Stress Induces the Danger-Associated Molecular Pattern HMGB-1 in the Hippocampus of Male Sprague Dawley Rats: A Priming Stimulus of Microglia and the NLRP3 Inflammasome
Open accessAbstract
Exposure to acute and chronic stressors sensitizes the proinflammatory response of microglia to a subsequent immune challenge. However, the proximal signal by which stressors prime microglia remains unclear. Here, high mobility group box-1 (HMGB-1) protein was explored as a potential mediator of stress-induced microglial priming and whether HMGB-1 does so via the nucleotide-binding domain, leucine-rich repeat, pyrin domain containing protein 3 (NLRP3) inflammasome. Exposure to 100 inescapable tail shocks (ISs) increased HMGB-1 and NLRP3 protein in the hippocampus and led isolated microglia to release HMGB-1 ex vivo. To determine whether HMGB-1 signaling is necessary for stress-induced sensitization of microglia, the HMGB-1 antagonist BoxA was injected into the cisterna magna before IS. Hippocampal microglia were isolated 24 h later and stimulated with LPS ex vivo to probe for stress-induced sensitization of proinflammatory responses. Previous IS potentiated gene expression of NLRP3 and proinflammatory cytokines to LPS, that is, microglia were sensitized. Treatment with BoxA abolished this effect. To determine whether HMGB-1 is sufficient to prime microglia, IS was replaced with intracerebral administration of disulfide or fully reduced HMGB-1. Intracerebral disulfide HMGB-1 mimicked the effect of the stressor, because microglia isolated from HMGB-1-treated rats expressed exaggerated NLRP3 and proinflammatory cytokine expression after LPS treatment, whereas fully reduced HMGB-1 had no effect. The present results suggest that the CNS innate immune system can respond to an acute stressor as if it were cellular damage, thereby releasing the danger signal HMGB-1 in the brain to prime microglia by acting on the NLRP3 inflammasome, in preparation for a later immune challenge.
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?
Exposure to acute stress (inescapable tailshock) increases NLRP3 protein in the hippocampus up to 24 h after stress treatment; microglial IL-1β was not increased at that time-point post stress.
“We have also found that exposure to acute stress, in this case inescapable tailshock, increases NLRP3 protein in the hippocampus up to 24 h after stress treatment; however, microglial IL-1β was not increased at that time-point post stress (Weber et al, 2015).”
From Danger Signals and Inflammasomes: Stress-Evoked Sterile Inflammation in Mood Disorders (2017) · cites this paper as Weber et al, 2015
Intracisterna magna administration of an HMGB1 antagonist (box A) before stress exposure blocked the potentiated microglial proinflammatory response to an immune challenge ex vivo.
“we found that intracisterna magna administration of an HMGB1 antagonist (box A) before stress exposure blocked the potentiated microglial proinflammatory response to an immune challenge ex vivo.”
From Danger Signals and Inflammasomes: Stress-Evoked Sterile Inflammation in Mood Disorders (2017) · cites this paper as Weber et al, 2015
Exposure to an acute stressor (inescapable tailshock) induces HMGB1 in the hippocampus concomitant with increased protein levels of active NF-κB and NLRP3 protein.
“We recently found that exposure to an acute stressor (inescapable tailshock) induces HMGB1 in the hippocampus concomitant with increased protein levels of active NF-κB and NLRP3 protein (Weber et al, 2015).”
From Danger Signals and Inflammasomes: Stress-Evoked Sterile Inflammation in Mood Disorders (2017) · cites this paper as Weber et al, 2015
Treatment of hippocampal microglia with the TLR4 agonist LPS resulted in a potentiated IL-1β response in animals exposed to stress 24 h earlier, suggesting that the NLRP3 inflammasome was primed by initial stress exposure.
“treatment of hippocampal microglia with the TLR4 agonist LPS resulted in a potentiated IL-1β response in animals exposed to stress 24 h earlier, suggesting that the NLRP3 inflammasome was primed by initial stress exposure.”
From Danger Signals and Inflammasomes: Stress-Evoked Sterile Inflammation in Mood Disorders (2017) · cites this paper as Weber et al, 2015
HMGB-1 is highly expressed in the CNS and implicated in a variety of neuroinflammatory conditions, including stress.
“Recently, HMGB-1 was found to be highly expressed in the CNS and was implicated in a variety of neuroinflammatory conditions (Kang et al, 2014), including stress (Weber et al, 2015).”
From Repeated Social Defeat, Neuroinflammation, and Behavior: Monocytes Carry the Signal (2017) · cites this paper as Weber et al, 2015
HMGB-1 protein is increased in the hippocampus following a series of repeated tail shock and persists for at least 24 h later.
“For example, HMGB-1 protein is increased in the hippocampus following a series of repeated tail shock and persists for at least 24 h later (Weber et al, 2015).”
From Repeated Social Defeat, Neuroinflammation, and Behavior: Monocytes Carry the Signal (2017) · cites this paper as Weber et al, 2015
Pharmacological antagonism of the receptor targets for HMGB-1 blocked the effect of stress to prime microglia.
“Pharmacological antagonism of the receptor targets for HMGB-1 blocked the effect of stress to prime microglia (Weber et al, 2013(Weber et al, , 2015)).”
