Microglia as a source and target of cytokines
Open accessAbstract
Cytokines constitute a significant portion of the immuno‐ and neuromodulatory messengers that can be released by activated microglia. By virtue of potent effects on resident and invading cells, microglial cyto‐ and chemokines regulate innate defense mechanisms, help the initiation and influence the type of immune responses, participate in the recruitment of leukocytes to the CNS, and support attempts of tissue repair and recovery. Microglia can also receive cyto‐ and chemokine signals as part of auto‐ and paracrine communications with astrocytes, neurons, the endothelium, and leukocyte infiltrates. Strong responses and modulatory influences can be demonstrated, adding to the emerging view that microglial behavior is highly dependent on the (cytokine) environment and that reactions to a challenge may vary with the stimulation context. In principle, microglial activation aims at CNS protection. However, failed microglial engagement due to excessive or sustained activation could significantly contribute to acute and chronic neuropathologies. Dysregulation of microglial cytokine production could thereby promote harmful actions of the defense mechanisms, result in direct neurotoxicity, as well as disturb neural cell functions as they are sensitive to cytokine signaling. GLIA 40:140–155, 2002. © 2002 Wiley‐Liss, Inc.
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?
Cellular and molecular mechanisms resulting from injury or infections that underlie the development of proinflammatory cytokines and chemokines in the CNS are canonically triggered and modulated by astrocytes and microglia.
“Cellular and molecular mechanisms resulting from injury or infections, underlying the development of proinflammatory cytokines and chemokines in the CNS, are canonically triggered and modulated by astrocytes and microglia (Hanisch, 2002; Murphy et al., 1997)”
From Arbovirus infection increases the risk for the development of neurodegenerative disease pathology in the murine model (2024) · cites this paper as Hanisch, 2002
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
Death Receptors: Signaling and Modulation
Ashkenazi, A., & Dixit, V. M. (1998) · Science · doi:10.1126/science.281.5381.1305 · Cited by 5,866 · see citing works
Immunization with amyloid-β attenuates Alzheimer-disease-like pathology in the PDAPP mouse
Schenk, D., Barbour, R., Dunn, W., Gordon, G., Grajeda, H., Guido, T., Hu, K., Huang, J., Johnson-Wood, K., Khan, K., et al. (1999) · Nature · doi:10.1038/22124 · Cited by 3,160 · see citing works
“Inflammatory” Cytokines: Neuromodulators in Normal Brain?
Vitkovic, L., Bockaert, J., & Jacque, C. (2000) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2000.740457.x · Cited by 506 · see citing works
Banks, W. A., Ortiz, L., Plotkin, S. R., & Kastin, A. J. (1991) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)20576-6 · Cited by 474 · cited 1× · see citing works
“This may involve transportassisted BBB penetration of circulating IL-1, effects triggered at this border, true central IL-1 actions, and afferent fiber pathways stimulated by peripheral IL-1 (Banks et al., 1991; Banks and Kastin, 1997).”
BackgroundExpression of CX <sub>3</sub> CR1 chemokine receptors on neurons and their role in neuronal survival
Meucci, O., Fatatis, A., Simen, A. A., & Miller, R. J. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.090017497 · Cited by 385 · see citing works
Carlson, N. G., Wieggel, W. A., Chen, J., Bacchi, A., Rogers, S. W., & Gahring, L. C. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.163.7.3963 · Cited by 301 · cited 2× · see citing works
“Nevertheless, it is important to emphasize that too little cytokine signaling can be as deleterious as too much (Carlson et al., 1999; Mason et al., 2001).”
BackgroundRogers, J., & Lue, L.-F. (2001) · Neurochemistry International · doi:10.1016/s0197-0186(01)00040-7 · Cited by 236 · see citing works
Yates, S. L., Burgess, L. H., Kocsis‐Angle, J., Antal, J. M., Dority, M. D., Embury, P. B., Piotrkowski, A. M., & Brunden, K. R. (2000) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2000.0741017.x · Cited by 202 · see citing works
Electrophysiological properties of microglial cells in normal and pathologic rat brain slices
Boucsein, C., Kettenmann, H., & Nolte, C. (2000) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2000.00100.x · Cited by 166 · see citing works
Flagged first, then by citations
Research works printed but not linked: 8
- Dinarello CA. 1998b. Interleukin-1. In: Thomson A, editor. The cyto- kine handbook. San Diego: Academic Press. p 35-72.
- Giulian D. 1995. Microglia and neuronal dysfunction. In: Kettenmann H, Ransom BR, editors. Neuroglia. New York: Oxford University Press. p 671-684.
- Hanisch UK. 2001a. Microglia as a source and target of cytokine activities in the brain. In: Streit WJ, editor. Microglia in the degen- erating and regenerating CNS. New York: Springer Verlag. p 79 - 124.
- Hanisch UK. 2001b. Effects of interleukin-2 and interferons on the nervous system. In: Ader R, Felten DL, Cohen N, edsitors. Psycho- neuroimmunology. San Diego: Academic Press. p 585-631.
