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https://www.readbyqxmd.com/read/29351125/central-inhibition-of-granulocyte-macrophage-colony-stimulating-factor-is-analgesic-in-experimental-neuropathic-pain
#1
Louise S C Nicol, Peter Thornton, Jon P Hatcher, Colin P Glover, Carl I Webster, Matthew Burrell, Kessia Hammett, Clare A Jones, Matthew A Sleeman, Andrew Billinton, Iain Chessell
With less than 50% of patients responding to the current standard of care and poor efficacy and selectivity of current treatments, neuropathic pain continues to be an area of considerable unmet medical need. Biological therapeutics such as monoclonal antibodies (mAbs) provide better intrinsic selectivity; however, delivery to the central nervous system (CNS) remains a challenge. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is well described in inflammation-induced pain, and early-phase clinical trials evaluating its antagonism have exemplified its importance as a peripheral pain target...
January 16, 2018: Pain
https://www.readbyqxmd.com/read/29349661/pkm2-is-involved-in-neuropathic-pain-by-regulating-erk-and-stat3-activation-in-rat-spinal-cord
#2
Binbin Wang, Siyuan Liu, Bingbing Fan, Xingguo Xu, Yonglin Chen, Rongxiang Lu, Zhongling Xu, Xiaojuan Liu
BACKGROUND: Pyruvate kinase isozymes M2 (PKM2), as a member of pyruvate kinase family, plays a role of glycolytic enzyme in glucose metabolism. It also functions as protein kinase in cell proliferation, signaling, immunity, and gene transcription. In this study, the role of PKM2 in neuropathic pain induced by chronic constriction injury (CCI) was investigated. METHODS: Rats were randomly grouped to establish CCI models. PKM2, extracellular regulated protein kinases (EKR), p-ERK, signal transducers and activators of transcription (STAT3), p-STAT3, phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) and p-PI3K/AKT proteins expression in spinal cord was examined by Western blot analysis...
January 18, 2018: Journal of Headache and Pain
https://www.readbyqxmd.com/read/29349289/mixed-neurodevelopmental-and-neurodegenerative-pathology-in-nhe6-null-mouse-model-of-christianson-syndrome
#3
Meiyu Xu, Qing Ouyang, Jingyi Gong, Matthew F Pescosolido, Brandon S Pruett, Sasmita Mishra, Michael Schmidt, Richard N Jones, Ece D Gamsiz Uzun, Sofia B Lizarraga, Eric M Morrow
Christianson syndrome (CS) is an X-linked disorder resulting from loss-of-function mutations in SLC9A6, which encodes the endosomal Na+/H+ exchanger 6 (NHE6). Symptoms include early developmental delay, seizures, intellectual disability, nonverbal status, autistic features, postnatal microcephaly, and progressive ataxia. Neuronal development is impaired in CS, involving defects in neuronal arborization and synaptogenesis, likely underlying diminished brain growth postnatally. In addition to neurodevelopmental defects, some reports have supported neurodegenerative pathology in CS with age...
November 2017: ENeuro
https://www.readbyqxmd.com/read/29348018/myocardial-inflammation-predicts-remodeling-and-neuroinflammation-after-myocardial-infarction
#4
James T Thackeray, Henri C Hupe, Yong Wang, Jens P Bankstahl, Georg Berding, Tobias L Ross, Johann Bauersachs, Kai C Wollert, Frank M Bengel
BACKGROUND: The local inflammatory tissue response after acute myocardial infarction (MI) determines subsequent healing. Systemic interaction may induce neuroinflammation as a precursor to neurodegeneration. OBJECTIVES: This study sought to assess the influence of MI on cardiac and brain inflammation using noninvasive positron emission tomography (PET) of the heart-brain axis. METHODS: After coronary artery ligation or sham surgery, mice (n = 49) underwent serial whole-body PET imaging of the mitochondrial translocator protein (TSPO) as a marker of activated macrophages and microglia...
