Angiotensin II AT1 Receptor Blockade Ameliorates Brain Inflammation
Open accessAbstract
Brain inflammation has a critical role in the pathophysiology of brain diseases of high prevalence and economic impact, such as major depression, schizophrenia, post-traumatic stress disorder, Parkinson's and Alzheimer's disease, and traumatic brain injury. Our results demonstrate that systemic administration of the centrally acting angiotensin II AT(1) receptor blocker (ARB) candesartan to normotensive rats decreases the acute brain inflammatory response to administration of the bacterial endotoxin lipopolysaccharide (LPS), a model of brain inflammation. The broad anti-inflammatory effects of candesartan were seen across the entire inflammatory cascade, including decreased production and release to the circulation of centrally acting proinflammatory cytokines, repression of nuclear transcription factors activation in the brain, reduction of gene expression of brain proinflammatory cytokines, cytokine and prostanoid receptors, adhesion molecules, proinflammatory inducible enzymes, and reduced microglia activation. These effects are widespread, occurring not only in well-known brain target areas for circulating proinflammatory factors and LPS, that is, hypothalamic paraventricular nucleus and the subfornical organ, but also in the prefrontal cortex, hippocampus, and amygdala. Candesartan reduced the associated anorexic effects, and ameliorated associated body weight loss and anxiety. Direct anti-inflammatory effects of candesartan were also documented in cultured rat microglia, cerebellar granule cells, and cerebral microvascular endothelial cells. ARBs are widely used in the treatment of hypertension and stroke, and their anti-inflammatory effects contribute to reduce renal and cardiac failure. Our results indicate that these compounds may offer a novel and safe therapeutic approach for the treatment of brain disorders.
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?
ACE-I/ARBs are capable of reducing neuroinflammation.
“However, these agents are also capable of reducing neuroinflammation (Benicky et al, 2011;Welty et al, 2015)”
From Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond (2017) · cites this paper as Benicky et al, 2011
The Discussion reports that ARBs reduced inflammatory responses in the brains of normotensive rats, supporting the ARB portion of the claim. The paper does not establish that ACE inhibitors reduce neuroinflammation; its findings concern AT1 receptor blockers. No page numbers are available in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measured
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
The rat brain in stereotaxic coordinates
Palkovits, M. (1983) · Neuropeptides · doi:10.1016/0143-4179(83)90049-5 · Cited by 28,959 · see citing works
The Rat Brain in Stereotaxic Coordinates
Paxinos, G., & Watson, C. (1983) · Elsevier eBooks · doi:10.1016/c2009-0-63235-9 · Cited by 28,585 · see citing works
From inflammation to sickness and depression: when the immune system subjugates the brain
Dantzer, R., O'Connor, J. C., Freund, G. G., Johnson, R. W., & Kelley, K. W. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2297 · Cited by 7,395 · see citing works
Inflammation and Its Discontents: The Role of Cytokines in the Pathophysiology of Major Depression
Miller, A. H., Maletic, V., & Raison, C. L. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.11.029 · Cited by 3,848 · see citing works
Mechanisms underlying inflammation in neurodegeneration
Glass, C. K., Saijo, K., Winner, B., Marchetto, M. C., & Gage, F. H. (2010) · Cell · doi:10.1016/j.cell.2010.02.016 · Cited by 3,580 · see citing works
Quantification of histochemical staining by color deconvolution.
Ruifrok, A. C. C., & Johnston, D. A. (2001) · PubMed · Cited by 2,029 · see citing works
McEwen, B. S. (2008) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2007.11.071 · Cited by 1,864 · see citing works
Characterization of ameboid microglia isolated from developing mammalian brain
Giulian, D., & Baker, T. J. (1986) · Journal of Neuroscience · doi:10.1523/jneurosci.06-08-02163.1986 · Cited by 1,300 · see citing works
Beg, A. A., Finco, T. S., Nantermet, P. V., & Baldwin, A. S. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.6.3301 · Cited by 1,027 · see citing works
Regulation of innate immune responses in the brain
Rivest, S. (2009) · Nature Reviews Immunology · doi:10.1038/nri2565 · Cited by 843 · see citing works
A new blood–brain barrier model using primary rat brain endothelial cells, pericytes and astrocytes
Nakagawa, S., Deli, M. A., Kawaguchi, H., Shimizudani, T., Shimono, T., Kittel, Á., Tanaka, K., & Niwa, M. (2009) · Neurochemistry International · doi:10.1016/j.neuint.2008.12.002 · Cited by 728 · see citing works
Brain-immune communication pathways
Quan, N., & Banks, W. A. (2007) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2007.05.005 · Cited by 626 · see citing works
Henry, C. J., Huang, Y., Wynne, A. M., & Godbout, J. P. (2009) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2008.09.002 · Cited by 565 · see citing works