From Repeated Social Defeat, Neuroinflammation, and Behavior: Monocytes Carry the Signal (2017) · cites this paper as Weber et al, 2015
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
1 retracted
Yang, H., Lundbäck, P., Ottosson, L., Erlandsson-Harris, H., Venereau, E., Bianchi, M. E., Al-Abed, Y., Andersson, U., Tracey, K. J., & Antoine, D. J. (2012) · Molecular Medicine · doi:10.2119/molmed.2011.00389 · Cited by 407 · see citing works
Self-citationRetractedGapped BLAST and PSI-BLAST: a new generation of protein database search programs
Altschul, S. (1997) · Nucleic Acids Research · doi:10.1093/nar/25.17.3389 · Cited by 73,302 · see citing works
Release of chromatin protein HMGB1 by necrotic cells triggers inflammation
Scaffidi, P., Misteli, T., & Bianchi, M. E. (2002) · Nature · doi:10.1038/nature00858 · Cited by 4,221 · see citing works
The Danger Model: A Renewed Sense of Self
Matzinger, P. (2002) · Science · doi:10.1126/science.1071059 · Cited by 4,205 · see citing works
Yang, Y., Li, S., Yang, Q., Shi, Y., Zheng, M., Liu, Y., Chen, F., Song, G., Xu, H., Wan, T., et al. (2014) · Cellular Physiology and Biochemistry · doi:10.1159/000358696 · Cited by 3,262 · see citing works
Bauernfeind, F. G., Horvath, G. L., Stutz, A., Alnemri, E. S., MacDonald, K. L., Speert, D. P., Fernandes‐Alnemri, T., Wu, J., Monks, B. G., Fitzgerald, K. A., et al. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0901363 · Cited by 3,006 · see citing works
DAMPs, PAMPs and alarmins: all we need to know about danger
Bianchi, M. E. (2007) · Journal of Leukocyte Biology · doi:10.1189/jlb.0306164 · Cited by 2,794 · see citing works
High-mobility group box 1 protein (HMGB1): nuclear weapon in the immune arsenal
Lotze, M. T., & Tracey, K. J. (2005) · Nature reviews. Immunology · doi:10.1038/nri1594 · Cited by 2,490 · see citing works
Self-citationThe Inflammasomes: Guardians of the Body
Martinon, F., Mayor, A., & Tschopp, J. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132715 · Cited by 2,436 · see citing works
Park, J. S., Svetkauskaite, D., He, Q., Kim, J., Strassheim, D., Ishizaka, A., & Abraham, E. H. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m306793200 · Cited by 1,560 · see citing works
Reversing established sepsis with antagonists of endogenous high-mobility group box 1
Yang, H., Ochani, M., Li, J., Qiang, X., Tanovic, M., Harris, H. E., Susarla, S. M., Ulloa, L., Wang, H., DiRaimo, R., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2434651100 · Cited by 1,126 · see citing works
Self-citationKang, R., Chen, R., Zhang, Q., Hou, W., Wu, S., Cao, L., Huang, J., Yu, Y., Fan, X.-G., Yan, Z., et al. (2014) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2014.05.001 · Cited by 956 · see citing works
HMGB1: Endogenous Danger Signaling
Klune, J. R., Dhupar, R., Cardinal, J., Billiar, T. R., & Tsung, A. (2008) · Molecular Medicine · doi:10.2119/2008-00034.klune · Cited by 762 · see citing works
Mutually exclusive redox forms of HMGB1 promote cell recruitment or proinflammatory cytokine release
Venereau, E., Casalgrandi, M., Schiraldi, M., Antoine, D. J., Cattaneo, A., De Marchis, F., Liu, J., Antonelli, A., Preti, A., Raeli, L., et al. (2012) · Journal of Experimental Medicine · doi:10.1084/jem.20120189 · Cited by 720 · cited 2× · see citing works
“Oxidation at all three cysteines abrogates both the chemotactic and proinflammatory properties of HMGB-1 (oxidized HMGB-1; Venereau et al., 2012).”
