Cited by 356Neuroinflammation and Neurodegeneration MechanismsTryptophan and brain disordersMedical Imaging Techniques and Applications

The DOI matches its Crossref record; 66 of the 66 references it cites were found in a registry or an index.

Imaging robust microglial activation after lipopolysaccharide administration in humans with PET

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Abstract

Significance: Neuroinflammation is a brain immune response that is associated with neurodegenerative diseases and is primarily driven by activation of microglia, the brain’s resident macrophages. Dysfunctional microglial activation may contribute to the behavioral changes observed in neurodegenerative diseases. Upon activation, microglia express translocator protein, which can be imaged with the radiotracer [ 11 C]PBR28 and positron emission tomography (PET) in the living human brain. We imaged healthy human subjects with [ 11 C]PBR28 and PET before and after i.v. administration of lipopolysaccharide (LPS), a potent immune activator. LPS produced a marked increase in brain microglial activation, peripheral inflammatory cytokine levels, and self-reported sickness symptoms. This imaging paradigm can provide a direct approach to test new medications for their potential to reduce acute neuroinflammation.

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Metadata

Authors
Sandiego, C. M., Gallezot, J.-D., Pittman, B., Nabulsi, N., Lim, K., Lin, S.-F., Matuskey, D., Lee, J.-Y., O’Connor, K. C., Huang, Y., Carson, R. E., Hannestad, J., & Cosgrove, K. P.
Affiliations
  • Yale University (US)
  • UCB Pharma (Belgium) (BE)
Venue
Proceedings of the National Academy of Sciences
Published
2015-09-18
Volume
112
Issue
40
Pages
12468-12473
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2145625835
Cited by
356
References
66
Citations by year
2026: 19 · 2025: 30 · 2024: 29 · 2023: 21 · 2022: 30 · 2021: 42 · 2020: 49 · 2019: 38 · 2018: 32 · 2017: 40 · 2016: 23 · 2015: 3
FWCI
17.46
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Yale University
  • National Institute on Aging (P50AG047270)
  • UCB Pharma
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
Keywords
microglial activation, neuroinflammation, lipopolysaccharide challenge, [11C]PBR28, translocator protein (TSPO), inflammatory cytokines, sickness behavior, systemic inflammation, anti-inflammatory drug testing
MeSH terms
Acetamides, Adult, Brain, Carbon Radioisotopes, Humans, Lipopolysaccharides, Male, Protein Binding, Pyridines, Reproducibility of Results, Biomarkers, Cytokines, Microglia, Receptors, GABA, Inflammation Mediators, Radiopharmaceuticals, Positron-Emission Tomography, Young Adult

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