Neuroinflammation in Schizophrenia-Related Psychosis: A PET Study
Doorduin, J., de Vries, E. F. J., Willemsen, A. T. M., de Groot, J. C., Dierckx, R., & Klein, H. C. (2009) · Journal of Nuclear Medicine · doi:10.2967/jnumed.109.066647 · Cited by 561 · see citing works
Li, N.-C., Lee, A., Whitmer, R. A., Kivipelto, M., Lawler, E., Kazis, L. E., & Wolozin, B. (2010) · BMJ · doi:10.1136/bmj.b5465 · Cited by 486 · see citing works
Brain and Pituitary Angiotensin
Saavedra, J. M. (1992) · Endocrine Reviews · doi:10.1210/edrv-13-2-329 · Cited by 460 · see citing works
Self-citationDiversity in the contribution of interleukin‐10 to T‐cell‐mediated immune regulation
Maynard, C. L., & Weaver, C. T. (2008) · Immunological Reviews · doi:10.1111/j.1600-065x.2008.00711.x · Cited by 404 · see citing works
Characterization and development of angiotensin II receptor subtypes (AT1 and AT2) in rat brain
Tsutsumi, K., & Saavedra, J. M. (1991) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1991.261.1.r209 · Cited by 336 · see citing works
Self-citationSavoia, C., & Schiffrin, E. L. (2007) · Clinical Science · doi:10.1042/cs20060247 · Cited by 326 · see citing works
Platten, M., Youssef, S., Hur, E. M., Ho, P. P.-K., Han, M. H., Lanz, T. V., Phillips, L., Goldstein, M. J., Bhat, R., Raine, C. S., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0903958106 · Cited by 321 · see citing works
The LPS receptor (CD14) links innate immunity with Alzheimer's disease
Fassbender, K., Walter, S., Kühl, S., Landmann, R., Ishii, K., Bertsch, T., Stalder, A. K., Muehlhauser, F., Liu, Y., Ulmer, A. J., et al. (2004) · The FASEB Journal · doi:10.1096/fj.03-0364fje · Cited by 307 · see citing works
Milligan, C. E., Cunningham, T. J., & Levitt, P. R. (1991) · The Journal of Comparative Neurology · doi:10.1002/cne.903140112 · Cited by 252 · see citing works
Inflammatory Cell Migration into the Central Nervous System: A Few New Twists on an Old Tale
Man, S., Ubogu, E. E., & Ransohoff, R. M. (2007) · Brain Pathology · doi:10.1111/j.1750-3639.2007.00067.x · Cited by 235 · see citing works
Pathways and mechanisms for cytokine signaling of the central nervous system.
Licinio, J., & Wong, M. L. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119846 · Cited by 220 · see citing works
Brain renin angiotensin in disease
Phillips, M. I., & de Oliveira, E. M. (2008) · Journal of Molecular Medicine · doi:10.1007/s00109-008-0331-5 · Cited by 196 · see citing works
Ando, H., Zhou, J., Macova, M., Imboden, H., & Saavedra, J. M. (2004) · Stroke · doi:10.1161/01.str.0000129788.26346.18 · Cited by 181 · see citing works
Self-citationFleegal, M. A., Doghu, S., & Banks, W. A. (2009) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2008.158 · Cited by 181 · see citing works
Taking 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
Hope, S., Melle, I. S., Aukrust, P., Steen, N. E., Birkenaes, A. B., Lorentzen, S., Agartz, I., Ueland, T., & Andreassen, O. A. (2009) · Bipolar Disorders · doi:10.1111/j.1399-5618.2009.00757.x · Cited by 152 · see citing works
Sympatho-adrenal responses of spontaneously hypertensive rats to immobilization stress
Květňanský, R., McCarty, R. C., Thoa, N. B., Lake, C. R., & Kopin, I. J. (1979) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1979.236.3.h457 · Cited by 140 · see citing works
Nishimura, Y., Ito, T., Hoe, K., & Saavedra, J. M. (2000) · Brain Research · doi:10.1016/s0006-8993(00)02377-5 · Cited by 136 · see citing works
Self-citationAnti-Inflammatory Effects of Angiotensin Receptor Blockers in the Brain and the Periphery
Benický, J., Sánchez-Lemus, E., Pavel, J., & Saavedra, J. M. (2009) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-009-9368-4 · Cited by 126 · see citing works
Self-citationDistribution of angiotensin type-1 receptor messenger RNA expression in the adult rat brain
Lenkei, Z., Palkovits, M., Corvol, P. L., & Llorens‐Cortés, C. (1997) · Neuroscience · doi:10.1016/s0306-4522(97)00328-x · Cited by 115 · see citing works
AT1A, AT1B, and AT2angiotensin II receptor subtype gene expression in rat brain
Jöhren, O., Inagami, T., & Saavedra, J. M. (1995) · Neuroreport · doi:10.1097/00001756-199512150-00024 · Cited by 114 · see citing works
Self-citationZhou, J., Ando, H., Macova, M., Dou, J., & Saavedra, J. M. (2005) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/sj.jcbfm.9600082 · Cited by 114 · see citing works
Self-citationSaavedra, J. M., Armando, I., Bregonzio, C., Juorio, A. V., Macova, M., Pavel, J., & Sánchez-Lemus, E. (2005) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300921 · Cited by 109 · see citing works
Self-citationRussell, V. A. (2003) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2003.08.010 · Cited by 107 · see citing works
The role of the central renin-angiotensin system in Parkinson’s disease
Mertens, B., Vanderheyden, P., Michotte, Y. M., & Sarre, S. (2009) · Journal of the Renin-Angiotensin-Aldosterone System · doi:10.1177/1470320309347789 · Cited by 99 · see citing works
Zhou, J., Pavel, J., Macova, M., Yu, Z., Imboden, H., Ge, L., Nishioku, T., Dou, J., DelGiacco, E., & Saavedra, J. M. (2006) · Stroke · doi:10.1161/01.str.0000217404.64352.d7 · Cited by 97 · see citing works