Self-citationWohleb, E. S., Hanke, M. L., Corona, A. W., Powell, N. D., Stiner, L. M., Bailey, M. T., Nelson, R. J., Godbout, J. P., & Sheridan, J. F. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.0450-11.2011 · Cited by 638 · see citing works
Frank, M. G., Baratta, M. V., Sprunger, D. B., Watkins, L. R., & Maier, S. F. (2007) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2006.03.005 · Cited by 578 · see citing works
Self-citationWohleb, E. S., Powell, N. D., Godbout, J. P., & Sheridan, J. F. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.1671-13.2013 · Cited by 563 · see citing works
Tynan, R. J., Naicker, S., Hinwood, M., Nalivaiko, E., Buller, K. M., Pow, D. V., Day, T. A., & Walker, F. R. (2010) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2010.02.001 · Cited by 531 · see citing works
Pan, Y., Chen, X.-Y., Zhang, Q.-Y., & Kong, L.-D. (2014) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2014.04.007 · Cited by 405 · see citing works
Early Release of HMGB-1 from Neurons after the Onset of Brain Ischemia
Qiu, J., Nishimura, M., Wang, Y., Sims, J. R., Qiu, S., Savitz, S. I., Salomone, S., & Moskowitz, M. A. (2007) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/sj.jcbfm.9600582 · Cited by 405 · see citing works
HMGB1 Develops Enhanced Proinflammatory Activity by Binding to Cytokines
Sha, Y., Zmijewski, J. W., Xu, Z., & Abraham, E. H. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.4.2531 · Cited by 393 · see citing works
Nair, A., & Bonneau, R. H. (2006) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2005.09.012 · Cited by 392 · see citing works
Structural Basis for the Proinflammatory Cytokine Activity of High Mobility Group Box 1
Li, J., Kokkola, R., TABIBZADEH, S. S., Yang, R., Ochani, M., Qiang, X., Harris, H. E., Czura, C. J., Wang, H., Ulloa, L., et al. (2003) · Molecular Medicine · doi:10.1007/bf03402105 · Cited by 371 · see citing works
Self-citationInterleukin‐1: A master regulator of neuroinflammation
Basu, A., Krady, J. K., & Levison, S. W. (2004) · Journal of Neuroscience Research · doi:10.1002/jnr.20266 · Cited by 367 · see citing works
Targeting HMGB1 in inflammation
Yang, H., & Tracey, K. J. (2010) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2009.11.019 · Cited by 351 · see citing works
Self-citationFrank, M. G., Miguel, Z. D., Watkins, L. R., & Maier, S. F. (2010) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2009.07.008 · Cited by 303 · see citing works
Self-citationSensing damage by the NLRP3 inflammasome
Leemans, J. C., Cassel, S. L., & Sutterwala, F. S. (2011) · Immunological Reviews · doi:10.1111/j.1600-065x.2011.01043.x · Cited by 281 · see citing works
Wohleb, E. S., Fenn, A. M., Pacenta, A. M., Powell, N. D., Sheridan, J. F., & Godbout, J. P. (2012) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2012.02.003 · Cited by 275 · see citing works
Munhoz, C. D., Lepsch, L. B., Kawamoto, E. M., Malta, M. B., Lima, L. D. S., Werneck Avellar, M. C., Sapolsky, R. M., & Scavone, C. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.4398-05.2006 · Cited by 274 · see citing works
Prior Stressor Exposure Sensitizes LPS-Induced Cytokine Production
Johnson, J. D., O'Connor, K. A., Deak, T., Stark, M., Watkins, L. R., & Maier, S. F. (2002) · Brain, Behavior, and Immunity · doi:10.1006/brbi.2001.0638 · Cited by 270 · see citing works
Self-citationvan Zoelen, M. A. D., Yang, H., Florquin, S., Meijers, J. C. M., Akira, S., Arnold, B., Nawroth, P. P., Bierhaus, A., Tracey, K. J., & van der Poll, T. (2009) · Shock · doi:10.1097/shk.0b013e318186262d · Cited by 262 · see citing works
Self-citationThe danger theory: 20 years later
Pradeu, T., & Cooper, E. L. (2012) · Frontiers in Immunology · doi:10.3389/fimmu.2012.00287 · Cited by 251 · see citing works
Fillman, S. G., Sinclair, D., Fung, S. J., Webster, M. J., & Shannon Weickert, C. (2014) · Translational Psychiatry · doi:10.1038/tp.2014.8 · Cited by 226 · see citing works
Cytokines, prostaglandins and nitric oxide in the regulation of stress-response systems
Gądek-Michalska, A., Tadeusz, J., Rachwalska, P., & Bugajski, J. (2013) · Pharmacological Reports · doi:10.1016/s1734-1140(13)71527-5 · Cited by 225 · see citing works
Stress increases vulnerability to inflammation in the rat prefrontal cortex
de Pablos, R. M., Villarán, R. F., Argüelles, S., Herrera, A. J., Venero, J. L., Ayala, A., Cano, J., & Machado, A. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.0802-06.2006 · Cited by 215 · see citing works
Analysis of proinflammatory activity of highly purified eukaryotic recombinant HMGB1 (amphoterin)
Rouhiainen, A., Tumova, S., Valmu, L., Kalkkinen, N., & Rauvala, H. (2007) · Journal of Leukocyte Biology · doi:10.1189/jlb.0306200 · Cited by 214 · see citing works
HMGB1 and leukocyte migration during trauma and sterile inflammation
Vénéreau, E., Schiraldi, M., Uguccioni, M., & Bianchi, M. E. (2012) · Molecular Immunology · doi:10.1016/j.molimm.2012.10.037 · Cited by 213 · see citing works
Toll-like receptor (TLR) and inflammasome actions in the central nervous system