- Streit WJ, Hurley SD, McGraw TS, Semple-Rowland SL. 2000b. Com- parative evaluation of cytokine profiles and reactive gliosis supports a critical role for interleukin-6 in neuron-glia signaling during regeneration. J Neurosci Res 61:10 -20.
- Vilcek J. 1998. The cytokines: an overview. In: Thomson A, editor. The cytokine handbook. San Diego: Academic Press. p 1-20.
- Ware CF, Santee S, Glass A. 1998. Tumor necrosis factor-related ligands and receptors. In: Thomson A, editor. The cytokine hand- book. San Diego: Academic Press. p 549 -592.
- Zhang M, Tracey KJ. 1998. Tumor necrosis factor. In: Thomson A, editor. The cytokine handbook. San Diego: Academic Press. p 517-548.
Cited by
Sorted by citations
A Meta-Analysis of Cytokines in Major Depression
Dowlati, Y., Herrmann, N., Swardfager, W., Liu, H., Sham, L., Reim, E. K., & Lanctôt, K. L. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.09.033 · Cited by 4,729 · see citing works
Kettenmann, H., Hanisch, U.-K., Noda, M., & Verkhratsky, A. (2011) · Physiological Reviews · doi:10.1152/physrev.00011.2010 · Cited by 3,547 · see citing works
Self-citationNeuroinflammation and microglial activation in Alzheimer disease: where do we go from here?
Leng, F., & Edison, P. (2021) · Nature Reviews Neurology · doi:10.1038/s41582-020-00435-y · Cited by 3,179 · see citing works
Inflammation in obesity, diabetes, and related disorders
Rohm, T. V., Meier, D. T., Olefsky, J. M., & Donath, M. Y. (2022) · Immunity · doi:10.1016/j.immuni.2021.12.013 · Cited by 2,066 · see citing works
Onset and Progression in Inherited ALS Determined by Motor Neurons and Microglia
Boillée, S., Yamanaka, K., Lobsiger, C. S., Copeland, N. G., Jenkins, N. A., Kassiotis, G., Kollias, G., & Cleveland, D. W. (2006) · Science · doi:10.1126/science.1123511 · Cited by 1,623 · see citing works
Inflammation is detrimental for neurogenesis in adult brain
Ekdahl, C. T., Claasen, J.-H., Bonde, S., Kokaia, Z., & Lindvall, O. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2234031100 · Cited by 1,559 · see citing works
The cellular and signaling networks linking the immune system and metabolism in disease
Osborn, O., & Olefsky, J. M. (2012) · Nature Medicine · doi:10.1038/nm.2627 · Cited by 1,551 · 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
Glia and pain: Is chronic pain a gliopathy?
Ji, R., Berta, T., & Nedergaard, M. (2013) · Pain · doi:10.1016/j.pain.2013.06.022 · Cited by 1,193 · see citing works
“Interestingly, even acute opioid treatment after a subcutaneous injection results in marked SGC reaction in DRGs at 2 hours when morphine analgesia declines [18] (Table 1).”
BackgroundA Meta-Analysis of Cytokines in Alzheimer's Disease
Swardfager, W., Lanctôt, K., Rothenburg, L., Wong, A., Cappell, J., & Herrmann, N. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.06.012 · Cited by 1,108 · see citing works
Proinflammatory Cytokines, Aging, and Age-Related Diseases
Michaud, M., Balardy, L., Moulis, G., Gaudin, C., Peyrot, C., Vellas, B., Cesari, M., & Nourhashemi, F. (2013) · Journal of the American Medical Directors Association · doi:10.1016/j.jamda.2013.05.009 · Cited by 1,094 · see citing works
Microglia in the adult brain arise from Ly-6ChiCCR2+ monocytes only under defined host conditions
Mildner, A., Schmidt, H., Nitsche, M., Merkler, D., Hanisch, U.-K., Mack, M., Heikenwalder, M., Brück, W., Priller, J., & Prinz, M. (2007) · Nature Neuroscience · doi:10.1038/nn2015 · Cited by 1,089 · see citing works
Self-citationStout, R. D., Jiang, C., Matta, B., Tietzel, I., Watkins, S. K., & Suttles, J. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.1.342 · Cited by 968 · see citing works
Biran, R., Martin, D. C., & Tresco, P. A. (2005) · Experimental Neurology · doi:10.1016/j.expneurol.2005.04.020 · Cited by 893 · see citing works
Selective Ablation of Proliferating Microglial Cells Exacerbates Ischemic Injury in the Brain
Lalancette-Hébert, M., Gowing, G., Simard, A., Weng, Y. C., & Kriz, J. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.5360-06.2007 · Cited by 874 · see citing works
Neuronal ‘On’ and ‘Off’ signals control microglia
Biber, K., Neumann, H., Inoue, K., & Boddeke, H. W. G. M. (2007) · Trends in Neurosciences · doi:10.1016/j.tins.2007.08.007 · Cited by 787 · see citing works
Functional plasticity of macrophages: reversible adaptation to changing microenvironments
Stout, R. D., & Suttles, J. (2004) · Journal of Leukocyte Biology · doi:10.1189/jlb.0504272 · Cited by 751 · see citing works
Tumor necrosis factor alpha: A link between neuroinflammation and excitotoxicity
Olmos, G., & Lladó, J. (2014) · Mediators of Inflammation · doi:10.1155/2014/861231 · Cited by 730 · see citing works
“Although astrocytes and neurons are able to produce TNF-α [34–36], it is assumed that microglia are the major source of this cytokine during neuroinflammation [37, 38].”
