Systemic inflammatory cells fight off neurodegenerative disease
Abstract
Treatment of Alzheimer disease or amyotrophic lateral sclerosis with anti-inflammatory drugs (to prevent disease or slow its progression) has yielded mixed results, despite evidence indicating that local cytotoxic inflammation occurs in these conditions. Here, through consideration of the importance of immune cell origin (resident versus blood-derived immune cells) and activity (pro-inflammatory versus anti-inflammatory activity) under neurodegenerative conditions, we propose a model that reconciles these seemingly inconsistent data. We suggest that systemic immune cells (CD4(+) T cells and peripheral blood-derived monocytes) must be recruited to the CNS to modify potentially destructive local inflammation, and that the failure of systemic anti-inflammatory drug therapies to arrest neurodegenerative disease progression might result from drug-induced suppression of such recruitment. Thus, we propose that an appreciation of the distinctive temporal and spatial contributions of resident and systemic leukocytes to disease progression is essential for the development of effective therapeutic regimens.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
Maintenance of certain brain functions is dependent on T cell actions in the CNS.
“maintenance of certain brain functions is dependent on T cell actions in the CNS (31, 32)”
From Inflammatory T helper 17 cells promote depression-like behavior in mice (2013) · cites this paper as [32]
T cells are present and functional in the brain where they modulate higher functions, such as cognition.
“previous findings that T cells are present and functional in the brain (32) where they modulate higher functions, such as cognition.”
From Inflammatory T helper 17 cells promote depression-like behavior in mice (2013) · cites this paper as [32]
Cites
The Amyloid Hypothesis of Alzheimer’s Disease: Progress and Problems on the Road to Therapeutics
Hardy, J., & Selkoe, D. J. (2002) · Science · doi:10.1126/science.1072994 · Cited by 13,864 · see citing works
Microglia: Active sensor and versatile effector cells in the normal and pathologic brain
Hanisch, U.-K., & Kettenmann, H. (2007) · Nature Neuroscience · doi:10.1038/nn1997 · Cited by 3,676 · see citing works
Activation of microglial cells by β-amyloid protein and interferon-γ
Meda, L., Cassatella, M. A., Szendrei, G. I., Otvos, L., Baron, P., Villalba, M., Ferrari, D., & Rossi, F. (1995) · Nature · doi:10.1038/374647a0 · Cited by 1,314 · see citing works
Wyss-Coray (2006) · doi:10.1038/nm1484 · Cited by 1,284 · see citing works
Inflammation in Neurodegenerative Disease—A Double-Edged Sword
Wyss-Coray, T., & Mucke, L. (2002) · Neuron · doi:10.1016/s0896-6273(02)00794-8 · Cited by 1,235 · see citing works
Ziv, Y., Ron, N., Butovsky, O., Landa, G., Sudai, E., Greenberg, N., Cohen, H., Kipnis, J., & Schwartz, M. (2006) · Nature Neuroscience · doi:10.1038/nn1629 · Cited by 1,209 · see citing works
Self-citationMolecular biology of amyotrophic lateral sclerosis: insights from genetics
Pasinelli, P., & Brown, R. H. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn1971 · Cited by 1,107 · see citing works
Zhu, S., Stavrovskaya, I. G., Drozda, M., Kim, B. Y. S., Ona, V. O., Li, M., Sarang, S. S., Liu, A. S., Hartley, D. M., Wu, D. C., et al. (2002) · Nature · doi:10.1038/417074a · Cited by 1,071 · see citing works
Three or more routes for leukocyte migration into the central nervous system
Ransohoff, R. M., Kivisäkk, P., & Kidd, G. (2003) · Nature Reviews Immunology · doi:10.1038/nri1130 · Cited by 1,052 · see citing works
Classification and prediction of clinical Alzheimer's diagnosis based on plasma signaling proteins
Ray, S., Britschgi, M., Herbert, C., Takeda-Uchimura, Y., Boxer, A., Blennow, K., Friedman, L. F., Galasko, D. R., Jutel, M., Karydas, A., et al. (2007) · Nature Medicine · doi:10.1038/nm1653 · Cited by 1,048 · see citing works
Autoimmune T cells protect neurons from secondary degeneration after central nervous system axotomy
Moalem‐Taylor, G., Leibowitz‐Amit, R., Yoles, E., Mor, F., Cohen, I. R., & Schwartz, M. (1999) · Nature Medicine · doi:10.1038/4734 · Cited by 882 · see citing works
Self-citationShechter, R., London, A., Varol, C., Raposo, C., Cusimano, M., Yovel, G., Rolls, A., Mack, M., Pluchino, S., Martino, G., et al. (2009) · PLoS Medicine · doi:10.1371/journal.pmed.1000113 · Cited by 770 · see citing works
Self-citationImmune activation in brain aging and neurodegeneration: too much or too little?