Hanamsagar, R., Hanke, M. L., & Kielian, T. (2012) · Trends in Immunology · doi:10.1016/j.it.2012.03.001 · Cited by 203 · see citing works
Agalave, N. M., Larsson, M., Abdelmoaty, S., Su, J., Baharpoor, A., Lundbäck, P., Palmblad, K., Andersson, U., Harris, H. E., & Svensson, C. I. (2014) · Pain · doi:10.1016/j.pain.2014.06.007 · Cited by 179 · see citing works
Frank, M. G., Wieseler‐Frank, J., Watkins, L. R., & Maier, S. F. (2005) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2005.06.026 · Cited by 164 · see citing works
Self-citationHemorrhagic Shock Activation of NLRP3 Inflammasome in Lung Endothelial Cells
Xiang, M., Shi, X., Li, Y., Xu, J., Yin, L., Xiao, G., Scott, M. J., Billiar, T. R., Wilson, M. A., & Fan, J. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1102093 · Cited by 155 · see citing works
Stress is critical for LPS-induced activation of microglia and damage in the rat hippocampus
Espinosa-Oliva, A. M., de Pablos, R. M., Villarán, R. F., Argüelles, S., Venero, J. L., Machado, A., & Cano, J. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2009.01.012 · Cited by 151 · see citing works
Weber, M. D., Frank, M. G., Sobesky, J. L., Watkins, L. R., & Maier, S. F. (2013) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2013.03.004 · Cited by 93 · see citing works
Self-citationHigh-Mobility Group Box 1 Mediates Persistent Splenocyte Priming in Sepsis Survivors
Valdés‐Ferrer, S. I., Rosas‐Ballina, M., Olofsson, P. S., Lü, B., Dancho, M. E., Li, J., Yang, H., Pavlov, V. A., Chavan, S. S., & Tracey, K. J. (2013) · Shock · doi:10.1097/shk.0000000000000050 · Cited by 52 · see citing works
Self-citationHolguin, A., Frank, M. G., Biedenkapp, J. C., Nelson, K., Lippert, D. C., Watkins, L. R., Rudy, J. W., & Maier, S. F. (2007) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2006.11.014 · Cited by 35 · see citing works
Self-citationCassetta, L., Fortunato, O., Adduce, L., Rizzi, C., Hering, J., Rovere, P. Q., Bianchi, M. E., Alfano, M., & Poli, G. (2009) · AIDS · doi:10.1097/qad.0b013e328325a47e · Cited by 28 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Depression as a Microglial Disease
Yirmiya, R., Rimmerman, N., & Reshef, R. (2015) · Trends in Neurosciences · doi:10.1016/j.tins.2015.08.001 · Cited by 944 · see citing works
Inflammation: The Common Pathway of Stress-Related Diseases
Liu, Y.-Z., Wang, Y.-X., & Jiang, C.-L. (2017) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2017.00316 · Cited by 800 · see citing works
Integrating neuroimmune systems in the neurobiology of depression
Wohleb, E. S., Franklin, T., Iwata, M., & Duman, R. S. (2016) · Nature Reviews Neuroscience · doi:10.1038/nrn.2016.69 · Cited by 668 · see citing works
Brites, D., & Fernandes, A. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00476 · Cited by 599 · see citing works
“Increased high mobility group box-1 (HMGB-1) protein was demonstrated to be increased in the hippocampus of male Sprague Dawley rats after tail shocks and to be responsible for microglia priming by acting on the NLRP3 inflammasome (Weber et al., 2015).”
BackgroundThe role of inflammation and microglial activation in the pathophysiology of psychiatric disorders
Réus, G. Z., Fries, G. R., Stertz, L., Badawy, M., Passos, I. C., Barichello, T., Kapczinski, F., & Quevedo, J. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2015.05.018 · Cited by 594 · see citing works
Wang, M., Pan, W., Xu, Y., Zhang, J., Wan, J., & Jiang, H. (2022) · Journal of Inflammation Research · doi:10.2147/jir.s350109 · Cited by 461 · see citing works
Yang, D., Han, Z., & Oppenheim, J. J. (2017) · Immunological Reviews · doi:10.1111/imr.12577 · Cited by 412 · see citing works
Paudel, Y. N., Shaikh, M. F., Chakraborti, A., Kumari, Y., Aledo-Serrano, Á., Aleksovska, K., Alvim, M. K. M., & Othman, I. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00628 · Cited by 311 · see citing works
The role of neuroimmune signaling in alcoholism
Crews, F. T., Lawrimore, C. J., Walter, T. J., & Coleman, L. G. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.01.031 · Cited by 321 · see citing works
Danger signals in stroke and their role on microglia activation after ischemia
Gülke, E., Gelderblom, M., & Magnus, T. (2018) · Therapeutic Advances in Neurological Disorders · doi:10.1177/1756286418774254 · Cited by 321 · see citing works
Fann, D. Y., Lim, Y., Cheng, Y., Lok, K. Z., Chunduri, P., Baik, S.-H., Drummond, G. R., Dheen, S. T., Sobey, C. G., Jo, D., et al. (2017) · Molecular Neurobiology · doi:10.1007/s12035-017-0394-9 · Cited by 311 · see citing works
Microglia in depression: current perspectives
Jia, X., Gao, Z., & Hu, H. (2020) · Science China Life Sciences · doi:10.1007/s11427-020-1815-6 · Cited by 283 · see citing works
Repeated Social Defeat, Neuroinflammation, and Behavior: Monocytes Carry the Signal
Weber, M. D., Godbout, J. P., & Sheridan, J. F. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.102 · Cited by 283 · see citing works
