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https://www.readbyqxmd.com/read/28445714/the-toll-like-receptor-2-agonist-pam3csk4-is-neuroprotective-after-spinal-cord-injury
#1
Nicole S Stivers, Nicolas Pelisch, Ben C Orem, Joshua Williams, Jacqueline M Nally, David P Stirling
Microglia/macrophage activation and recruitment following spinal cord injury (SCI) is associated with both detrimental and reparative functions. Stimulation of the innate immune receptor Toll-like receptor-2 (TLR2) has shown to be beneficial following SCI, and it increases axonal regeneration following optic nerve crush. However, the mechanism(s) remain unclear. As microglia express high levels of TLR2, we hypothesized that modulating the microglial response to injury using a specific TLR2 agonist, Pam3CSK4, would prevent secondary-mediated white matter degeneration following SCI...
April 23, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28387890/effects-of-propofol-and-dexmedetomidine-anesthesia-on-th1-th2-of-rat-spinal-cord-injury
#2
F-Y He, W-Z Feng, J Zhong, W Xu, H-Y Shao, Y-R Zhang
OBJECTIVE: Spinal cord injury (SCI) patients had major trauma during surgery, which thus necessitates optimal choice of anesthesia drugs. The specific selection of anesthesia agents may affect body immune system. Therefore, this study aims to investigate the anesthesia effect of propofol and dexmedetomidine on the rat SCI and their effects of Th1/Th2. MATERIALS AND METHODS: Improved ALLEN's pouching method was used to generate rat SCI model. The SCI rat models were further divided into propofol and dexmedetomidine group for analyzing anesthesia time, duration, post-op analgesia time, SCI sensory function Reuter score...
March 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28306359/spinal-cord-injuries-how-could-cell-therapy-help
#3
Anna Badner, Ahad M Siddiqui, Michael G Fehlings
Spinal cord injury (SCI) is a devastating condition, where regenerative failure and cell loss lead to paralysis. The heterogeneous and time-sensitive pathophysiology has made it difficult to target tissue repair. Despite many medical advances, there are no effective regenerative therapies. As stem cells offer multi-targeted and environmentally responsive benefits, cell therapy is a promising treatment approach. Areas covered: This review highlights the cell therapies being investigated for SCI, including Schwann cells, olfactory ensheathing cells, mensenchymal stem/stromal cells, neural precursors, oligodendrocyte progenitors, embryonic stem cells, and induced pluripotent stem cells...
May 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28266523/abnormalities-in-a-to-i-rna-editing-patterns-in-cns-injuries-correlate-with-dynamic-changes-in-cell-type-composition
#4
Nurit Gal-Mark, Lea Shallev, Sahar Sweetat, Michal Barak, Jin Billy Li, Erez Y Levanon, Eli Eisenberg, Oded Behar
Adenosine to Inosine (A-to-I) RNA editing is a co- or post-transcriptional mechanism that modifies genomically encoded nucleotides at the RNA level. A-to-I RNA editing is abundant in the brain, and altered editing levels have been reported in various neurological pathologies and following spinal cord injury (SCI). The prevailing concept is that the RNA editing process itself is dysregulated by brain pathologies. Here we analyzed recent RNA-seq data, and found that, except for few mammalian conserved editing sites, editing is significantly higher in neurons than in other cell populations of the brain...
