scholarly journals From positron emission tomography to cell analysis of the 18-kDa Translocator Protein in mild traumatic brain injury

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Clément Delage ◽  
Nicolas Vignal ◽  
Coralie Guerin ◽  
Toufik Taib ◽  
Clément Barboteau ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Positron Emission Tomography ◽  
Flow Cytometry ◽  
Microglial Activation ◽  
Translocator Protein ◽  
Emission Tomography ◽  
Flow Cytometry Analysis ◽  
Positron Emission ◽  
The Brain ◽  
Tspo Expression

AbstractTraumatic brain injury (TBI) leads to a deleterious neuroinflammation, originating from microglial activation. Monitoring microglial activation is an indispensable step to develop therapeutic strategies for TBI. In this study, we evaluated the use of the 18-kDa translocator protein (TSPO) in positron emission tomography (PET) and cellular analysis to monitor microglial activation in a mild TBI mouse model. TBI was induced on male Swiss mice. PET imaging analysis with [18F]FEPPA, a TSPO radiotracer, was performed at 1, 3 and 7 days post-TBI and flow cytometry analysis on brain at 1 and 3 days post-TBI. PET analysis showed no difference in TSPO expression between non-operated, sham-operated and TBI mice. Flow cytometry analysis demonstrated an increase in TSPO expression in ipsilateral brain 3 days post-TBI, especially in microglia, macrophages, lymphocytes and neutrophils. Moreover, microglia represent only 58.3% of TSPO+ cells in the brain. Our results raise the question of the use of TSPO radiotracer to monitor microglial activation after TBI. More broadly, flow cytometry results point the lack of specificity of TSPO for microglia and imply that microglia contribute to the overall increase in TSPO in the brain after TBI, but is not its only contributor.

scholarly journals TSPO: an emerging role in appetite for a therapeutically promising biomarker

Open Biology ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 210173
Author(s):  
Joshua Wang ◽  
Kate Beecher
Keyword(s):  
Positron Emission Tomography ◽  
Side Effect ◽  
Western Diet ◽  
Translocator Protein ◽  
Emission Tomography ◽  
Side Effect Profile ◽  
Synaptic Protein ◽  
Diet Induced Obesity ◽  
Positron Emission ◽  
The Brain

There is accumulating evidence that an obesogenic Western diet causes neuroinflammatory damage to the brain, which then promotes further appetitive behaviour. Neuroinflammation has been extensively studied by analysing the translocator protein of 18 kDa (TSPO), a protein that is upregulated in the inflamed brain following a damaging stimulus. As a result, there is a rich supply of TSPO-specific agonists, antagonists and positron emission tomography ligands. One TSPO ligand, etifoxine, is also currently used clinically for the treatment of anxiety with a minimal side-effect profile. Despite the neuroinflammatory pathogenesis of diet-induced obesity, and the translational potential of targeting TSPO, there is sparse literature characterizing the effect of TSPO on appetite. Therefore, in this review, the influence of TSPO on appetite is discussed. Three putative mechanisms for TSPO's appetite-modulatory effect are then characterized: the TSPO–allopregnanolone–GABA A R signalling axis, glucosensing in tanycytes and association with the synaptic protein RIM-BP1. We highlight that, in addition to its plethora of functions, TSPO is a regulator of appetite. This review ultimately suggests that the appetite-modulating function of TSPO should be further explored due to its potential therapeutic promise.

scholarly journals Depiction of microglial activation in aging and dementia: Positron emission tomography with [11C]DPA713 versus [11C](R)PK11195

2016 ◽  
Vol 37 (3) ◽  
pp. 877-889 ◽  
Author(s):  
Masamichi Yokokura ◽  
Tatsuhiro Terada ◽  
Tomoyasu Bunai ◽  
Kyoko Nakaizumi ◽  
Kiyokazu Takebayashi ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Microglial Activation ◽  
Second Generation ◽  
Neuronal Degeneration ◽  
Brain Regions ◽  
Translocator Protein ◽  
Emission Tomography ◽  
Binding Potential ◽  
Healthy Elderly ◽  
Positron Emission

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 [11C]( R)PK11195 and a second-generation tracer [11C]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. An analysis of variance showed category-dependent elevation in levels of [11C]DPA713 BPND in all brain regions and showed a significant increase in the AD group, whereas no significant changes among groups were found when [11C]( R)PK11195 BPND was used. Cognito-mnemonic scores were significantly correlated with [11C]DPA713 BPND levels in many brain regions, whereas [11C]( R)PK11195 BPND failed to correlate with the scores. As mentioned elsewhere, the present results confirmed that the second-generation TSPO tracer [11C]DPA713 has a greater sensitivity to TSPO in both aging and neuronal degeneration than [11C]( R)PK11195. Positron emission tomography with [11C]DPA713 is suitable for the delineation of in vivo microglial activation occurring globally over the cerebral cortex irrespective of aging and degeneration.