Lucin, K. M., & Wyss-Coray, T. (2009) · Neuron · doi:10.1016/j.neuron.2009.08.039 · Cited by 679 · see citing works
Efficacy of minocycline in patients with amyotrophic lateral sclerosis: a phase III randomised trial
Gordon, P. H., Moore, D. H., Miller, R. G., Florence, J. M., Verheijde, J. L., Doorish, C., Hilton, J. F., Spitalny, G. M., MacArthur, R. B., Mitsumoto, H., et al. (2007) · The Lancet Neurology · doi:10.1016/s1474-4422(07)70270-3 · Cited by 649 · see citing works
Kipnis, J., Cohen, H., Cardon, M., Ziv, Y., & Schwartz, M. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0402268101 · Cited by 510 · see citing works
Self-citationBeers, D. R., Henkel-Tigges, J., Zhao, W., Wang, J., & Appel, S. H. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0807419105 · Cited by 468 · see citing works
Anti-inflammatory drugs and Alzheimer disease
McGeer, P. L., McGeer, E. G., Rogers, J., & Sibley, J. T. (1990) · The Lancet · doi:10.1016/0140-6736(90)91101-f · Cited by 437 · see citing works
Blocking TGF-β–Smad2/3 innate immune signaling mitigates Alzheimer-like pathology
Town, T., Laouar, Y., Pittenger, C., Mori, T., Szekely, C. A., Tan, J., Duman, R. S., & Flavell, R. A. (2008) · Nature Medicine · doi:10.1038/nm1781 · Cited by 422 · see citing works
Butovsky, O., Koronyo-Hamaoui, M., Kunis, G., Ophir, E., Landa, G., Cohen, H., & Schwartz, M. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0604681103 · Cited by 388 · see citing works
Self-citationT lymphocytes potentiate endogenous neuroprotective inflammation in a mouse model of ALS
Chiu, I., Chen, A., Zheng, Y., Kosaras, B., Tsiftsoglou, S., Vartanian, T., Brown, R. H., & Carroll, M. (2008) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.0804610105 · Cited by 374 · see citing works
Simard, A. R., & Rivest, S. (2004) · The FASEB Journal · doi:10.1096/fj.04-1517fje · Cited by 354 · see citing works
Wolf, S. A., Steiner, B., Akpinarli, A., Kammertoens, T., Nassenstein, C., Braun, A., Blankenstein, T., & Kempermann, G. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0801218 · Cited by 329 · see citing works
Ineffective phagocytosis of amyloid-β by macrophages of Alzheimer's disease patients
Fiala, M., Lin, J., Ringman, J. M., Kermani-Arab, V., Tsao, G., Patel, A. J., Lossinsky, A. S., Graves, M. C., Gustavson, A. R., Sayre, J. W., et al. (2005) · Journal of Alzheimer s Disease · doi:10.3233/jad-2005-7304 · Cited by 328 · see citing works
Trial of celecoxib in amyotrophic lateral sclerosis
Cudkowicz, M., Shefner, J. M., Schoenfeld, D., Zhang, H., Andreasson, K. I., Rothstein, J. D., & Drachman, D. B. (2006) · Annals of Neurology · doi:10.1002/ana.20903 · Cited by 302 · see citing works
Can the immune system be harnessed to repair the CNS?
Popovich, P. G., & Longbrake, E. E. (2008) · Nature reviews. Neuroscience · doi:10.1038/nrn2398 · Cited by 287 · see citing works
Biomarkers of Alzheimer disease in plasma
Irizarry, M. C. (2004) · NeuroRx · doi:10.1602/neurorx.1.2.226 · Cited by 269 · see citing works
Adaptive Immune Neuroprotection in G93A-SOD1 Amyotrophic Lateral Sclerosis Mice
Banerjee, R., Mosley, R. L., Reynolds, A. D., Dhar, A., Jackson-Lewis, V. R., Gordon, P. H., Przedborski, S., & Gendelman, H. E. (2008) · PLoS ONE · doi:10.1371/journal.pone.0002740 · Cited by 198 · see citing works
Polymorphisms in Inflammatory Genes and the Risk of Alzheimer Disease
McGeer, P. L. (2001) · Archives of Neurology · doi:10.1001/archneur.58.11.1790 · Cited by 192 · see citing works
Frenkel, D., Maron, R., Burt, D. S., & Weiner, H. L. (2005) · Journal of Clinical Investigation · doi:10.1172/jci23241 · Cited by 186 · see citing works
Risk of dementia and AD with prior exposure to NSAIDs in an elderly community-based cohort
Breitner, J. C. S., Haneuse, S., Walker, R. L., Dublin, S., Crane, P. K., Gray, S. L., & Larson, E. B. (2009) · Neurology · doi:10.1212/wnl.0b013e3181a18691 · Cited by 175 · see citing works
From bone marrow to microglia: barriers and avenues
Davoust, N., Vuaillat, C., Androdias, G., & Nataf, S. (2008) · Trends in Immunology · doi:10.1016/j.it.2008.01.010 · Cited by 173 · see citing works
Altered lymphocyte distribution in Alzheimer’s disease
RICHARTZSALZBURGER, E., BATRA, A., STRANSKY, E., LASKE, C., KOHLER, N., BARTELS, M., BUCHKREMER, G., & SCHOTT, K. (2007) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2006.01.010 · Cited by 167 · see citing works