March 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28261102/genetic-and-pharmacological-inhibition-of-p38%C3%AE-improves-locomotor-recovery-after-spinal-cord-injury
#5
Hiroki Umezawa, Yusuke Naito, Kensuke Tanaka, Kento Yoshioka, Kenichi Suzuki, Tatsuhiko Sudo, Masahiko Hagihara, Masahiko Hatano, Koichiro Tatsumi, Yoshitoshi Kasuya
One of the mitogen-activated protein kinases, p38α plays a crucial role in various inflammatory diseases and apoptosis of various types of cells. In this study, we investigated the pathophysiological roles of p38α in spinal cord injury (SCI), using a mouse model. Lateral hemisection at T9 of the SC was performed in wild type (WT) and p38α(+/-) mice (p38α(-/-) showed embryonic lethality). p38α(+/-) mice showed a better functional recovery from SCI-associated paralyzed hindlimbs compared to WT mice at 7 days post-injury (dpi), which remained until 28 dpi (an end time point of monitoring the behavior)...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28259912/role-of-hypoxia%C3%A2-inducible-factor%C3%A2-1%C3%AE-in-autophagic-cell-death-in-microglial-cells-induced-by-hypoxia
#6
Xintao Wang, Jun Ma, Qiang Fu, Lei Zhu, Zhiling Zhang, Fan Zhang, Nan Lu, Aimin Chen
Microglial cells are phagocytic cells of the central nervous system (CNS) and have been proposed to be a primary component of the innate immune response and maintain efficient CNS homeostasis. Microglial cells are activated during various phases of tissue repair and participate in various pathological conditions in the CNS. Following spinal cord injury (SCI), anoxemia is a key problem that results in tissue destruction. Hypoxia‑inducible factor 1‑α (HIF‑1α) may protect hypoxic cells from apoptosis or necrosis under ischemic and anoxic conditions...
April 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28255705/f%C3%A3-rster-resonance-energy-transfer-to-study-tcr-pmhc-interactions-in-the-immunological-synapse
#7
Gerhard J Schütz, Johannes B Huppa
T-cell antigen recognition is remarkably efficient: when scanning the surface of antigen-presenting cells (APCs), T-cells can detect the presence of just a few single antigenic peptide/MHCs (pMHCs), which are often vastly outnumbered by structurally similar non-stimulatory endogenous pMHCs (Irvine et al., Nature 419(6909):845-849, 2002; Purbhoo et al., Nat Immunol 5(5):524-530, 2004; Huang et al., Immunity 39(5):846-857, 2013). How T-cells achieve this is still enigmatic, in particular in view of the rather moderate affinity that TCRs typically exert for antigenic pMHCs, at least when measured in vitro (Davis et al...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28223917/gene-expression-profiling-in-the-injured-spinal-cord-of-trachemys-scripta-elegans-an-amniote-with-self-repair-capabilities
#8
Adrián Valentin-Kahan, Gabriela B García-Tejedor, Carlos Robello, Omar Trujillo-Cenóz, Raúl E Russo, Fernando Alvarez-Valin
Slider turtles are the only known amniotes with self-repair mechanisms of the spinal cord that lead to substantial functional recovery. Their strategic phylogenetic position makes them a relevant model to investigate the peculiar genetic programs that allow anatomical reconnection in some vertebrate groups but are absent in others. Here, we analyze the gene expression profile of the response to spinal cord injury (SCI) in the turtle Trachemys scripta elegans. We found that this response comprises more than 1000 genes affecting diverse functions: reaction to ischemic insult, extracellular matrix re-organization, cell proliferation and death, immune response, and inflammation...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28201982/transcriptome-profile-of-rat-genes-in-injured-spinal-cord-at-different-stages-by-rna-sequencing
#9
Ling-Ling Shi, Nan Zhang, Xiu-Mei Xie, Yue-Juan Chen, Rui Wang, Lin Shen, Jian-Sheng Zhou, Jian-Guo Hu, He-Zuo Lü
BACKGROUND: Spinal cord injury (SCI) results in fatal damage and currently has no effective treatment. The pathological mechanisms of SCI remain unclear. In this study, genome-wide transcriptional profiling of spinal cord samples from injured rats at different time points after SCI was performed by RNA-Sequencing (RNA-Seq). The transcriptomes were systematically characterized to identify the critical genes and pathways that are involved in SCI pathology. RESULTS: RNA-Seq results were obtained from total RNA harvested from the spinal cords of sham control rats and rats in the acute, subacute, and chronic phases of SCI (1 day, 6 days and 28 days after injury, respectively; n = 3 in every group)...
