. Spinal stimulation leads to impressive improvements in motor function along with some benefits to autonomic functions such as bladder control. Nonetheless, the precise mechanisms underlying these improvements and the optimal spinal stimulation approaches for restoration of motor function are largely unknown...
September 2017: Physiology
https://www.readbyqxmd.com/read/28813843/addition-of-forelimb-training-reduces-gains-from-robotic-gait-training-in-a-rat-model-of-spinal-cord-injury
#3
Nathan D Neckel, Haining Dai, Olga C Rodriguez
To restore locomotor function following spinal cord injury the disrupted descending supraspinal drive needs to be re-connected to regions caudal to the injury. Robotic gait training aims to facilitate recovery by stimulating the proprioceptive networks of the legs in a coordinated walking pattern while the descending supraspinal connections are re-established. In incomplete injuries, it is believed that the interneuronal networks near the injury site form relay circuits to reroute the supraspinal signals through the spared tissue...
July 2017: IEEE ... International Conference on Rehabilitation Robotics: [proceedings]
https://www.readbyqxmd.com/read/28795657/body-system-effects-of-a-multi-modal-training-program-targeting-chronic-motor-complete-thoracic-spinal-cord-injury
#4
Katie Gant, Kathleen Nagle, Rachel Cowan, Edelle Field-Fote, Mark Nash, Jochen Kressler, Christine K Thomas, Mabelin Castellanos, Eva Widerstrom-Noga, Kimberly D Anderson
The safety and efficacy of pharmacologic and cellular transplantation strategies are currently being evaluated in people with spinal cord injury. In studies of people with chronic spinal cord injuries, it is thought that functional recovery will be best achieved when drug or cell therapies are combined with rehabilitation protocols. However, any functional recovery due to the therapy may be confounded by the conditioned state of the body and by training-induced effects on neuroplasticity. For this reason, we sought to investigate the effects of a multi-modal training program on several body systems...
August 10, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28780172/contribution-of-plasma-membrane-calcium-atpases-to-neuronal-maladaptive-responses-focus-on-spinal-nociceptive-mechanisms-and-neurodegeneration
#5
REVIEW
Veronika Khariv, Stella Elkabes
Plasma membrane calcium ATPases (PMCAs) are ion pumps that expel Ca(2+) from cells and maintain Ca(2+) homeostasis. Four isoforms and multiple splice variants play important and non-overlapping roles in cellular function and integrity and have been implicated in diseases including disorders of the central nervous system (CNS). In particular, one of these isoforms, PMCA2, is critical for spinal cord (SC) neuronal function. PMCA2 expression is decreased in SC neurons at onset of symptoms in animal models of multiple sclerosis...
August 2, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28760862/myelinogenic-plasticity-of-oligodendrocyte-precursor-cells-following-spinal-cord-contusion-injury
#6
P Assinck, G J Duncan, J R Plemel, M J Lee, J S Stratton, S B Manesh, J Liu, L M Ramer, S H Kang, D E Bergles, J Biernaskie, W Tetzlaff
Spontaneous remyelination occurs after spinal cord injury (SCI), but the extent of myelin repair and identity of the cells responsible remain incompletely understood and contentious. We assessed the cellular origin of new myelin by fate mapping PDGFRα+, Olig2+, and P0+ cells following contusion SCI in mice. Oligodendrocyte precursor cells (OPCs; PDGFRα+) produced oligodendrocytes responsible for de novo ensheathment of ∼30% of myelinated spinal axons at injury epicenter three months after SCI, demonstrating that these resident cells are a major contributor to oligodendrocyte regeneration...
July 31, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28737113/micrornas-roles-in-regulating-neuroinflammation
#7
Andrew D Gaudet, Laura K Fonken, Linda R Watkins, Randy J Nelson, Phillip G Popovich
MicroRNAs (miRNAs) are small noncoding RNAs that broadly affect cellular and physiological function in all multicellular organisms. Here, the role of miRNAs in neuroinflammation is considered. miRNAs are 21- to 23-oligonucleotide RNAs that regulate translation of specific RNAs by binding to complementary regulatory RNA sequences, thereby causing mRNA degradation or sequestration. More than 5000 miRNAs likely exist in humans, and each miRNA binds an average of 200 RNAs. Specific immunomodulatory miRNAs can regulate a set of RNAs in a coordinated manner, suggesting that effective miRNA-based therapeutic manipulations for neuroinflammatory conditions may be revealed...
