Systemic inflammation induces acute behavioral and cognitive changes and accelerates neurodegenerative disease.
Open accessAbstract
BACKGROUND: Chronic neurodegeneration results in microglial activation, but the contribution of inflammation to the progress of neurodegeneration remains unclear. We have shown that microglia express low levels of proinflammatory cytokines during chronic neurodegeneration but are "primed" to produce a more proinflammatory profile after systemic challenge with bacterial endotoxin (lipopolysaccharide [LPS]). METHODS: Here, we investigated whether intraperitoneal (IP) challenge with LPS, to mimic systemic infection, in the early stages of prion disease can 1) produce exaggerated acute behavioral (n = 9) and central nervous system (CNS) inflammatory (n = 4) responses in diseased animals compared with control animals, and 2) whether a single LPS challenge can accelerate disease progression (n = 34-35). RESULTS: Injection of LPS (100 microg/kg), at 12 weeks postinoculation (PI), resulted in heightened CNS interleukin-1 beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and interferon-beta (IFN-beta) transcription and microglial IL-1beta translation in prion-diseased animals relative to control animals. This inflammation caused exaggerated impairments in burrowing and locomotor activity, and induced hypothermia and cognitive changes in prion-diseased animals that were absent in LPS-treated control animals. At 15 weeks PI, LPS (500 microg/kg) acutely impaired motor coordination and muscle strength in prion-diseased but not in control animals. After recovery, these animals also showed earlier onset of disease-associated impairments on these parameters. CONCLUSIONS: These data demonstrate that transient systemic inflammation superimposed on neurodegenerative disease acutely exacerbates cognitive and motor symptoms of disease and accelerates disease progression. These deleterious effects of systemic inflammation have implications for the treatment of chronic neurodegeneration and associated delirium.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Macrophages are one of the main producers of inflammatory cytokines.
“macrophages are known to be one of the main producers of inflammatory cytokines”
From Alzheimer’s disease-associated protective variant Plcg2-P522R modulates peripheral macrophage function in a sex-dimorphic manner (2024) · cites this paper as [2]
The Discussion (Exaggerated Sickness Behavior and Microglial Priming; page unavailable) reports IL-1β production by hippocampal microglia after systemic LPS challenge. The paper does not establish that macrophages generally are among the main producers of inflammatory cytokines; its finding concerns microglia under a specific condition. (LLM, conf=0.78)
Experimental — accuracy not yet measuredChronic inflammatory cytokines can exacerbate neurodegeneration.
“which, when chronic, can exacerbate neurodegeneration [2–4]”
From Alzheimer’s disease-associated protective variant Plcg2-P522R modulates peripheral macrophage function in a sex-dimorphic manner (2024) · cites this paper as [2]
The Abstract Conclusions report that transient systemic inflammation accelerates neurodegenerative disease, and the Discussion Conclusion cites evidence that systemic IL-1β exacerbates neurodegeneration. Neither passage establishes that chronic exposure to inflammatory cytokines causes the exacerbation; the paper says its mechanism remains unclear. Page numbers are unavailable in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredAnimal studies demonstrated that systemic immune activation by viral, bacterial, or parasitic infections results in impaired memory functioning.
“Studies in experimental animals demonstrated that systemic immune activation by viral, bacterial, or parasitic infections result in impaired memory functioning [18], [19], [20], [21], [22], [23].”
From Dose-dependent effects of endotoxin on neurobehavioral functions in humans (2011) · cites this paper as [18]
Systemic endotoxin precipitates brain pathology in mice expressing prions, APP variants or TAU variants or mice with α-synuclein injected in the brain.
“and systemic endotoxin precipitates brain pathology in mice expressing prions [74], APP variants [33] or TAU variants [69] or mice with α-synuclein injected in the brain [46].”
From The endotoxin hypothesis of neurodegeneration (2019) · cites this paper as [74]
A series of studies using a ME7 prion disease model showed dystrophic morphology of microglia and enhanced expression of inflammatory mediators such as IL-1β and COX-2 following in vivo LPS challenge; the exaggerated inflammatory changes in ME7 mice were also associated with impairments in spatial learning.