Microglia in Pain: Detrimental and Protective Roles in Pathogenesis and Resolution of Pain
Chen, G., Zhang, Y., Qadri, Y. J., Serhan, C. N., & Ji, R. (2018) · Neuron · doi:10.1016/j.neuron.2018.11.009 · Cited by 791 · see citing works
A new type of microglia gene targeting shows TAK1 to be pivotal in CNS autoimmune inflammation
Goldmann, T., Wieghofer, P., Müller, P. F., Wolf, Y., Varol, D., Yona, S., Brendecke, S. M., Kierdorf, K., Staszewski, O., Datta, M., et al. (2013) · Nature Neuroscience · doi:10.1038/nn.3531 · Cited by 688 · see citing works
Austin, P. J., & Moalem-Taylor, G. (2010) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2010.08.013 · Cited by 607 · see citing works
“…a plethora of pro-inflammatorymediators such as; IL-1β (Chauvet et al., 2001), TNF (Hide et al., 2000), IL-6 (Shigemoto-Mogami et al., 2001), NO (Martucci et al., 2008), and PGE2 (Svensson et al., 2003), many of which enhance activation of spinal neurons (Hanisch, 2002; Watkins et al., 2001).”
Neuroinflammation in Alzheimer disease
Heneka, M. T., van der Flier, W. M., Jessen, F., Hoozemanns, J., Thal, D. R., Boche, D., Brosseron, F., Teunissen, C., Zetterberg, H., Jacobs, A. H., et al. (2025) · Nature Reviews Immunology · doi:10.1038/s41577-024-01104-7 · Cited by 638 · see citing works
“Another study found several types of microglial reactivity states 182 similar to those that account for cytokine secretion in the human brain 183 .”
The immune system and developmental programming of brain and behavior
Bilbo, S. D., & Schwarz, J. M. (2012) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2012.08.006 · Cited by 579 · see citing works
“Sick animals exhibit several well-characterized behavioral changes, including reductions in food and water intake, activity, exploration, increased sleep, and reduced social and sexual interactions (Hart, 1988).”
BackgroundMicroglia activation in retinal degeneration
Langmann, T. (2007) · Journal of Leukocyte Biology · doi:10.1189/jlb.0207114 · Cited by 496 · see citing works
Perego, C., Fumagalli, S., & Simoni, M. G. D. (2011) · Journal of Neuroinflammation · doi:10.1186/1742-2094-8-174 · Cited by 504 · see citing works
Bidirectional Microglia–Neuron Communication in Health and Disease
Szepesi, Z., Manouchehrian, O., Bachiller, S., & Deierborg, T. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00323 · Cited by 459 · see citing works
“, and Hanisch, U. K. (2006). Microglial phenotype: is the commitment reversible? Trends Neurosci.”
BackgroundMicroglia: actively surveying and shaping neuronal circuit structure and function
Wake, H., Moorhouse, A. J., Miyamoto, A., & Nabekura, J. (2013) · Trends in Neurosciences · doi:10.1016/j.tins.2012.11.007 · Cited by 448 · see citing works
Microglial phenotype: is the commitment reversible?
