Regional induction of tumor necrosis factor alpha expression in the mouse brain after systemic lipopolysaccharide administration.
Open accessAbstract
Tumor necrosis factor alpha (TNF-alpha) is a cytokine that is responsible, in part, for several aspects of the acute-phase response to inflammation, including the generation of fever. TNF-alpha has direct effects on central nervous system neurons deep within the hypothalamus that are involved in producing the febrile response, but the blood-brain barrier prevents circulating TNF-alpha from having access to these sites. We therefore have hypothesized that TNF-alpha may be produced in the brain and used as a mediator in the cerebral components of the acute-phase response. We used in situ hybridization to determine the distribution of production of TNF-alpha mRNA in the mouse brain after systemic administration of lipopolysaccharide. During the initial phase of fever, hybridization was observed in perivascular cells and neurons in circumventricular organs, including the vascular organ of the lamina terminalis, median eminence, and area postrema, as well as along the ventral surface of the medulla; hybridization was also prominent over many cell in the meninges. During the late phase of the response, hybridization was observed over neurons in the pericircumventricular nuclei such as the anteroventral periventricular and arcuate nuclei of the hypothalamus and the nucleus of the solitary tract. TNF-alpha produced by a cascade of neurons within the brain may participate in the complex autonomic, neuroendocrine, metabolic, and behavioral responses to infection and inflammation.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Cites
Detection of circulating tumor necrosis factor after endotoxin administration
Michie, H. R., Manogue, K. R., Spriggs, D. R., Revhaug, A., O'Dwyer, S., Dinarello, C. A., Cerami, A., Wolff, S. M., & Wilmore, D. W. (1988) · New England Journal of Medicine · doi:10.1056/nejm198806093182301 · Cited by 1,677 · see citing works
Perivascular microglial cells of the CNS are bone marrow-derived and present antigen in vivo
Hickey, W. F., & Kimura, H. (1988) · Science · doi:10.1126/science.3276004 · Cited by 1,466 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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 · see citing works
Tracey, K. J. (2002) · Nature · doi:10.1038/nature01321 · Cited by 3,728 · see citing works
Regulation of the Hypothalamic-Pituitary-Adrenal Axis by Cytokines: Actions and Mechanisms of Action
TURNBULL, A. V., & RIVIER, C. L. (1999) · Physiological Reviews · doi:10.1152/physrev.1999.79.1.1 · Cited by 1,297 · see citing works
Role of Pro-Inflammatory Cytokines Released from Microglia in Neurodegenerative Diseases
Smith, J. A., Das, A., Ray, S. K., & Banik, N. L. (2012) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2011.10.004 · Cited by 1,165 · see citing works
Control of brain development, function, and behavior by the microbiome
Sampson, T. R., & Mazmanian, S. K. (2015) · Cell Host & Microbe · doi:10.1016/j.chom.2015.04.011 · Cited by 1,093 · see citing works
Immune modulation of the hypothalamic-pituitary-adrenal (HPA) axis during viral infection
Silverman, M. N., Pearce, B. D., Biron, C. A., & Miller, A. H. (2005) · Viral Immunology · doi:10.1089/vim.2005.18.41 · Cited by 506 · see citing works
Chakravarty, S., & Herkenham, M. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.4268-04.2005 · Cited by 396 · see citing works
Dantzer, R., Konsman, J.-P., Bluthé, R.-M., & Kelley, K. W. (2000) · Autonomic Neuroscience · doi:10.1016/s1566-0702(00)00220-4 · Cited by 400 · see citing works
Psychoneuroimmunology of early-life stress: the hidden wounds of childhood trauma?