July 1, 2017: Neuroscientist: a Review Journal Bringing Neurobiology, Neurology and Psychiatry
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
#8
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/28722682/activation-of-the-nrf2-are-signaling-pathway-by-probucol-contributes-to-inhibiting-inflammation-and-neuronal-apoptosis-after-spinal-cord-injury
#9
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/28712480/bee-venom-acupuncture-reduces-interleukin-6-increases-interleukin-10-and-induces-locomotor-recovery-in-a-model-of-spinal-cord-compression
#10
Raquel Nascimento de Souza, Fernanda Kohn Silva, Magda Alves de Medeiros
Spinal cord injuries (SCIs) initiate a series of molecular and cellular events in which inflammatory responses can lead to major neurological dysfunctions. The present study aims to investigate whether bee venom (BV) acupuncture applied at acupoints ST36 (Zusanli) and GV3 (Yaoyangquan) could minimize locomotor deficits and the magnitude of neural tissue losses, and change the balance between pro- and anti-inflammatory cytokines after an SCI by compression. Wistar rats were subjected to an SCI model by compression in which a 2-French Fogarty embolectomy catheter was inflated in the extradural space...
June 2017: Journal of Acupuncture and Meridian Studies
https://www.readbyqxmd.com/read/28696010/myelin-as-an-inflammatory-mediator-myelin-interactions-with-complement-macrophages-and-microglia-in-spinal-cord-injury
#11
REVIEW
Timothy J Kopper, John C Gensel
Spinal cord injury (SCI) triggers chronic intraspinal inflammation consisting of activated resident and infiltrating immune cells (especially microglia/macrophages). The environmental factors contributing to this protracted inflammation are not well understood; however, myelin lipid debris is a hallmark of SCI. Myelin is also a potent macrophage stimulus and target of complement-mediated clearance and inflammation. The downstream effects of these neuroimmune interactions have the potential to contribute to ongoing pathology or facilitate repair...
July 11, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28695279/epigenetic-regulation-of-neural-stem-cell-differentiation-towards-spinal-cord-regeneration
#12
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/28687659/neutrophils-induce-astroglial-differentiation-and-migration-of-human-neural-stem-cells-via-c1q-and-c3a-synthesis
#13
Mitra J Hooshmand, Hal X Nguyen, Katja M Piltti, Francisca Benavente, Samuel Hong, Lisa Flanagan, Nobuko Uchida, Brian J Cummings, Aileen J Anderson
Inflammatory processes play a key role in pathophysiology of many neurologic diseases/trauma, but the effect of immune cells and factors on neurotransplantation strategies remains unclear. We hypothesized that cellular and humoral components of innate immunity alter fate and migration of human neural stem cells (hNSC). In these experiments, conditioned media collected from polymorphonuclear leukocytes (PMN) selectively increased hNSC astrogliogenesis and promoted cell migration in vitro. PMN were shown to generate C1q and C3a; exposure of hNSC to PMN-synthesized concentrations of these complement proteins promoted astrogliogenesis and cell migration...
August 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28679106/macrophage-migration-inhibitory-factor-a-multifaceted-cytokine-implicated-in-multiple-neurological-diseases
#14
REVIEW
Marcel F Leyton-Jaimes, Joy Kahn, Adrian Israelson
Macrophage migration inhibitory factor (MIF) is a conserved cytokine found as a homotrimer protein. It is found in a wide spectrum of cell types in the body including neuronal and non-neuronal cells. MIF is implicated in several biological processes; chemo-attraction, cytokine activity, and receptor binding, among other functions. More recently, a chaperone-like activity has been added to its repertoire. In this review, we focus on the implication of MIF in the central nervous system and peripheries, its role in neurological disorders, and the mechanisms by which MIF is regulated...
July 2, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28665182/systemic-administration-of-exosomes-released-from-mesenchymal-stromal-cells-attenuates-apoptosis-inflammation-and-promotes-angiogenesis-after-spinal-cord-injury-in-rats
#15
Jiang-Hu Huang, Xiao-Ming Yin, Yang Xu, Chun-Cai Xu, Xi Lin, Fu-Biao Ye, Yong Cao, Fei-Yue Lin
Spinal cord injury (SCI) is one of the most common devastating injuries, which causes permanent disabilities such as paralysis and loss of movement or sensation. The precise pathogenic mechanisms of the disease remain unclear, and, as of yet, there is no effective cure. Mesenchymal stem cells (MSCs) show promise as an effective therapy in the experimental models of SCI. MSCs secrete various factors that can modulate a hostile environment, which is called the paracrine effect. Among these paracrine molecules, exosome is considered to be the most valuable therapeutic factor...