Self-citationFrank, M. G., Weber, M. D., Watkins, L. R., & Maier, S. F. (2015) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2015.03.010 · Cited by 237 · see citing works
Self-citationPsychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms
Inserra, A., De Gregorio, D., & Gobbi, G. (2021) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000056 · Cited by 232 · see citing works
Danger Signals and Inflammasomes: Stress-Evoked Sterile Inflammation in Mood Disorders
Fleshner, M., Frank, M., & Maier, S. F. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.125 · Cited by 216 · see citing works
Self-citationDepression and sterile inflammation: essential role of danger associated molecular patterns
Franklin, T. C., Xu, C., & Duman, R. S. (2018) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2017.10.025 · Cited by 204 · see citing works
Wang, Z., Meng, S., Cao, L., Chen, Y., Zuo, Z., & Peng, S. (2018) · Journal of Neuroinflammation · doi:10.1186/s12974-018-1137-1 · Cited by 209 · see citing works
Franklin, T., Wohleb, E. S., Zhang, Y., Fogaça, M. V., Hare, B. D., & Duman, R. S. (2017) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.06.034 · Cited by 173 · see citing works
Zhang, S., Hu, L., Jiang, J., Li, H., Wu, Q. J., Ooi, K., Wang, J., Feng, Y., Zhu, D., & Xia, C. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-019-1673-3 · Cited by 179 · see citing works
Cheng, Y., Pardo, M., Armini, R. D. S., Martinez, A., Mouhsine, H., Zagury, J.-F., Jope, R. S., & Beurel, E. (2016) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2015.12.012 · Cited by 174 · see citing works
Inflammasomes link vascular disease with neuroinflammation and brain disorders
Lénárt, N., Brough, D., & Dénes, Á. (2016) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x16662043 · Cited by 169 · see citing works
Neuron–Microglia Interactions in Mental Health Disorders: “For Better, and For Worse”
Wohleb, E. S. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00544 · Cited by 164 · see citing works
Inflammasomes in neurological diseases: emerging pathogenic and therapeutic concepts
Mamik, M. K., & Power, C. (2017) · Brain : a journal of neurology · doi:10.1093/brain/awx133 · Cited by 151 · see citing works
Microglia: Neuroimmune-sensors of stress
Frank, M. G., Fonken, L. K., Watkins, L. R., & Maier, S. F. (2019) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2019.01.001 · Cited by 160 · see citing works
Self-citationToll-like receptor signaling and stages of addiction
Crews, F. T., Walter, T. J., Coleman, L. G., & Vetreno, R. P. (2017) · Psychopharmacology · doi:10.1007/s00213-017-4560-6 · Cited by 159 · see citing works
Frank, M. G., Weber, M. D., Watkins, L. R., & Maier, S. F. (2015) · Neurobiology of Stress · doi:10.1016/j.ynstr.2015.12.004 · Cited by 148 · see citing works
Self-citationRole of neuro-immunological factors in the pathophysiology of mood disorders
Bhattacharya, A., Derecki, N. C., Lovenberg, T. W., & Drevets, W. C. (2016) · Psychopharmacology · doi:10.1007/s00213-016-4214-0 · Cited by 149 · see citing works
P2X7 receptor mediates NLRP3 inflammasome activation in depression and diabetes
Wang, D., Wang, H., Gao, H., Zhang, H., Zhang, H., Wang, Q., & Sun, Z. (2020) · Cell & Bioscience · doi:10.1186/s13578-020-00388-1 · Cited by 145 · see citing works
Palmitoylethanolamide: A Natural Compound for Health Management
Clayton, P., Hill, M., Bogoda, N. O., Subah, S., & Venkatesh, R. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22105305 · Cited by 145 · see citing works
The Alarmin HMGB1 Mediates Age-Induced Neuroinflammatory Priming
Fonken, L. K., Frank, M. G., Kitt, M. M., D'Angelo, H. M., Norden, D. M., Weber, M. D., Barrientos, R. M., Godbout, J. P., Watkins, L. R., & Maier, S. F. (2016) · The Journal of Neuroscience · doi:10.1523/jneurosci.1161-16.2016 · Cited by 139 · see citing works
Self-citationNeuroendocrine Regulation of Brain Cytokines After Psychological Stress
Johnson, J. D., Barnard, D. F., Kulp, A. C., & Mehta, D. M. (2019) · Journal of the Endocrine Society · doi:10.1210/js.2019-00053 · Cited by 135 · see citing works
Wang, B., Huang, X., Pan, X., Zhang, T., Hou, C., Su, W., Liu, L.-L., Li, J., & Wang, Y. (2020) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2020.06.019 · Cited by 134 · see citing works
Frank, M. G., Weber, M. D., Fonken, L. K., Hershman, S. A., Watkins, L. R., & Maier, S. F. (2016) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2015.10.009 · Cited by 133 · see citing works
Self-citationChecks and balances: The glucocorticoid receptor and NFĸB in good times and bad
Bekhbat, M., Rowson, S. A., & Neigh, G. N. (2017) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2017.05.001 · Cited by 133 · see citing works
Wohleb, E. S., & Delpech, J.-C. (2016) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2016.04.013 · Cited by 128 · see citing works
Principles of inflammasome priming and inhibition: implications for psychiatric disorders
Herman, F. J., & Pasinetti, G. M. (2018) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2018.06.010 · Cited by 115 · see citing works
Stressed and Inflamed, Can GSK3 Be Blamed?