January 23, 2018: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/29340071/hypoxia-inducible-factor-1%C3%AE-regulates-microglial-functions-affecting-neuronal-survival-in-the-acute-phase-of-ischemic-stroke-in-mice
#5
Seoyeon Bok, Young-Eun Kim, Youngsik Woo, Soeun Kim, Suk-Jo Kang, Yoontae Lee, Sang Ki Park, Irving L Weissman, G-One Ahn
Cells universally adapt to ischemic conditions by turning on a transcription factor hypoxia-inducible factor (HIF), in which its role is known to differ widely across many different types of cells. Given that microglia have been reported as an essential mediator of neuroinflammation in many brain diseases, we examined the role of HIF in microglia in the progression of an acute phase of ischemic stroke by challenging our novel strains of myeloid-specific Hif-1α or Hif-2α knockout (KO) mice created by Cre-loxP system via middle cerebral artery occlusion (MCAO)...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29339006/food-allergy-induces-alteration-in-brain-inflammatory-status-and-cognitive-impairments
#6
Liqing Zhou, Long Chen, Xiaohuan Li, Tingyu Li, Zhifang Dong, Yu Tian Wang
Accumulating evidence supports an increase in emotional and behavioral problems in patients with food allergy, but the underlying mechanism remains poorly understood. Here we found that in addition to inducing an increase of allergic factors in serum, food allergy also increased levels of antigen-specific immunoglobulins and mast cell marker in the brain. In particular, food allergy increased the number of total microglia and the percentage of active microglia in the cerebral cortex and hippocampal CA1 areas, and induced the increase of TNF-α in the cerebral cortex...
January 12, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/29338384/human-umbilical-cord-mesenchymal-stem-cells-preserve-adult-newborn-neurons-and-reduce-neurological-injury-after-cerebral-ischemia-by-reducing-the-number-of-hypertrophic-microglia-macrophages
#7
Willie Lin, Yogi Chang-Yo Hsuan, Mao-Tsun Lin, Ting-Wei Kuo, Cheng-Hsien Lin, Yu-Chin Su, Ko-Chi Niu, Ching-Ping Chang, Hung-Jung Lin
Microglia are the first source of a neuroinflammatory cascade, which seems to be involved in every phase of stroke-related neuronal damage. Two weeks after transient middle cerebral artery occlusion (MCAO), vehicle-treated rats displayed higher numbers of total ionized calcium-binding adaptor molecule 1 (Iba-1)-positive cells, greater cell body areas of Iba-1-positive cells, and higher numbers of hypertrophic Iba-1-positive cells (with a cell body area over 80 μm2) in the ipsilateral ischemic brain regions including the frontal cortex, striatum, and parietal cortex...
November 2017: Cell Transplantation
https://www.readbyqxmd.com/read/29331684/reprogramming-neurodegeneration-in-the-big-data-era
#8
REVIEW
Lujia Zhou, Patrik Verstreken
Recent genome-wide association studies (GWAS) have identified numerous genetic risk variants for late-onset Alzheimer's disease (AD) and Parkinson's disease (PD). However, deciphering the functional consequences of GWAS data is challenging due to a lack of reliable model systems to study the genetic variants that are often of low penetrance and non-coding identities. Pluripotent stem cell (PSC) technologies offer unprecedented opportunities for molecular phenotyping of GWAS variants in human neurons and microglia...
January 10, 2018: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/29329985/the-scavenger-activity-of-the-human-p2x7-receptor-differs-from-p2x7-pore-function-by-insensitivity-to-antagonists-genetic-variation-and-sodium-concentration-relevance-to-inflammatory-brain-diseases
#9
Amber Ou, Ben J Gu, James S Wiley
Activation of P2X7 receptors is widely recognised to initiate proinflammatory responses. However P2X7 also has a dual function as a scavenger receptor which is active in the absence of ATP and plasma proteins and may be important in central nervous system (CNS) diseases. Here, we investigated both P2X7 pore formation and its phagocytic function in fresh human monocytes (as a model of microglia) by measuring ATP-induced ethidium dye uptake and fluorescent bead uptake respectively. This was studied in monocytes expressing various polymorphic variants as well as in the presence of different P2X7 antagonists and ionic media...
January 9, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29328072/immunomodulatory-effect-of-cd200-positive-human-placenta-derived-stem-cells-in-the-early-phase-of-stroke
#10
TaeHo Kong, Ji-Min Park, Ji Hyon Jang, C-Yoon Kim, Sang-Hun Bae, Yuri Choi, Yun-Hwa Jeong, Chul Kim, Sung Woon Chang, Joopyung Kim, Jisook Moon
Human placenta amniotic membrane-derived mesenchymal stem cells (AMSCs) regulate immune responses, and this property can be exploited to treat stroke patients via cell therapy. We investigated the expression profile of AMSCs cultured under hypoxic conditions and observed interesting expression changes in various genes involved in immune regulation. CD200, an anti-inflammatory factor and positive regulator of TGF-β, was more highly expressed under hypoxic conditions than normoxic conditions. Furthermore, AMSCs exhibited inhibition of pro-inflammatory cytokine expression in co-cultures with LPS-primed BV2 microglia, and this effect was decreased in CD200-silenced AMSCs...
