{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T12:48:43Z","timestamp":1780922923093,"version":"3.54.1"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,5,2]],"date-time":"2020-05-02T00:00:00Z","timestamp":1588377600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,5,2]],"date-time":"2020-05-02T00:00:00Z","timestamp":1588377600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","award":["ZIAMH002795"],"award-info":[{"award-number":["ZIAMH002795"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["ZIAMH002793"],"award-info":[{"award-number":["ZIAMH002793"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neuroinflammation"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Cyclooxygenase-2 (COX-2), which is rapidly upregulated by inflammation, is a key enzyme catalyzing the rate-limiting step in the synthesis of several inflammatory prostanoids. Successful positron emission tomography (PET) radioligand imaging of COX-2 in vivo could be a potentially powerful tool for assessing inflammatory response in the brain and periphery. To date, however, the development of PET radioligands for COX-2 has had limited success.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>The novel PET tracer [<jats:sup>11<\/jats:sup>C]MC1 was used to examine COX-2 expression [1] in the brains of four rhesus macaques at baseline and after injection of the inflammogen lipopolysaccharide (LPS) into the right putamen, and [2] in the joints of two human participants with rheumatoid arthritis and two healthy individuals. In the primate study, two monkeys had one LPS injection, and two monkeys had a second injection 33 and 44 days, respectively, after the first LPS injection. As a comparator, COX-1 expression was measured using [<jats:sup>11<\/jats:sup>C]PS13.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>COX-2 binding, expressed as the ratio of specific to nondisplaceable uptake (<jats:italic>BP<\/jats:italic><jats:sub>ND<\/jats:sub>) of [<jats:sup>11<\/jats:sup>C]MC1, increased on day 1 post-LPS injection; no such increase in COX-1 expression, measured using [<jats:sup>11<\/jats:sup>C]PS13, was observed. The day after the second LPS injection, a brain lesion (~\u20090.5 cm in diameter) with high COX-2 density and high <jats:italic>BP<\/jats:italic><jats:sub>ND<\/jats:sub> (1.8) was observed. Postmortem brain analysis at the gene transcript or protein level confirmed in vivo PET results. An incidental finding in an unrelated monkey found a line of COX-2 positivity along an incision in skull muscle, demonstrating that [<jats:sup>11<\/jats:sup>C]MC1 can localize inflammation peripheral to the brain. In patients with rheumatoid arthritis, [<jats:sup>11<\/jats:sup>C]MC1 successfully imaged upregulated COX-2 in the arthritic hand and shoulder and apparently in the brain. Uptake was blocked by celecoxib, a COX-2 preferential inhibitor.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Taken together, these results indicate that [<jats:sup>11<\/jats:sup>C]MC1 can image and quantify COX-2 upregulation in both monkey brain after LPS-induced neuroinflammation and in human peripheral tissue with inflammation.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial registration<\/jats:title>\n                <jats:p><jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link> NCT03912428. Registered April 11, 2019.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12974-020-01804-6","type":"journal-article","created":{"date-parts":[[2020,5,2]],"date-time":"2020-05-02T08:05:33Z","timestamp":1588406733000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["PET measurement of cyclooxygenase-2 using a novel radioligand: upregulation in primate neuroinflammation and first-in-human study"],"prefix":"10.1186","volume":"17","author":[{"given":"Stal","family":"Shrestha","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min-Jeong","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Eldridge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael L.","family":"Lehmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Frankland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeih-San","family":"Liow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zu-Xi","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Cortes-Salva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay","family":"Telu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioline D.","family":"Henter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan","family":"Gallagher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Hoon","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Megan","family":"Fredericks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chelsie","family":"Poffenberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Tye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanira","family":"Ruiz-Perdomo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda Juarez","family":"Anaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose A.","family":"Montero Santamaria","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert L.","family":"Gladding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sami S.","family":"Zoghbi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Fujita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James D.","family":"Katz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor W.","family":"Pike","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert B.","family":"Innis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,5,2]]},"reference":[{"key":"1804_CR1","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1111\/jnc.13607","volume":"139","author":"DJ DiSabato","year":"2016","unstructured":"DiSabato DJ, Quan N, Godbout JP. Neuroinflammation: the devil is in the details. J Neurochem. 2016;139:136\u201353.","journal-title":"J Neurochem"},{"key":"1804_CR2","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1038\/nrd3295","volume":"9","author":"R Rupprecht","year":"2010","unstructured":"Rupprecht R, Papadopoulos V, Rammes G, Baghai TC, Fan J, Akula N, et al. Translocator protein (18 kDa) (TSPO) as a therapeutic target for neurological and psychiatric disorder. Nat Rev Drug Discov. 2010;9:971\u201388.","journal-title":"Nat Rev Drug Discov"},{"key":"1804_CR3","doi-asserted-by":"publisher","first-page":"874","DOI":"10.1177\/0271678X17742004","volume":"39","author":"G Rizzo","year":"2019","unstructured":"Rizzo G, Veronese M, Tonietto M, Bodini B, Stankoff B, Wimberley C, et al. Generalization of endothelial modelling of TSPO PET imaging: considerations on tracer affinities. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. 2019;39:874\u201385.","journal-title":"Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism"},{"key":"1804_CR4","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1001\/jamaneurol.2016.3764","volume":"74","author":"JM Coughlin","year":"2017","unstructured":"Coughlin JM, Wang Y, Minn I, Bienko N, Ambinder EB, Xu X, et al. Imaging of glial cell activation and white matter integrity in brains of active and recently retired national football league players. JAMA Neurol. 2017;74:67\u201374.","journal-title":"JAMA Neurol"},{"key":"1804_CR5","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1212\/WNL.42.4.811","volume":"42","author":"EW Johnson","year":"1992","unstructured":"Johnson EW, de Lanerolle NC, Kim JH, Sundaresan S, Spencer DD, Mattson RH, et al. \"Central\" and \"peripheral\" benzodiazepine receptors: opposite changes in human epileptogenic tissue. Neurology. 1992;42:811\u20135.","journal-title":"Neurology."},{"issue":"1","key":"1804_CR6","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/S0163-7827(03)00037-7","volume":"43","author":"M Murakami","year":"2004","unstructured":"Murakami M, Kudo I. Recent advances in molecular biology and physiology of the prostaglandin E2-biosynthetic pathway. Prog Lipid Res. 2004;43(1):3\u201335.","journal-title":"Prog Lipid Res"},{"key":"1804_CR7","first-page":"15","volume":"49","author":"LJ Crofford","year":"1997","unstructured":"Crofford LJ. COX-1 and COX-2 tissue expression: implications and predictions. The Journal of rheumatology Supplement. 