Jope, R. S., Cheng, Y., Lowell, J. A., Worthen, R. J., Sitbon, Y. H., & Beurel, E. (2016) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2016.10.009 · Cited by 122 · see citing works
Neuroinflammatory priming to stress is differentially regulated in male and female rats
Fonken, L. K., Frank, M. G., Gaudet, A. D., D’Angelo, H. M., Daut, R. A., Hampson, E. C., Ayala, M. T., Watkins, L. R., & Maier, S. F. (2018) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2018.03.005 · Cited by 115 · see citing works
Self-citationThe Relationship between Stress, Inflammation, and Depression
Kim, I. B., Lee, J.-H., & Park, S. (2022) · Biomedicines · doi:10.3390/biomedicines10081929 · Cited by 126 · see citing works
Milligan Armstrong, A., Porter, T., Quek, H., White, A., Haynes, J., Jackaman, C., Villemagne, V., Munyard, K., Laws, S. M., Verdile, G., et al. (2021) · Biological Reviews · doi:10.1111/brv.12750 · Cited by 116 · see citing works
The Microbiota-Gut-Immune-Glia (MGIG) Axis in Major Depression
Rudzki, L., & Maes, M. H. J. (2020) · Molecular Neurobiology · doi:10.1007/s12035-020-01961-y · Cited by 114 · see citing works
The Pro-inflammatory Effects of Glucocorticoids in the Brain
Duque, É. D. A., & Munhoz, C. D. (2016) · Frontiers in Endocrinology · doi:10.3389/fendo.2016.00078 · Cited by 115 · see citing works
Zhao, Z., Wang, Y., Zhou, R., Li, Y., Gao, Y., Tu, D., Wilson, B., Song, S., Feng, J., Hong, J.-S., et al. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-1728-5 · Cited by 109 · see citing works
Lian, Y., Gong, H., Wu, T., Su, W., Zhang, Y., Yang, Y., Wei, P., Zhang, T., Zhou, J., Jiang, C., et al. (2016) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2016.09.017 · Cited by 105 · see citing works
Wang, B., Lian, Y., Su, W., Wei, P., Dong, X. W., Liu, L.-L., Gong, H., Zhang, T., Jiang, C., & Wang, Y. (2017) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2017.11.017 · Cited by 105 · see citing works
Molecular isoforms of high-mobility group box 1 are mechanistic biomarkers for epilepsy
Walker, L. E., Frigerio, F., Ravizza, T., Ricci, E., Tse, K., Jenkins, R. E., Sills, G. J., Jorgensen, A., Porcu, L., Thippeswamy, T., et al. (2017) · Journal of Clinical Investigation · doi:10.1172/jci92001 · Cited by 102 · see citing works
RetractedDeak, T., Quinn, M., Cidlowski, J. A., Victoria, N. C., Murphy, A. Z., & Sheridan, J. F. (2015) · Stress · doi:10.3109/10253890.2015.1053451 · Cited by 102 · see citing works
Haj-Mirzaian, A., Amiri, S., Amini-Khoei, H., Hosseini, M.-J., Haj-Mirzaian, A., Momeny, M., Rahimi-Balaei, M., & Dehpour, A. R. (2017) · Neuroscience · doi:10.1016/j.neuroscience.2017.10.023 · Cited by 100 · see citing works
Peng, H., Geil, C., Chen, K. Y., McClain, J. A., & Nixon, K. (2017) · Alcohol · doi:10.1016/j.alcohol.2017.02.175 · Cited by 95 · see citing works
Inserra, A., Mastronardi, C. A., Rogers, G. B., Licinio, J., & Wong, M. (2018) · Molecular Neurobiology · doi:10.1007/s12035-018-1359-3 · Cited by 95 · see citing works
Stress and aging act through common mechanisms to elicit neuroinflammatory priming
Fonken, L. K., Frank, M. G., Gaudet, A. D., & Maier, S. F. (2018) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2018.07.012 · Cited by 94 · see citing works
Self-citationFrank, M. G., Fonken, L. K., Dolzani, S. D., Annis, J. L., Siebler, P. H., Schmidt, D., Watkins, L. R., Maier, S. F., & Lowry, C. A. (2018) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2018.05.020 · Cited by 91 · see citing works
Self-citationInnate Immune Signaling and Alcohol Use Disorders
Coleman, L. G., & Crews, F. T. (2018) · Handbook of experimental pharmacology · doi:10.1007/164_2018_92 · Cited by 90 · see citing works
Sterile Neuroinflammation and Strategies for Therapeutic Intervention
Banjara, M., & Ghosh, C. (2017) · International Journal of Inflammation · doi:10.1155/2017/8385961 · Cited by 87 · see citing works
Welcome, M. O. (2020) · Inflammopharmacology · doi:10.1007/s10787-020-00712-8 · Cited by 85 · see citing works
Effect of Systemic Inflammation in the CNS: A Silent History of Neuronal Damage
Solano, M. V. M., Lara, C. S., Sánchez-Garibay, C., Soto-Rojas, L. O., Escobedo-Ávila, I., Tena‐Suck, M. L., Ortiz-Butrón, R., Choreño-Parra, J. A., Romero‐López, J. P., & Meléndez-Camargo, M. E. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241511902 · Cited by 77 · see citing works
Stress disinhibits microglia via down-regulation of CD200R: A mechanism of neuroinflammatory priming
Frank, M. G., Fonken, L. K., Annis, J. L., Watkins, L. R., & Maier, S. F. (2017) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2017.11.001 · Cited by 77 · see citing works
Self-citationVisentin, A. P. V., Colombo, R., Scotton, E., Fracasso, D. S., Rosa, A. R., Branco, C. S., & Salvador, M. M. (2020) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2020/2972968 · Cited by 77 · see citing works
Alcohol and Stress Activation of Microglia and Neurons: Brain Regional Effects
