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PK11195 microglia

Leonardo Iaccarino, Luca Presotto, Valentino Bettinardi, Luigi Gianolli, Ignazio Roiter, Sabina Capellari, Piero Parchi, Pietro Cortelli, Daniela Perani
Objective: Postmortem studies reported significant microglia activation in association with neuronal apoptosis in Fatal Familial Insomnia (FFI), indicating a specific glial response, but negative evidence also exists. An in vivo study of local immune responses over FFI natural course may contribute to the understanding of the underlying pathogenesis. Methods: We included eight presymptomatic subjects (mean ± SD age:44.13 ± 3.83 years) carrying the pathogenic D178N-129met FFI mutation, one symptomatic patient (male, 45 yrs...
January 2018: Annals of Clinical and Translational Neurology
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...
March 2018: Neurobiology of Disease
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
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
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
Sophie E Holmes, Rainer Hinz, Silke Conen, Catherine J Gregory, Julian C Matthews, Jose M Anton-Rodriguez, Alexander Gerhard, Peter S Talbot
BACKGROUND: Major depressive disorder is associated with raised peripheral inflammatory markers. Mounting evidence also suggests that inflammation is involved in suicidal behavior. However, the involvement of inflammation in the brains of individuals with depression, and its association with suicidal ideation, needs further clarification. Translocator protein (TSPO), which is upregulated in activated glia (predominantly microglia), can be measured as an indication of neuroinflammation in vivo using positron emission tomography and TSPO-specific radioligands...
January 1, 2018: Biological Psychiatry
Divya Raj, Zhuoran Yin, Marjolein Breur, Janine Doorduin, Inge R Holtman, Marta Olah, Ietje J Mantingh-Otter, Debby Van Dam, Peter P De Deyn, Wilfred den Dunnen, Bart J L Eggen, Sandra Amor, Erik Boddeke
Chronic neuroinflammation, which is primarily mediated by microglia, plays an essential role in aging and neurodegeneration. It is still unclear whether this microglia-induced neuroinflammation occurs globally or is confined to distinct brain regions. In this study, we investigated microglia activity in various brain regions upon healthy aging and Alzheimer's disease (AD)-related pathology in both human and mouse samples. In purified microglia isolated from aging mouse brains, we found a profound gene expression pattern related to pro-inflammatory processes, phagocytosis, and lipid homeostasis...
2017: Frontiers in Molecular Neuroscience
Morten Gersel Stokholm, Alex Iranzo, Karen Østergaard, Mónica Serradell, Marit Otto, Kristina Bacher Svendsen, Alicia Garrido, Dolores Vilas, Per Borghammer, Joan Santamaria, Arne Møller, Carles Gaig, David J Brooks, Eduardo Tolosa, Nicola Pavese
BACKGROUND: Findings from longitudinal follow-up studies in patients with idiopathic rapid-eye-movement sleep behaviour disorder (IRBD) have shown that most patients will eventually develop the synucleinopathies Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy. Neuroinflammation in the form of microglial activation is present in synucleinopathies and is a potential therapeutic target to halt or delay the neurodegenerative process. We aimed to investigate whether neuroinflammation is present in patients with IRBD and its possible relation to nigrostriatal dopamine function...
October 2017: Lancet Neurology
Mattia Veronese, Tiago Reis Marques, Peter S Bloomfield, Gaia Rizzo, Nisha Singh, Deborah Jones, Erjon Agushi, Dominic Mosses, Alessandra Bertoldo, Oliver Howes, Federico Roncaroli, Federico E Turkheimer
The 18 kDa translocator protein (TSPO) is a marker of microglia activation in the central nervous system and represents the main target of radiotracers for the in vivo quantification of neuroinflammation with positron emission tomography (PET). TSPO PET is methodologically challenging given the heterogeneous distribution of TSPO in blood and brain. Our previous studies with the TSPO tracers [(11)C]PBR28 and [(11)C]PK11195 demonstrated that a model accounting for TSPO binding to the endothelium improves the quantification of PET data...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
Leonardo Iaccarino, Rosa Maria Moresco, Luca Presotto, Orso Bugiani, Sandro Iannaccone, Giorgio Giaccone, Fabrizio Tagliavini, Daniela Perani
Microgliosis is part of the immunobiology of Creutzfeldt-Jakob disease (CJD). This is the first report using (11)C-(R)-PK11195 PET imaging in vivo to measure 18 kDa translocator protein (TSPO) expression, indexing microglia activation, in symptomatic CJD patients, followed by a postmortem neuropathology comparison. One genetic CJD (gCJD) patient, two sporadic CJD (sCJD) patients, one variant CJD (vCJD) patient (mean ± SD age, 47.50 ± 15.95 years), and nine healthy controls (mean ± SD age, 44.00 ± 11...