Schwartz, M., Butovsky, O., Brück, W., & Hanisch, U.-K. (2006) · Trends in Neurosciences · doi:10.1016/j.tins.2005.12.005 · Cited by 434 · see citing works
Self-citationNeuroinflammatory processes in Alzheimer’s disease
Heneka, M. T., O’Banion, M. K., Terwel, D., & Kummer, M. P. (2010) · Journal of Neural Transmission · doi:10.1007/s00702-010-0438-z · Cited by 433 · see citing works
Michelucci, A., Heurtaux, T., Grandbarbe, L., Morga, E., & Heuschling, P. (2009) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2009.02.003 · Cited by 411 · see citing works
Schilling, M., Besselmann, M., Leonhard, C., Mueller, M., Ringelstein, E. B., & Kiefer, R. (2003) · Experimental Neurology · doi:10.1016/s0014-4886(03)00082-7 · Cited by 375 · see citing works
Felger, J. C., & Miller, A. H. (2012) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2012.09.003 · Cited by 394 · see citing works
“Once in the CNS, peripheral inflammatory cytokines or activated immune cells can dramatically influence the tone of local inflammatory networks and propagate neuroinflammation by activating local production of cytokines [84, 104, 171] and inflammatory signaling pathways, such as nuclear factor (NF)-kappaB, janus kinas…”
BackgroundNeuroinflammation and Perioperative Neurocognitive Disorders
Subramaniyan, S., & Terrando, N. (2019) · Anesthesia & Analgesia · doi:10.1213/ane.0000000000004053 · Cited by 453 · see citing works
Zhuang, Z.-Y., Kawasaki, Y., Tan, P.-H., Wen, Y.-R., Huang, J., & Ji, R.-R. (2007) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2006.11.003 · Cited by 371 · see citing works
Montgomery, S. L., & Bowers, W. J. (2011) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-011-9287-2 · Cited by 365 · see citing works
Ling, W., Fraser, J. L., Lu, Z.-Y., Hu, X.-Y., & Yu, S. P. (2012) · Neurobiology of Disease · doi:10.1016/j.nbd.2012.03.002 · Cited by 355 · see citing works
“Dysregulation of microglial cytokine production could thereby promote harmful actions of the defense mechanisms, result in direct neurotoxicity, as well as disturb neural cell functions (Hanisch, 2002; Ohmi et al., 2003).”
BackgroundMicroglia mediate postoperative hippocampal inflammation and cognitive decline in mice
Feng, X., Valdearcos, M., Uchida, Y., Lutrin, D., Maze, M., & Koliwad, S. K. (2017) · JCI Insight · doi:10.1172/jci.insight.91229 · Cited by 362 · see citing works
“The surgically-induced hippocampal production of MCP-1 we observed, however, does not preclude the possibility that mechanisms other than HMGB1 may also contribute to vagal afferents that can regulate microglia (32), cytokines crossing the BBB by diffusion or active transport and regulating microglia under feedback co…”
BackgroundNeurodegeneration and Inflammation—An Interesting Interplay in Parkinson’s Disease
Marogianni, C., Sokratous, M., Dardiotis, E., Hadjigeorgiou, G. M., Bogdanos, D. P., & Xiromerisiou, G. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21228421 · Cited by 369 · see citing works
“Other common stimuli for microglia activation, both in vitro and in vivo, are interferon (IFN)-γ, β-amyloid (Aβ), lipopolysaccharide (LPS), and α-synuclein [22].”
BackgroundHayley, S., Poulter, M. O., Merali, Z., & Anisman, H. (2005) · Neuroscience · doi:10.1016/j.neuroscience.2005.03.051 · Cited by 324 · see citing works
Features of Microglia and Neuroinflammation Relevant to Environmental Exposure and Neurotoxicity
Kraft, A. D., & Harry, G. J. (2011) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph8072980 · Cited by 330 · see citing works
“In addition, they can regulate the production of neurotrophic factors by neurons and other glia via cytokine production [80-83].”
BackgroundNeuroinflammation in schizophrenia especially focused on the role of microglia
Monji, A., Kato, T. A., Mizoguchi, Y., Horikawa, H., Seki, Y., Kasai, M., Yamauchi, Y., Yamada, S., & Kanba, S. (2013) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2011.12.002 · Cited by 314 · see citing works
The molecular profile of microglia under the influence of glioma
Li, W., & Graeber, M. B. (2012) · Neuro-Oncology · doi:10.1093/neuonc/nos116 · Cited by 341 · see citing works
Taylor, D. L., Jones, F., Kubota, E. S. F. C. S., & Pocock, J. M. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.4456-04.2005 · Cited by 308 · see citing works
Microglia amplify inflammatory activation of astrocytes in manganese neurotoxicity
Kirkley, K. S., Popichak, K. A., Afzali, M. F., Legare, M. E., & Tjalkens, R. B. (2017) · Journal of Neuroinflammation · doi:10.1186/s12974-017-0871-0 · Cited by 323 · see citing works
“Increased expression and release of TNF by microglia often occurs early in neurodegenerative diseases such as PD and human immunodeficiency virus-induced dementia and appears to be important for subsequent glial reactivity [44].”
BackgroundWright, A. L., Zinn, R., Hohensinn, B., Konen, L. M., Beynon, S. B., Tan, R. P., Clark, I. A., Abdipranoto, A., & Vissel, B. (2013) · PLoS ONE · doi:10.1371/journal.pone.0059586 · Cited by 310 · see citing works
The Impact of Systemic Inflammation on Neurodevelopment
Jiang, N. M., Cowan, M. N., Moonah, S. N., & Petri, W. A. (2018) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2018.06.008 · Cited by 330 · see citing works
Microglia Activation as a Biomarker for Traumatic Brain Injury
Hernandez‐Ontiveros, D. G., Tajiri, N., Acosta, S., Giunta, B. N., Tan, J., & Borlongan, C. V. (2013) · Frontiers in Neurology · doi:10.3389/fneur.2013.00030 · Cited by 274 · see citing works
“Likewise, endogenous inducers act as inflammatory mediators, such as platelet-activating factor (PAF), lipids, serum proteins, or complement factors; additionally, disturbances in ATP and [K+] levels may cause microglia activation (Hanisch, 2002).”
