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https://www.readbyqxmd.com/read/29348317/head-to-head-comparison-of-11c-pbr28-and-18f-ge180-for-the-quantification-of-tspo-in-the-human-brain
#1
Paolo Zanotti-Fregonara, Belen Pascual, Gaia Rizzo, Meixiang Yu, Neha Pal, David Beers, Randall Carter, Stanley Appel, Nazem Atassi, Joseph Masdeu
Introduction:18F-GE180 is a third-generation positron emission tomography (PET) tracer to quantify the translocator protein TSPO, a biomarker for inflammation. The aim of this study was to compare head-to-head 18F-GE180 to the well-established translocator protein (TSPO) tracer 11C-PBR28, by scanning with either tracer during the same day in the same subjects. Materials and Methods: Five subjects underwent a 90-minute PET scan with 11C-PBR28 in the morning and 18F-GE180 in the afternoon. A metabolite-corrected arterial input function was obtained in each subject for both tracers, and the brain uptake was quantified with a two-tissue compartmental model...
January 18, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29348018/myocardial-inflammation-predicts-remodeling-and-neuroinflammation-after-myocardial-infarction
#2
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/29343269/microglial-activation-mediates-chronic-mild-stress-induced-depressive-and-anxiety-like-behavior-in-adult-rats
#3
Ya-Lin Wang, Qiu-Qin Han, Wen-Qing Gong, Dong-Hui Pan, Li-Zheng Wang, Wei Hu, Min Yang, Bing Li, Jin Yu, Qiong Liu
BACKGROUND: Depression is a heterogeneous disorder, with the exact neuronal mechanisms causing the disease yet to be discovered. Recent work suggests it is accompanied by neuro-inflammation, characterized, in particular, by microglial activation. However, microglial activation and its involvement in neuro-inflammation and stress-related depressive disorders are far from understood. METHODS: We utilized multiple detection methods to detect the neuro-inflammation in the hippocampus of rats after exposure to chronic mild stress (CMS)...
January 17, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29342117/assessment-of-tspo-in-a-rat-experimental-autoimmune-myocarditis-model-a-comparison-study-between-18f-fluoromethyl-pbr28-and-18f-cb251
#4
Ga Ram Kim, Jin Chul Paeng, Jae Ho Jung, Byung Seok Moon, Antonio Lopalco, Nunzio Denora, Byung Chul Lee, Sang Eun Kim
Overexpression of the 18-kDa translocator protein (TSPO) is closely linked to inflammatory responses in the heart, including myocarditis, which can lead to myocardial necrosis. In vivo assessment of inflammatory responses has enabled the precise diagnosis of myocarditis to improve clinical outcomes. Here, we evaluated TSPO overexpression in a rat model of experimental autoimmune myocarditis (EAM) compared to healthy rats using two TSPO radiotracers, [18F]fluoromethyl-PBR28 ([18F]1) and [18F]CB251 ([18F]2). All radiolabeling methods were successfully applied to an automated module for the reproducible preparation of TSPO radiotracers...
