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https://www.readbyqxmd.com/read/29159046/imaging-of-glia-activation-in-people-with-primary-lateral-sclerosis
#1
Sabrina Paganoni, Mohamad J Alshikho, Nicole R Zürcher, Paul Cernasov, Suma Babu, Marco L Loggia, James Chan, Daniel B Chonde, David Izquierdo Garcia, Ciprian Catana, Caterina Mainero, Bruce R Rosen, Merit E Cudkowicz, Jacob M Hooker, Nazem Atassi
Background: Glia activation is thought to contribute to neuronal damage in several neurodegenerative diseases based on preclinical and human post-mortem studies, but its role in primary lateral sclerosis (PLS) is unknown. Objectives: To localize and measure glia activation in people with PLS compared to healthy controls (HC). Methods: Ten participants with PLS and ten age-matched HCs underwent simultaneous magnetic resonance (MR) and proton emission tomography (PET)...
2018: NeuroImage: Clinical
https://www.readbyqxmd.com/read/29150726/tspo-imaging-using-the-novel-pet-ligand-18-f-ge-180-quantification-approaches-in-patients-with-multiple-sclerosis
#2
Lena Vomacka, Nathalie Lisa Albert, Simon Lindner, Marcus Unterrainer, Christoph Mahler, Matthias Brendel, Larissa Ermoschkin, Astrid Gosewisch, Anika Brunegraf, Christopher Buckley, Tania Kümpfel, Rainer Rupprecht, Sibylle Ziegler, Martin Kerschensteiner, Peter Bartenstein, Guido Böning
BACKGROUND: PET ligands targeting the translocator protein (TSPO) represent promising tools to visualise neuroinflammation. Here, we analysed parameters obtained in dynamic and static PET images using the novel TSPO ligand [(18)F]GE-180 in patients with relapsing remitting multiple sclerosis (RRMS) and an approach for semi-quantitative assessment of this disease in clinical routine. Seventeen dynamic [(18)F]GE-180 PET scans of RRMS patients were evaluated (90 min). A pseudo-reference region (PRR) was defined after identification of the least disease-affected brain area by voxel-based comparison with six healthy controls (HC) and upon exclusion of voxels suspected of being affected in static 60-90 min p...
October 26, 2017: EJNMMI Research
https://www.readbyqxmd.com/read/29146879/2-cl-mgv-1-ameliorates-apoptosis-in-the-thalamus-and-hippocampus-and-cognitive-deficits-after-cortical-infarct-in-rats
#3
Yicong Chen, Leo Veenman, Sukhdev Singh, Fubing Ouyang, Jiahui Liang, Weixian Huang, Ilan Marek, Jinsheng Zeng, Moshe Gavish
BACKGROUND AND PURPOSE: Focal cortical infarction causes neuronal apoptosis in the ipsilateral nonischemic thalamus and hippocampus, which is potentially associated with poststroke cognitive deficits. TSPO (translocator protein) is critical in regulating mitochondrial apoptosis pathways. We examined the effects of the novel TSPO ligand 2-(2-chlorophenyl)quinazolin-4-yl dimethylcarbamate (2-Cl-MGV-1) on poststroke cognitive deficits, neuronal mitochondrial apoptosis, and secondary damage in the ipsilateral thalamus and hippocampus after cortical infarction...
November 16, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/29135382/generalization-of-endothelial-modelling-of-tspo-pet-imaging-considerations-on-tracer-affinities
#4
Gaia Rizzo, Mattia Veronese, Matteo Tonietto, Benedetta Bodini, Bruno Stankoff, Catriona Wimberley, Sonia Lavisse, Michel Bottlaender, Peter S Bloomfield, Oliver Howes, Paolo Zanotti-Fregonara, Federico E Turkheimer, Alessandra Bertoldo
The 18 kDa translocator protein (TSPO) is a marker of microglia activation and the main target of positron emission tomography (PET) ligands for neuroinflammation. Previous works showed that accounting for TSPO endothelial binding improves PET quantification for [(11)C]PBR28, [(18)F]DPA714 and [(11)C]-R-PK11195. It is still unclear, however, whether the vascular signal is tracer-dependent. This work aims to explore the relationship between the TSPO vascular and tissue components for PET tracers with varying affinity, also assessing the impact of affinity towards the differentiability amongst kinetics and the ensuing ligand amenability to cluster analysis for the extraction of a reference region...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/29135331/imaging-microglial-activation-and-amyloid-burden-in-amnestic-mild-cognitive-impairment
#5
Dunja Knezevic, Nicolaas Paul Lg Verhoeff, Sina Hafizi, Antonio P Strafella, Ariel Graff-Guerrero, Tarek Rajji, Bruce G Pollock, Sylvain Houle, Pablo M Rusjan, Romina Mizrahi
Amnestic mild cognitive impairment (aMCI) is defined as a transitional state between normal aging and Alzheimer's disease (AD). Given the replicated finding of increased microglial activation in AD, we sought to investigate whether microglial activation is also elevated in aMCI and whether it is related to amyloid beta (Aβ) burden in-vivo . Eleven aMCI participants and 14 healthy volunteers completed positron emission tomography (PET) scans with [(18)F]-FEPPA and [(11)C]-PIB. Given the known sensitivity in affinity of second-generation TSPO radioligands, participants were genotyped for the TSPO polymorphism and only high-affinity binders were included...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/29127449/determining-a-threshold-sub-acute-dose-leading-to-minimal-physiological-alterations-following-prolonged-exposure-to-the-nerve-agent-vx-in-rats
#6
E Bloch-Shilderman, I Rabinovitz, I Egoz, G Yacov, N Allon, U Nili
VX, a potent inhibitor of cholinesterase (ChE), is considered as one of the most toxic, persistent and least volatile nerve agents. VX is absorbed in various environmental surfaces and is gradually released long after its initial dispersal. Its toxicity is mainly caused by disrupting central and peripheral cholinergic nervous system activity, leading to potential long-term detrimental effects on health. The primary objective of the present study was to assess the threshold VX dose leading to minimal physiological alterations following prolonged VX exposure...