Self-citationCandesartan inhibits Toll-like receptor expression and activity both in vitro and in vivo
Dasu, M. R. K., Riosvelasco, A. C., & Jialal, I. (2008) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2008.04.010 · Cited by 93 · see citing works
Ramipril mitigates radiation-induced impairment of neurogenesis in the rat dentate gyrus
Jenrow, K. A., Brown, S. L., Liu, J., Kolozsvary, A. J. J., Lapanowski, K., & Kim, J. H. (2010) · Radiation Oncology · doi:10.1186/1748-717x-5-6 · Cited by 82 · see citing works
How the immune and nervous systems interact during disease-associated anorexia
Konsman, J. P., & Dantzer, R. (2001) · Nutrition · doi:10.1016/s0899-9007(01)00602-5 · Cited by 80 · see citing works
Miyoshi, M., Miyano, K., Moriyama, N., Taniguchi, M., & Watanabe, T. (2008) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2007.06014.x · Cited by 77 · see citing works
Sirén, A., Heldman, E., Doron, D. A., Lysko, P. G., Yue, T. L., Liu, Y., FEUERSTEIN, G. Z., & Hallenbeck, J. M. (1992) · Stroke · doi:10.1161/01.str.23.11.1643 · Cited by 69 · see citing works
Seltzer, A. M., Bregonzio, C., Armando, I., Baiardi, G., & Saavedra, J. M. (2004) · Brain Research · doi:10.1016/j.brainres.2004.06.079 · Cited by 63 · see citing works
Self-citationLiu, Y., Lo, Y., Li, Q., Crews, F. T., Wilson, B. C., Chen, H.-L., Wu, H.-M., Chen, S., Wei, K., Lu, R., et al. (2010) · Neuropharmacology · doi:10.1016/j.neuropharm.2010.10.002 · Cited by 62 · see citing works
Hoshino, T., Namba, T., Takehara, M., Nakaya, T., Sugimoto, Y., Araki, W., Narumiya, S., Suzuki, T., & Mizushima, T. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.003269 · Cited by 61 · see citing works
LOSARTAN INFLUENCES BEHAVIOURAL EFFECTS OF ANGIOTENSIN II(3–7) IN RATS
Karwowska-Polecka, W., Kułakowska, A., Wisniewski, K., & Braszko, J. J. (1997) · Pharmacological Research · doi:10.1006/phrs.1997.0239 · Cited by 60 · see citing works
Recent Patents in CNS Drug Discovery: The Management of Inflammation in the Central Nervous System
Nimmo, A. J., & Vink, R. (2009) · Recent Patents on CNS Drug Discovery · doi:10.2174/157488909788452997 · Cited by 57 · see citing works
V�is�nen, J., Ihalainen, J. A., Tanila, H., & Ċastrén, E. (2004) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-004-6918-7 · Cited by 52 · see citing works
Weinberg, A. J., Zappe, D., Ashton, M., & Weinberg, M. S. (2004) · American Journal of Nephrology · doi:10.1159/000078950 · Cited by 52 · see citing works
Sánchez-Lemus, E., Murakami, Y., Larráyoz, I. M., Moughamian, A. J., Pavel, J., Nishioku, T., & Saavedra, J. M. (2008) · Endocrinology · doi:10.1210/en.2008-0242 · Cited by 50 · see citing works
Self-citationSánchez-Lemus, E., Benický, J., Pavel, J., Larráyoz, I. M., Zhou, J., Baliova, M., Nishioku, T., & Saavedra, J. M. (2009) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.90962.2008 · Cited by 47 · see citing works
Self-citationDifferential anxiolytic effect of enalapril and losartan in normotensive and renal hypertensive rats
Srinivasan, J., Suresh, B., & Ramanathan, M. (2003) · Physiology & Behavior · doi:10.1016/s0031-9384(03)00036-2 · Cited by 44 · see citing works
Sánchez-Lemus, E., Benický, J., Pavel, J., & Saavedra, J. M. (2009) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2009.04.012 · Cited by 43 · see citing works
Self-citationGao, X., Margolis, R. L., Leeds, P. R., Hough, C. J., Post, R. M., & Chuang, D. (1995) · Brain Research · doi:10.1016/0006-8993(95)01066-1 · Cited by 41 · see citing works
Self-citationLOSARTAN INFLUENCES BEHAVIOURAL EFFECTS OF ANGIOTENSIN II IN RATS
Kułakowska, A., Karwowska-Polecka, W., WIŚNIEWSKI, K., & Braszko, J. J. (1996) · Pharmacological Research · doi:10.1006/phrs.1996.0073 · Cited by 40 · see citing works
Schmerbach, K., Schefe, J. H., Krikov, M., Müller, S., Villringer, A., Kintscher, U., Unger, T., & Thoene-Reineke, C. (2008) · Brain Research · doi:10.1016/j.brainres.2008.02.032 · Cited by 39 · see citing works
Pan, W., Yu, C., Hsuchou, H., & Kastin, A. J. (2010) · Cellular Physiology and Biochemistry · doi:10.1159/000315081 · Cited by 39 · see citing works
Candesartan reduces the innate immune response to lipopolysaccharide in human monocytes
Larráyoz, I. M., Pang, T., Benický, J., Pavel, J., Sánchez-Lemus, E., & Saavedra, J. M. (2009) · Journal of Hypertension · doi:10.1097/hjh.0b013e3283314bc7 · Cited by 32 · see citing works
Self-citationSeeger, H., Lippert, C., Wallwiener, D. R., & Mueck, A. O. (2001) · Journal of the Renin-Angiotensin-Aldosterone System · doi:10.3317/jraas.2001.016 · Cited by 19 · see citing works
More indirect evidence of potential neuroprotective benefits of angiotensin receptor blockers
Anderson, C. S. (2010) · Journal of Hypertension · doi:10.1097/hjh.0b013e3283371355 · Cited by 17 · see citing works
Kim, Y. S., Honkaniemi, J., Sharp, F. R., & Täuber, M. G. (2004) · Molecular Brain Research · doi:10.1016/j.molbrainres.2004.06.009 · Cited by 16 · see citing works