January 17, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29332041/in-vivo-visualization-of-tau-accumulation-microglial-activation-and-brain-atrophy-in-a-mouse-model-of-tauopathy-rtg4510
#5
Ai Ishikawa, Masaki Tokunaga, Jun Maeda, Takeharu Minamihisamatsu, Masafumi Shimojo, Hiroyuki Takuwa, Maiko Ono, Ruiqing Ni, Shigeki Hirano, Satoshi Kuwabara, Bin Ji, Ming-Rong Zhang, Ichio Aoki, Tetsuya Suhara, Makoto Higuchi, Naruhiko Sahara
BACKGROUND: Tau imaging using PET is a promising tool for the diagnosis and evaluation of tau-related neurodegenerative disorders, but the relationship among PET-detectable tau, neuroinflammation, and neurodegeneration is not yet fully understood. OBJECTIVE: We aimed to elucidate sequential changes in tau accumulation, neuroinflammation, and brain atrophy by PET and MRI in a tauopathy mouse model. METHODS: rTg4510 transgenic (tg) mice expressing P301L mutated tau and non-tg mice were examined with brain MRI and PET imaging (analyzed numbers: tg = 17, non-tg = 13; age 2...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29328425/bioinformatics-analysis-of-the-cdk2-functions-in-neuroblastoma
#6
Lijuan Bo, Bo Wei, Zhanfeng Wang, Daliang Kong, Zheng Gao, Zhuang Miao
The present study aimed to elucidate the potential mechanism of cyclin-dependent kinase 2 (CDK2) in neuroblastoma progression and to identify the candidate genes associated with neuroblastoma with CDK2 silencing. The microarray data of GSE16480 were obtained from the gene expression omnibus database. This dataset contained 15 samples: Neuroblastoma cell line IMR32 transfected with CDK2 shRNA at 0, 8, 24, 48 and 72 h (n=3 per group; total=15). Significant clusters associated with differentially expressed genes (DEGs) were identified using fuzzy C‑Means algorithm in the Mfuzz package...
December 29, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29326362/-18f-pbr111-pet-imaging-in-healthy-controls-and-schizophrenia-test-retest-reproducibility-and-quantification-of-neuroinflammation
#7
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/29326355/18f-fedac-as-a-targeting-agent-for-activated-macrophages-in-dba-1-mice-with-collagen-induced-arthritis-comparison-with-18f-fdg
#8
Seock-Jin Chung, Hai-Jeon Yoon, Gi Jeong Cheon, Hyewon Youn, Mi Jeong Kim, Lin Xie, Yun-Sang Lee, Jae Min Jeong, June-Key Chung, Keon Wook Kang, Ming-Rong Zhang
Activated macrophages have been known to play pivotal roles in the pathogenesis of rheumatoid arthritis (RA). 18F-FEDAC is a radiolabeled ligand for the translocator protein (TSPO), which is abundant in activated macrophages. We evaluated the feasibility of 18F-FEDAC in a murine RA model. Methods: RAW 264.7 mouse macrophages were activated by lipopolysaccharide. TSPO expression levels in activated and inactivated macrophages were measured by quantitative polymerase chain reaction (qPCR) and western blotting...
January 11, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29315754/tspo-regulation-in-reactive-gliotic-diseases
#9
REVIEW
Adam M McNeela, Charles Bernick, Rochelle M Hines, Dustin J Hines
The brain is the most metabolically active organ in the body. This high metabolic demand is apparent in that 60% of the brain is comprised of mitochondria-enriched cells. A disruption of the brain's ability to meet this immense metabolic demand is central to the pathogenesis of a multitude of neurological disorders, which range from depression to Alzheimer's disease. Central to these pathologies are glial signaling and energy metabolism cascades regulating apoptosis and inflammation. Thus, diseases causing inflammation and disruption of metabolism can be correlated with glial reactivity...
January 6, 2018: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/29305671/investigation-into-the-effects-of-tenilsetam-on-markers-of-neuroinflammation-in-gfap-il6-mice
#10
Erika Gyengesi, Huazheng Liang, Christopher Millington, Sandra Sonego, Daniel Sirijovski, Dhanushka Gunawardena, Karthik Dhananjayan, Madhuri Venigalla, Garry Niedermayer, Gerald Münch
PURPOSE: To test the short- and long-term effects of Tenilsetam on chronic neuroinflammation in the GFAP-IL6 mouse. METHODS: From 3 months of age, GFAP-IL6 mice were divided into 2 groups and fed with Tenilsetam enriched food pellets or control food pellets, respectively, for either 5 or 15 months. Total numbers of Iba-1+ microglia, TSPO+ cells were determined using an unbiased stereological method. Levels of methylglyoxal and TNF-α in the cerebellar homogenate were tested using HPLC and ELISA, respectively...