Butovsky, O., Kunis, G., Koronyo‐Hamaoui, M., & Schwartz, M. (2007) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2007.05652.x · Cited by 167 · see citing works
Self-citationTaking Advantage of the Systemic Immune System to Cure Brain Diseases
Yong, V. W., & Rivest, S. (2009) · Neuron · doi:10.1016/j.neuron.2009.09.035 · Cited by 165 · see citing works
Dual effect of CD4 + CD25 + regulatory T cells in neurodegeneration: A dialogue with microglia
Kipnis, J., Avidan, H., Caspi, R. R., & Schwartz, M. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0404842101 · Cited by 163 · see citing works
Self-citationSchwartz, M., & Shechter, R. (2010) · Molecular Psychiatry · doi:10.1038/mp.2010.31 · Cited by 129 · see citing works
Self-citationProtective autoimmunity against the enemy within: fighting glutamate toxicity
Schwartz, M. H. (2003) · Trends in Neurosciences · doi:10.1016/s0166-2236(03)00126-7 · Cited by 128 · see citing works
Self-citationKoronyo‐Hamaoui, M., Ko, M. K., Koronyo, Y., Azoulay, D., Seksenyan, A., Kunis, G., Pham, M. D., Bakhsheshian, J., Rogeri, P. S., Black, K. L., et al. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06402.x · Cited by 113 · see citing works
Self-citationVaccination as a Novel Approach for Treating Depressive Behavior
Lewitus, G. M., Wilf-Yarkoni, A., Ziv, Y., Shabat-Simon, M., Gersner, R., Zangen, A., & Schwartz, M. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.07.014 · Cited by 109 · see citing works
Self-citationKang, J., & Rivest, S. (2007) · The Journal of Cell Biology · doi:10.1083/jcb.200705046 · Cited by 94 · see citing works
Immunity and cognition: what do age-related dementia, HIV-dementia and ‘chemo-brain’ have in common?
Kipnis, J., Derecki, N. C., Yang, C., & Scrable, H. (2008) · Trends in Immunology · doi:10.1016/j.it.2008.07.007 · Cited by 90 · see citing works
Boster, A. L., Edan, G., Frohman, E., Javed, A., Stüve, O., Tselis, A. C., Weiner, H. L., Weinstock‐Guttman, B., & Khan, O. (2008) · The Lancet Neurology · doi:10.1016/s1474-4422(08)70020-6 · Cited by 73 · see citing works
Microglial NO induces delayed neuronal death following acute injury in the striatum
Takeuchi, A., Isobe, K., Miyaishi, O., Sawada, M., Fan, Z., Nakashima, I., & Kiuchi, K. (1998) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.1998.00168.x · Cited by 70 · see citing works
Immune senescence and brain aging: can rejuvenation of immunity reverse memory loss?
Ron‐Harel, N., & Schwartz, M. (2009) · Trends in Neurosciences · doi:10.1016/j.tins.2009.03.003 · Cited by 56 · see citing works
Self-citationThymic involution, a co‐morbidity factor in amyotrophic lateral sclerosis
Seksenyan, A., Ron‐Harel, N., Azoulay, D., Cahalon, L., Cardon, M., Rogeri, P. S., Ko, M. K., Weil, M., Bulvik, S., Rechavi, G., et al. (2009) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2009.00863.x · Cited by 37 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
A Unique Microglia Type Associated with Restricting Development of Alzheimer’s Disease
Keren-Shaul, H., Spinrad, A., Weiner, A., Matcovitch-Natan, O., Dvir-Szternfeld, R., Ulland, T. K., David, E., Baruch, K., Lara-Astaiso, D., Toth, B., et al. (2017) · Cell · doi:10.1016/j.cell.2017.05.018 · Cited by 5,493 · see citing works
Self-citationImmune 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
The role of inflammation in epilepsy
Vezzani, A., French, J., Bartfai, T., & Baram, T. Z. (2011) · Nature Reviews Neurology · doi:10.1038/nrneurol.2010.178 · Cited by 1,876 · see citing works
Beers, D. R., Henkel-Tigges, J., Zhao, W., Wang, J., Huang, A., Wen, S., Liao, B., & Appel, S. H. (2011) · Brain · doi:10.1093/brain/awr074 · Cited by 427 · see citing works
Neuroprotective strategies involving ROS in Alzheimer disease
Dumont, M., & Beal, M. F. (2011) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2010.11.026 · Cited by 402 · see citing works
Vezzani, A., Maroso, M., Balosso, S., Sanchez, M.-A., & Bartfai, T. (2011) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2011.03.018 · Cited by 402 · see citing works
Schwartz, M., & Baruch, K. (2014) · The EMBO Journal · doi:10.1002/embj.201386609 · Cited by 349 · see citing works
Self-citationMicroglia Function in Alzheimer’s Disease
