ArticleGlia2021
Activated microglia do not increase 18 kDa translocator protein (TSPO) expression in the multiple sclerosis brain.
Article in Glia, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
56 citing papers in PubMed, 3 syntheses or guidelines pooled it, 86 citations in OpenAlex.
- Evaluating the Clinical Utility of TSPO-PET in MS and the Influence of Methodological Heterogeneity: A Systematic Review and Meta-Analysis.Neurology(R) neuroimmunology & neuroinflammation · 2026Pooled it
- Association between FDG- and TSPO-PET signals across human and animal studies investigating neurodegenerative conditions: a systematic review.Molecular psychiatry · 2026Pooled it
- Imaging the inflammatory phenotype in migraine.The journal of headache and pain · 2022Pooled it
- Insights into the complex relationship between pain and imaging-detected structural damage in knee osteoarthritis.Skeletal radiology · 2026Review
- Towards a Whole-Body Assessment of Pain Using the 18 kDa Translocator Protein (TSPO) as a Broad-Spectrum Imaging Marker of Inflammation.European journal of pain (London, England) · 2026Review
- Astrocyte Activation Persists after Recovery of Myelin and Motor Deficits in the Cuprizone Model: a Longitudinal PET and CNS Tissue Analysis Study.Molecular imaging and biology · 2026Article
- Feasibility of multimodal metabolic analysis for detecting early changes in acute neuroinflammation.Journal of neuroinflammation · 2026Article
- A radiolabeled dendrimer non-invasively identifies and tracks innate immune cell activation in a mouse model of experimental autoimmune encephalomyelitis.Nature communications · 2026Article
- From scavenger to victim: mechanism and treatment of microglial ferroptosis in white matter injury disease.Frontiers in immunology · 2026Review
- Critical role of translocator protein (TSPO) in neuronal mitochondrial dysfunction and mental stress-exacerbated ischemic injury following stroke.Translational psychiatry · 2025Article
- Refining seizure foci localization: the potential of TSPO-PET.Acta epileptologica · 2025Review
- Evaluating the Protective Effects of Silymarin Along with a Cholesterol-Supplemented Diet Against Demyelination in an EAE Mouse Model of Multiple Sclerosis: Lipidomic and Inflammatory Aspects.Molecular neurobiology · 2025Article
- Broad rim lesions are a new pathological and imaging biomarker for rapid disease progression in multiple sclerosis.Nature medicine · 2025Article
- Characteristics of TSPO expression in marmoset EAE.Journal of neuroinflammation · 2025Article
- 18 kDa TSPO targeting drives polarized human microglia towards a protective and restorative neurosteroidome profile.Cellular and molecular life sciences : CMLS · 2025Article
- Integrating TSPO-PET imaging with metabolomics for enhanced prognostic accuracy in multiple sclerosis.BMJ neurology open · 2025Article
- PhenotypingMultiple sclerosis (Houndmills, Basingstoke, England) · 2024Article
- Imaging chronic active lesions in multiple sclerosis: a consensus statement.Brain : a journal of neurology · 2024Review
- Article
- Early Blood-Brain Barrier Impairment as a Pathological Hallmark in a Novel Model of Closed-Head Concussive Brain Injury (CBI) in Mice.International journal of molecular sciences · 2024Article
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7 authors at 4 institutions in 2 countries.
Funding
Abstract
To monitor innate immune responses in the CNS, the 18 kDa Translocator protein (TSPO) is a frequently used target for PET imaging. The frequent assumption that increased TSPO expression in the human CNS reflects pro-inflammatory activation of microglia has been extrapolated from rodent studies. However, TSPO expression does not increase in activated human microglia in vitro. Studies of multiple sclerosis (MS) lesions reveal that TSPO is not restricted to pro-inflammatory microglia/macrophages, but also present in homeostatic or reparative microglia. Here, we investigated quantitative relationships between TSPO expression and microglia/macrophage phenotypes in white matter and lesions of brains with MS pathology. In white matter from brains with no disease pathology, normal appearing white matter (NAWM), active MS lesions and chronic active lesion rims, over 95% of TSPO+ cells are microglia/macrophages. Homeostatic microglial markers in NAWM and control tissue are lost/reduced in active lesions and chronic active lesion rims, reflecting cell activation. Nevertheless, pixel analysis of TSPO+ cells (n = 12,225) revealed that TSPO expression per cell is no higher in active lesions and chronic active lesion rims (where myeloid cells are activated) relative to NAWM and control. This data suggests that whilst almost all the TSPO signal in active lesions, chronic active lesion rims, NAWM and control is associated with microglia/macrophages, their TSPO expression predominantly reflects cell density and not activation phenotype. This finding has implications for the interpretation of TSPO PET signal in MS and other CNS diseases, and further demonstrates the limitation of extrapolating TSPO biology from rodents to humans.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.