January 5, 2018: Pharmaceutical Research
https://www.readbyqxmd.com/read/29301931/translocator-protein-as-an-imaging-marker-of-macrophage-and-stromal-activation-in-ra-pannus
#11
Nehal Narayan, David Owen, Harpreet Mandhair, Erica Smyth, Francesco Carlucci, Azeem Saleem, Roger Gunn, Eugenii Ilan A Rabiner, Lisa Wells, Stephanie Dakin, Afsie Sabokbar, Peter Taylor
Positron Emission Tomography (PET) radioligands targeted to Translocator protein (TSPO), offer a highly sensitive and specific means of imaging joint inflammation in rheumatoid arthritis (RA). Through high expression of TSPO on activated macrophages, TSPO PET has been widely reported in several studies of RA as a means of imaging synovial macrophages in vivo. However, this premise does not take into account the ubiquitous expression of TSPO. This study aimed to investigate TSPO expression in major cellular constituents of RA pannus; monocytes, macrophages, fibroblast-like synoviocytes (FLS) and CD4+ T lymphocytes, to more accurately interpret TSPO PET signal from RA synovium...
January 4, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29300865/crispr-cas9-mediated-tspo-gene-mutations-lead-to-reduced-mitochondrial-membrane-potential-and-steroid-formation-in-ma-10-mouse-tumor-leydig-cells
#12
Jinjiang Fan, Kevin Wang, Barry Zirkin, Vassilios Papadopoulos
The outer mitochondrial membrane translocator protein (TSPO) binds cholesterol with high affinity and is involved in mediating its delivery into mitochondria, the rate-limiting step in hormone-induced steroidogenesis. Specific ligand binding to TSPO has been shown to initiate steroid formation. However, recent studies of the genetic deletion of Tspo have provided conflicting results. Here we address and extend previous studies by examining the effects of Tspo - specific mutations on steroid formation in the hormone- and cAMP-responsive MA-10 cells, using the CRISPR/Cas9 system...
December 28, 2017: Endocrinology
https://www.readbyqxmd.com/read/29299119/identifying-mitotane-induced-mitochondria-associated-membranes-dysfunctions-metabolomic-and-lipidomic-approaches
#13
Ségolène Hescot, Larbi Amazit, Marie Lhomme, Simon Travers, Anais DuBow, Stephanie Battini, Geoffrey Boulate, Izzie Jacques Namer, Anne Lombes, Anatol Kontush, Alessio Imperiale, Eric Baudin, Marc Lombes
Mitotane (o,p'DDD), the most effective drug in adrenocortical carcinoma, concentrates into the mitochondria and impacts mitochondrial functions. To address the molecular mechanisms of mitotane action and to identify its potential target, metabolomic and lipidomic approaches as well as imaging analyses were employed in human adrenocortical H295R cells allowing identification of Mitochondria-Associated Membranes dysfunction as a critical impact of mitotane. Study of intracellular energetic metabolites by NMR spectroscopy showed that mitotane significantly decreased aspartate while concomitantly increased glutamate content in a time- and concentration-dependent manner...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29274431/trajectory-of-inflammatory-and-microglial-activation-markers-in-the-postnatal-rabbit-brain-following-intrauterine-endotoxin-exposure
#14
Zhi Zhang, Amar Jyoti, Bindu Balakrishnan, Monica Williams, Sarabdeep Singh, Diane C Chugani, Sujatha Kannan
BACKGROUND: Maternal infection is a risk factor for periventricular leukomalacia and cerebral palsy (CP) in neonates. We have previously demonstrated hypomyelination and motor deficits in newborn rabbits, as seen in patients with cerebral palsy, following maternal intrauterine endotoxin administration. This was associated with increased microglial activation, primarily involving the periventricular region (PVR). In this study we hypothesized that maternal intrauterine inflammation leads to a pro-inflammatory environment in the PVR that is associated with microglial activation in the first 2 postnatal weeks...
