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SCI, Inflammation

Sanjay Tewari, George Renney, John Brewin, Kate Gardner, Fenella Kirkham, Baba Inusa, James E Barrett, Stephan Menzel, Swee Lay Thein, Malcolm Ward, David C Rees
Silent cerebral infarction is the commonest neurological abnormality in children with sickle cell anemia, affecting 30-40% 14 year olds. There are no known biomarkers to identify children with silent cerebral infarcts and the pathological basis is also unknown. We used an unbiased proteomic discovery approach to identify plasma proteins differing in concentration between children with and without silent cerebral infarcts. Clinical parameters and plasma samples were analysed from 51 children (mean age 11.8 years, range 6-18) with sickle cell anemia (HbSS)...
March 15, 2018: Haematologica
Dasa Cizkova, Veronika Cubinkova, Tomas Smolek, Adriana-Natalia Murgoci, Jan Danko, Katarina Vdoviakova, Filip Humenik, Milan Cizek, Jusal Quanico, Isabelle Fournier, Michel Salzet
It was recently shown that the conditioned medium (CM) of mesenchymal stem cells can enhance viability of neural and glial cell populations. In the present study, we have investigated a cell-free approach via CM from rat bone marrow stromal cells (MScCM) applied intrathecally (IT) for spinal cord injury (SCI) recovery in adult rats. Functional in vitro test on dorsal root ganglion (DRG) primary cultures confirmed biological properties of collected MScCM for production of neurosphere-like structures and axon outgrowth...
March 15, 2018: International Journal of Molecular Sciences
Yoshitoshi Kasuya, Hiroki Umezawa, Masahiko Hatano
Spinal cord injury (SCI) consists of three phases-acute, secondary, and chronic damages-and limiting the development of secondary damage possibly improves functional recovery after SCI. A major component of the secondary phase of SCI is regarded as inflammation-triggered events: induction of cytokines, edema, microglial activation, apoptosis of cells including oligodendrocytes and neurons, demyelination, formation of the astrocytic scar, and so on. Two major stress-activated protein kinases (SAPKs)-c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK)-are activated in various types of cells in response to cellular stresses such as apoptotic stimuli and inflammatory waves...
March 15, 2018: International Journal of Molecular Sciences
Naohiro Uezono, Yicheng Zhu, Yusuke Fujimoto, Tetsuro Yasui, Taito Matsuda, Masahide Nakajo, Masahiko Abematsu, Takao Setoguchi, Shuji Mori, Hideo K Takahashi, Setsuro Komiya, Masahiro Nishibori, Kinichi Nakashima
Together with residual host neurons, transplanted neural stem cell (NSC)-derived neurons play a critical role in reconstructing disrupted neural circuits after spinal cord injury (SCI). Since a large number of tracts are disrupted and the majority of host neurons die around the lesion site as the damage spreads, minimizing this spreading and preserving the lesion site are important for attaining further improvements in reconstruction. High mobility group box-1 (HMGB1) is a damage-associated molecular pattern protein that triggers sterile inflammation after tissue injury...
March 8, 2018: Stem Cells
Amanda Phuong Tran, Philippa Mary Warren, Jerry Silver
Since no approved therapies to restore mobility and sensation following spinal cord injury (SCI) currently exist, a better understanding of the cellular and molecular mechanisms following SCI that compromise regeneration or neuroplasticity is needed to develop new strategies to promote axonal regrowth and restore function. Physical trauma to the spinal cord results in vascular disruption that, in turn, causes blood-spinal cord barrier rupture leading to hemorrhage and ischemia, followed by rampant local cell death...
April 1, 2018: Physiological Reviews
Yona Goldshmit, Ghil Jona, Eran Schmukler, Shira Solomon, Ronit Pinkas-Kramarski, Angela Ruban
Neurotrauma causes immediate elevation of extracellular glutamate levels, which creates excitotoxicity and facilitates inflammation, glial scar formation and consequently neuronal death. Finding factors that reduce the inflammatory response, glial scar formation and increase neuronal survival and neurite outgrowth, are of major importance for improving the outcome after spinal cord injury (SCI). In the present study, we evaluated a new treatment aiming to remove CNS glutamate into the systemic blood circulation by intravenous administration of blood glutamate scavengers (BGS) such as recombinant enzyme glutamate-oxaloacetate transaminase (rGOT1) and its co-substrate...
March 1, 2018: Journal of Neurotrauma
Jason R Guercio, Jason E Kralic, Eric J Marrotte, Michael L James
CONTEXT: Current treatment of spinal cord injury (SCI) focuses on cord stabilization to prevent further injury, rehabilitation, management of non-motor symptoms, and prevention of complications. Currently, no approved treatments are available, and limited treatment options exist for symptoms and complications associated with chronic SCI. This review describes the pharmacotherapy landscape in SCI from both commercial and research and development (R&D) standpoints through March 2015...