January 12, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29327816/brain-cortex-microglia-derived-exosomes-novel-nanoparticles-for-glioma-therapy
#11
Adriana-Natalia Murgoci, Dasa Cizkova, Petra Majerova, Eva Petrovova, Lubomir Medvecky, Isabelle Fournier, Michel Salzet
The function and integrity of nervous system require interactive exchanges among neurons and glial cells. Exosomes and other extracellular vesicles (EVs) are emerging as a key mediator of intercellular communication, capable to transfer nucleic acids, proteins and lipids, influencing numerous functional and pathological aspects of both donor and recipient cells. The immune response mediated by microglia derived exosomes are most prominently involved in the spread of neuroinflammation, neurodegenerative disorders and brain cancer...
January 12, 2018: Chemphyschem: a European Journal of Chemical Physics and Physical Chemistry
https://www.readbyqxmd.com/read/29327228/postoperative-intermittent-fasting-prevents-hippocampal-oxidative-stress-and-memory-deficits-in-a-rat-model-of-chronic-cerebral-hypoperfusion
#12
Yuan Hu, Miao Zhang, Yunyun Chen, Ying Yang, Jun-Jian Zhang
PURPOSE: Whether intermittent fasting (IF) treatment after stroke can prevent its long-term detrimental effects remains unknown. Here, we investigate the effects of postoperative IF on cognitive deficits and its underlying mechanisms in a permanent two-vessel occlusion (2VO) vascular dementia rat model. METHODS: Rats were subjected to either IF or ad libitum feeding 1 week after 2VO surgery. The cognition of rats was assessed using the novel object recognition (NOR) task and Morris water maze (MWM) 8 weeks after surgery...
January 11, 2018: European Journal of Nutrition
https://www.readbyqxmd.com/read/29326362/-18f-pbr111-pet-imaging-in-healthy-controls-and-schizophrenia-test-retest-reproducibility-and-quantification-of-neuroinflammation
#13
Julie Ottoy, Livia De Picker, Jeroen Verhaeghe, Steven Deleye, Leonie Wyffels, Lauren Kosten, Bernard Sabbe, Violette Coppens, Maarten Timmers, Luc Van Nueten, Sarah Ceyssens, Sigrid Stroobants, Manuel Morrens, Steven Staelens
Activated microglia express the translocator protein (TSPO) on the outer mitochondrial membrane. 18F-PBR111 is a second-generation positron emission tomography (PET) ligand that specifically binds the TSPO, allowing in-vivo visualization and quantification of neuroinflammation. The aim of this study is to evaluate if the test-retest variability of 18F-PBR111 in healthy controls is acceptable to detect a psychosis-associated neuroinflammatory signal in schizophrenia. Methods: Dynamic 90-min 18F-PBR111 scans were obtained in 17 healthy male controls (HC) and 11 male schizophrenia patients during a psychotic episode (SP)...
January 11, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29323194/human-mesenchymal-stromal-cell-derived-extracellular-vesicles-modify-microglial-response-and-improve-clinical-outcomes-in-experimental-spinal-cord-injury
#14
Katherine A Ruppert, Tin T Nguyen, Karthik S Prabhakara, Naama E Toledano Furman, Amit K Srivastava, Matthew T Harting, Charles S Cox, Scott D Olson
No current clinical intervention can alter the course of acute spinal cord injury (SCI), or appreciably improve neurological outcome. Mesenchymal stromal cells (MSCs) have been shown to modulate the injury sequelae of SCI largely via paracrine effects, although the mechanisms remain incompletely understood. One potential modality is through secretion of extracellular vesicles (EVs). In this study, we investigate whether systemic administration of EVs isolated from human MSCs (MSCEv) has the potential to be efficacious as an alternative to cell-based therapy for SCI...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29323156/ischemia-induced-neuronal-cell-death-is-mediated-by-chemokine-receptor-cx3cr1
#15
Jinkun Wang, Yan Gan, Pengcheng Han, Junxiang Yin, Qingwei Liu, Soha Ghanian, Feng Gao, Guanghui Gong, Zhiwei Tang
The chemokine fractalkine (CX3CL1) and its receptor CX3CR1 play a fundamental role in the pathophysiology of stroke. Previous studies have focused on a paracrine interaction between neurons that produce fractalkine and microglia that express CX3CR1 receptors in the central nervous system. Recent findings have demonstrated the functional expression of CX3CR1 receptors by hippocampal neurons, suggesting their involvement in neuroprotective and neurodegenerative actions. To elucidate the roles of neuronal CX3CR1 in neurodegeneration induced by ischemic stroke, a mouse model of permanent middle cerebral artery occlusion (pMCAO) was employed...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29323027/micrornas-in-parkinson-s-disease-and-emerging-therapeutic-targets
#16
REVIEW
Bridget Martinez, Philip V Peplow
Parkinson's disease (PD) is the second most common age-related neurodegenerative disorder, with the clinical main symptoms caused by a loss of dopaminergic neurons in the substantia nigra, corpus striatum and brain cortex. Over 90% of patients with PD have sporadic PD and occur in people with no known family history of the disorder. Currently there is no cure for PD. Treatment with medications to increase dopamine relieves the symptoms but does not slow down or reverse the damage to neurons in the brain. Increasing evidence points to inflammation as a chief mediator of PD with inflammatory response mechanisms, involving microglia and leukocytes, activated following loss of dopaminergic neurons...