Solito, E., & Sastre, M. (2012) · Frontiers in Pharmacology · doi:10.3389/fphar.2012.00014 · Cited by 347 · see citing works
Puy, L., Parry‐Jones, A., Sandset, E. C., Dowlatshahi, D. D., Ziai, W., & Cordonnier, C. (2023) · Nature Reviews Disease Primers · doi:10.1038/s41572-023-00424-7 · Cited by 346 · see citing works
Neuroplastic changes in depression: A role for the immune system
Eyre, H., & Baune, B. T. (2012) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2012.03.019 · Cited by 319 · see citing works
Myeloid microvesicles are a marker and therapeutic target for neuroinflammation
Verderio, C., Muzio, L., Turola, E., Bergami, A., Novellino, L., Ruffini, F., Riganti, L., Corradini, I., Francolini, M., Garzetti, L., et al. (2012) · Annals of Neurology · doi:10.1002/ana.23627 · Cited by 299 · see citing works
Boutajangout, A., Ingadottir, J., Davies, P., & Sigurdsson, E. M. (2011) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2011.07337.x · Cited by 306 · see citing works
In vitro Models of Neurodegenerative Diseases
Slanzi, A., Iannoto, G., Rossi, B., Zenaro, E., & Constantin, G. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.00328 · Cited by 293 · see citing works
GABA is an effective immunomodulatory molecule
Jin, Z., Mendu, S. K., & Birnir, B. (2013) · Amino Acids · doi:10.1007/s00726-011-1193-7 · Cited by 289 · see citing works
Hamer, M., Sabia, S., Batty, G. D., Shipley, M. J., Tabák, A. G., Singh-Manoux, A., & Kivimaki, M. (2012) · Circulation · doi:10.1161/circulationaha.112.103879 · Cited by 280 · see citing works
How Do Immune Cells Support and Shape the Brain in Health, Disease, and Aging?
Schwartz, M., Kipnis, J., Rivest, S., & Prat, A. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.3241-13.2013 · Cited by 256 · see citing works
Self-citationInflammatory T helper 17 cells promote depression-like behavior in mice
Beurel, E., Harrington, L. E., & Jope, R. S. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.09.021 · Cited by 254 · see citing works
Neurological Disease as a Failure of Brain-Immune Crosstalk: The Multiple Faces of Neuroinflammation
Schwartz, M., & Deczkowska, A. (2016) · Trends in Immunology · doi:10.1016/j.it.2016.08.001 · Cited by 246 · see citing works
Self-citationMartino, G., Pluchino, S., Bonfanti, L., & Schwartz, M. (2011) · Physiological Reviews · doi:10.1152/physrev.00032.2010 · Cited by 240 · see citing works
Self-citationShechter, R., & Schwartz, M. (2012) · The Journal of Pathology · doi:10.1002/path.4106 · Cited by 225 · see citing works
Self-citationInflammation and prevention of epileptogenesis
Ravizza, T., Balosso, S., & Vezzani, A. (2011) · Neuroscience Letters · doi:10.1016/j.neulet.2011.02.040 · Cited by 199 · see citing works
Neuroimmunological effects of physical exercise in depression
Eyre, H. A., & Baune, B. T. (2011) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2011.09.015 · Cited by 188 · see citing works
Effects of Physical Exercise on Neuroinflammation, Neuroplasticity, Neurodegeneration, and Behavior
Svensson, M., Lexell, J. E., & Deierborg, T. (2014) · Neurorehabilitation and neural repair · doi:10.1177/1545968314562108 · Cited by 189 · see citing works
Kennedy, G., Hardman, R. J., Macpherson, H., Scholey, A. B., & Pipingas, A. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160665 · Cited by 187 · see citing works
Anti-inflammatory effects of spermidine in lipopolysaccharide-stimulated BV2 microglial cells
Choi, Y. H., & Park, H. M. (2012) · Journal of Biomedical Science · doi:10.1186/1423-0127-19-31 · Cited by 174 · see citing works
Functions of microglia in the central nervous system—beyond the immune response
Wake, H., Moorhouse, A. J., & Nabekura, J. (2011) · Neuron Glia Biology · doi:10.1017/s1740925x12000063 · Cited by 167 · see citing works
Bhattarai, P., Thomas, A. K., Cosacak, M. I., Papadimitriou, C., Mashkaryan, V., Froc, C., Reinhardt, S., Kurth, T., Dahl, A., Zhang, Y., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.09.075 · Cited by 151 · see citing works
Telomere shortening in neurological disorders: an abundance of unanswered questions
Eitan, E., Hutchison, E. R., & Mattson, M. P. (2014) · Trends in Neurosciences · doi:10.1016/j.tins.2014.02.010 · Cited by 158 · see citing works
Andersen, H. H., Johnsen, K. B., & Moos, T. (2014) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-013-1509-8 · Cited by 151 · see citing works