November 10, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/29127254/steroidogenic-abnormalities-in-translocator-protein-knockout-mice-and-significance-in-the-aging-male
#7
Anna M Barron, Bin Ji, Seiji Kito, Tetsuya Suhara, Makoto Higuchi
The translocator protein (TSPO) has been proposed to act as a key component in a complex important for mitochondrial cholesterol importation, which is the rate-limiting step in steroid hormone synthesis. However, TSPO function in steroidogenesis has recently been challenged by the development of TSPO knockout (TSPO-KO) mice, as they exhibit normal baseline gonadal testosterone and adrenal corticosteroid production. Here we demonstrate that despite normal androgen levels in young male TSPO-KO mice, TSPO deficiency alters steroidogenic flux and results in reduced total steroidogenic output...
November 10, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/29114179/tspo-pet-imaging-from-microglial-activation-to-peripheral-sterile-inflammatory-diseases
#8
REVIEW
Bérenger Largeau, Anne-Claire Dupont, Denis Guilloteau, Maria-João Santiago-Ribeiro, Nicolas Arlicot
Peripheral sterile inflammatory diseases (PSIDs) are a heterogeneous group of disorders that gathers several chronic insults involving the cardiovascular, respiratory, gastrointestinal, or musculoskeletal system and wherein inflammation is the cornerstone of the pathophysiology. In PSID, timely characterization and localization of inflammatory foci are crucial for an adequate care for patients. In brain diseases, in vivo positron emission tomography (PET) exploration of inflammation has matured over the last 20 years, through the development of radiopharmaceuticals targeting the translocator protein-18 kDa (TSPO) as molecular biomarkers of activated microglia...
2017: Contrast Media & Molecular Imaging
https://www.readbyqxmd.com/read/29079733/analgesic-effects-and-pharmacologic-mechanisms-of-the-gelsemium-alkaloid-koumine-on-a-rat-model-of-postoperative-pain
#9
Bo-Jun Xiong, Ying Xu, Gui-Lin Jin, Ming Liu, Jian Yang, Chang-Xi Yu
Postoperative pain (POP) of various durations is a common complication of surgical procedures. POP is caused by nerve damage and inflammatory responses that are difficult to treat. The neuroinflammation-glia-steroid network is known to be important in POP. It has been reported that the Gelsemium alkaloid koumine possesses analgesic, anti-inflammatory and neurosteroid modulating activities. This study was undertaken to test the analgesic effects of koumine against POP and explore the underlying pharmacologic mechanisms...
October 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29076866/antidepressant-like-effect-of-fluoxetine-may-depend-on-translocator-protein-activity-and-pretest-session-duration-in-forced-swimming-test-in-mice
#10
Nikita V Kudryashov, Tatiana S Kalinina, Alexander A Shimshirt, Anton O Korolev, Anna V Volkova, Tatiana A Voronina
The antidepressant-like effect of fluoxetine (20 mg/kg i.p.) has been assessed using the forced swimming test (FST) in IRC (CD-1) mice exposed or not to a pretest session of different duration (5 or 20 min). The influence of the mitochondrial translocator protein (TSPO) activity on the antidepressant-like effect of fluoxetine (20 mg/kg i.p.) in the FST was also studied. The antidepressant-like effect of fluoxetine was observed only in mice subjected to a 5-min pretest session 24 h before the FST. The TSPO antagonist PK11195 [1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide; 1 or 3 mg/kg i...