December 20, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/29242722/recent-progress-in-the-development-of-tspo-pet-ligands-for-neuroinflammation-imaging-in-neurological-diseases
#15
REVIEW
Md Maqusood Alam, Jihye Lee, Sang-Yoon Lee
Neuroinflammation is heavily associated with various neurological diseases including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and stroke. It is strongly characterized by the activation of microglia which can be visualized using position emission tomography (PET). Traditionally, translocator protein 18 kDa (TSPO) has been the preferred target for imaging the inflammatory progression of the microglial component. TSPO is expressed in the outer mitochondrial membrane and present in very low concentrations in the healthy human brain, but is markedly upregulated in response to brain injury and inflammation...
December 2017: Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/29211020/an-updated-view-of-translocator-protein-tspo
#16
EDITORIAL
Nunzio Denora, Giovanni Natile
Decades of study on the role of mitochondria in living cells have evidenced the importance of the 18 kDa mitochondrial translocator protein (TSPO), first discovered in the 1977 as an alternative binding site for the benzodiazepine diazepam in the kidneys. This protein participates in a variety of cellular functions, including cholesterol transport, steroid hormone synthesis, mitochondrial respiration, permeability transition pore opening, apoptosis, and cell proliferation. Thus, TSPO has become an extremely attractive subcellular target for the early detection of disease states that involve the overexpression of this protein and the selective mitochondrial drug delivery...
December 6, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29207414/tspo-pet-imaging-to-assess-cerebral-microglial-activation-in-multiple-sclerosis
#17
Tarun Singhal, Howard L Weiner, Rohit Bakshi
No abstract text is available yet for this article.
October 2017: Seminars in Neurology
https://www.readbyqxmd.com/read/29203847/reconceptualization-of-translocator-protein-as-a-biomarker-of-neuroinflammation-in-psychiatry
#18
T Notter, J M Coughlin, A Sawa, U Meyer
A great deal of interest in psychiatric research is currently centered upon the pathogenic role of inflammatory processes. Positron emission tomography (PET) using radiolabeled ligands selective for the 18 kDa translocator protein (TSPO) has become the most widely used technique to assess putative neuroimmune abnormalities in vivo. Originally used to detect discrete neurotoxic damages, TSPO has generally turned into a biomarker of 'neuroinflammation' or 'microglial activation'. Psychiatric research has mostly accepted these denotations of TSPO, even if they may be inadequate and misleading under many pathological conditions...
January 2018: Molecular Psychiatry
https://www.readbyqxmd.com/read/29203457/non-invasive-estimation-of-11c-pbr28-binding-potential
#19
Martin Schain, Francesca Zanderigo, R Todd Ogden, William C Kreisl
[11C]PBR28 is a PET radioligand used to estimate densities of the 18 kDa translocator protein (TSPO) in vivo. Since there is no suitable reference region, arterial blood samples are required for full quantification. Here, we evaluate a methodology for full quantification of [11C]PBR28 PET data that does not require either a reference region or blood samples. Simultaneous estimation (SIME) uses time-activity curves from several brain regions to estimate binding potential (BPND), a theoretically more sensitive outcome measure than total distribution volume...
December 1, 2017: NeuroImage
https://www.readbyqxmd.com/read/29201010/microglia-and-brain-plasticity-in-acute-psychosis-and-schizophrenia-illness-course-a-meta-review
#20
REVIEW
Livia J De Picker, Manuel Morrens, Steven A Chance, Delphine Boche
Objective: Schizophrenia poses a tremendous health, social, and economic burden upon patients and society, indicating current treatment options remain inadequate. Recent findings from several lines of evidence have pointed to the importance of immune system involvement in not only premorbid neurodevelopmental but also subsequent symptom generation and aging processes of brain change in schizophrenia. In this meta-review, we use the summarized evidence from recent quantitative systematic reviews (SRs) and meta-analyses of several subspecialties to critically evaluate the hypothesis that immune-related processes shape the symptomatic presentation and illness course of schizophrenia, both directly and indirectly through altered neuroplasticity...
2017: Frontiers in Psychiatry
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