Morari, J., Anhê, G. F., do Nascimento, L. F. R., de Moura, R. F., Razolli, D. S., Solon, C., Guadagnini, D., de Souza, G. F. P., Mattos, A. H. B., Tobar, N., et al. (2014) · Diabetes · doi:10.2337/db13-1495 · Cited by 147 · see citing works
Treating Depression and Depression-Like Behavior with Physical Activity: An Immune Perspective
Eyre, H. A., Papps, E., & Baune, B. T. (2013) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2013.00003 · Cited by 144 · see citing works
Resveratrol Role in Autoimmune Disease—A Mini-Review
Oliveira, A., Monteiro, V. S., Navegantes-Lima, K. C., Reis, J. F., Gomes, R. D. S., Rodrigues, D. V. S., Gaspar, S. L. D. F., & Monteiro, M. C. (2017) · Nutrients · doi:10.3390/nu9121306 · Cited by 145 · see citing works
The privileged immunity of immune privileged organs: the case of the eye
Benhar, I., London, A., & Schwartz, M. (2012) · Frontiers in Immunology · doi:10.3389/fimmu.2012.00296 · Cited by 144 · see citing works
Self-citationImmune cell trafficking from the brain maintains CNS immune tolerance
Mohammad, M. G., Tsai, V. W.-W., Ruitenberg, M. J., Hassanpour, M., Li, H., Hart, P. H., Breit, S. N., Sawchenko, P. E., & Brown, D. A. (2014) · Journal of Clinical Investigation · doi:10.1172/jci71544 · Cited by 131 · see citing works
Béland, L.-C., Markovinovic, A., Jakovac, H., De Marchi, F., Bilic, E., Mazzini, L., Kriz, J., & Munitic, I. (2020) · Brain Communications · doi:10.1093/braincomms/fcaa124 · Cited by 125 · see citing works
Park, G., Kim, H. G., Ju, M. S., Ha, S. K., Park, Y., Kim, S. Y., & Oh, M. S. (2013) · Acta Pharmacologica Sinica · doi:10.1038/aps.2013.57 · Cited by 119 · see citing works
Mechanisms of Altered Redox Regulation in Neurodegenerative Diseases—Focus on S-Glutathionylation
Liedhegner, E. S., Gao, X., & Mieyal, J. J. (2011) · Antioxidants and Redox Signaling · doi:10.1089/ars.2011.4119 · Cited by 116 · see citing works
Bernstein, K. E., Koronyo, Y., Salumbides, B. C., Sheyn, J., Pelissier, L., Lopes, D. H. J., Shah, K. H., Bernstein, E. A., Fuchs, D.-T. S., Yu, J. J.-Y., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci66541 · Cited by 117 · see citing works
Are there roles for brain cell senescence in aging and neurodegenerative disorders?
Tan, F. C. C., Hutchison, E. R., Eitan, E., & Mattson, M. P. (2014) · Biogerontology · doi:10.1007/s10522-014-9532-1 · Cited by 116 · see citing works
Juknat, A., Pietr, M., Kozela, E., Rimmerman, N., Levy, R., Gao, F., Coppola, G., Geschwind, D. H., & Vogel, Z. (2013) · PLoS ONE · doi:10.1371/journal.pone.0061462 · Cited by 117 · see citing works
Ferretti, M. T., Allard, S., Partridge, V., Ducatenzeiler, A., & Cuello, A. C. (2012) · Journal of Neuroinflammation · doi:10.1186/1742-2094-9-62 · Cited by 115 · see citing works
Maguire, M., & Maguire, G. (2018) · Reviews in the Neurosciences · doi:10.1515/revneuro-2018-0024 · Cited by 111 · see citing works
Glial scar and immune cell involvement in tissue remodeling and repair following acute CNS injuries
Rapôso, C., & Schwartz, M. (2014) · Glia · doi:10.1002/glia.22676 · Cited by 107 · see citing works
Self-citationMietelska‐Porowska, A., & Wojda, U. (2017) · Journal of Immunology Research · doi:10.1155/2017/4626540 · Cited by 107 · see citing works
The Effects of Anesthetics and Perioperative Medications on Immune Function: A Narrative Review
Ackerman, R. S., Luddy, K. A., Icard, B. E., Fernández, J. P., Gatenby, R. A., & Muncey, A. R. (2021) · Anesthesia & Analgesia · doi:10.1213/ane.0000000000005607 · Cited by 101 · see citing works
Overview of Traumatic Brain Injury: An Immunological Context
Nizamutdinov, D., & Shapiro, L. A. (2017) · Brain Sciences · doi:10.3390/brainsci7010011 · Cited by 99 · see citing works
Emerging roles of microglial activation and non-motor symptoms in Parkinson's disease
Doorn, K. J., Lucassen, P. J., Boddeke, H. W. G. M., Prins, M., Berendse, H. W., Drukarch, B., & van Dam, A. (2012) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2012.06.005 · Cited by 97 · see citing works
Neuroinflammation and central nervous system regeneration in vertebrates
Kyritsis, N., Kızıl, Ç., & Brand, M. (2013) · Trends in Cell Biology · doi:10.1016/j.tcb.2013.08.004 · Cited by 96 · see citing works
Perspectives on neuroinflammation and excitotoxicity: A neurotoxic conspiracy?