October 25, 2017: Behavioural Pharmacology
https://www.readbyqxmd.com/read/29074640/tspo-mutations-in-rats-and-a-human-polymorphism-impair-the-rate-of-steroid-synthesis
#11
David R Owen, Jinjiang Fan, Enrico Campioli, Sathvika Venugopal, Andrew Midzak, Edward Daly, Aline Harlay, Leeyah Issop, Vincenzo Libri, Dimitra Kalogiannopoulou, Eduardo Oliver, Enrique Gallego-Colon, Alessandro Colasanti, Les Huson, Ilan Rabiner, Puvan Suppiah, Charles Essagian, Paul M Matthews, Vassilios Papadopoulos
The 18 kDa translocator protein (TSPO) is a ubiquitous conserved outer mitochondrial membrane protein implicated in numerous cell and tissue functions, including steroid hormone biosynthesis, respiration, cell proliferation and apoptosis.  TSPO binds with high affinity to cholesterol and numerous compounds, is expressed at high levels in steroid-synthesizing tissues, and mediates cholesterol import into mitochondria, which is the rate-limiting step in steroid formation.  In humans, the rs6971 polymorphism on the TSPO gene leads to an amino acid substitution in the fifth transmembrane loop of the protein, which is where the cholesterol-binding domain of TSPO is located, and this polymorphism has been associated with anxiety-related disorders...
October 26, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/29064155/assessing-inflammation-in-acute-intracerebral-hemorrhage-with-pk11195-pet-and-dynamic-contrast-enhanced-mri
#12
Kamran A Abid, Oluwaseun A Sobowale, Laura M Parkes, Josephine Naish, Geoff J M Parker, Daniel du Plessis, David Brough, Jack Barrington, Stuart M Allan, Rainer Hinz, Adrian R Parry-Jones
BACKGROUND AND PURPOSE: Studies in animal models suggest that inflammation is a major contributor to secondary injury after intracerebral hemorrhage (ICH). Direct, noninvasive monitoring of inflammation in the human brain after ICH will facilitate early-phase development of anti-inflammatory treatments. We sought to investigate the feasibility of multimodality brain imaging in subacute ICH. METHODS: Acute ICH patients were recruited to undergo multiparametric MRI (including dynamic contrast-enhanced measurement of blood-brain barrier transfer constant (K(trans) ) and PET with [(11) C]-(R)-PK11195)...
October 24, 2017: Journal of Neuroimaging: Official Journal of the American Society of Neuroimaging
https://www.readbyqxmd.com/read/29054730/the-translocator-protein-18kda-and-its-role-in-neuropsychiatric-disorders
#13
REVIEW
Tatiana Barichello, Lutiana R Simões, Allan Collodel, Vijayasree V Giridharan, Felipe Dal-Pizzol, Danielle Macedo, Joao Quevedo
Translocator protein (TSPO) is an 18kDa translocator membrane protein expressed in the outer mitochondrial membrane of steroid-synthesizing cells in the central and peripheral nervous systems. TSPO is involved in cellular functions, including the regulation of cell proliferation, transport of cholesterol to the inner mitochondrial membranes of glial cells, regulation of mitochondrial quality control, and haem synthesis. In the brain, TSPO has been extensively used as a biomarker of injury and inflammation. Indeed, TSPO was up-regulated in several inflammatory and neurodegenerative diseases...
October 18, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/29054675/evidence-of-fatigue-disordered-sleep-and-peripheral-inflammation-but-not-increased-brain-tspo-expression-in-seasonal-allergy-a-11-c-pbr28-pet-study
#14
Sandra Tamm, Simon Cervenka, Anton Forsberg, Johanna Estelius, Johan Grunewald, Pär Gyllfors, Bianka Karshikoff, Eva Kosek, Jon Lampa, Catarina Lensmar, Victoria Strand, Torbjörn Åkerstedt, Christer Halldin, Martin Ingvar, Caroline Olgart Höglund, Mats Lekander
Allergy is associated with non-specific symptoms such as fatigue, sleep problems and impaired cognition. One explanation could be that the allergic inflammatory state includes activation of immune cells in the brain, but this hypothesis has not been tested in humans. The aim of the present study was therefore to investigate seasonal changes in the glial cell marker translocator protein (TSPO), and to relate this to peripheral inflammation, fatigue and sleep, in allergy. We examined 18 patients with severe seasonal allergy, and 13 healthy subjects in and out-of pollen season using positron emission tomography (n = 15/13) and the TSPO radioligand [(11)C]PBR28...