April 28, 2017: Molecular Neurobiology
David Vállez García, Janine Doorduin, Daniele de Paula Faria, Rudi A J O Dierckx, Erik F J de Vries
Fingolimod was the first oral drug approved for multiple sclerosis treatment. Its principal mechanism of action is blocking of lymphocyte trafficking. In addition, recent studies have shown its capability to diminish microglia activation. The effect of preventive and curative fingolimod treatment on the time-course of neuroinflammation was investigated in the experimental autoimmune encephalomyelitis rat model for multiple sclerosis. Neuroinflammatory progression was followed in Dark Agouti female rats after immunization...
September 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
Teruyo Hosoya, Dai Fukumoto, Takeharu Kakiuchi, Shingo Nishiyama, Shigeyuki Yamamoto, Hiroyuki Ohba, Hideo Tsukada, Takatoshi Ueki, Kohji Sato, Yasuomi Ouchi
BACKGROUND: Upregulated levels of 18-kDa translocator proteins (TSPO) and type 2 endocannabinoid receptors (CB2) are considered to reflect different aspects of microglia-related neuroinflammatory responses in the brain. Relative to the increase in the TSPO expression that occurs slightly later during neuroinflammation in a proinflammatory fashion, CB2 activation is considered to relate to the neuroprotective responses that occurs predominantly at an early stage of brain disorders. These findings, however, were deduced from studies with different animal samples under different experimental settings...
March 29, 2017: Journal of Neuroinflammation
Zhen Fan, David J Brooks, Aren Okello, Paul Edison
Amyloid-β deposition, neuroinflammation and tau tangle formation all play a significant role in Alzheimer's disease. We hypothesized that there is microglial activation early on in Alzheimer's disease trajectory, where in the initial phase, microglia may be trying to repair the damage, while later on in the disease these microglia could be ineffective and produce proinflammatory cytokines leading to progressive neuronal damage. In this longitudinal study, we have evaluated the temporal profile of microglial activation and its relationship between fibrillar amyloid load at baseline and follow-up in subjects with mild cognitive impairment, and this was compared with subjects with Alzheimer's disease...
March 1, 2017: Brain: a Journal of Neurology
Brenna M Flannery, Donald A Bruun, Douglas J Rowland, Christopher N Banks, Adam T Austin, David L Kukis, Yonggang Li, Byron D Ford, Daniel J Tancredi, Jill L Silverman, Simon R Cherry, Pamela J Lein
BACKGROUND: Acute intoxication with organophosphorus (OP) cholinesterase inhibitors can trigger convulsions that progress to life-threatening status epilepticus. Survivors face long-term morbidity including mild-to-severe decline in memory. It is posited that neuroinflammation plays a key role in the pathogenesis of OP-induced neuropsychiatric deficits. Rigorous testing of this hypothesis requires preclinical models that recapitulate relevant phenotypic outcomes. Here, we describe a rat model of acute intoxication with the OP diisopropylfluorophosphate (DFP) that exhibits persistent neuroinflammation and cognitive impairment...
October 12, 2016: Journal of Neuroinflammation
Thalia F van der Doef, Lot D de Witte, Arjen L Sutterland, Ellen Jobse, Maqsood Yaqub, Ronald Boellaard, Lieuwe de Haan, Jonas Eriksson, Adriaan A Lammertsma, René S Kahn, Bart N M van Berckel
Evidence is accumulating that immune dysfunction is involved in the pathophysiology of schizophrenia. It has been hypothesized that microglia activation is present in patients with schizophrenia. Various in vivo and post-mortem studies have investigated this hypothesis, but as yet with inconclusive results. Microglia activation is associated with elevations in 18 kDa translocator protein (TSPO) levels, which can be measured with the positron emission tomography (PET) tracer (R)-[(11)C]PK11195. The purpose of the present study was to investigate microglia activation in psychosis in vivo at an early stage of the disease...