February 15, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28170444/impaired-toll-like-receptor-7-and-9-induced-immune-activation-in-chronic-spinal-cord-injured-patients-contributes-to-immune-dysfunction
#10
Gozde Gucluler, Emre Adiguzel, Bilgi Gungor, Tamer Kahraman, Mayda Gursel, Bilge Yilmaz, Ihsan Gursel
Reduced immune activation or immunosuppression is seen in patients withneurological diseases. Urinary and respiratory infections mainly manifested as septicemia and pneumonia are the most frequent complications following spinal cord injuries and they account for the majority of deaths. The underlying reason of these losses is believed to arise due to impaired immune responses to pathogens. Here, we hypothesized that susceptibility to infections of chronic spinal cord injured (SCI) patients might be due to impairment in recognition of pathogen associated molecular patterns and subsequently declining innate and adaptive immune responses that lead to immune dysfunction...
2017: PloS One
https://www.readbyqxmd.com/read/28123490/reduced-inflammatory-cell-recruitment-and-tissue-damage-in-spinal-cord-injury-by-acellular-spinal-cord-scaffold-seeded-with-mesenchymal-stem-cells
#11
Yu-Hai Wang, Jian Chen, Jing Zhou, Feng Nong, Jin-Han Lv, Jia Liu
Therapy using acellular spinal cord (ASC) scaffolds seeded with bone marrow stromal cells (BMSCs) has previously been shown to restore function of the damaged spinal cord and improve functional recovery in a rat model of acute hemisected spinal cord injury (SCI). The aim of the present study was to determine whether BMSCs and ASC scaffolds promote the functional recovery of the damaged spinal cord in a rat SCI model through regulation of apoptosis and immune responses. Whether this strategy regulates secondary inflammation, which is characterized by the infiltration of immune cells and inflammatory mediators to the lesion site, in SCI repair was investigated...
January 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28123029/newly-formed-endothelial-cells-regulate-myeloid-cell-activity-following-spinal-cord-injury-via-expression-of-cd200-ligand
#12
Merav Cohen, Hila Ben-Yehuda, Ziv Porat, Catarina Raposo, Siamon Gordon, Michal Schwartz
The central nervous system (CNS) is endowed with several immune-related mechanisms that contribute to its protection and maintenance in homeostasis and under pathology. Here, we discovered an additional mechanism that controls inflammatory responses within the CNS milieu under injurious conditions, involving CD200 ligand (CD200L) expressed by newly formed endothelial cells. We observed that CD200L is constitutively expressed in the mouse healthy CNS by endothelial cells of the blood-cerebrospinal fluid barrier and of the spinal cord meninges, but not by the endothelium of the blood-spinal cord barrier...
January 25, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28077367/electroacupuncture-alleviates-the-inflammatory-response-via-effects-on-m1-and-m2-macrophages-after-spinal-cord-injury
#13
Jiagui Zhao, Rongyi Zhang, Likui Wang, Yuanhai Li
BACKGROUND: Macrophages/microglia are important effector cells at the site of spinal cord injury (SCI). M1-type macrophages facilitate innate immunity to remove foreign microbes and wound debris from the injury site. M2-type macrophages exhibit tissue repair properties and attenuate production of pro-inflammatory cytokines. Regulation of the polarisation of M1/M2 macrophages may affect the inflammatory response in SCI and may be related to neurotrophin-3 (NT-3). Electroacupuncture (EA) at GV acupuncture points can be used as an adjuvant therapy for SCI...
January 11, 2017: Acupuncture in Medicine: Journal of the British Medical Acupuncture Society
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
#14
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/28039398/spinal-cord-injury-modulates-the-lung-inflammatory-response-in-mechanically-ventilated-rats-a-comparative-animal-study
#15
Karine Truflandier, Eric Beaumont, Karim Maghni, Michel De Marchie, Emmanuel Charbonney, Jadranka Spahija
Mechanical ventilation (MV) is widely used in spinal injury patients to compensate for respiratory muscle failure. MV is known to induce lung inflammation, while spinal cord injury (SCI) is known to contribute to local inflammatory response. Interaction between MV and SCI was evaluated in order to assess the impact it may have on the pulmonary inflammatory profile. Sprague Dawley rats were anesthetized for 24 h and randomized to receive either MV or not. The MV group included C4-C5 SCI, T10 SCI and uninjured animals...