Viviani, B., Boraso, M., Marchetti, N., & Marinovich, M. (2014) · NeuroToxicology · doi:10.1016/j.neuro.2014.03.004 · Cited by 97 · see citing works
Abnormalities in chemokine levels in schizophrenia and their clinical correlates
Hong, S., Lee, E., Martin, A. S., Soontornniyomkij, B., Soontornniyomkij, V., Achim, C. L., Reuter, C., Irwin, M. R., Eyler, L. T., & Jeste, D. V. (2016) · Schizophrenia Research · doi:10.1016/j.schres.2016.09.019 · Cited by 91 · see citing works
Boutej, H., Rahimian, R., Thammisetty, S. S., Béland, L., Lalancette–Hébert, M., & Križ, J. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.11.058 · Cited by 90 · see citing works
Interleukin-18, From Neuroinflammation to Alzheimers Disease
Bossù, P., Ciaramella, A., Salani, F., Vanni, D., Palladino, I., Caltagirone, C., & Scapigliati, G. (2010) · Current Pharmaceutical Design · doi:10.2174/138161210794519147 · Cited by 88 · see citing works
Abnormal Changes in NKT Cells, the IGF-1 Axis, and Liver Pathology in an Animal Model of ALS
Finkelstein, A., Kunis, G., Seksenyan, A., Ronen, A., Berkutzki, T., Azoulay, D., Koronyo‐Hamaoui, M., & Schwartz, M. (2011) · PLoS ONE · doi:10.1371/journal.pone.0022374 · Cited by 89 · see citing works
Self-citationArdestani, P. M., Evans, A. K., Yi, B., Nguyen, T., Coutellier, L. D., & Shamloo, M. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.01.010 · Cited by 88 · see citing works
‘As above, so below’ examining the interplay between emotion and the immune system
Brod, S., Rattazzi, L., Piras, G., & D’Acquisto, F. (2014) · Immunology · doi:10.1111/imm.12341 · Cited by 86 · see citing works
Chemokine receptor CXCR2: Physiology regulator and neuroinflammation controller?
Veenstra, M., & Ransohoff, R. M. (2012) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2012.02.016 · Cited by 86 · see citing works
Protective Autoimmunity: A Unifying Model for the Immune Network Involved in CNS Repair
Schwartz, M., & Raposo, C. (2014) · The Neuroscientist · doi:10.1177/1073858413516799 · Cited by 86 · see citing works
Self-citationRETRACTED: Screening for novel central nervous system biomarkers in veterans with Gulf War Illness
Abou-Donia, M. B., Conboy, L. A., Kokkotou, E. G., Jacobson, E., EL-Masry, E. M., Elkafrawy, P., Neely, M. L., Bass, C. R., & Sullivan, K. A. (2017) · Neurotoxicology and Teratology · doi:10.1016/j.ntt.2017.03.002 · Cited by 84 · see citing works
RetractedRegulation by glycogen synthase kinase-3 of inflammation and T cells in CNS diseases
Beurel, E. (2011) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2011.00018 · Cited by 82 · see citing works
Choi, Y. H. (2012) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2012.979 · Cited by 82 · see citing works
Migration of blood cells to β-amyloid plaques in Alzheimer's disease
Hohsfield, L. A., & Humpel, C. (2015) · Experimental Gerontology · doi:10.1016/j.exger.2015.03.002 · Cited by 79 · see citing works
Zhu, D., Yang, N., Liu, Y., Zheng, J., Ji, C., & Zuo, P. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-151090 · Cited by 78 · see citing works
Nussenblatt, R. B., Lee, R., Chew, E. Y., Wei, L., Liu, B., Sen, H. N., Dick, A. D., & Ferris, F. L. (2014) · American Journal of Ophthalmology · doi:10.1016/j.ajo.2014.03.014 · Cited by 75 · see citing works
Regulation of interleukin-1 in acute brain injury
Brough, D., Tyrrell, P. J., & Allan, S. M. (2011) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2011.06.002 · Cited by 75 · see citing works
Neuroinflammatory Signaling in the Pathogenesis of Alzheimer’s Disease
Uddin, M. S., Kabir, M. T., Jalouli, M., Rahman, M. A., Jeandet, P., Behl, T., Alexiou, A. T., Albadrani, G. M., Abdel‐Daim, M. M., Perveen, A., et al. (2021) · Current Neuropharmacology · doi:10.2174/1570159x19666210826130210 · Cited by 76 · see citing works
Potential therapeutic applications of exosomes in different autoimmune diseases
Xu, H. M., Jia, S., & Xu, H. (2019) · Clinical Immunology · doi:10.1016/j.clim.2019.06.006 · Cited by 73 · see citing works
The role of the immune system in driving neuroinflammation
Ní Chasaide, C., & Lynch, M. A. (2020) · Brain and Neuroscience Advances · doi:10.1177/2398212819901082 · Cited by 72 · see citing works