October 18, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29031071/discovery-of-thienopyrrolotriazine-derivatives-to-protect-mitochondrial-function-against-a%C3%AE-induced-neurotoxicity
#15
TaeHun Kim, Woo Seung Son, Mohammad Neaz Morshed, Ashwini M Londhe, Seo Yun Jung, Jong-Hyun Park, Woo-Kyu Park, Sang Min Lim, Ki Duk Park, Sung Jin Cho, Kyu-Sung Jeong, Jiyoun Lee, Ae Nim Pae
Recovery of mitochondrial dysfunction has gained increasing attention as an alternative therapeutic strategy for Alzheimer's disease (AD). Recent studies suggested that the 18 kDa mitochondrial translocator protein (TSPO) has the potential to serve as a drug target for the treatment of AD. In this study, we generated a structure-based pharmacophore model and virtually screened a commercial library, identifying SVH07 as a virtual hit, which contained a tricyclic core structure, thieno[2',3':4,5]pyrrolo[1,2-d][1,2,4]triazine group...
December 1, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29026945/tspo-pet-using-18-f-ge-180-a-new-perspective-in-neurooncology
#16
EDITORIAL
Karl-Josef Langen, Antje Willuweit
No abstract text is available yet for this article.
December 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28992974/diazepam-treatment-reduces-inflammatory-cells-and-mediators-in-the-central-nervous-system-of-rats-with-experimental-autoimmune-encephalomyelitis
#17
Nicolás Fernández Hurst, Samanta R Zanetti, Natalia S Báez, Mario J Bibolini, Cecilia Bouzat, German A Roth
Benzodiazepines are psychoactive drugs and some of them also affect immune cells. We here characterized the inflammatory and infiltrating immune cells in the central nervous system (CNS) during the acute phase of experimental autoimmune encephalomyelitis (EAE) in animals treated with Diazepam. Also, we evaluated the expression of Translocator Protein (18kDa) (TSPO), which is a biomarker of neuroinflammatory diseases. The results indicate that Diazepam exerts protective effects on EAE development, decreasing the incidence of the disease and reducing the number of inflammatory cells in CNS, with a concomitant decrease of TSPO levels in brain tissue and CNS inflammatory CD11b(+) cells...
September 30, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28988133/coupling-between-physiological-tspo-expression-in-brain-and-myocardium-allows-stabilization-of-late-phase-cerebral-18-f-ge180-pet-quantification
#18
Maximilian Deussing, Tanja Blume, Lena Vomacka, Christoph Mahler, Carola Focke, Andrei Todica, Marcus Unterrainer, Nathalie L Albert, Simon Lindner, Barbara von Ungern-Sternberg, Karlheinz Baumann, Andreas Zwergal, Peter Bartenstein, Jochen Herms, Axel Rominger, Matthias Brendel
OBJECTIVES: PET imaging of the 18 kDa translocator protein (TSPO), a biomarker of microglial activity, receives growing interest in clinical and preclinical applications of neuroinflammatory and neurodegenerative brain diseases. In globally affected brains, intra-cerebral pseudo reference regions are not feasible. Consequently, many brain-independent approaches have been attempted, including SUV analysis and normalization to muscle- or heart uptake, aiming to stabilize quantitative analysis...
October 5, 2017: NeuroImage
https://www.readbyqxmd.com/read/28986511/neuroinflammation-appears-early-and-then-plateaus-in-a-mouse-model-of-alzheimer-s-disease-shown-by-pet-imaging
#19
Francisco R López-Picón, Anniina Snellman, Olli Eskola, Semi Helin, Olof Solin, Merja Haaparanta-Solin, Juha O Rinne
Rationale: Neuroinflammation has been associated with different neurological diseases including Alzheimer's disease (AD). In AD, the translocator protein 18kDa (TSPO) is overexpressed in the activated microglia that surround the β-amyloid plaques. In the current longitudinal study, using a mouse model of AD, we evaluated the association between β-amyloid deposition and neuroinflammation in AD. Methods: To monitor the longitudinal changes in β-amyloid deposition and neuroinflammation, we used in vivo PET imaging and ex vivo autoradiography with (11)C-PIB and a TSPO tracer, (18)F-GE-180, in the APP23 mouse model of AD...
October 6, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28983743/pet-imaging-of-human-brown-adipose-tissue-with-the-tspo-tracer-11-c-pbr28
#20
Chongzhao Ran, Daniel S Albrecht, Miriam A Bredella, Jing Yang, Jian Yang, Steven H Liang, Aaron M Cypess, Marco L Loggia, Nazem Atassi, Anna Moore
PURPOSE: Brown adipose tissue (BAT) in adult humans has been recently rediscovered and intensively investigated as a new potential therapeutic target for obesity and type 2 diabetes (T2D). However, reliable assessment of BAT mass in vivo represents a considerable challenge. The purpose of this investigation is to demonstrate for the first time that human BAT depots can be imaged with a translocator protein (TSPO)-specific positron emission tomography (PET) tracer [(11)C]PBR28 under thermoneutral conditions...
October 5, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
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