2016: NPJ Schizophrenia
J Yankam Njiwa, N Costes, C Bouillot, S Bouvard, S Fieux, G Becker, E Levigoureux, G Kocevar, C Stamile, J B Langlois, R Bolbos, C Bonnet, L Bezin, L Zimmer, A Hammers
Inflammation may play a role in the development of epilepsy after brain insults. [(11)C]-( R)-PK11195 binds to TSPO, expressed by activated microglia. We quantified [(11)C]-( R)-PK11195 binding during epileptogenesis after pilocarpine-induced status epilepticus (SE), a model of temporal lobe epilepsy. Nine male rats were studied thrice (D0-1, D0 + 6, D0 + 35, D0 = SE induction). In the same session, 7T T2-weighted images and DTI for mean diffusivity (MD) and fractional anisotropy (FA) maps were acquired, followed by dynamic PET/CT...
April 2017: Journal of Cerebral Blood Flow and Metabolism
Alexander Gerhard
Microglial activation is a key aspect of the neuroinflammatory process in neurodegenerative disorders including idiopathic and atypical parkinsonian disorders. With positron emission tomography (PET) it has become possible to image this phenomenon in vivo and over the last years patterns of microglia activation corresponding with the known distribution of neuropathological changes in these disorders have been demonstrated using this technique. In addition the effects of interventions aimed at suppressing microglia activation as part of interventional trials have successfully been demonstrated...
2016: Clinical and Translational Imaging: Reviews in Nuclear Medicine and Molecular Imaging
Xiang Kong, Song Luo, Jin Rong Wu, Shawn Wu, Carlo N De Cecco, U Joseph Schoepf, Adam J Spandorfer, Chun Yan Wang, Ying Tian, Hui Juan Chen, Guang Ming Lu, Gui Fen Yang, Long Jiang Zhang
Neuroinflammation is considered to be the pathogenesis of hepatic encephalopathy (HE), and imaging neuroinflammation is implicated in HE management. (11)C-PK11195, a typical translocator protein (TSPO) radiotracer, is used for imaging neuroinflammation. However, it has inherent limitations, such as short half-life and limited availability. The purpose of this study was to demonstrate the efficiency of new generation TSPO radiotracer, (18)F-DPA-714, in detecting and monitoring neuroinflammation of chronic HE...
2016: Theranostics
Masamichi Yokokura, Tatsuhiro Terada, Tomoyasu Bunai, Kyoko Nakaizumi, Kiyokazu Takebayashi, Yasuhide Iwata, Etsuji Yoshikawa, Masami Futatsubashi, Katsuaki Suzuki, Norio Mori, Yasuomi Ouchi
The presence of activated microglia in the brains of healthy elderly people is a matter of debate. We aimed to clarify the degree of microglial activation in aging and dementia as revealed by different tracers by comparing the binding potential (BPND) in various brain regions using a first-generation translocator protein (TSPO) tracer [(11)C]( R)PK11195 and a second-generation tracer [(11)C]DPA713. The BPND levels, estimated using simplified reference tissue models, were compared among healthy young and elderly individuals and patients with Alzheimer's disease (AD) and were correlated with clinical scores...
March 2017: Journal of Cerebral Blood Flow and Metabolism
Cornelius K Donat, Khaled Gaber, Jürgen Meixensberger, Peter Brust, Lars H Pinborg, Henrik H Hansen, Jens D Mikkelsen
After traumatic brain injury (TBI), secondary injuries develop, including neuroinflammatory processes that contribute to long-lasting impairments. These secondary injuries represent potential targets for treatment and diagnostics. The translocator protein 18 kDa (TSPO) is expressed in activated microglia cells and upregulated in response to brain injury and therefore a potential biomarker of the neuroinflammatory processes. Second-generation radioligands of TSPO, such as [(123)I]CLINDE, have a higher signal-to-noise ratio as the prototype ligand PK11195...
June 2016: Neuromolecular Medicine
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