“A series of studies using a ME7 prion disease model showed dystrophic morphology of microglia and enhanced expression of inflammatory mediators such as IL-1β and COX-2 following in vivo LPS challenge.The exaggerated inflammatory changes in ME7 mice were also associated with impairments in spatial learning (Cunningham et al, 2009).”
From Microglia Priming with Aging and Stress (2017) · cites this paper as Cunningham et al, 2009
In prion disease, microglia appear to express low levels of pro-inflammatory cytokines during chronic neurodegeneration but may be in a "primed" state.
“In prion disease, microglia appear to express low levels of pro-inflammatory cytokines during chronic neurodegeneration but may be in a “primed” state [8].”
From MicroRNA 146a (miR-146a) Is Over-Expressed during Prion Disease and Modulates the Innate Immune Response and the Microglial Activation State (2012) · cites this paper as [8]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Glutamate neurotoxicity and diseases of the nervous system
Choi, D. W. (1988) · Neuron · doi:10.1016/0896-6273(88)90162-6 · Cited by 8,152 · see citing works
Inflammation and Alzheimer’s disease
Akiyama, H. (2000) · Neurobiology of Aging · doi:10.1016/s0197-4580(00)00124-x · Cited by 4,514 · see citing works
Cunningham, C., Wilcockson, D. C., Campion, S., Lunnon, K., & Perry, V. H. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.2614-05.2005 · Cited by 768 · see citing works
Self-citationCytokine-induced sickness behaviour: a neuroimmune response to activation of innate immunity
Dantzer, R. (2004) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2004.07.040 · Cited by 743 · see citing works
Kitazawa, M., Oddo, S., Yamasaki, T. R., Green, K. N., & LaFerla, F. M. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.2868-05.2005 · Cited by 697 · see citing works
Delirium Superimposed on Dementia: A Systematic Review
Fick, D. M., Agostini, J. V., & Inouye, S. K. (2002) · Journal of the American Geriatrics Society · doi:10.1046/j.1532-5415.2002.50468.x · Cited by 638 · see citing works
Interleukin 1 signaling occurs exclusively via the type I receptor.
Sims, J. E., Gayle, M. A., Slack, J. L., Alderson, M. R., Bird, T. A., Giri, J. G., Colotta, F., Re, F., Mantovani, A., & Shanebeck, K. D. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.13.6155 · Cited by 610 · see citing works
Etminan, M., Gill, S., & Samii, A. (2003) · BMJ · doi:10.1136/bmj.327.7407.128 · Cited by 511 · see citing works
NSAIDs and Alzheimer disease: Epidemiological, animal model and clinical studies
McGeer, P. L., & McGeer, E. G. (2007) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2006.03.013 · Cited by 498 · see citing works
The impact of systemic infection on the progression of neurodegenerative disease
Perry, V. H., Newman, T. A., & Cunningham, C. (2003) · Nature Reviews Neuroscience · doi:10.1038/nrn1032 · Cited by 428 · see citing works
Self-citationThe risk of dementia and death after delirium
Rockwood, K. J. (1999) · Age and Ageing · doi:10.1093/ageing/28.6.551 · Cited by 410 · see citing works
Chen, J., Buchanan, J. B., Sparkman, N. L., Godbout, J. P., Freund, G. G., & Johnson, R. W. (2007) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2007.08.014 · Cited by 396 · 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
The Association Between Delirium and Cognitive Decline: A Review of the Empirical Literature
Jackson, J. C., Gordon, S. M., Hart, R. P., Hopkins, R. O., & Ely, E. W. (2004) · Neuropsychology Review · doi:10.1023/b:nerv.0000028080.39602.17 · Cited by 386 · see citing works
Altered antigen expression of microglia in the aged rodent CNS
Perry, V. H., Matyszak, M. K., & Fearn, S. (1993) · Glia · doi:10.1002/glia.440070111 · Cited by 364 · see citing works
Self-citationPrevalence and detection of delirium in elderly emergency department patients.