February 27, 2018: Journal of Spinal Cord Medicine
Azizul Haque, Rachel Polcyn, Denise Matzelle, Naren L Banik
Neurodegeneration is a complex process that leads to irreversible neuronal damage and death in spinal cord injury (SCI) and various neurodegenerative diseases, which are serious, debilitating conditions. Despite exhaustive research, the cause of neuronal damage in these degenerative disorders is not completely understood. Elevation of cell surface α-enolase activates various inflammatory pathways, including the production of pro-inflammatory cytokines, chemokines, and some growth factors that are detrimental to neuronal cells...
February 18, 2018: Brain Sciences
J Dai, L-J Xu, G-D Han, H-L Sun, G-T Zhu, H-T Jiang, G-Y Yu, X-M Tang
OBJECTIVE: Spinal cord injury (SCI) is a severe trauma to the central nervous system. Long non-coding RNAs have been reported to play essential roles in spinal cord injury. This study mainly explored the role of micro-125 in the regulation of spinal cord injury by regulating STAT3. MATERIALS AND METHODS: The stable mouse model of cervical spinal cord contusion was established by Infinite Horizon spinal cord striker, and the model mice' motor function was analyzed...
February 2018: European Review for Medical and Pharmacological Sciences
Jianjun Yuan, Xueli Zhang, Rusen Zhu, Zijian Cui, Wei Hu
The present study used a spinal cord injury (SCI) model to evaluate whether sparstolonin B was able to prevent SCI, and to investigate the underlying signaling mechanism. Sparstolonin B attenuated the SCI‑induced Batto, Beattie and Bresnahan score and water content in rats. Sparstolonin B attenuated the mRNA expression of proinflammatory cytokines interleukin (IL)‑18, IL‑6, IL‑1β, and IL‑23, decreased the levels of tumor necrosis factor‑α and interferon‑γ, and decreased caspase‑3 activity and apoptosis regulator Bax protein expression in SCI rats...
February 6, 2018: Molecular Medicine Reports
Eva Szekiova, Lucia Slovinska, Juraj Blasko, Jana Plsikova, Dasa Cizkova
Objectives In this study, a new approach was used with an in vitro model in which neural cells were exposed to conditioned media from the injured spinal cord (SCI-CM) mimicking a local inflammatory microenvironment . Subsequently, the neuroprotective effect of rat adipose tissue-derived msesenchymal stem cell-conditioned media (ATMSC-CM) was investigated through a cell-free based therapy, which was used to treat cortical neurons and astrocytes under inflammation. Methods Primary cell cultures isolated from postnatal day (P6) Wistar rat brain cortex were exposed to SCI-CM derived from the central lesion, rostral and caudal segments of injured spinal cord...
January 31, 2018: Neurological Research
Wang Wei, Chen Shurui, Zhou Zipeng, Dai Hongliang, Wang Hongyu, Li Yuanlong, Zhou Kang, Shen Zhaoliang, Guo Yue, Liu Chang, Xifan Mei
The nuclear factor E2-related factor 2 (Nrf2)/antioxidant response element signaling pathway plays a substantial role in preventing oxidative stress-related diseases. Aspirin has been shown to exert several pharmacological effects by inducing the expression of the heme oxygenase-1 (HO-1) protein. However, the effects of aspirin on spinal cord injury (SCI) have rarely been studied. Therefore, we sought to investigate the neuroprotective effects of aspirin after SCI. We employed a spinal cord contusion model in Sprague-Dawley rats, and aspirin was administered intraperitoneally for 7 days...
January 29, 2018: Neuroreport
Salim Senturk, Mesut Emre Yaman, Hasan Emre Aydin, Guven Guney, Ismail Bozkurt, Kemal Paksoy, Ahmet Atilla Abdioglu
AIM: Reversing the disastrous effects spinal cord injury has become the most prominent topic of neuroscience. Although many therapeutic interventions are being examined, there is yet no definitive cure for spinal cord injury (SCI). In view of this, an experimental study on rats after spinal trauma was performed to test the effects of a natural phenol; Resveratrol. MATERIAL AND METHODS: 18 Sprague Dawley rats were randomly divided into three groups. All groups underwent thoracic laminectomy...
December 6, 2017: Turkish Neurosurgery
K Truflandier, E Beaumont, E Charbonney, K Maghni, Michel De Marchie, J Spahija
RATIONALE: Spinal cord injury (SCI) may induce significant respiratory muscle weakness and paralysis, which in turn may cause a patient to require ventilator support. Central nervous system alterations can also exacerbate local inflammatory responses with immune cell infiltration leading to additional risk of inflammation at the injury site. Although mechanical ventilation is the traditional treatment for respiratory insufficiency, evidence has shown that it may directly affect distant organs through systemic inflammation...