scholarly journals Temporal and spatial changes in reactive astrogliosis examined by 18F-THK5351 positron emission tomography in a patient with severe traumatic brain injury

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Tetsuhiro Hatakeyama ◽  
Kenya Kawakita ◽  
Nobuyuki Kawai ◽  
Hajime Shishido ◽  
Yuka Yamamoto ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Positron Emission Tomography ◽  
Brain Injury ◽  
Emission Tomography ◽  
Reactive Astrogliosis ◽  
Positron Emission ◽  
Spatial Changes ◽  
Severe Tbi ◽  
Temporal And Spatial ◽  
The Brain

Abstract Background The positron emission tomography (PET) radioligand 18F-THK5351 is now used to evaluate monoamine oxidase B expression in the reactive astrogliosis seen in various central nervous diseases. Traumatic brain injury (TBI) is known to induce reactive astrogliosis in the lesion site. This is a first report to examine the spatial and temporal changes in reactive astrogliosis as evaluated by 18F-THK5351 after a severe TBI. Case presentation A 27-year-old man suffering from a severe TBI with multiple brain contusions was examined using 18F-THK5351 PET/CT in the subacute and chronic phases after the injury. The first PET scan, performed 46 days after the TBI, showed intense uptake of 18F-THK5351 in and around the brain contusions. The second PET scan, performed 271 days after the TBI, showed reduced uptake of 18F-THK5351 at the original sites of the brain contusions and increased uptakes in the white matter surrounding the contusions and the corpus callosum. The patient exhibited sustained improvement of neuropsychological impairment between the two PET examinations and remarkable recovery from the severe TBI. Conclusions There were evident temporal and spatial changes in 18F-THK5351 uptake in the traumatized brain between the two PET examinations. These changes may have been related to the remarkable neurological recovery in this patient. The degree and distribution of reactive astrogliosis detected by 18F-THK5351 PET may be useful in assessing pathophysiology and predicting prognosis in TBI patients.

Synthesis of two novel [18F]fluorobenzene-containing radiotracers via spirocyclic iodonium ylides and positron emission tomography imaging of translocator protein (18 kDa) in ischemic brain

2018 ◽  
Vol 16 (37) ◽  
pp. 8325-8335 ◽  
Author(s):  
Masayuki Fujinaga ◽  
Katsushi Kumata ◽  
Yiding Zhang ◽  
Akiko Hatori ◽  
Tomoteru Yamasaki ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Positron Emission Tomography Imaging ◽  
Translocator Protein ◽  
Emission Tomography ◽  
Ischemic Brain ◽  
Tomography Imaging ◽  
Positron Emission ◽  
Translocator Protein 18 Kda ◽  
Iodonium Ylides ◽  
The Brain

A new radiotracer for imaging TSPO: Ki, 0.70 nM and no radiolabeled metabolite in the brain.

scholarly journals Traumatic brain injury induces elevation of Co in the human brain

Metallomics ◽  
2015 ◽  
Vol 7 (1) ◽  
pp. 66-70 ◽  
Author(s):  
Blaine R. Roberts ◽  
Dominic J. Hare ◽  
Catriona A. McLean ◽  
Alison Conquest ◽  
Monica Lind ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Positron Emission Tomography ◽  
Brain Injury ◽  
Human Brain ◽  
Injury Severity ◽  
Acute Brain Injury ◽  
Emission Tomography ◽  
Positron Emission ◽  
The Brain

Following acute brain injury (<3 hours post-event), cobalt levels in the brain are significantly elevated. This elevation may have important implications for positron emission tomography neuroimaging for assessing brain injury severity.

scholarly journals The 18-kDa mitochondrial translocator protein in gliomas: from the bench to bedside

2015 ◽  
Vol 43 (4) ◽  
pp. 579-585 ◽  
Author(s):  
Karolina Janczar ◽  
Zhangjie Su ◽  
Isabella Raccagni ◽  
Andrea Anfosso ◽  
Charlotte Kelly ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Molecular Imaging ◽  
Pet Imaging ◽  
Tumour Cells ◽  
Translocator Protein ◽  
Emission Tomography ◽  
Normal Brain ◽  
Ideal Candidate ◽  
Positron Emission ◽  
The Brain

The 18-kDa mitochondrial translocator protein (TSPO) is known to be highly expressed in several types of cancer, including gliomas, whereas expression in normal brain is low. TSPO functions in glioma are still incompletely understood. The TSPO can be quantified pre-operatively with molecular imaging making it an ideal candidate for personalized treatment of patient with glioma. Studies have proposed to exploit the TSPO as a transporter of chemotherapics to selectively target tumour cells in the brain. Our studies proved that positron emission tomography (PET)-imaging can contribute to predict progression of patients with glioma and that molecular imaging with TSPO-specific ligands is suitable to stratify patients in view of TSPO-targeted treatment. Finally, we proved that TSPO in gliomas is predominantly expressed by tumour cells.

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