A conceptual revolution in the relationships between the brain and immunity
Schwartz, M., & Kipnis, J. (2010) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2010.12.015 · Cited by 71 · see citing works
Self-citationHussein, S. S. S., Kamarudin, M. N. A., & Kadir, H. A. (2015) · The American Journal of Chinese Medicine · doi:10.1142/s0192415x15500548 · Cited by 70 · see citing works
Kwon, M., Noh, M., Oh, K., Cho, K., Kang, B., Kim, K., Kim, Y., & Kim, S. H. (2014) · Journal of Neurochemistry · doi:10.1111/jnc.12814 · Cited by 70 · see citing works
Peña‐Altamira, E., Prati, F., Massenzio, F., Virgili, M., Contestabile, A., Bolognesi, M. L., & Monti, B. (2015) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.2016.1121237 · Cited by 70 · see citing works
Molecular and genetic inflammation networks in major human diseases
Zhao, Y., Forst, C. V., Sayegh, C. E., Wang, I., Yang, X., & Zhang, B. (2016) · Molecular BioSystems · doi:10.1039/c6mb00240d · Cited by 71 · see citing works
Fingolimod: A Disease-Modifier Drug in a Mouse Model of Amyotrophic Lateral Sclerosis
Potenza, R. L., De Simone, R., Armida, M., Mazziotti, V., Pèzzola, A., Popoli, P., & Minghetti, L. (2016) · Neurotherapeutics · doi:10.1007/s13311-016-0462-2 · Cited by 69 · see citing works
Park, H. Y., Kim, N. D., Kim, G., Hwang, H. J., Kim, B., Kim, W., & Choi, Y. H. (2012) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2012.04.034 · Cited by 66 · see citing works
Lampron, A., Lessard, M., & Rivest, S. (2012) · Cell Transplantation · doi:10.3727/096368911x593154 · Cited by 65 · see citing works
Böhm, C., Chen, F., Sévalle, J., Qamar, S., Dodd, R. B., Li, Y., Schmitt‐Ulms, G., Fraser, P. E., & George‐Hyslop, P. S. (2015) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2015.02.016 · Cited by 63 · see citing works
McMahon, J. M., McQuaid, S., Reynolds, R., & FitzGerald, U. (2012) · Multiple Sclerosis Journal · doi:10.1177/1352458512438455 · Cited by 61 · see citing works
Santarsieri, M., Kumar, R. G., Kochanek, P. M., Berga, S. L., & Wagner, A. K. (2014) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2014.09.003 · Cited by 58 · see citing works
A potential role for the PD1/PD-L1 pathway in the neuroinflammation of Alzheimer's disease
Saresella, M., Calabrese, E., Marventano, I., Piancone, F., Gatti, A. V., Farina, E., Alberoni, M., & Clerici, M. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2011.03.004 · Cited by 55 · see citing works
How can we improve clinical trials in amyotrophic lateral sclerosis?
Gordon, P. H., & Meininger, V. (2011) · Nature Reviews Neurology · doi:10.1038/nrneurol.2011.147 · Cited by 55 · see citing works
A phase-specific neuroimmune model of clinical depression
Eyre, H. A., Stuart, M. J., & Baune, B. T. (2014) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2014.06.011 · Cited by 55 · see citing works
Functional Macrophage Heterogeneity in a Mouse Model of Autoimmune Central Nervous System Pathology
London, A., Benhar, I., Mattapallil, M. J., Mack, M., Caspi, R. R., & Schwartz, M. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1202076 · Cited by 55 · see citing works
Self-citationMadrid, A. S., Rasmussen, K. L., Rode, L., Frikke‐Schmidt, R., Nordestgaard, B. G., & Bojesen, S. E. (2019) · European Journal of Epidemiology · doi:10.1007/s10654-019-00563-w · Cited by 54 · see citing works
Interplay between immunity and amyotrophic lateral sclerosis: Clinical impact
Marchi, F. D., Munitić, I., Amedei, A., Berry, J. D., Feldman, E. L., Aronica, E., Nardo, G., Weehaeghe, D. V., Niccolai, E., Prtenjača, N., et al. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.06.027 · Cited by 52 · see citing works
Dietary phytochemicals modulate intestinal epithelial barrier dysfunction and autoimmune diseases
Ganesan, K., Quiles, J. L., Daglia, M., Xiao, J., & Xu, B. (2021) · Food Frontiers · doi:10.1002/fft2.102 · Cited by 54 · see citing works
Mukhara, D., Oh, U., & Neigh, G. N. (2020) · Handbook of clinical neurology · doi:10.1016/b978-0-444-64123-6.00017-5 · Cited by 58 · see citing works
Lidocaine attenuates lipopolysaccharide-induced inflammatory responses in microglia