Watanabe, K., Taniguchi, M., Miyoshi, M., Shimizu, H., Imoto, T., Sato, K., & Watanabe, T. (2005) · Peptides · doi:10.1016/j.peptides.2005.11.005 · Cited by 11 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Haroon, E., Raison, C. L., & Miller, A. H. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2011.205 · Cited by 1,000 · see citing works
Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond
Michopoulos, V., Powers, A., Gillespie, C. F., Ressler, K. J., & Jovanovic, T. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.146 · Cited by 786 · see citing works
Daniele, S. G., Béraud, D., Davenport, C., Cheng, K., Yin, H., & Maguire-Zeiss, K. A. (2015) · Science Signaling · doi:10.1126/scisignal.2005965 · Cited by 303 · see citing works
The role of the innate immune system in psychiatric disorders
Jones, K. A., & Thomsen, C. (2013) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2012.10.002 · Cited by 274 · see citing works
Swink, T. D., Vining, E. P. G., & Freeman, J. M. (1997) · Advances in Pediatrics · doi:10.1016/s0065-3101(24)00055-0 · Cited by 242 · see citing works
Angiotensin II AT1 receptor blockers as treatments for inflammatory brain disorders
Saavedra, J. M. (2012) · Clinical Science · doi:10.1042/cs20120078 · Cited by 219 · see citing works
Self-citationNeuroprotective Effects of Angiotensin Receptor Blockers
Villapol, S., & Saavedra, J. M. (2014) · American Journal of Hypertension · doi:10.1093/ajh/hpu197 · Cited by 214 · see citing works
Self-citationWang, Y., Huang, Y., Xu, Y., Ruan, W., Wang, H., Zhang, Y., Saavedra, J. M., Zhang, L., Huang, Z., & Pang, T. (2017) · Antioxidants and Redox Signaling · doi:10.1089/ars.2017.7003 · Cited by 203 · see citing works
Self-citationDrug delivery to the brain in Alzheimer's disease: Consideration of the blood–brain barrier
Banks, W. A. (2012) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2011.12.005 · Cited by 184 · see citing works
The role of the immune system in posttraumatic stress disorder
Katrinli, Ş., Oliveira, N. C. D. S., Felger, J. C., Michopoulos, V., & Smith, A. K. (2022) · Translational Psychiatry · doi:10.1038/s41398-022-02094-7 · Cited by 177 · see citing works
Immunology of Major Depression
Müller, N. (2014) · NeuroImmunoModulation · doi:10.1159/000356540 · Cited by 175 · see citing works
Autonomic-Immune-Vascular Interaction
Zubcevic, J. A., Waki, H., Raizada, M. K., & Paton, J. F. R. (2011) · Hypertension · doi:10.1161/hypertensionaha.111.169748 · Cited by 167 · see citing works
Hypothalamic inflammation: a double‐edged sword to nutritional diseases
Cai, D., & Liu, T. (2011) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2011.06388.x · Cited by 159 · see citing works
Neurorestoration after traumatic brain injury through angiotensin II receptor blockage
Villapol, S., Balarezo, M. G., Affram, K. O., Saavedra, J. M., & Symes, A. J. (2015) · Brain · doi:10.1093/brain/awv172 · Cited by 154 · see citing works
Self-citationPosttraumatic stress disorder: A metabolic disorder in disguise?
Michopoulos, V., Vester, A., & Neigh, G. (2016) · Experimental Neurology · doi:10.1016/j.expneurol.2016.05.038 · Cited by 152 · see citing works
Khoury, N. M., Marvar, P. J., Gillespie, C. F., Wingo, A., Schwartz, A., Bradley, B., Kramer, M., & Ressler, K. J. (2012) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.11m07316 · Cited by 136 · see citing works
Xu, Y., Xu, Y., Wang, Y., Wang, Y., He, L., Jiang, Z., Huang, Z., Liao, H., Li, J., Saavedra, J. M., et al. (2015) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2015.07.015 · Cited by 138 · see citing works
Self-citationThe renin–angiotensin system: a possible new target for depression
Vian, J., Pereira, C. L., Chavarria, V., Köhler, C. A., Stubbs, B., Quevedo, J., Kim, S., Carvalho, A. F., Berk, M., & Fernandes, B. S. (2017) · BMC Medicine · doi:10.1186/s12916-017-0916-3 · Cited by 132 · see citing works
Brudey, C., Park, J., Wiaderkiewicz, J., Kobayashi, I., Mellman, T. A., & Marvar, P. J. (2015) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00343.2014 · Cited by 131 · see citing works
The interplay between Angiotensin II, TLR4 and hypertension
Biancardi, V. C., Bomfim, G. F., Reis, W. L., Al-Gassimi, S., & Nunes, K. P. (2017) · Pharmacological Research · doi:10.1016/j.phrs.2017.03.017 · Cited by 126 · see citing works
Villapol, S., Yaszemski, A. K., Logan, T. T., Sánchez-Lemus, E., Saavedra, J. M., & Symes, A. J. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2012.152 · Cited by 125 · see citing works
Self-citationBiancardi, V. C., Stranahan, A. M., Krause, E. G., de Kloet, A. D., & Stern, J. E. (2015) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00247.2015 · Cited by 116 · see citing works
Wang, J., Pang, T., Hafko, R., Benický, J., Sánchez-Lemus, E., & Saavedra, J. M. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.11.022 · Cited by 107 · see citing works
Self-citationCell-based and pharmacological neurorestorative therapies for ischemic stroke
Venkat, P., Shen, Y., Chopp, M., & Chen, J. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.08.036 · Cited by 99 · see citing works
Repurposed molecules for antiepileptogenesis: Missing an opportunity to prevent epilepsy?