Walter, T. J., Vetreno, R. P., & Crews, F. T. (2017) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.13511 · Cited by 75 · see citing works
Rosciszewski, G., Cadena, V., Auzmendi, J., Cieri, M. B., Lukin, J., Rossi, A. R., Murta, V., Villarreal, A., Reinés, A. G., Gomes, F. C. A., et al. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00380 · Cited by 74 · see citing works
Marón, F. J. M., Ferder, L., Saraví, F. D., & Manucha, W. A. (2018) · Stress · doi:10.1080/10253890.2018.1542683 · Cited by 76 · see citing works
Stress-induced neuroinflammatory priming is time of day dependent
Fonken, L. K., Weber, M. D., Daut, R. A., Kitt, M. M., Frank, M. G., Watkins, L. R., & Maier, S. F. (2016) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2016.01.006 · Cited by 72 · see citing works
Self-citationFrank, M. G., Adhikary, S., Sobesky, J. L., Weber, M. D., Watkins, L. R., & Maier, S. F. (2015) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2015.08.001 · Cited by 70 · see citing works
Self-citationZhang, H., Ding, L., Shen, T., & Peng, D. (2019) · General Psychiatry · doi:10.1136/gpsych-2019-100084 · Cited by 67 · see citing works
Prowse, N. A., & Hayley, S. P. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.09.018 · Cited by 67 · see citing works
Zhou, Z., Hou, J., Mo, Y., Ren, M., Yang, G., Qu, Z., & Hu, Y. (2019) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2019.172857 · Cited by 66 · see citing works
Frank, M. G., Fonken, L. K., Watkins, L. R., & Maier, S. F. (2020) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2020.05.063 · Cited by 66 · see citing works
Self-citationSobesky, J. L., D’Angelo, H. M., Weber, M. D., Anderson, N. D., Frank, M. G., Watkins, L. R., Maier, S. F., & Barrientos, R. M. (2016) · eNeuro · doi:10.1523/eneuro.0113-16.2016 · Cited by 64 · see citing works
Self-citationXie, J., Bi, B., Qin, Y., Dong, W., Zhong, J., Li, M., Cheng, Y., Xu, J., & Wang, H. (2020) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2020.11.029 · Cited by 61 · see citing works
Gut microbiota and neuropsychiatric disorders: Implications for neuroendocrine-immune regulation
Ge, T., Yao, X., Zhao, H., Yang, W., Zou, X., Peng, F., Li, B., & Cui, R. (2021) · Pharmacological Research · doi:10.1016/j.phrs.2021.105909 · Cited by 62 · see citing works
Lifestyle Shapes the Dialogue between Environment, Microglia, and Adult Neurogenesis
Valero, J., Paris, I., & Sierra, A. (2016) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.6b00009 · Cited by 60 · see citing works
Kim, I., Lee, H., Kim, S.-W., Lee, H., Choi, J., Han, P., & Lee, J.-K. (2018) · Cell Death and Disease · doi:10.1038/s41419-018-0438-8 · Cited by 60 · see citing works
Neuroimmune and Inflammatory Signals in Complex Disorders of the Central Nervous System
Liberman, A. C., Trías, E., Chagas, L. D. S., Trindade, P., Pereira, M. D. S., Refojo, D., Hedin‐Pereira, C., & Serfaty, C. A. (2018) · NeuroImmunoModulation · doi:10.1159/000494761 · Cited by 61 · see citing works
NOD-like Receptors in the Eye: Uncovering Its Role in Diabetic Retinopathy
Lim, R. R., Wieser, M. E., Ganga, R., Barathi, V. A., Lakshminarayanan, R., Mohan, R. R., Hainsworth, D. P., & Chaurasia, S. S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21030899 · Cited by 58 · see citing works
Espinosa‐García, C., Atif, F., Yousuf, S., Sayeed, I., Neigh, G. N., & Stein, D. G. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21113740 · Cited by 59 · see citing works
AC-YVAD-CMK Inhibits Pyroptosis and Improves Functional Outcome after Intracerebral Hemorrhage
Lin, X., Ye, H., Siaw-Debrah, F., Pan, S., He, Z., Ni, H., Xu, Z., Jin, K., Zhuge, Q., & Huang, L. (2018) · BioMed Research International · doi:10.1155/2018/3706047 · Cited by 58 · see citing works
Horowitz, M. A., Cattaneo, A., Cattane, N., Lopizzo, N., Tojo, L. M., Bakunina, N., Musaelyan, K., Borsini, A., Zunszain, P. A., & Pariante, C. M. (2020) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2020.03.012 · Cited by 57 · see citing works
How Stress Shapes Neuroimmune Function: Implications for the Neurobiology of Psychiatric Disorders
Koo, J. W., & Wohleb, E. S. (2020) · Biological Psychiatry · doi:10.1016/j.biopsych.2020.11.007 · Cited by 58 · see citing works
The role of tryptophan metabolism in postpartum depression
Duan, K., Ma, J., Wang, S., Huang, Z., Zhou, Y., & Yu, H. (2018) · Metabolic Brain Disease · doi:10.1007/s11011-017-0178-y · Cited by 56 · see citing works
Microglial Responses to Stress-Induced Depression: Causes and Consequences
Afridi, R., & Suk, K. (2023) · Cells · doi:10.3390/cells12111521 · Cited by 58 · see citing works
Liu, L., Zhao, Z., Lu, L., Liu, J., Sun, J., & Dong, J. (2019) · International Immunopharmacology · doi:10.1016/j.intimp.2019.105799 · Cited by 53 · see citing works
Zhang, F. F., Morioka, N., Harano, S., Nakamura, Y., Liu, K., Nishibori, M., Hisaoka‐Nakashima, K., & Nakata, Y. (2015) · Journal of Neurochemistry · doi:10.1111/jnc.13434 · Cited by 52 · see citing works