BackgroundArcuri, C., Mecca, C., Bianchi, R., Giambanco, I., & Donato, R. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00191 · Cited by 279 · see citing works
“Additionally, DAMPs are recognized by microglia through ion channels and neurotransmitter receptors that contribute to clear the brain parenchyma from cell debris and help to begin tissue repair after injury.”
BackgroundInfluentialPuberty and adolescence as a time of vulnerability to stressors that alter neurobehavioral processes
Holder, M. K., & Blaustein, J. D. (2014) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2013.10.004 · Cited by 279 · see citing works
Central Nervous System Targets: Glial Cell Mechanisms in Chronic Pain
Donnelly, C. R., Andriessen, A. S., Chen, G., Wang, K., Jiang, C., Maixner, W. D., & Ji, R. (2020) · Neurotherapeutics · doi:10.1007/s13311-020-00905-7 · Cited by 302 · see citing works
Blood–brain barrier permeable nano immunoconjugates induce local immune responses for glioma therapy
Galstyan, A., Markman, J. L., Shatalova, E. S., Chiechi, A., Korman, A. J., Patil, R., Klymyshyn, D., Tourtellotte, W. G., Israel, L. L., Braubach, O., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-11719-3 · Cited by 306 · see citing works
Inflammasomes in neuroinflammation and changes in brain function: a focused review
Singhal, G., Jaehne, E. J., Corrigan, F., Toben, C. G., & Baune, B. T. (2014) · Frontiers in Neuroscience · doi:10.3389/fnins.2014.00315 · Cited by 365 · see citing works
“Glial cells, microglia, and astrocytes, are the primary immune effector cells and express various cytokines in the CNS (Rothwell et al., 1996; Hanisch, 2002).”
BackgroundNeuroprotective function for ramified microglia in hippocampal excitotoxicity
Vinet, J., van Weering, H. R., Heinrich, A., Kälin, R. E., Wegner, A., Brouwer, N., Heppner, F. L., van Rooijen, N., Boddeke, H. W., & Biber, K. (2012) · Journal of Neuroinflammation · doi:10.1186/1742-2094-9-27 · Cited by 274 · see citing works
Janelsins, M. C., Mastrangelo, M. A., Oddo, S., LaFerla, F. M., Federoff, H. J., & Bowers, W. J. (2005) · Journal of Neuroinflammation · doi:10.1186/1742-2094-2-23 · Cited by 260 · 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
The blood-brain barrier, chemokines and multiple sclerosis
Holman, D. W., Klein, R. S., & Ransohoff, R. M. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2010.07.019 · Cited by 247 · see citing works
Potter, K. A., Buck, A. C., Self, W. K., & Capadona, J. R. (2012) · Journal of Neural Engineering · doi:10.1088/1741-2560/9/4/046020 · Cited by 239 · see citing works
“It is understood that upon activation, microglia cells release pro-inflammatory cytokines, nitric oxide and reactive oxygen species; all of which highly impact the permeability of the localized vasculature and neuronal survival [11, 24, 25, 59, 65].”
BackgroundMicroglia in Alzheimer's Disease: Exploring How Genetics and Phenotype Influence Risk
McQuade, A., & Blurton-Jones, M. (2019) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.01.045 · Cited by 244 · see citing works
The changing phenotype of microglia from homeostasis to disease
Luo, X., & Chen, S. (2012) · Translational Neurodegeneration · doi:10.1186/2047-9158-1-9 · Cited by 232 · see citing works
“To do this with high efficiency, microglia must be variable, adaptive to their environment and capable of integrating various inputs and responding appropriately [92,93].”
BackgroundMicroglia in the CNS: Immigrants from another world
Prinz, M., & Mildner, A. (2010) · Glia · doi:10.1002/glia.21104 · Cited by 236 · see citing works
“Increasing the number of vessel-associated macrophages could potentially be beneficial, whereas the reduction of this cell population could lead to an exacerbation of the symptoms as demonstrated recently (Hawkes and McLaurin, 2009).”
BackgroundHosseini, S., Wilk, E., Michaelsen-Preusse, K., Gerhauser, I., Baumgärtner, W., Geffers, R., Schughart, K., & Korte, M. (2018) · The Journal of Neuroscience · doi:10.1523/jneurosci.1740-17.2018 · Cited by 236 · see citing works
Morris, G. P., Clark, I. A., Zinn, R., & Vissel, B. (2013) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2013.07.002 · Cited by 236 · see citing works
“The most well-known mechanism by which both active and resting microglia could contribute to synaptic plasticity is via their release of various synaptically active molecules including cytokines (Hanisch, 2002; Mallat & Chamak, 1994; Streit & Xue, 2012).”