Élie, M., Rousseau, F., Cole, M. G., Primeau, F., McCusker, J., & Bellavance, F. (2000) · Europe PMC (PubMed Central) · Cited by 345 · see citing works
Spatial memory dissociations in mice lacking GluR1
Reisel, D., Bannerman, D. M., Schmitt, W. B., Deacon, R. M. J., Jonathan Flint, C., Borchardt, T., Seeburg, P. H., & Rawlins, J. N. P. (2002) · Nature Neuroscience · doi:10.1038/nn910 · Cited by 343 · see citing works
Self-citationPott Godoy, M. C., Tarelli, R., Ferrari, C. C., Sarchi, M. I., & Pitossi, F. J. (2008) · Brain · doi:10.1093/brain/awn101 · Cited by 335 · see citing works
Peripheral infection and aging interact to impair hippocampal memory consolidation
Barrientos, R. M., Higgins, E. A., Biedenkapp, J. C., Sprunger, D. B., Wright-Hardesty, K. J., Watkins, L. R., Rudy, J. W., & Maier, S. F. (2006) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.03.010 · Cited by 330 · see citing works
Systemic infection, interleukin 1beta, and cognitive decline in Alzheimer's disease
Holmes, C. (2003) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.74.6.788 · Cited by 330 · see citing works
mRNA up-regulation of MHC II and pivotal pro-inflammatory genes in normal brain aging
Frank, M. G., Barrientos, R. M., Biedenkapp, J. C., Rudy, J. W., Watkins, L. R., & Maier, S. F. (2006) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.03.013 · Cited by 327 · see citing works
Cunningham, C., Campion, S., Teeling, J., Felton, L., & Perry, V. H. (2007) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2006.12.007 · Cited by 318 · see citing works
Burrowing in rodents: a sensitive method for detecting behavioral dysfunction
Deacon, R. M. J. (2006) · Nature Protocols · doi:10.1038/nprot.2006.19 · Cited by 314 · see citing works
Self-citationAcute Delirium and Functional Decline in the Hospitalized Elderly Patient
Murray, A. M., Levkoff, S. E., Wetle, T. T., Beckett, L. A., Cleary, P. D., Schor, J. D., Lipsitz, L. A., Rowe, J. W., & Evans, D. A. (1993) · Journal of Gerontology · doi:10.1093/geronj/48.5.m181 · Cited by 294 · see citing works
Synaptic changes characterize early behavioural signs in the ME7 model of murine prion disease
Cunningham, C. M., Deacon, R. M. J., Wells, H., Boche, D., Waters, S., Diniz, C. W. P., Scott, H., Rawlins, J. N. P., & Perry, V. H. (2003) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2003.02662.x · Cited by 266 · see citing works
Self-citationNguyen, M. D., D'Aigle, T., Gowing, G., Julien, J.-P., & Rivest, S. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.4786-03.2004 · Cited by 248 · see citing works
Peripheral infection evokes exaggerated sickness behaviour in pre-clinical murine prion disease
Combrinck, M. I., Perry, V. H., & Cunningham, C. (2002) · Neuroscience · doi:10.1016/s0306-4522(02)00030-1 · Cited by 231 · see citing works
Self-citationHow does peripheral lipopolysaccharide induce gene expression in the brain of rats?
Singh, A. K., & Jiang, Y. (2004) · Toxicology · doi:10.1016/j.tox.2004.04.015 · Cited by 223 · see citing works
The potential of anti-inflammatory drugs for the treatment of Alzheimer's disease
Aisen, P. S. S. (2002) · The Lancet Neurology · doi:10.1016/s1474-4422(02)00133-3 · Cited by 201 · see citing works
EVIDENCE FOR AN EARLY INFLAMMATORY RESPONSE IN THE CENTRAL NERVOUS SYSTEM OF MICE WITH SCRAPIE
Betmouni, S., Perry, V. H., & Gordon, J. L. (1996) · Neuroscience · doi:10.1016/0306-4522(96)00212-6 · Cited by 196 · see citing works
Self-citationInflammatory processes induce beta-amyloid precursor protein changes in mouse brain.