Klein, P., Friedman, A., Hameed, M. Q., Kaminski, R. M., Bar‐Klein, G., Klitgaard, H., Koepp, M. J., Jóźwiak, S., Prince, D. A., Rotenberg, A., et al. (2020) · Epilepsia · doi:10.1111/epi.16450 · Cited by 99 · see citing works
Lee, T. C., Greene-Schloesser, D. M., Payne, V. S., Diz, D. I., Hsu, F., Kooshki, M., Mustafa, R. Z., Riddle, D. R., Zhao, W., Chan, M. D., et al. (2012) · Radiation Research · doi:10.1667/rr2731.1 · Cited by 96 · see citing works
Mowry, F. E., Peaden, S. C., Stern, J. E., & Biancardi, V. C. (2021) · Pharmacological Research · doi:10.1016/j.phrs.2021.105877 · Cited by 97 · see citing works
Blood-Brain Barrier Crossing Renin-Angiotensin Drugs and Cognition in the Elderly: A Meta-Analysis
Ho, J. K., Moriarty, F., Manly, J. J., Larson, E. B., Evans, D. A., Rajan, K. B., Hudak, E. M., Hassan, L., Liu, E., Sato, N., et al. (2021) · Hypertension · doi:10.1161/hypertensionaha.121.17049 · Cited by 94 · see citing works
Angiotensins as therapeutic targets beyond heart disease
Passos-Silva, D. G., Brandan, E., & Santos, R. A. S. (2015) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2015.03.001 · Cited by 95 · see citing works
Pang, T., Wang, J., Benický, J., Sánchez-Lemus, E., & Saavedra, J. M. (2012) · Journal of Neuroinflammation · doi:10.1186/1742-2094-9-102 · Cited by 93 · see citing works
Self-citationSaavedra, J. M. (2011) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-011-9754-6 · Cited by 91 · see citing works
Self-citationRabie, M. A., Abd El Fattah, M. A., Nassar, N. N., El-Abhar, H. S., & Abdallah, D. M. (2018) · Biochemical Pharmacology · doi:10.1016/j.bcp.2018.01.047 · Cited by 90 · see citing works
Bhat, S. A., Sood, A., Shukla, R., & Hanif, K. (2018) · Molecular Neurobiology · doi:10.1007/s12035-018-1272-9 · Cited by 82 · see citing works
Jafari, Z., Bigham, A., Sadeghi, S., Dehdashti, S. M., Rabiee, N., Abedivash, A., Bagherzadeh, M., Nasseri, B., Karimi‐Maleh, H., Sharifi, E., et al. (2021) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.1c01144 · Cited by 85 · see citing works
The role of anti-inflammatory treatment in psychiatric disorders.
Müller, N. (2013) · PubMed · Cited by 82 · see citing works
Candesartan ameliorates brain inflammation associated with Alzheimer's disease
Torika, N., Asraf, K., Apte, R. N., & Fleisher‐Berkovich, S. (2018) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.12802 · Cited by 82 · see citing works
Evidence to Consider Angiotensin II Receptor Blockers for the Treatment of Early Alzheimer’s Disease
Saavedra, J. M. (2016) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-015-0327-y · Cited by 81 · see citing works
Self-citationImmunological aspects of the treatment of depression and schizophrenia
Müller, N. (2017) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2017.19.1/nmueller · Cited by 80 · see citing works
Beneficial effects of Angiotensin II receptor blockers in brain disorders
Saavedra, J. M. (2017) · Pharmacological Research · doi:10.1016/j.phrs.2017.06.017 · Cited by 79 · see citing works
Self-citationBryniarski, P., Nazimek, K., & Marcinkiewicz, J. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031772 · Cited by 72 · see citing works
Amhaoul, H., Ali, I., Mola, M., Eetveldt, A. V., Szewczyk, K., Missault, S., Bielen, K., Kumar-Singh, S., Rech, J., Lord, B., et al. (2016) · Neuropharmacology · doi:10.1016/j.neuropharm.2016.01.018 · Cited by 67 · see citing works
Immune signaling mechanisms of PTSD risk and symptom development: insights from animal models
Deslauriers, J., Powell, S. B., & Risbrough, V. B. (2017) · Current Opinion in Behavioral Sciences · doi:10.1016/j.cobeha.2017.01.005 · Cited by 67 · see citing works
Telmisartan attenuates diabetes induced depression in rats
Aswar, U. M., Chepurwar, S., Shintre, S., & Aswar, M. K. (2016) · Pharmacological Reports · doi:10.1016/j.pharep.2016.12.004 · Cited by 66 · see citing works
Gonzalez, A. D., Wang, G., Waters, E. M., Gonzales, K. L., Speth, R. C., Kempen, T. A. V., Marques-Lopes, J., Young, C. N., Butler, S. D., Davisson, R. L., et al. (2012) · Neuroscience · doi:10.1016/j.neuroscience.2012.08.039 · Cited by 64 · see citing works
de Kloet, A. D., Liu, M., Rodríguez, V., Krause, E. G., & Sumners, C. (2015) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00078.2015 · Cited by 64 · see citing works
Radler, M. E., Hale, M. W., & Kent, S. (2013) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2013.11.014 · Cited by 64 · see citing works
Pang, T., Benický, J., Wang, J., Orečná, M., Sánchez-Lemus, E., & Saavedra, J. M. (2011) · Journal of Hypertension · doi:10.1097/hjh.0b013e32834dde5f · Cited by 63 · see citing works
Self-citationAntiepileptogenic and neuroprotective effects of losartan in kainate model of temporal lobe epilepsy
Tchekalarova, J. D., Ivanova, N. M., Pechlivanova, D., Atanasova, D., Lazarov, N., Kortenska, L., Mitreva, R., Lozanov, V. S., & Stoynev, A. G. (2014) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2014.10.005 · Cited by 58 · see citing works
Targeting toll‐like receptor 4 signalling pathways: can therapeutics pay the toll for hypertension?