BackgroundThe Ischemic Environment Drives Microglia and Macrophage Function
Fumagalli, S., Perego, C., Pischiutta, F., Zanier, E. R., & Simoni, M. G. D. (2015) · Frontiers in Neurology · doi:10.3389/fneur.2015.00081 · Cited by 245 · see citing works
“This feature together with the lack of a lymphatic system, low constitutive levels of major histocompatibility complex (MHC) class I and II molecules, local production of suppressive factors, and limited numbers of cerebral artery; MCP-1, monocyte chemoattractant protein 1 (also known as CCL2); MCSF, macrophage colony…”
BackgroundInfluentialCurrent status of chemokines in the adult CNS
Goazigo, A. R.-L., Steenwinckel, J. V., Rostène, W. H., & Parsadaniantz, S. M. (2013) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2013.02.001 · Cited by 237 · see citing works
“In the CNS, CCL2 is also produced by glial cells (Barna et al., 1994; Berman et al., 1996; Glabinski et al., 1996; Hanisch, 2002).”
BackgroundMicroglia-neuron crosstalk: Signaling mechanism and control of synaptic transmission
Marinelli, S., Basilico, B., Marrone, M. C., & Ragozzino, D. (2019) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2019.05.017 · Cited by 233 · see citing works
Absence of CX3CR1 impairs the internalization of Tau by microglia
Bolós, M., Llorens-Martín, M., Perea, J. R., Jurado-Arjona, J., Rábano, A., Hernández, F., & Avila, J. (2017) · Molecular Neurodegeneration · doi:10.1186/s13024-017-0200-1 · Cited by 231 · see citing works
“These microglial functions are regulated by communication between neurons, astrocytes and microglia [8] through cytokines, chemokines, trophic factors, and other molecules.”
BackgroundJanelsins, M. C., Mastrangelo, M. A., Park, K. M., Sudol, K. L., Narrow, W. C., Oddo, S., LaFerla, F. M., Callahan, L. M., Federoff, H. J., & Bowers, W. J. (2008) · The American Journal of Pathology · doi:10.2353/ajpath.2008.080528 · Cited by 220 · see citing works
The many facets of macrophages in rheumatoid arthritis
Siouti, E., & Andreakos, E. (2019) · Biochemical Pharmacology · doi:10.1016/j.bcp.2019.03.029 · Cited by 249 · see citing works
The role of cytokines in modulating learning and memory and brain plasticity
Bourgognon, J.-M., & Cavanagh, J. (2020) · Brain and Neuroscience Advances · doi:10.1177/2398212820979802 · Cited by 247 · see citing works
“In response to infections, stress, degenerative diseases or any changes in the nervous system both activated astrocytes and microglia produce cytokines that modulate a large variety of physiological and pathological processes (Hanisch, 2002; Hanisch and Kettenmann, 2007; Sofroniew, 2013).”
BackgroundMicroglia: An Interface between the Loss of Neuroplasticity and Depression
Singhal, G., & Baune, B. T. (2017) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2017.00270 · Cited by 252 · see citing works
“These findings are consistent with the previously published reviews and may be associated with the hyperactivity of microglia in the brain (Hanisch, 2002; Schroeter et al., 2008; Smith et al., 2012).”
BackgroundResultEvidence for a Dysregulated Immune System in the Etiology of Psychiatric Disorders
Gibney, S. M., & Drexhage, H. A. (2013) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-013-9462-8 · Cited by 237 · see citing works
Brain-immune interactions in perinatal hypoxic-ischemic brain injury
Li, B., Concepcion, K. R., Meng, X., & Zhang, L. (2017) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2017.10.006 · Cited by 230 · see citing works
WNT signaling in activated microglia is proinflammatory
Halleskog, C., Mulder, J., Dahlström, J., Mackie, K., Hortobágyi, T., Tanila, H., Puli, L., Färber, K., Harkany, T., & Schulte, G. (2010) · Glia · doi:10.1002/glia.21081 · Cited by 216 · see citing works
“Diverse signaling molecules—including growth factors, neurotransmitters, and morphogens—may instruct microglia functions (Hanisch, 2002; Pocock and Kettenmann, 2007), thus emphasizing that the temporal and spatial dynamics of communication between microglia and neurons, astrocytes or…”
BackgroundDai, J.-N., Zong, Y., Zhong, L.-M., Li, Y.-M., Zhang, W., Bian, L.-G., Ai, Q.-L., Liu, Y.-D., Sun, J., & Lu, D. (2011) · PLoS ONE · doi:10.1371/journal.pone.0021891 · Cited by 217 · see citing works
“In addition, microglial cells in the healthy brain do not express iNOS, but they become activated to produce iNOS and release a large amount of NO following ischemic, traumatic, neurotoxic or inflammatory damage [12,37,38,39].”