Yuan, T., Li, Z., Li, X., Yu, G., Wang, N., & Yang, X. (2014) · Journal of Surgical Research · doi:10.1016/j.jss.2014.05.023 · Cited by 52 · see citing works
Meningeal and choroid plexus cells—Novel drug targets for CNS disorders
Dragunow, M. (2013) · Brain Research · doi:10.1016/j.brainres.2013.01.013 · Cited by 50 · see citing works
Neonatal BCG vaccination of mice improves neurogenesis and behavior in early life
Yang, J., Qi, F., Gu, H., Zou, J., Yang, Y., Yuan, Q., & Yao, Z. (2015) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2015.10.012 · Cited by 50 · see citing works
Collmann, F. M., Pijnenburg, R., Taj, S. H., Minassian, A., Folz‐Donahue, K., Kukat, C., Aswendt, M., & Hoehn, M. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01236 · Cited by 50 · see citing works
Finding a better drug for epilepsy: Antiinflammatory targets
Dedeurwaerdere, S., Friedman, A., Fabene, P. F., Mazarati, A. M., Murashima, Y. L., Vezzani, A., & Baram, T. Z. (2012) · Epilepsia · doi:10.1111/j.1528-1167.2012.03520.x · Cited by 49 · see citing works
Leung, M. C. P., Yip, K. K., Ho, J. Y. S., Siu, F. K. W., Li, W. C., & Garner, B. (2014) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-014-9550-4 · Cited by 48 · see citing works
Evidence for peripheral immune activation in amyotrophic lateral sclerosis
Chen, X., Feng, W., Huang, R., Guo, X., Chen, Y., Zheng, Z., & Shang, H. (2014) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2014.09.025 · Cited by 48 · see citing works
Myeloid Dendritic Cells are Potential Players in Human Neurodegenerative Diseases
Bossù, P., Spalletta, G., Caltagirone, C., & Ciaramella, A. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00632 · Cited by 48 · see citing works
Alrouji, M., Al-Kuraishy, H. M., Al-Gareeb, A. I., Saad, H. M., & Batiha, G. E.-S. (2023) · Inflammopharmacology · doi:10.1007/s10787-023-01192-2 · Cited by 47 · see citing works
Thelin, E. P., Hall, C. E., Gupta, K., Carpenter, K. L. H., Chandran, S., Hutchinson, P. J., Patani, R., & Helmy, A. E. (2017) · Journal of Neurotrauma · doi:10.1089/neu.2017.5155 · Cited by 47 · see citing works
Glycans in Sera of Amyotrophic Lateral Sclerosis Patients and Their Role in Killing Neuronal Cells
Edri‐Brami, M., Rosental, B., Hayoun, D., Welt, M., Rosen, H., Wirguin, I., Nefussy, B., Drory, V. E., Porgador, A., & Lichtenstein, R. G. (2012) · PLoS ONE · doi:10.1371/journal.pone.0035772 · Cited by 45 · see citing works
Bakalash, S., Pham, M. D., Koronyo, Y., Salumbides, B. C., Kramerov, A. A., Seidenberg, H., Berel, D., Black, K. L., & Koronyo‐Hamaoui, M. (2011) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.11-7498 · Cited by 44 · see citing works
Retinal microglia are critical for subretinal neovascular formation
Usui‐Ouchi, A., Usui, Y., Kurihara, T., Aguilar, E., Dorrell, M. I., Ideguchi, Y., Sakimoto, S., Bravo, S., & Friedlander, M. (2020) · JCI Insight · doi:10.1172/jci.insight.137317 · Cited by 44 · see citing works
Lymphocytes in neuroprotection, cognition and emotion: Is intolerance really the answer?
Rook, G. A. W., Lowry, C. A., & Raison, C. L. (2010) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2010.12.005 · Cited by 42 · see citing works
- Authors
- Schwartz, M., & Shechter, R.
- Affiliations
- Weizmann Institute of Science (IL)
- Corresponding author
- Schwartz, Michal
- Venue
- Nature Reviews Neurology
- Published
- 2010-06-08
- Volume
- 6
- Issue
- 7
- Pages
- 405-410
- ISSN
- 1759-4758 (ISSN-L)
- 1759-4766
- OpenAlex
- W2081117923
- Cited by
- 240
- References
- 45
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 3 · 2023: 9 · 2022: 4 · 2021: 10 · 2020: 18 · 2019: 9 · 2018: 5 · 2017: 17 · 2016: 19 · 2015: 15 · 2014: 33 · 2013: 21 · 2012: 34
- FWCI
- 2.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Neurology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- neurodegenerative diseases, systemic inflammation, microglia, amyotrophic lateral sclerosis, Alzheimer's disease, anti-inflammatory agents, CD4+ T cells, monocytes, immune cell recruitment, disease progression
- MeSH terms
- Anti-Inflammatory Agents, Non-Steroidal, Humans, Immune System Diseases, Inflammation, Leukocytes, Macrophages, Microglia, Neurodegenerative Diseases, Adaptive Immunity
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