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
Open accessAbstract
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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“Adding endotoxin at such levels to blood of healthy humans induces systemic inflammation and brain microglial activation.”
From The endotoxin hypothesis of neurodegeneration (2019) · cites this paper as [15]
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“data from endotoxin administration to healthy volunteers indicates that radiolabelled TSPO ligands can readily identify cellular activation in several regions of the brain following a potent peripheral immune stimulus63.”
From The role of inflammation in depression: from evolutionary imperative to modern treatment target (2016) · cites this paper as [63]
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“Thus, a relatively mild dose of blood endotoxin (e.g. less than that found in Alzheimer’s patients) can cause acute microglial activation within the brain.”
From The endotoxin hypothesis of neurodegeneration (2019) · cites this paper as [15]
In the citing paper
“Human neuroimaging findings show heightened microglia activation after LPS administration that produces depressive-like sickness symptoms [79].”
From The menace of obesity to depression and anxiety prevalence (2022) · cites this paper as [79]
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Cites
Exploring the full spectrum of macrophage activation
Mosser, D. M., & Edwards, J. P. (2008) · Nature Reviews Immunology · doi:10.1038/nri2448 · Cited by 9,144
Polazzi, E., Mengoni, I., Caprini, M., Peña‐Altamira, E., Kurtys, E., & Monti, B. (2012) · Neurosignals · doi:10.1159/000337115 · Cited by 9,023
Glutamate neurotoxicity and diseases of the nervous system
Choi, D. W. (1988) · Neuron · doi:10.1016/0896-6273(88)90162-6 · Cited by 8,188
From inflammation to sickness and depression: when the immune system subjugates the brain
Dantzer, R., O'Connor, J. C., Freund, G. G., Johnson, R. W., & Kelley, K. W. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2297 · Cited by 7,395
Neuroinflammation in Alzheimer's disease
Heneka, M. T., Carson, M. J., Khoury, J. E., Landreth, G. E., Brosseron, F., Feinstein, D. L., Jacobs, A. H., Wyss-Coray, T., Vitorica, J., Ransohoff, R. M., et al. (2015) · The Lancet Neurology · doi:10.1016/s1474-4422(15)70016-5 · Cited by 6,226
Microglia: a sensor for pathological events in the CNS
Kreutzberg, G. W. (1996) · Trends in Neurosciences · doi:10.1016/0166-2236(96)10049-7 · Cited by 4,396
Microglial M1/M2 polarization and metabolic states
Orihuela, R., McPherson, C. A., & Harry, G. J. (2016) · British Journal of Pharmacology · doi:10.1111/bph.13139 · Cited by 2,070
Consensus Nomenclature for in vivo Imaging of Reversibly Binding Radioligands
Innis, R. B., Cunningham, V. J., Delforge, J., Fujita, M., Gjedde, A., Gunn, R. N., Holden, J., Houle, S., Huang, S.-C., Ichise, M., et al. (2007) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/sj.jcbfm.9600493 · Cited by 1,955
Self-citationImmune modulation of learning, memory, neural plasticity and neurogenesis
Yirmiya, R., & Goshen, I. (2011) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2010.10.015 · Cited by 1,483
Papadopoulos, V., Baraldi, M., Guilarte, T. R., Knudsen, T. B., Lacapère, J.-J., Lindemann, P., Norenberg, M. D., Nutt, D., Weizman, A., Zhang, M.-R., et al. (2006) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2006.06.005 · Cited by 1,389
Cited by
Sorted by citations
The role of inflammation in depression: from evolutionary imperative to modern treatment target
Miller, A. H., & Raison, C. L. (2016) · Nature Reviews Immunology · doi:10.1038/nri.2015.5 · Cited by 3,942
The Sleep-Immune Crosstalk in Health and Disease
Besedovsky, L., Lange, T., & Haack, M. (2019) · Physiological Reviews · doi:10.1152/physrev.00010.2018 · Cited by 1,479
Neuroimmune Interactions: From the Brain to the Immune System and Vice Versa
Dantzer, R. (2018) · Physiological Reviews · doi:10.1152/physrev.00039.2016 · Cited by 1,073
Inflammation, glutamate, and glia: a trio of trouble in mood disorders
Haroon, E., Miller, A. H., & Sanacora, G. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.199 · Cited by 584
The endotoxin hypothesis of neurodegeneration
Brown, G. C. (2019) · Journal of Neuroinflammation · doi:10.1186/s12974-019-1564-7 · Cited by 457
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)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2015-09-18
- Volume
- 112
- Issue
- 40
- Pages
- 12468-12473
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4603509
- 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
- bronze
- doi.org
- 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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