BackgroundGibney, S. M., McGuinness, B. W., Prendergast, C., Harkin, A., & Connor, T. J. (2012) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2012.11.010 · Cited by 220 · see citing works
Glioblastoma-associated microglia and macrophages: targets for therapies to improve prognosis
Poon, C. C., Sarkar, S., Yong, V. W., & Kelly, J. J. (2017) · Brain · doi:10.1093/brain/aww355 · Cited by 246 · see citing works
Gyoneva, S., & Traynelis, S. F. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.458901 · Cited by 204 · see citing works
Microglia of Prefrontal White Matter in Suicide
Schnieder, T. P., Trencevska, I., Rosoklija, G., Stankov, A., Mann, J. J., Smiley, J., & Dwork, A. J. (2014) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0000000000000107 · Cited by 202 · see citing works
“Microglia are the immunologic sentinel cells of the CNS and its main producers of cytokines (10, 11).”
Microglia in the healthy and degenerating retina: Insights from novel mouse models
Karlstetter, M., Ebert, S., & Langmann, T. (2010) · Immunobiology · doi:10.1016/j.imbio.2010.05.010 · Cited by 197 · see citing works
Gui, W.-S., Xiao, W., Mai, C.-L., Murugan, M., Wu, L., Xin, W., Zhou, L., & Liu, X. (2016) · Molecular Pain · doi:10.1177/1744806916646784 · Cited by 198 · see citing works
Role of Microglia in CNS Autoimmunity
Goldmann, T., & Prinz, M. (2013) · Clinical and Developmental Immunology · doi:10.1155/2013/208093 · Cited by 195 · see citing works
“In addition to cytokines, microglia are also activated by and are able to release diverse chemoattractant chemokines, such as CCL2, CCL3, CCL4, CCL5, CXCL10, and/or CCL12 [47, 48, 52, 62, 63] (Figure 1).”
Ebneter, A., Casson, R. J., Wood, J. P. M., & Chidlow, G. (2010) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.10-5284 · Cited by 198 · see citing works
Pharmacological Modulation of Functional Phenotypes of Microglia in Neurodegenerative Diseases
Song, G. J., & Suk, K. (2017) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00139 · Cited by 199 · see citing works
“Microglia can promote neurotoxicity via the release of several pro-inflammatory mediators, such as nitric oxide, interleukin (IL)-1β, and tumor necrosis factor-alpha (TNF-α) (Hanisch, 2002; Block et al., 2007).”
BackgroundFunctional diversity of microglia – how heterogeneous are they to begin with?
Hanisch, U.-K. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00065 · Cited by 195 · see citing works
“…endogenous and especially CNS-intrinsic (homeostatic and damageor degeneration-related) factors takes influences on the activity state and activity recruitment of microglia, as listed previously (Hanisch, 2002; Hanisch and Kettenmann, 2007; Kettenmann et al., 2011; Hanisch, 2012, 2013).”
BackgroundSelf-citationSinghrao, S. K., Harding, A., Poole, S., Kesavalu, L., & Crean, S. (2015) · Mediators of Inflammation · doi:10.1155/2015/137357 · Cited by 195 · see citing works
“Together these factors lead to vital neurons being destroyed and enhanced maintenance of chronic inflammation with consequences for development of disease [98, 113, 122–125].”
BackgroundKaur, C., Rathnasamy, G., & Ling, E. (2012) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-012-9347-2 · Cited by 208 · see citing works
Prenatal infection leads to ASD-like behavior and altered synaptic pruning in the mouse offspring
de Cossío, L. F., Guzman, A. S., van der Veldt, S., & Luheshi, G. N. (2016) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2016.09.028 · Cited by 214 · see citing works
Arteaga-Henríquez, G., Simon, M. S., Burger, B., Weidinger, E., Wijkhuijs, A. J. M., Arolt, V., Birkenhäger, T. K., Musil, R., Müller, N., & Drexhage, H. A. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00458 · Cited by 215 · see citing works
Microglia and Spinal Cord Synaptic Plasticity in Persistent Pain
Taves, S., Berta, T., Chen, G., & Ji, R. (2013) · Neural Plasticity · doi:10.1155/2013/753656 · Cited by 179 · see citing works
“IL-1 𝛽 is induced in astrocytes, neurons, and microglia in inflammatory and neuropathic pain [77–80].”
Glia and alpha-synuclein in neurodegeneration: A complex interaction
Brück, D., Wenning, G. K., Stefanova, N., & Fellner, L. (2015) · Neurobiology of Disease · doi:10.1016/j.nbd.2015.03.003 · Cited by 202 · see citing works
“, 2011), or vice versa microglial activation can induce astrogliosis (Balasingam et al., 1996; Hanisch, 2002; Rohl et al., 2007).”