Nunes, K. P., de Oliveira, A. A., Mowry, F. E., & Biancardi, V. C. (2018) · British Journal of Pharmacology · doi:10.1111/bph.14438 · Cited by 58 · see citing works
Renz‐Polster, H., Tremblay, M., Bienzle, D., & Fischer, J. E. (2022) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2022.888232 · Cited by 53 · see citing works
Waki, H., Hendy, E. B., Hindmarch, C. C. T., Gouraud, S. S., Toward, M. A., Kasparov, S., Murphy, D., & Paton, J. F. R. (2012) · Hypertension · doi:10.1161/hypertensionaha.112.192252 · Cited by 53 · see citing works
Salmani, H., Hosseini, M., Baghcheghi, Y., Moradi‐Marjaneh, R., & Mokhtari‐Zaer, A. (2019) · Cytokine · doi:10.1016/j.cyto.2019.154860 · Cited by 53 · see citing works
Li, Z., Cao, Y., Li, L., Liang, Y., Tian, X., Mo, N., Liu, Y., Li, M., Chui, D., & Guo, X. (2014) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2014.04.153 · Cited by 52 · see citing works
Gong, X., Hu, H. Z., Qiao, Y., Xu, P., Yang, M., Dang, R., Han, W., Guo, Y., Chen, D., & Jiang, P. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00318 · Cited by 52 · see citing works
Hypertension and Its Impact on Stroke Recovery: From a Vascular to a Parenchymal Overview
Maïer, B., & Kubis, N. (2019) · Neural Plasticity · doi:10.1155/2019/6843895 · Cited by 55 · see citing works
Wang, Y., Ruan, W., Mi, J., Xu, J., Wang, H., Cao, Z., Saavedra, J. M., Zhang, L., Lin, H., & Pang, T. (2017) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2017.08.006 · Cited by 52 · see citing works
Self-citationKonno, S., Hirooka, Y., Kishi, T., & Sunagawa, K. (2012) · Journal of Hypertension · doi:10.1097/hjh.0b013e328357fa98 · Cited by 48 · see citing works
Intranasal telmisartan ameliorates brain pathology in five familial Alzheimer’s disease mice
Torika, N., Asraf, K., Cohen, H., & Fleisher‐Berkovich, S. (2017) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2017.04.001 · Cited by 47 · see citing works
Phipps, J. A., Dixon, M. A., Jobling, A. I., Wang, A. Y., Greferath, U., Vessey, K. A., & Fletcher, E. L. (2019) · Experimental Eye Research · doi:10.1016/j.exer.2019.107753 · Cited by 48 · see citing works
Brownstein, D. J., Salagre, E., Köhler, C., Stubbs, B., Vian, J., Pereira, C., Chavarria, V., Karmakar, C., Turner, A., Quevedo, J., et al. (2018) · Australian & New Zealand Journal of Psychiatry · doi:10.1177/0004867417721654 · Cited by 46 · see citing works
“Drugs that decrease angiotensin II activity have pleiotropic mechanisms of action that suggest potential efficacy as novel psychotropic agents for neuropsychiatric disorders (Benicky et al., 2011; Borrajo et al., 2014; De Souza et al., 2015; Kume et al., 2012; Li et al., 2010) and neuroprotection (Cernes et al.”
BackgroundMethodInfluentialAngiotensin Receptor Blockers and Cognition: a Scoping Review
Zhou, Z., Orchard, S. G., Nelson, M. R., Fravel, M. A., & Ernst, M. E. (2023) · Current Hypertension Reports · doi:10.1007/s11906-023-01266-0 · Cited by 47 · see citing works
Xue, B., Zhang, Y., & Johnson, A. K. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00650 · Cited by 47 · see citing works
Neuroimmune communication in hypertension and obesity: A new therapeutic angle?