Brugg, B., Lemaigre‐Dubreuil, Y., Huber, G., Wollman, E. E., Delhaye‐Bouchaud, N., & Mariani, J. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.7.3032 · Cited by 191 · see citing works
Effects of cytotoxic hippocampal lesions in mice on a cognitive test battery
Deacon, R. M. J., Bannerman, D. M., Kirby, B. P., Croucher, A. P., & Rawlins, J. N. P. (2002) · Behavioural Brain Research · doi:10.1016/s0166-4328(01)00451-x · Cited by 189 · see citing works
Self-citationCauses and prognosis of delirium in elderly patients admitted to a district general hospital
George, J. M., Bleasdale, S., & SINGLETON, S. J. (1997) · Age and Ageing · doi:10.1093/ageing/26.6.423 · Cited by 181 · see citing works
Sly, L. M., KRZESICKI, R. F., Brashler, J. R., Buhl, A.-L., McKinley, D. D., Carter, D. B., & Chin, J. E. (2001) · Brain Research Bulletin · doi:10.1016/s0361-9230(01)00730-4 · Cited by 174 · see citing works
Early behavioural changes in scrapie‐affected mice and the influence of dapsone
Guenther, K. M., Deacon, R. M. J., Perry, V. H., & Rawlins, J. N. P. (2001) · European Journal of Neuroscience · doi:10.1046/j.0953-816x.2001.01645.x · Cited by 150 · see citing works
Self-citationPrognostic Significance of Delirium in Frail Older People
Pitkälä, K. H., Laurila, J., Strandberg, T. E., & Tilvis, R. S. (2004) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000082888 · Cited by 143 · see citing works
Sub-pyrogenic systemic inflammation impacts on brain and behavior, independent of cytokines
Teeling, J. L., Felton, L. M., Deacon, R. M. J., Cunningham, C. M., Rawlins, J. N. P., & Perry, V. H. (2007) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2007.01.012 · Cited by 140 · see citing works
Self-citationSparkman, N. L., Martin, L. A., Calvert, W. S., & Boehm, G. W. (2005) · Behavioural Brain Research · doi:10.1016/j.bbr.2004.10.011 · Cited by 123 · see citing works
Age-dependent and -independent behavioral deficits in Tg2576 mice
Deacon, R. M. J., Cholerton, L. L., Talbot, K., Nair‐Roberts, R. G., Sanderson, D. J., Romberg, C., Koroś, E., Bornemann, K. D., & Rawlins, J. N. P. (2008) · Behavioural Brain Research · doi:10.1016/j.bbr.2007.12.024 · Cited by 118 · see citing works
Self-citationBrown, T. M., & Boyle, M. F. (2002) · BMJ · doi:10.1136/bmj.325.7365.644 · Cited by 117 · see citing works
Lerner, A. J., Hedera, P., Koss, E., Stuckey, J. C., & Friedland, R. P. (1997) · Alzheimer Disease & Associated Disorders · doi:10.1097/00002093-199703000-00004 · Cited by 112 · see citing works
Sparkman, N. L., Kohman, R. A., Garcia, A. K., & Boehm, G. W. (2005) · Physiology & Behavior · doi:10.1016/j.physbeh.2005.04.015 · Cited by 93 · see citing works
Bacterial endotoxin-induced behavioral alterations in two variations of the Morris water maze
Sparkman, N. L., Kohman, R. A., Scott, V. J., & Boehm, G. W. (2005) · Physiology & Behavior · doi:10.1016/j.physbeh.2005.07.016 · Cited by 92 · see citing works
Cunningham, C. M., Boche, D., & Perry, V. H. (2002) · Neuropathology and Applied Neurobiology · doi:10.1046/j.1365-2990.2002.00383.x · Cited by 80 · see citing works
Self-citationRahkonen, T., Mâkelà, H., Paanila, S., Halonen, P. M., Slvenius, J., & Sulkava, R. O. (2000) · International Psychogeriatrics · doi:10.1017/s1041610200006591 · Cited by 76 · see citing works
Absence of Detectable IL-1β Production in Murine Prion Disease: A Model of Chronic Neurodegeneration
Walsh, D. T., Betmouni, S., & Perry, V. H. (2001) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/60.2.173 · Cited by 71 · see citing works
Self-citationFelton, L. M., Cunningham, C. M., Rankine, E. L., Waters, S., Boche, D., & Perry, V. H. (2005) · Neurobiology of Disease · doi:10.1016/j.nbd.2005.03.008 · Cited by 70 · see citing works
Self-citationCoxibs and Alzheimer's disease: Should they stay or should they go?