Cellular and molecular mechanisms of immunomodulation in the brain through environmental enrichment
Singhal, G., Jaehne, E. J., Corrigan, F., & Baune, B. T. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00097 · Cited by 186 · see citing works
“…their overexpression or sustained stimulation can result in enhanced production of cytokines (e.g., IL-1β and TNF-α; Sawada et al., 1989; Hanisch, 2002), as well as in the expression of class I and II major histocompatibility complex antigens as seen in a RCT in rodents and in the…”
BackgroundExtracellular caspase-6 drives murine inflammatory pain via microglial TNF-α secretion
Berta, T., Park, C., Xu, Z., Xie, R.-G., Liu, T., Lü, N., Liu, Y., & Ji, R. (2014) · Journal of Clinical Investigation · doi:10.1172/jci72230 · Cited by 195 · see citing works
“org Volume 124 Number 3 March 2014 Because microglia are a major source of spinal TNF-α (Figure 6B) (40), we examined a possible contribution of spinal microglia to CASP6-evoked allodynia.”
Cerebral ischemic damage in diabetes: an inflammatory perspective
Shukla, V., Shakya, A. K., Pérez‐Pinzón, M. A., & Dave, K. R. (2017) · Journal of Neuroinflammation · doi:10.1186/s12974-016-0774-5 · Cited by 201 · see citing works
Can oral infection be a risk factor for Alzheimer's disease?
Olsen, I., & Singhrao, S. K. (2015) · Journal of Oral Microbiology · doi:10.3402/jom.v7.29143 · Cited by 182 · see citing works
“As a consequence, the brain glial cells are able to generate a local and complete innate immune system when challenged by foreign agents (26, 48-50).”
BackgroundZhao, H., Wang, J., Gao, L., Wang, R., Liu, X., Gao, Z., Tao, Z., Xu, C., Song, J., Ji, X., et al. (2013) · Stroke · doi:10.1161/strokeaha.111.000504 · Cited by 173 · see citing works
“change into an amoeboid shape, increased phagocytosis, and release of cytokines.(22,23) Our in vivo study exhibited that ICV”
BackgroundDysregulated neuronal–microglial cross-talk during aging, stress and inflammation
Jurgens, H. A., & Johnson, R. W. (2012) · Experimental Neurology · doi:10.1016/j.expneurol.2010.11.014 · Cited by 179 · see citing works
“In response to inflammatory stimuli, microglia are rapidly activated and undergo a morphological transformation with shorter, stouter processes (i.e. deramified) and larger soma size (Hanisch, 2002; Hanisch and Kettenmann, 2007; Long et al., 1998).”
BackgroundHe, W., McConnell, G. C., & Bellamkonda, R. V. (2006) · Journal of Neural Engineering · doi:10.1088/1741-2560/3/4/009 · Cited by 177 · see citing works
Molecular mechanisms linking neuroinflammation and neurodegeneration in MS
Ellwardt, E., & Zipp, F. (2014) · Experimental Neurology · doi:10.1016/j.expneurol.2014.02.006 · Cited by 176 · see citing works
Neuroinflammation and Parkinson’s Disease—From Neurodegeneration to Therapeutic Opportunities
Araújo, B., Caridade-Silva, R., Soares-Guedes, C., Martins‐Macedo, J., Gomes, E. D., Monteiro, S., & Teixeira, F. G. (2022) · Cells · doi:10.3390/cells11182908 · Cited by 198 · see citing works
“Microglia are one of the primary cell types in neuroinflammatory reactions, providing the first line of defense and protection against infection and injury [14].”
BackgroundGarcía‐Mesa, Y., Jay, T. R., Checkley, M. A., Luttge, B. G., Dobrowolski, C. N., Valadkhan, S., Landreth, G. E., Karn, J., & Alvarez-Carbonell, D. (2016) · Journal of NeuroVirology · doi:10.1007/s13365-016-0499-3 · Cited by 184 · see citing works
“Upon administration of pro-inflammatory stimuli, microglia may release different combinations of cytokines that include interferons, interleukins, TGF-β, GM-CSF, PDGF, EGF, FGF, IGF, NGF, neurotrophins, and BDNF (Hanisch 2002).”
- Authors
- Hanisch, U.
- Affiliations
- Max Delbrück Center (DE)
- Corresponding author
- Hanisch, Uwe‐Karsten
- Venue
- Glia
- Publisher
- Wiley
- Published
- 2002-10-04
- Volume
- 40
- Issue
- 2
- Pages
- 140-155
- ISSN
- 0894-1491 (ISSN-L)
- 1098-1136
- OpenAlex
- W2090804892
- Cited by
- 1,645
- References
- 0
- Citations by year
- 2026: 29 · 2025: 39 · 2024: 62 · 2023: 59 · 2022: 68 · 2021: 85 · 2020: 82 · 2019: 76 · 2018: 85 · 2017: 79 · 2016: 70 · 2015: 81 · 2014: 86 · 2013: 94 · 2012: 93
- FWCI
- 4.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Glia (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Keywords
- microglia, cytokines, chemokines, microglial activation, neuroinflammation, neuroprotection, astrocyte-microglia interaction, tissue repair, neurotoxicity, neuropathology, innate immunity
- MeSH terms
- Animals, Cell Communication, Endocrine System, Endothelium, Vascular, Humans, Neuroglia, Neurons, Cytokines, Microglia
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