de Kloet, A. D., Krause, E. G., Shi, P. D., Zubcevic, J. A., Raizada, M. K., & Sumners, C. (2013) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2013.02.005 · Cited by 45 · see citing works
Role of brain renin–angiotensin system in depression: A new perspective
Ali, N. H., Al-Kuraishy, H. M., Al-Gareeb, A. I., Albuhadily, A. K., Hamad, R. S., Alexiou, A. T., Papadakis, M., Saad, . M., & Batiha, G. E. (2023) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.14525 · Cited by 45 · see citing works
Villapol, S., Kryndushkin, D. S., Balarezo, M. G., Campbell, A., Saavedra, J. M., Shewmaker, F. P., & Symes, A. J. (2015) · American Journal Of Pathology · doi:10.1016/j.ajpath.2015.06.016 · Cited by 44 · see citing works
Self-citationPremer, C., Lamondin, C., Mitzey, A. M., Speth, R. C., & Brownfield, M. S. (2013) · International Journal of Hypertension · doi:10.1155/2013/175428 · Cited by 44 · see citing works
Neuroinflammation in hypertension: the renin-angiotensin system versus pro-resolution pathways
Mowry, F. E., & Biancardi, V. C. (2019) · Pharmacological Research · doi:10.1016/j.phrs.2019.04.029 · Cited by 44 · see citing works
Ayaz, B. D., & Zubcevic, J. A. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2020.104677 · Cited by 43 · see citing works
The Neuroinflammatory Role of Pericytes in Epilepsy
Yamanaka, G., Takata, F., Kataoka, Y., Kanou, K., Morıchı, S., Dohgu, S., & Kawashima, H. (2021) · Biomedicines · doi:10.3390/biomedicines9070759 · Cited by 44 · see citing works
ELKAHLOUN, A. G., Hafko, R., & Saavedra, J. M. (2016) · Alzheimer s Research & Therapy · doi:10.1186/s13195-015-0167-5 · Cited by 43 · see citing works
Self-citationRecent Advances in the Endogenous Brain Renin-Angiotensin System and Drugs Acting on It
Aswar, U. M., Patil, R., Nilam, G., & Bodhankar, S. L. (2021) · Journal of the Renin-Angiotensin-Aldosterone System · doi:10.1155/2021/9293553 · Cited by 43 · see citing works
The role of the brain renin-angiotensin system (RAS) in mild traumatic brain injury (TBI)
Vadhan, J. D., & Speth, R. C. (2021) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107684 · Cited by 42 · see citing works
Hou, Y., Li, N., Xie, G., Wang, J., Yuan, Q., Jia, C., Liu, X., Li, G., Tang, Y., & Wang, B. (2015) · Journal of Functional Foods · doi:10.1016/j.jff.2015.10.002 · Cited by 41 · see citing works
Self-citationPang, T., Sun, L., Wang, T., Jiang, Z., Liao, H., & Zhang, L. (2014) · Acta Pharmacologica Sinica · doi:10.1038/aps.2013.199 · Cited by 41 · see citing works
Self-citationWang, L. A., Hiller, H., Smith, J. A., de Kloet, A. D., & Krause, E. G. (2016) · Physiological Genomics · doi:10.1152/physiolgenomics.00029.2016 · Cited by 39 · see citing works
Chronically infused angiotensin II induces depressive-like behavior via microglia activation
Park, H., You, M., Yang, B., Jang, K. B., Yoo, J., Choi, H. J., Lee, S., Bang, M., & Kwon, M. (2020) · Scientific Reports · doi:10.1038/s41598-020-79096-2 · Cited by 40 · see citing works
Salmani, H., Hosseini, M., Beheshti, F., Baghcheghi, Y., Sadeghnia, H., Soukhtanloo, M., Shafei, M., & Khazaei, M. (2018) · Life Science · doi:10.1016/j.lfs.2018.04.033 · Cited by 36 · see citing works
Comparative immunogenetics of autism and schizophrenia
Crespi, B. J., & Thiselton, D. L. (2011) · Genes Brain & Behavior · doi:10.1111/j.1601-183x.2011.00710.x · Cited by 39 · see citing works
Candesartan could ameliorate the COVID-19 cytokine storm
ELKAHLOUN, A. G., & Saavedra, J. M. (2020) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.110653 · Cited by 40 · see citing works
Self-citationAlthammer, F., Roy, R. K., Kirchner, M. K., Campos‐Lira, E., Whitley, K. E., Davis, S., Montanez, J., Ferreira‐Neto, H. C., Danh, J. P., Feresin, R. G., et al. (2023) · Hypertension · doi:10.1161/hypertensionaha.123.21070 · Cited by 38 · see citing works
Differential effect of angiotensin II and blood pressure on hippocampal inflammation in mice
Iulita, M. F., Vallerand, D., Beauvillier, M., Haupert, N., Ulysse, C. A., Gagné, A., Vernoux, N., Duchemin, S., Boily, M., Tremblay, M., et al. (2018) · Journal of Neuroinflammation · doi:10.1186/s12974-018-1090-z · Cited by 38 · see citing works
Inflammation: A Mediator Between Hypertension and Neurodegenerative Diseases
Youwakim, J., & Girouard, H. (2021) · American Journal of Hypertension · doi:10.1093/ajh/hpab094 · Cited by 37 · see citing works
Angiotensin Receptor Blockers Are Not Just for Hypertension Anymore
Saavedra, J. M. (2021) · Physiology · doi:10.1152/physiol.00036.2020 · Cited by 37 · see citing works
Self-citationDoege, C., Luedde, M., & Kostev, K. (2022) · JAMA Neurology · doi:10.1001/jamaneurol.2022.3413 · Cited by 37 · see citing works
Candesartan ameliorates impaired fear extinction induced by innate immune activation