Firuzi, O., & Praticò, D. (2006) · Annals of Neurology · doi:10.1002/ana.20774 · Cited by 54 · see citing works
Cunningham, C. M., Wilcockson, D. C., Boche, D., & Perry, V. H. (2005) · Journal of Virology · doi:10.1128/jvi.79.8.5174-5184.2005 · Cited by 53 · see citing works
Self-citationLearning impairments of hippocampal-lesioned mice in a paddling pool.
Deacon, R. M. J., & Rawlins, J. N. P. (2002) · Behavioral Neuroscience · doi:10.1037//0735-7044.116.3.472 · Cited by 42 · see citing works
Self-citation[A NEW METHOD FOR THE MEASUREMENT OF MUSCLE RELAXATION IN WHITE MICE].
Kondziella, W. (1964) · PubMed · Cited by 42 · see citing works
Learning impairments of hippocampal-lesioned mice in a paddling pool.
Deacon, R. M. J., & Rawlins, J. N. P. (2002) · Behavioral Neuroscience · doi:10.1037/0735-7044.116.3.472 · Cited by 37 · see citing works
Self-citationAge increases vulnerability to bacterial endotoxin-induced behavioral decrements
Kohman, R. A., Tarr, A. J., Byler, S. L., & Boehm, G. W. (2007) · Physiology & Behavior · doi:10.1016/j.physbeh.2007.03.032 · Cited by 36 · see citing works
Lipid A-induced tolerance and hyperreactivity to hypothermia in mice
GREER, G. G., & Rietschel, E. (1978) · Infection and Immunity · doi:10.1128/iai.19.2.357-368.1978 · Cited by 30 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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 · see citing works
Self-citationInouye, S. K., Westendorp, R. G., & Saczynski, J. S. (2014) · The Lancet · doi:10.1016/s0140-6736(13)60688-1 · Cited by 3,722 · see citing works
Immune attack: the role of inflammation in Alzheimer disease
Heppner, F. L., Ransohoff, R. M., & Becher, B. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn3880 · Cited by 2,134 · see citing works
Microglia in neurodegenerative disease
Perry, V. H., Nicoll, J. A. R., & Holmes, C. (2010) · Nature Reviews Neurology · doi:10.1038/nrneurol.2010.17 · Cited by 1,543 · see citing works
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 · see citing works
Systemic inflammation and disease progression in Alzheimer disease
Holmes, C., Cunningham, C., Zotova, E., Woolford, J., Dean, C., Kerr, S., Culliford, D., & Perry, V. H. (2009) · Neurology · doi:10.1212/wnl.0b013e3181b6bb95 · Cited by 1,139 · see citing works
Self-citationMicroglial priming in neurodegenerative disease
Perry, V. H., & Holmes, C. (2014) · Nature Reviews Neurology · doi:10.1038/nrneurol.2014.38 · Cited by 1,127 · see citing works
Self-citationMicroglial Activation and Chronic Neurodegeneration
Lull, M. E., & Block, M. L. (2010) · Neurotherapeutics · doi:10.1016/j.nurt.2010.05.014 · Cited by 1,047 · see citing works
Microglia and neurodegeneration: The role of systemic inflammation
Cunningham, C. (2013) · Glia · doi:10.1002/glia.22350 · Cited by 769 · see citing works
Self-citationNeuropathogenesis of Delirium: Review of Current Etiologic Theories and Common Pathways
Maldonado, J. R. (2013) · The American Journal of Geriatric Psychiatry · doi:10.1016/j.jagp.2013.09.005 · Cited by 745 · see citing works
Regulation of Tau Pathology by the Microglial Fractalkine Receptor
Bhaskar, K., Konerth, M., Kokiko-Cochran, O. N., Cardona, A., Ransohoff, R. M., & Lamb, B. T. (2010) · Neuron · doi:10.1016/j.neuron.2010.08.023 · Cited by 639 · see citing works
Delirium pathophysiology: An updated hypothesis of the etiology of acute brain failure
Maldonado, J. R. (2018) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.4823 · Cited by 617 · see citing works
The interface between delirium and dementia in elderly adults