December 2016: Physiological Reports
https://www.readbyqxmd.com/read/28025434/il-1%C3%AE-tnf-%C3%AE-and-il-6-levels-in-gingival-fluid-and-serum-of-patients-with-ischemic-stroke
#16
Anna Wytrykowska, Maria Prosba-Mackiewicz, Walenty M Nyka
It has been documented that an increase of immune cells in periodontitis may stimulate the process of atherosclerosis and lead to ischemic stroke. The aim of this study was to investigate whether there is any significant difference in serum and gingival crevicular fluid (GCF) cytokine concentrations between patients with early ischemic stroke (IS) and a control group. Eighty-six patients were consecutively enrolled for this study, 50 with ischemic stroke and 36 as a control group with no previous stroke. Only dentulous patients were included...
2016: Journal of Oral Science
https://www.readbyqxmd.com/read/28003635/effects-of-stat3-inhibitors-on-neural-functional-recovery-after-spinal-cord-injury-in-rats
#17
Meng Cui, Xinlong Ma, Jie Sun, Jinquan He, Lin Shen, Fangguo Li
Spinal cord injuries (SCIs) can induce primary and secondary injury, resulting in severe neurological damage and dysfunction in patients. Studies have reported that signal transducer and activator of transcription 3 (STAT3) plays an important role in the inflammatory immune response and neural stem cell differentiation. In order to examine whether a STAT3 inhibitor can prevent worsening of an SCI and promote neural stem cell differentiation, a rat model of surgically induced SCI was created and rats were treated with the STAT3 inhibitor S31-201...
January 16, 2017: Bioscience Trends
https://www.readbyqxmd.com/read/27994070/characterization-of-meningeal-type-2-innate-lymphocytes-and-their-response-to-cns-injury
#18
Sachin P Gadani, Igor Smirnov, Ashtyn T Smith, Christopher C Overall, Jonathan Kipnis
The meningeal space is occupied by a diverse repertoire of immune cells. Central nervous system (CNS) injury elicits a rapid immune response that affects neuronal survival and recovery, but the role of meningeal inflammation remains poorly understood. Here, we describe type 2 innate lymphocytes (ILC2s) as a novel cell type resident in the healthy meninges that are activated after CNS injury. ILC2s are present throughout the naive mouse meninges, though are concentrated around the dural sinuses, and have a unique transcriptional profile...
February 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27994015/newly-formed-endothelial-cells-regulate-myeloid-cell-activity-following-spinal-cord-injury-via-expression-of-cd200-ligand
#19
Merav Cohen, Hila Ben-Yehuda, Ziv Porat, Catarina Raposo, Siamon Gordon, Michal Schwartz
The central nervous system (CNS) is endowed with several immune-related mechanisms that contribute to its protection and maintenance in homeostasis and under pathology. Here, we discovered an additional mechanism that controls inflammatory responses within the CNS milieu under injurious conditions, involving CD200 ligand (CD200L) expressed by newly-formed endothelial cells. We observed that CD200L is constitutively expressed in the mouse healthy CNS by endothelial cells of the blood-cerebrospinal fluid barrier and of the spinal cord meninges, but not by the endothelium of the blood-spinal cord barrier...
December 19, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27987156/immunotherapy-of-uveal-melanoma-vaccination-against-cancer
#20
Mirko Kummer, Beatrice Schuler-Thurner
Uveal melanoma is the most frequently occurring primary intraocular tumor in adults, with an incidence of about 5 out of 100,000 per year, the incidence rising with increasing age (Lipski, Klin Monbl Augenheilkd 230:1005-1019, 2013; Metz et al., Klin Monbl Augenheilkd 230:686-691, 2013; Singh and Topham, Ophthalmology 110:956-961, 2003). Often diagnosed late due to a lack of early symptoms, this kind of melanoma is associated with a poor prognosis. Approximately 50 % of the patients develop distant metastases (Lipski, Klin Monbl Augenheilkd 230:1005-1019, 2013; Metz et al...
2017: Methods in Molecular Biology
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