Danese, A., & J Lewis, S. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.198 · Cited by 393 · see citing works
Cytokines and the central nervous system
Szelényi, J. (2001) · Brain Research Bulletin · doi:10.1016/s0361-9230(01)00428-2 · Cited by 358 · see citing works
Review: Systemic inflammation and<scp>A</scp>lzheimer's disease
Holmes, C. (2013) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2012.01307.x · Cited by 356 · see citing works
The Neuropathology of Septic Shock
Sharshar, T., Annane, D., de la Gradmaison, G. L., Brouland, J. P., Hopkinson, N. S., & Gray, F. (2004) · Brain Pathology · doi:10.1111/j.1750-3639.2004.tb00494.x · Cited by 348 · see citing works
Cytokine, sickness behavior, and depression
Dantzer, R. (2006) · Neurologic Clinics · doi:10.1016/j.ncl.2006.03.003 · Cited by 340 · see citing works
Sharshar, T., Gray, F., de la Grandmaison, G. L., Hopklnson, N. S., Ross, E., Dorandeu, A., Orlikowski, D., Raphael, J.-C., Gajdos, P., & Annane, D. (2003) · The Lancet · doi:10.1016/s0140-6736(03)14899-4 · Cited by 341 · see citing works
Hidden wounds? inflammatory links between childhood trauma and psychopathology
Danese, A., & Baldwin, J. R. (2017) · Annual Review of Psychology · doi:10.1146/annurev-psych-010416-044208 · Cited by 286 · see citing works
Molecular Basis of Sickness Behavior<sup>a</sup>
DANTZER, R., BLUTHÉ, R., GHEUSI, G., CREMONA, S., LAYÉ, S., PARNET, P., & KELLEY, K. W. (1998) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1998.tb08321.x · Cited by 249 · see citing works
Pathways and mechanisms for cytokine signaling of the central nervous system.
Licinio, J., & Wong, M. L. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119846 · Cited by 220 · see citing works
Karalis, K., Muglia, L. J., Bae, D., Hilderbrand, H., & Majzoub, J. A. (1997) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(96)00178-6 · Cited by 203 · see citing works
Vallières, L., & Rivest, S. (1999) · Endocrinology · doi:10.1210/endo.140.9.6983 · Cited by 157 · see citing works
O'Sullivan, J. B., Ryan, K. M., Curtin, N. M., Harkin, A., & Connor, T. J. (2009) · The International Journal of Neuropsychopharmacology · doi:10.1017/s146114570800967x · Cited by 146 · see citing works
Goujon, E., Parnet, P., Layé, S., Combe, C., & Dantzer, R. (1996) · Molecular Brain Research · doi:10.1016/0169-328x(95)00242-k · Cited by 128 · see citing works
Breese, G. R., Knapp, D. J., Overstreet, D. H., Navarro, M., Wills, T. A., & Angel, R. A. (2008) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301468 · Cited by 110 · see citing works
KAPCALA, L. P., CHAUTARD, T., & ESKAY, R. L. (1995) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1995.tb44699.x · Cited by 103 · see citing works
Nadeau, S., & Rivest, S. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.169.6.3370 · Cited by 94 · see citing works
Zielinski, M. R., Dunbrasky, D. L., Taishi, P., Souza, G., & Krueger, J. M. (2013) · Sleep · doi:10.5665/sleep.2892 · Cited by 94 · see citing works
Coelho, A.-M., Fioramonti, J., & Bueno, L. (2000) · Brain Research Bulletin · doi:10.1016/s0361-9230(00)00269-0 · Cited by 31 · see citing works
Ruud, J., Wilhelms, D. B., Nilsson, A., Eskilsson, A., Tang, Y., Ströhle, P., Caesar, R., Schwaninger, M., Wunderlich, T., Bäckhed, F., et al. (2013) · The FASEB Journal · doi:10.1096/fj.12-225433 · Cited by 29 · see citing works
- Authors
- Breder, C. D., Hazuka, C., Ghayur, T., Klug, C., Huginin, M., Yasuda, K., Teng, M., & Saper, C. B.
- Affiliations
- University of Chicago (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1994-11-22
- Volume
- 91
- Issue
- 24
- Pages
- 11393-11397
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC45237
- OpenAlex
- W2024248428
- Cited by
- 226
- References
- 2
- Citations by year
- 2025: 1 · 2024: 4 · 2023: 3 · 2022: 1 · 2021: 6 · 2020: 5 · 2019: 4 · 2018: 4 · 2017: 2 · 2016: 7 · 2015: 4 · 2014: 7 · 2013: 7 · 2012: 8
- FWCI
- 9.43
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Diabetes Association
- National Institute of General Medical Sciences (GM-07183, T32GM007183)
- National Institute of Neurological Disorders and Stroke (R01NS022835, NS-22835)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD-07009)
- Topics
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Thermal Regulation in Medicine
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- TNF-α, lipopolysaccharide, fever, acute phase response, circumventricular organs, hypothalamus, median eminence, area postrema, lamina terminalis, meninges, perivascular cells, neuroinflammation, infection and inflammation
- MeSH terms
- Acute-Phase Reaction, Animals, Base Sequence, Brain, Lipopolysaccharides, Mice, Inbred BALB C, Molecular Sequence Data, RNA, Messenger, Salmonella typhimurium, Tumor Necrosis Factor-alpha, Gene Expression, DNA Primers, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