December 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/29321225/humanized-trem2-mice-reveal-microglia-intrinsic-and-extrinsic-effects-of-r47h-polymorphism
#17
Wilbur M Song, Satoru Joshita, Yingyue Zhou, Tyler K Ulland, Susan Gilfillan, Marco Colonna
Alzheimer's disease (AD) is a neurodegenerative disease that causes late-onset dementia. The R47H variant of the microglial receptor TREM2 triples AD risk in genome-wide association studies. In mouse AD models, TREM2-deficient microglia fail to proliferate and cluster around the amyloid-β plaques characteristic of AD. In vitro, the common variant (CV) of TREM2 binds anionic lipids, whereas R47H mutation impairs binding. However, in vivo, the identity of TREM2 ligands and effect of the R47H variant remain unknown...
January 10, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29316776/phagocytic-roles-of-glial-cells-in-healthy-and-diseased-brains
#18
REVIEW
Yeon-Joo Jung, Won-Suk Chung
Glial cells are receiving much attention since they have been recognized as important regulators of many aspects of brain function and disease. Recent evidence has revealed that two different glial cells, astrocytes and microglia, control synapse elimination under normal and pathological conditions via phagocytosis. Astrocytes use the MEGF10 and MERTK phagocytic pathways, and microglia use the classical complement pathway to recognize and eliminate unwanted synapses. Notably, glial phagocytosis also contributes to the clearance of disease-specific protein aggregates, such as β-amyloid, huntingtin, and α-synuclein...
January 10, 2018: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/29315334/immune-related-genetic-enrichment-in-frontotemporal-dementia-an-analysis-of-genome-wide-association-studies
#19
Iris Broce, Celeste M Karch, Natalie Wen, Chun C Fan, Yunpeng Wang, Chin Hong Tan, Naomi Kouri, Owen A Ross, Günter U Höglinger, Ulrich Muller, John Hardy, Parastoo Momeni, Christopher P Hess, William P Dillon, Zachary A Miller, Luke W Bonham, Gil D Rabinovici, Howard J Rosen, Gerard D Schellenberg, Andre Franke, Tom H Karlsen, Jan H Veldink, Raffaele Ferrari, Jennifer S Yokoyama, Bruce L Miller, Ole A Andreassen, Anders M Dale, Rahul S Desikan, Leo P Sugrue
BACKGROUND: Converging evidence suggests that immune-mediated dysfunction plays an important role in the pathogenesis of frontotemporal dementia (FTD). Although genetic studies have shown that immune-associated loci are associated with increased FTD risk, a systematic investigation of genetic overlap between immune-mediated diseases and the spectrum of FTD-related disorders has not been performed. METHODS AND FINDINGS: Using large genome-wide association studies (GWASs) (total n = 192,886 cases and controls) and recently developed tools to quantify genetic overlap/pleiotropy, we systematically identified single nucleotide polymorphisms (SNPs) jointly associated with FTD-related disorders-namely, FTD, corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), and amyotrophic lateral sclerosis (ALS)-and 1 or more immune-mediated diseases including Crohn disease, ulcerative colitis (UC), rheumatoid arthritis (RA), type 1 diabetes (T1D), celiac disease (CeD), and psoriasis...
January 2018: PLoS Medicine
https://www.readbyqxmd.com/read/29310519/intranasal-stem-cell-treatment-as-a-novel-therapy-for-subarachnoid-hemorrhage
#20
Cora H Nijboer, Elke Kooijman, Cindy T van Velthoven, Erik Van Tilborg, Ivo A Tiebosch, Niels Eijkelkamp, Rick M Dijkhuizen, Jozef Kesecioglu, Cobi Heijnen
Subarachnoid hemorrhage (SAH) represents a major health problem in Western society due to high mortality and morbidity, and the relative young age of patients. Currently, efficacious therapeutic options are very limited. Mesenchymal stem cell (MSC) administration has been shown to improve functional outcome and lesion size in experimental models of stroke and neonatal hypoxic-ischemic brain injury. Here we studied the therapeutic potential of intranasally administered bone marrow-derived MSCs relatively late post-insult using a rat endovascular puncture model for SAH...
January 8, 2018: Stem Cells and Development
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