Fong, T. G., Davis, D., Growdon, M. E., Albuquerque, A., & Inouye, S. K. (2015) · The Lancet Neurology · doi:10.1016/s1474-4422(15)00101-5 · Cited by 595 · see citing works
The endotoxin hypothesis of neurodegeneration
Brown, G. C. (2019) · Journal of Neuroinflammation · doi:10.1186/s12974-019-1564-7 · Cited by 457 · see citing works
Norden, D. M., Muccigrosso, M. M., & Godbout, J. P. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2014.10.028 · Cited by 413 · see citing works
Microglia Priming with Aging and Stress
Niraula, A., Sheridan, J. F., & Godbout, J. P. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.185 · Cited by 398 · 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
Sankowski, R., Mader, S., & Valdés-Ferrer, S. I. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00028 · Cited by 351 · see citing works
Inflammatory dysregulation of blood monocytes in Parkinson’s disease patients
Grozdanov, V., Bliederhaeuser, C., Ruf, W. P., Roth, V., Fundel-Clemens, K., Zondler, L., Brenner, D., Martin-Villalba, A., Hengerer, B., Kassubek, J., et al. (2014) · Acta Neuropathologica · doi:10.1007/s00401-014-1345-4 · Cited by 295 · see citing works
Aging‐dependent changes of microglial cells and their relevance for neurodegenerative disorders
Von Bernhardi, R., Tichauer, J. E., & Eugenín, J. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06537.x · Cited by 258 · see citing works
Neurodegeneration by Activation of the Microglial Complement-Phagosome Pathway
Bodea, L.-G., Wang, Y., Linnartz-Gerlach, B., Kopatz, J., Sinkkonen, L., Musgrove, R., Kaoma, T., Muller, A., Vallar, L., Di Monte, D. A., et al. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.5002-13.2014 · Cited by 234 · see citing works
Davis, D. H. J., Muniz-Terrera, G., Keage, H. A. D., Stephan, B. C. M., Fleming, J., Ince, P. G., Matthews, F. E., Cunningham, C., Ely, E. W., MacLullich, A. M. J., et al. (2017) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2016.3423 · Cited by 252 · see citing works
Self-citationDose-dependent effects of endotoxin on neurobehavioral functions in humans
Grigoleit, J.-S., Kullmann, J. S., Wolf, O. T., Hammes, F., Wegner, A., Jablonowski, S., Engler, H., Gizewski, E., Oberbeck, R., & Schedlowski, M. (2011) · PLoS ONE · doi:10.1371/journal.pone.0028330 · Cited by 241 · see citing works
André, C., Dinel, A.-L., Ferreira, G., Layé, S., & Castanon, N. (2014) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2014.03.012 · Cited by 241 · see citing works
Aas, M., Dazzan, P., Mondelli, V., Melle, I., Murray, R. M., & Pariante, C. M. (2014) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2013.00182 · Cited by 230 · see citing works
Hart, A. D., Wyttenbach, A., Hugh Perry, V., & Teeling, J. L. (2012) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2011.11.006 · Cited by 230 · see citing works
Cunningham, C., & Hennessy, E. (2015) · Alzheimer's Research & Therapy · doi:10.1186/s13195-015-0117-2 · Cited by 211 · see citing works
Self-citationSipilä, P. N., Heikkilä, N., Lindbohm, J. V., Hakulinen, C., Vahtera, J., Elovainio, M., Suominen, S., Väänänen, A., Koskinen, A., Nyberg, S. T., et al. (2021) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(21)00144-4 · Cited by 197 · see citing works
Kahn, M. S., Kranjac, D., Alonzo, C. A., Haase, J. H., Cedillos, R. O., McLinden, K. A., Boehm, G. W., & Chumley, M. J. (2012) · Behavioural Brain Research · doi:10.1016/j.bbr.2012.01.010 · Cited by 177 · see citing works
Periodontal microorganisms and Alzheimer disease – A causative relationship?