Quiñones-Cordero, M. M., Maldonado, L., Velázquez, B., & Porter, J. T. (2015) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2015.10.017 · Cited by 38 · see citing works
Gouveia, T. L. F., Frangiotti, M. I. B., de Brito, J. M. V., Neto, E. F. D. C., Sakata, M. M., Febba, A. C. S., Casarini, D. E., Amado, D., Cavalheiro, É. A., de Almeida, S. S., et al. (2012) · Neurochemistry International · doi:10.1016/j.neuint.2012.04.012 · Cited by 37 · see citing works
Kehoe, P. G., Blair, P. S., Howden, B., Thomas, D. L., Malone, I. B., Horwood, J., Clement, C., Selman, L. E., Baber, H., Lane, A., et al. (2017) · Journal of Alzheimer's Disease · doi:10.3233/jad-170101 · Cited by 35 · see citing works
Muneer, P. M. A., Bhowmick, S., & Briski, N. (2017) · Molecular Neurobiology · doi:10.1007/s12035-017-0812-z · Cited by 37 · see citing works
Abdelkader, N. F., El‐Latif, A. M. A., & Khattab, M. M. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.117388 · Cited by 36 · see citing works
Repeated Stress Exaggerates Lipopolysaccharide-Induced Inflammatory Response in the Rat Spleen
Lauková, M., Vargovič, P., Rokytová, I., Manz, G., & Květňanský, R. (2017) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-017-0546-5 · Cited by 34 · see citing works
Glodzik, L., Rusinek, H., Kamer, A. R., Pirraglia, E., Tsui, W., Mosconi, L., Li, Y., McHugh, P. F., Murray, J., Williams, S., et al. (2016) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1016/j.dadm.2016.02.007 · Cited by 34 · see citing works
Gong, S., & Deng, F. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1053136 · Cited by 35 · see citing works
Müller, N., & Bechter, K. (2013) · Neurology Psychiatry and Brain Research · doi:10.1016/j.npbr.2013.04.004 · Cited by 35 · see citing works
Angiotensin II Peptide Vaccine Protects Ischemic Brain Through Reducing Oxidative Stress
Wakayama, K., Shimamura, M., Suzuki, J., Watanabe, R., Koriyama, H., Akazawa, H., Hironori Nakagami, A., Mochizuki, H., Isobe, M., & Morishita, R. (2017) · Stroke · doi:10.1161/strokeaha.116.016269 · Cited by 32 · see citing works
Mineralocorticoid Receptors, Neuroinflammation and Hypertensive Encephalopathy
Brocca, M. E., Pietranera, L., de Kloet, E. R., & Nicola, A. F. D. (2018) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-018-0610-9 · Cited by 32 · see citing works
Kongsui, R., Johnson, S. J., Graham, B. A., Nilsson, M., & Walker, F. R. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2015.09.061 · Cited by 31 · see citing works
The phosphoinositide‐3 kinase signaling is involved in neuroinflammation in hypertensive rats
Tan, X. L., Jiao, P., Wang, Y., Wu, Z.-T., Zeng, X., Li, M., & Wang, W. (2017) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.12679 · Cited by 32 · see citing works
Radler, M. E., Wright, B. J., Walker, F. R., Hale, M. W., & Kent, S. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2014.11.014 · Cited by 31 · see citing works
Zhou, J., Burns, M. P., Huynh, L. M., Villapol, S., Taub, D. D., Saavedra, J. M., & Blackman, M. R. (2017) · Frontiers in Endocrinology · doi:10.3389/fendo.2017.00231 · Cited by 31 · see citing works
Self-citationGee, M. S., Kim, S.-W., Kim, N., Lee, S. J., Oh, M. S., Jin, H. K., Bae, J., Inn, K., Kim, N., & Lee, J. K. (2018) · Neurochemical Research · doi:10.1007/s11064-018-2661-1 · Cited by 30 · see citing works
- Authors
- Benicky, J., Sánchez-Lemus, E., Honda, M., Pang, T., Orecna, M., Wang, J., Leng, Y., Chuang, D.-M., & Saavedra, J. M.
- Affiliations
- National Institutes of Health (US)
- Venue
- Neuropsychopharmacology
- Published
- 2010-12-08
- Volume
- 36
- Issue
- 4
- Pages
- 857-870
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC3055735
- OpenAlex
- W2120778240
- Cited by
- 254
- References
- 65
- Citations by year
- 2026: 12 · 2025: 16 · 2024: 18 · 2023: 16 · 2022: 15 · 2021: 22 · 2020: 19 · 2019: 17 · 2018: 14 · 2017: 26 · 2016: 14 · 2015: 22 · 2014: 14 · 2013: 8 · 2012: 12
- FWCI
- 5.42
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Health and Human Services
- National Institutes of Health
- Japan Society for the Promotion of Science
- National Institute of Mental Health (ZIAMH002762)
- NHLBI Division of Intramural Research
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Keywords
- candesartan, neuroinflammation, lipopolysaccharide, inflammatory cytokines, microglial activation, hypothalamic paraventricular nucleus, subfornical organ, prefrontal cortex, hippocampus, amygdala, anxiety, anorexia, anti-inflammatory activity, cerebellar granule cells, brain microvascular endothelial cells
- MeSH terms
- Animals, Animals, Newborn, Benzimidazoles, Biphenyl Compounds, Brain, Female, Inflammation, Lipopolysaccharides, Male, Rats, Inbred SHR, Tetrazoles, Rats, Sprague-Dawley, Rats, Wistar, Receptor, Angiotensin, Type 1, Angiotensin II Type 1 Receptor Blockers, Rats
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