August 18, 2017: Journal of Neurotrauma
https://www.readbyqxmd.com/read/28658664/differential-gene-and-lncrna-expression-in-the-lower-thoracic-spinal-cord-following-ischemia-reperfusion-induced-acute-kidney-injury-in-rats
#16
Qing-Quan Liu, Hui Liu, Zhi-Gang He, Shi-Jie Zhang, Bao-Wen Liu, Le Wang, Wen-Hui Qiu, Qing Xu, Hong-Bing Xiang, Yong-Man Lv
We used high-throughput RNA sequencing to analyze differential gene and lncRNA expression patterns in the lower thoracic spinal cord during ischemia/reperfusion (I/R)-induced acute kidney injury (AKI) in rats. We observed that of 32662 mRNAs, 4296 out were differentially expressed in the T8-12 segments of the spinal cord upon I/R-induced AKI. Among these, 62 were upregulated and 34 were downregulated in response to I/R (FDR < 0.05, |log2FC| > 1). Further, 52 differentially expressed lncRNAs (35 upregulated and 17 downregulated) were identified among 3849 lncRNA transcripts...
June 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28631619/modeling-trans-spinal-direct-current-stimulation-for-the-modulation-of-the-lumbar-spinal-motor-pathways
#17
Alexander Kuck, Dick Stegeman, Edwin van Asseldonk
OBJECTIVE: Trans-spinal direct current stimulation (tsDCS) is a potential new technique for the treatment of spinal cord injury (SCI). TsDCS aims to facilitate plastic changes in the neural pathways of the spinal cord with a positive effect on SCI recovery. To establish tsDCS as a possible treatment option for SCI, it is essential to gain a better understanding of its cause and effects. We seek to understand the acute effect of tsDCS, including the generated electric field (EF) and its polarization effect on the spinal circuits, to determine a cellular target...
June 20, 2017: Journal of Neural Engineering
https://www.readbyqxmd.com/read/28628593/consideration-of-dose-and-timing-when-applying-interventions-after-stroke-and-spinal-cord-injury
#18
D Michele Basso, Catherine E Lang
BACKGROUND AND PURPOSE: Nearly 4 decades of investigation into the plasticity of the nervous system suggest that both timing and dose could matter. This article provides a synopsis of our lectures at the IV STEP meeting, which presented a perspective of current data on the issues of timing and dose for adult stroke and spinal cord injury motor rehabilitation. SUMMARY OF KEY POINTS: For stroke, the prevailing evidence suggests that greater amounts of therapy do not result in better outcomes for upper extremity interventions, regardless of timing...
July 2017: Journal of Neurologic Physical Therapy: JNPT
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
#19
Hassan Al-Ali, Ying Ding, Tatiana Slepak, Wei Wu, Yan Sun, Yania Martinez, Xiao-Ming Xu, Vance P Lemmon, John L Bixby
The mammalian target of rapamycin (mTOR) positively regulates axon growth in the mammalian central nervous system (CNS). Although 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 twofold to threefold...
July 26, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28601045/microrna-494-improves-functional-recovery-and-inhibits-apoptosis-by-modulating-pten-akt-mtor-pathway-in-rats-after-spinal-cord-injury
#20
Huaguang Zhu, Rong Xie, Xiaodong Liu, Jiajun Shou, Wentao Gu, Shixin Gu, Xiaoming Che
Multiple cellular, molecular, and biochemical changes contribute to the etiology and treatment outcome of contusion spinal cord injury (SCI). MicroRNAs (miRNAs) aberrant expression have been found after SCI in recent studies. However, little is known about the functional significance of the unique role of miRNAs in SCI. Here, we established a rat SCI model and performed the miRNA microarray to analyze miRNAs expression at different times post-SCI. Microarray data revealed that 14 miRNAs were upregulated and 46 miRNAs were downregulated by 2 times compared with sham rat spinal cords, and miR-494 was one of the miRNAs being most significantly downregulated...
August 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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