Jungbauer, G., Stähli, A., Zhu, X., Auber Alberi, L., Sculean, A., & Eick, S. (2022) · Periodontology 2000 · doi:10.1111/prd.12429 · Cited by 174 · see citing works
Systemic Inflammation Modulates Fc Receptor Expression on Microglia during Chronic Neurodegeneration
Lunnon, K., Teeling, J. L., Tutt, A. L., Cragg, M. S., Glennie, M. J., & Perry, V. H. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.0903833 · Cited by 138 · see citing works
Self-citationSystemic inflammation and delirium: important co-factors in the progression of dementia
Cunningham, C. (2011) · Biochemical Society Transactions · doi:10.1042/bst0390945 · Cited by 153 · see citing works
Self-citationSaba, R., Gushue, S., Huzarewich, R. L. C. H., Manguiat, K., Medina, S., Robertson, C., & Booth, S. A. (2012) · PLoS ONE · doi:10.1371/journal.pone.0030832 · Cited by 151 · see citing works
Post-mortem analysis of neuroinflammatory changes in human Alzheimer’s disease
Gomez-Nicola, D., & Boche, D. (2015) · Alzheimer's Research & Therapy · doi:10.1186/s13195-015-0126-1 · Cited by 147 · see citing works
Teeling, J. L., Cunningham, C., Newman, T. A., & Perry, V. H. (2010) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2009.11.006 · Cited by 139 · see citing works
Self-citationThe Role of Neuroinflammation in Dementias
Pasqualetti, G., Brooks, D. J., & Edison, P. (2015) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-015-0531-7 · Cited by 133 · see citing works
Environment matters: microglia function and dysfunction in a changing world
Hanamsagar, R., & Bilbo, S. D. (2017) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2017.10.007 · Cited by 122 · see citing works
Targeting innate immunity for neurodegenerative disorders of the central nervous system
Andreasson, K. I., Bachstetter, A. D., Colonna, M., Ginhoux, F., Holmes, C., Lamb, B., Landreth, G., Lee, D. C., Low, D., Lynch, M. A., et al. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13667 · Cited by 126 · see citing works
Lasselin, J., Lekander, M., Axelsson, J., & Karshikoff, B. (2018) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2018.06.005 · Cited by 106 · see citing works
Johansson, J. U., Pradhan, S., Lokteva, L. A., Woodling, N. S., Ko, N., Brown, H. D., Wang, Q., Loh, C., Cekanaviciute, E., Buckwalter, M., et al. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.2203-13.2013 · Cited by 96 · see citing works
Hughes, M. M., Field, R. H., Perry, V. H., Murray, C. L., & Cunningham, C. (2010) · Glia · doi:10.1002/glia.21070 · Cited by 94 · see citing works
Self-citationSimon, E., Obst, J., & Gomez-Nicola, D. (2019) · Neuroscience · doi:10.1016/j.neuroscience.2018.01.059 · Cited by 83 · see citing works
ICU Survivorship—The Relationship of Delirium, Sedation, Dementia, and Acquired Weakness
Mart, M. F., Pun, B. T., Pandharipande, P., Jackson, J. C., & Ely, E. W. (2021) · Critical Care Medicine · doi:10.1097/ccm.0000000000005125 · Cited by 67 · see citing works
International drive to illuminate delirium: a developing public health blueprint for action
Khachaturian, A. S., Hayden, K. M., Devlin, J. W., Fleisher, L. A., Lock, S. L., Cunningham, C., Oh, E. S., Fong, T. G., Fick, D. M., Marcantonio, E. R., et al. (2020) · Alzheimer's & Dementia · doi:10.1002/alz.12075 · Cited by 60 · see citing works
Self-citationBidirectional Brain-Systemic Interactions and Outcomes After TBI
Faden, A. I., Barrett, J. P., Stoica, B. A., & Henry, R. J. (2021) · Trends in Neurosciences · doi:10.1016/j.tins.2020.12.004 · Cited by 57 · see citing works
Gildawie, K. R., Orso, R., Peterzell, S., Thompson, V., & Brenhouse, H. C. (2020) · Neuroscience Letters · doi:10.1016/j.neulet.2020.135381 · Cited by 46 · see citing works