Xu, E., Liu, J., Liu, H., Wang, X., & Xiong, H. (2018) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-018-9780-y · Cited by 52 · see citing works
Neuroinflammation in Response to Intracerebral Injections of Different HMGB1 Redox Isoforms
Aucott, H., Lundberg, J., Salo, H., Klevenvall, L., Damberg, P., Ottosson, L., Andersson, U., Holmin, S., & Harris, H. E. (2018) · Journal of Innate Immunity · doi:10.1159/000487056 · Cited by 51 · see citing works
Molecular insights into the therapeutic promise of targeting HMGB1 in depression
Rana, T., Behl, T., Mehta, V., Uddin, M. S., & BUNGAU, S. G. (2020) · Pharmacological Reports · doi:10.1007/s43440-020-00163-6 · Cited by 49 · see citing works
Impact of Stress on Epilepsy: Focus on Neuroinflammation—A Mini Review
Espinosa‐García, C., Zeleke, H., & Rojas, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22084061 · Cited by 50 · see citing works
The permissive role of glucocorticoids in neuroinflammatory priming
Frank, M. G., Watkins, L. R., & Maier, S. F. (2015) · Current Opinion in Endocrinology Diabetes and Obesity · doi:10.1097/med.0000000000000168 · Cited by 47 · see citing works
Self-citationXu, B., Zang, S., Li, S., Guo, J., Wang, J., Wang, D., Zhang, L.-P., Yang, H.-M., & Lian, S. (2018) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2018.11.313 · Cited by 47 · see citing works
Neuroinflammation and Mitochondrial Dysfunction Link Social Stress to Depression
Hollis, F., Pope, B. S., Gorman‐Sandler, E., & Wood, S. K. (2022) · Current topics in behavioral neurosciences · doi:10.1007/7854_2021_300 · Cited by 47 · see citing works
Vecchiarelli, H. A., Gandhi, C. P., Gray, J. M., Morena, M., Hassan, K. I., & Hill, M. N. (2015) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2015.07.026 · Cited by 45 · see citing works
Relevance of chronic stress and the two faces of microglia in Parkinson's disease
Herrera, A. J., Espinosa-Oliva, A. M., Carrillo-Jiménez, A., Oliva-Martín, M. J., García-Revilla, J., García-Quintanilla, A., de Pablos, R. M., & Venero, J. L. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00312 · Cited by 42 · see citing works
Mitochondrial DAMPs: Key mediators in neuroinflammation and neurodegenerative disease pathogenesis
Yu, H., Ren, K., Jin, Y., Zhang, L., Liu, H., Huang, Z., Zhang, Z., Chen, X., Yang, Y., & Wei, Z. (2024) · Neuropharmacology · doi:10.1016/j.neuropharm.2024.110217 · Cited by 44 · see citing works
Duan, J., Zhang, Q., Hu, X., Lu, D., Yu, W., & Bai, H. (2019) · Cellular Signalling · doi:10.1016/j.cellsig.2019.03.007 · Cited by 42 · see citing works
An emerging role for microglia in stress‐effects on memory
Sanguino‐Gómez, J., Buurstede, J. C., Abiega, O., Fitzsimons, C. P., Lucassen, P. J., Eggen, B. J. L., Lesuis, S. L., Meijer, O. C., & Krugers, H. J. (2021) · European Journal of Neuroscience · doi:10.1111/ejn.15188 · Cited by 43 · see citing works
Alarmins and central nervous system inflammation in HIV ‐associated neurological disorders
Gougeon, M. (2016) · Journal of Internal Medicine · doi:10.1111/joim.12570 · Cited by 41 · see citing works
Melbourne, J. K., Thompson, K. R., Peng, H., & Nixon, K. (2019) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2019.06.011 · Cited by 40 · see citing works
Medina‐Ceja, L., Salazar‐Sánchez, J. C., Ortega‐Ibarra, J., & Morales‐Villagrán, A. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20235976 · Cited by 41 · see citing works
Lang, L., Xu, B., Yuan, J., Li, S., Lian, S., Chen, Y., Guo, J., & Yang, H. (2020) · International Immunopharmacology · doi:10.1016/j.intimp.2020.106908 · Cited by 41 · see citing works
MicroRNA-574-5p Attenuates Acute Respiratory Distress Syndrome by Targeting HMGB1
He, B., Zhou, W., Rui, Y., Liu, L., Chen, B., & Su, X. (2020) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2020-0112oc · Cited by 41 · see citing works
- Authors
- Weber, M. D., Frank, M. G., Tracey, K. J., Watkins, L. R., & Maier, S. F.
- Affiliations
- University of Colorado Boulder (US)
- Northwell Health (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2015-01-07
- Volume
- 35
- Issue
- 1
- Pages
- 316-324
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC4287150
- OpenAlex
- W2087987871
- Cited by
- 215
- References
- 46
- Citations by year
- 2026: 10 · 2025: 10 · 2024: 12 · 2023: 11 · 2022: 20 · 2021: 21 · 2020: 25 · 2019: 19 · 2018: 24 · 2017: 25 · 2016: 21 · 2015: 16
- FWCI
- 15.29
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (MH096224, R21MH096224)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- HMGB1, NLRP3 inflammasome, microglial priming, hippocampus, inflammatory cytokines, lipopolysaccharide response, damage-associated molecular patterns
- MeSH terms
- NLR Family, Pyrin Domain-Containing 3 Protein, Animals, Carrier Proteins, Hippocampus, Male, Stress, Psychological, Rats, Sprague-Dawley, Microglia, Receptors, Cytoplasmic and Nuclear, HMGB1 Protein, Rats, Inflammasomes
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