January 17, 2018: Neuroscience Letters
Hui-Quan Duan, Qiu-Li Wu, Xue Yao, Bao-You Fan, Hong-Yu Shi, Chen-Xi Zhao, Yan Zhang, Bo Li, Chao Sun, Xiao-Hong Kong, Xin-Fu Zhou, Shi-Qing Feng
AIM: Spinal cord injury (SCI) leads to severe neural damage for which there is currently no effective treatment. Exploration of the neuroprotective effect among clinically approved drugs will speed up clinical translation of SCI. Nafamostat mesilate (NM) as a synthetic serine protease inhibitor has been used clinically in pancreatitis treatments. However, its effectiveness in SCI is unknown. The aim of this study was to confirm the efficacy of NM in ameliorating SCI. METHODS: Intraperitoneal administration of NM was performed on a contusion SCI model in Wistar rat...
January 19, 2018: CNS Neuroscience & Therapeutics
Fenzan Wu, Xiaojie Wei, Yanqing Wu, Xiaoxia Kong, Aiping Hu, Songlin Tong, Yanlong Liu, Fanhua Gong, Ling Xie, Jinjing Zhang, Jian Xiao, Hongyu Zhang
Spinal cord injury (SCI) is a severe nervous system disease that may lead to lifelong disability. Studies have shown that autophagy plays a key role in various diseases; however, the mechanisms regulating crosstalk between autophagy, inflammation and endoplasmic reticulum (ER) stress during SCI recovery remain unclear. This study was designed to investigate the mechanism by which chloroquine (CQ) inhibits autophagy-associated inflammation and ER-stress in rats during their recovery from acute SCI. We evaluated the locomotor function, level of autophagy, and levels of inflammatory cytokines and ER-stress associated proteins and examined the degradation of the key regulator of inflammation I-κBα through autophagy by analyzing the colocalization of I-κBα, p62 and LC3-II...
January 9, 2018: Journal of Neurotrauma
Paige Herman, Adam B Stein, Katie Gibbs, Ilya Korsunsky, Peter Gregersen, Ona Bloom
Infections are the leading cause of death for individuals with traumatic spinal cord injury (SCI). Along with increased infection rates, inflammation is often also observed in persons with chronic SCI. Together, immunological changes after SCI are also poised to impede neurological recovery and to mediate common medical consequences of SCI, including atherogenesis and neuropathic pain. The molecular mechanisms contributing to increased infection susceptibility and inflammation in persons living with SCI are poorly understood...
January 8, 2018: Journal of Neurotrauma
Leonardo Fonseca Rodrigues, Vivaldo Moura-Neto, Tania Cristina Leite de Sampaio E Spohr
Spinal cord injury (SCI) is considered an incurable condition, having a heterogenous recovery and uncertain prognosis. Therefore, a reliable prediction of the improvement in the acute phase could benefit patients. Physicians are unanimous in insisting that at the initial damage of the spinal cord (SC), the patient should be carefully evaluated in order to help selecting an appropriate neuroprotective treatment. However, currently, neurologic impairment after SCI is measured and classified by functional examination...
January 6, 2018: Molecular Neurobiology
Cheng-Hu Wang, Lin-Lin Zhu, Ke-Feng Ju, Jin-Long Liu, Kun-Peng Li
Delphinidin, a flavonoid polyphenolic compound, is widely found in nature and is used as a food supplement due to its pharmacological activity. The aims of the present study were to examine the anti-inflammatory effect of delphinidin in alleviating spinal cord injury (SCI)-induced inflammation in a rat model and to determine the underlying mechanisms in SCI. The Basso, Beattie, Bresnahan (BBB) scores of rats were assessed to evaluate the effect of delphinidin on the recovery of motor function. ELISA kits were also used to analyze the activities of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2) and caspase-3...
December 2017: Experimental and Therapeutic Medicine
Guodong Sun, Shuxian Yang, Guangchao Cao, Qianghua Wang, Jianlei Hao, Qiong Wen, Zhizhong Li, Kwok-Fai So, Zonghua Liu, Sufang Zhou, Yongxiang Zhao, Hengwen Yang, Libing Zhou, Zhinan Yin
Immune responses and neuroinflammation are critically involved in spinal cord injury (SCI). γδ T cells, a small subset of T cells, regulate the inflammation process in many diseases, yet their function in SCI is still poorly understood. In this paper, we demonstrate that mice deficient in γδ T cells (TCRδ-/- ) showed improved functional recovery after SCI. γδ T cells are detected at the lesion sites within 24 hours after injury and are predominantly of the Vγ4 subtype and express the inflammatory cytokine IFN-γ...
December 27, 2017: Journal of Experimental Medicine
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