Lifetime modulation of the pain system via neuroimmune and neuroendocrine interactions
Zouikr, I., & Karshikoff, B. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00276 · Cited by 45 · see citing works
Samaan, Z., McDermid Vaz, S., Bawor, M., Potter, T. H., Eskandarian, S., & Loeb, M. (2016) · PLOS ONE · doi:10.1371/journal.pone.0158364 · Cited by 42 · see citing works
Cerebrospinal Fluid Levels of Interleukin-8 in Delirium, Dementia, and Cognitively Healthy Patients
Sajjad, M. U., Blennow, K., Knapskog, A. B., Idland, A.-V., Chaudhry, F. A., Wyller, T. B., Zetterberg, H., & Watne, L. O. (2020) · Journal of Alzheimer’s Disease · doi:10.3233/jad-190941 · Cited by 34 · see citing works
Recent advances in psychoneuroimmunology: Inflammation in psychiatric disorders
Debnath, M., Doyle, K., Langan, C., McDonald, C., Leonard, B., & Cannon, D. (2011) · Translational Neuroscience · doi:10.2478/s13380-011-0019-0 · Cited by 28 · see citing works
Chouhan, J. K., Püntener, U., Booth, S. G., & Teeling, J. L. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.760721 · Cited by 24 · see citing works
Knopp, R. C., Baumann, K. K., Wilson, M. L., Banks, W. A., & Erickson, M. A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23042377 · Cited by 17 · see citing works
Staley, H. A., Jernigan, J. E., Bolen, M. L., Titus, A. M., Neighbarger, N., Cole, C., Menees, K. B., Wallings, R. L., & Tansey, M. G. (2024) · Journal of Neuroinflammation · doi:10.1186/s12974-024-03271-9 · Cited by 9 · see citing works
“These cells are considered to be the body’s first line of defense, and are main propagators of inflammation, which has been shown to exacerbate neurodegeneration [2–4].”
BackgroundInnate Immune Tolerance in Microglia Does Not Impact on Central Nervous System Prion Disease
Pal, R., Bradford, B. M., & Mabbott, N. A. (2022) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2022.918883 · Cited by 7 · see citing works
- Authors
- Cunningham, C., Campion, S., Lunnon, K., Murray, C. L., Woods, J. F. C., Deacon, R. M. J., Rawlins, J. N. P., & Perry, V. H.
- Affiliations
- Trinity College Dublin (IE)
- University of Southampton (GB)
- University of Oxford (GB)
- Corresponding author
- Cunningham, Colm
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2009-02
- Volume
- 65
- Issue
- 4
- Pages
- 304-312
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC2633437
- OpenAlex
- W2093984890
- Cited by
- 584
- References
- 55
- Citations by year
- 2026: 18 · 2025: 24 · 2024: 40 · 2023: 22 · 2022: 33 · 2021: 50 · 2020: 33 · 2019: 32 · 2018: 28 · 2017: 40 · 2016: 38 · 2015: 38 · 2014: 40 · 2013: 43 · 2012: 35
- FWCI
- 9.33
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Biological Psychiatry (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Open Research Exeter (University of Exeter) (publishedVersion, cc-by)
- ePrints Soton (University of Southampton) (submittedVersion)
- Figshare (submittedVersion)
- Funders
- Wellcome Trust
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- systemic inflammation, lipopolysaccharide, prion disease, neurodegeneration, microglial activation, IL-1β, TNF-α, interferon-beta, cognitive impairment, motor coordination, disease progression, behavior change, hypothermia, delirium
- MeSH terms
- Animals, Behavior, Animal, Body Temperature, Cognition, Female, Immunohistochemistry, Inflammation, Infusions, Parenteral, Lipopolysaccharides, Longitudinal Studies, Mice, Inbred C57BL, Motor Activity, Psychomotor Performance, Maze Learning, Neurodegenerative Diseases, Reverse Transcriptase Polymerase Chain Reaction, 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