1997;49:15\u20139.","journal-title":"The Journal of rheumatology Supplement"},{"key":"1804_CR8","doi-asserted-by":"crossref","unstructured":"Kumar JSD, Zanderigo F, Prabhakaran J, Rubin-Falcone H, Parsey RV, Mann JJ. In vivo evaluation of [11C]TMI, a COX-2 selective PET tracer, in baboons. Bioorg Med Chem Lett. 2018;28:3592\u20135.","DOI":"10.1016\/j.bmcl.2018.10.049"},{"key":"1804_CR9","first-page":"1700","volume":"44","author":"EFJ de Vries","year":"2003","unstructured":"de Vries EFJ, van Waarde A, Buursma AR, Vaalburg W. Synthesis and in vivo evaluation of 18F-Desbromo-DuP-697 as a PET tracer for cyclooxygenase-2 expression. J Nucl Med. 2003;44:1700\u20136.","journal-title":"J Nucl Med"},{"key":"1804_CR10","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1002\/jlcr.3160","volume":"57","author":"A Pacelli","year":"2014","unstructured":"Pacelli A, Greenman J, Cawthorne C, Smith G. Imaging COX-2 expression in cancer using PET\/SPECT radioligands: current status and future directions. J Labelled Comp Radiopharm. 2014;57:317\u201322.","journal-title":"J Labelled Comp Radiopharm"},{"key":"1804_CR11","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1186\/s13550-016-0192-9","volume":"6","author":"O Tietz","year":"2016","unstructured":"Tietz O, Wuest M, Marshall A, Glubrecht D, Hamann I, Wang M, et al. PET imaging of cyclooxygenase-2 (COX-2) in a pre-clinical colorectal cancer model. EJNMMI Res. 2016;6:37.","journal-title":"EJNMMI Res"},{"key":"1804_CR12","doi-asserted-by":"crossref","unstructured":"Cortes M, Shrestha S, Singh P, Morse CL, Jenko KJ, Montero Santamaria JA, et al. 2-(4-Methylsulfonylphenyl)pyrimidines as prospective radioligands for imaging cyclooxygenase-2 with PET \u2013 synthesis, triage, and radiolabeling. Molecules. 2018;23:pii: E2850.","DOI":"10.3390\/molecules23112850"},{"key":"1804_CR13","doi-asserted-by":"publisher","first-page":"2620","DOI":"10.1021\/acschemneuro.8b00103","volume":"9","author":"S Shrestha","year":"2018","unstructured":"Shrestha S, Singh P, Cortes-Salva MY, Jenko KJ, Ikawa M, Kim MJ, et al. 3-Substituted 1,5-diaryl-1 H-1,2,4-triazoles as prospective PET radioligands for imaging brain COX-1 in monkey. Part 2: selection and evaluation of [11C]PS13 for quantitative imaging. ACS Chem Neurosci. 2018;9:2620\u20137.","journal-title":"ACS Chem Neurosci"},{"key":"1804_CR14","doi-asserted-by":"publisher","first-page":"2610","DOI":"10.1021\/acschemneuro.8b00102","volume":"9","author":"P Singh","year":"2018","unstructured":"Singh P, Shrestha S, Cortes-Salva MY, Jenko KJ, Zoghbi SS, Morse CL, et al. 3-Substituted 1,5-diaryl-1H-1,2,4-triazoles as prospective PET radioligands for imaging brain COX-1 in monkey. Part 1: synthesis and pharmacology. ACS Chem Neurosci. 2018;9:2610\u20139.","journal-title":"ACS Chem Neurosci"},{"key":"1804_CR15","doi-asserted-by":"publisher","first-page":"1907","DOI":"10.2967\/jnumed.118.211144","volume":"59","author":"MJ Kim","year":"2018","unstructured":"Kim MJ, Shrestha S, Cortes M, Singh P, Morse CL, Liow JS, et al. Evaluation of two potent and selective PET radioligands to image COX-1 and COX-2 in rhesus monkeys. J Nucl Med. 2018;59:1907\u201312.","journal-title":"J Nucl Med"},{"key":"1804_CR16","doi-asserted-by":"publisher","first-page":"1095","DOI":"10.1172\/JCI117060","volume":"93","author":"LJ Crofford","year":"1994","unstructured":"Crofford LJ, Wilder RL, Ristimaki AP, Sano H, Remmers EF, Epps HR, et al. Cyclooxygenase-1 and -2 expression in rheumatoid synovial tissues. Effects of interleukin-1 beta, phorbol ester, and corticosteroids. J Clin Invest. 1994;93:1095\u2013101.","journal-title":"J Clin Invest"},{"key":"1804_CR17","doi-asserted-by":"publisher","first-page":"2569","DOI":"10.1002\/art.27584","volume":"62","author":"D Aletaha","year":"2010","unstructured":"Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO, et al. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology\/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010;62:2569\u201381.","journal-title":"Arthritis Rheum"},{"key":"1804_CR18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/jcbfm.2011.147","volume":"32","author":"DR Owen","year":"2012","unstructured":"Owen DR, Yeo AJ, Gunn RN, Song K, Wadsworth G, Lewis A, et al. An 18-kDa translocator protein (TSPO) polymorphism explains differences in binding affinity of the PET radioligand PBR28. Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism. 2012;32:1\u20135.","journal-title":"Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism"},{"key":"1804_CR19","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1021\/jm0707370","volume":"51","author":"E Briard","year":"2008","unstructured":"Briard E, Zoghbi SS, Imaizumi M, Gourley JP, Shetty HU, Hong J, et al. Synthesis and evaluation in monkey of two sensitive 11C-labeled aryloxyanilide ligands for imaging brain peripheral benzodiazepine receptors in vivo. J Med Chem. 2008;51:17\u201330.","journal-title":"J Med Chem"},{"key":"1804_CR20","first-page":"520","volume":"47","author":"SS Zoghbi","year":"2006","unstructured":"Zoghbi SS, Shetty HU, Ichise M, Fujita M, Imaizumi M, Liow JS, et al. PET imaging of the dopamine transporter with 18F-FECNT: a polar radiometabolite confounds brain radioligand measurements. J Nucl Med. 2006;47:520\u20137.","journal-title":"J Nucl Med"},{"key":"1804_CR21","doi-asserted-by":"publisher","first-page":"1014","DOI":"10.1002\/jps.2600830718","volume":"83","author":"MS Gandelman","year":"1994","unstructured":"Gandelman MS, Baldwin RM, Zoghbi SS, Zea-Ponce Y, Innis RB. Evaluation of ultrafiltration for the free-fraction determination of single photon emission computed tomography (SPECT) radiotracers: beta-CIT, IBF, and iomazenil. J Pharm Sci. 1994;83:1014\u20139.","journal-title":"J Pharm Sci"},{"key":"1804_CR22","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1021\/cn500138n","volume":"5","author":"P Zanotti-Fregonara","year":"2014","unstructured":"Zanotti-Fregonara P, Zhang Y, Jenko KJ, Gladding RL, Zoghbi SS, Fujita M, et al. Synthesis and evaluation of translocator 18 kDa protein (TSPO) positron emission tomography (PET) radioligands with low binding sensitivity to human single nucleotide polymorphism rs6971. ACS Chem Neurosci. 2014;5:963\u201371.","journal-title":"ACS Chem Neurosci"},{"key":"1804_CR23","doi-asserted-by":"publisher","first-page":"4506","DOI":"10.1021\/jm201703k","volume":"55","author":"S Castellano","year":"2012","unstructured":"Castellano S, Taliani S, Milite C, Pugliesi I, Da Pozzo E, Rizzetto E, et al. Synthesis and biological evaluation of 4-phenylquinazoline-2-carboxamides designed as a novel class of potent ligands of the translocator protein. J Med Chem. 2012;55:4506\u201310.","journal-title":"J Med Chem"},{"key":"1804_CR24","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1038\/jcbfm.2009.205","volume":"30","author":"A Martin","year":"2010","unstructured":"Martin A, Boisgard R, Theze B, Van Camp N, Kuhnast B, Damont A, et al. Evaluation of the PBR\/TSPO radioligand [18F]DPA-714 in a rat model of focal cerebral ischemia. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. 2010;30:230\u201341.","journal-title":"Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism"},{"key":"1804_CR25","doi-asserted-by":"publisher","first-page":"1437","DOI":"10.1242\/jcs.01737","volume":"118","author":"J-S Cadieux","year":"2005","unstructured":"Cadieux J-S, Leclerc P, St-Onge M, Dussault A-A, Laflamme C, Picard S, et al. Potentiation of neutrophil cyclooxygenase-2 by adenosine: an early anti-inflammatory signal. J Cell Sci. 2005;118:1437\u201347.","journal-title":"J Cell Sci"},{"key":"1804_CR26","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1186\/s13550-018-0401-9","volume":"8","author":"EM Richards","year":"2018","unstructured":"Richards EM, Zanotti-Fregonara P, Fujita M, Newman L, Farmer C, Ballard ED, et al. PET radioligand binding to translocator protein (TSPO) is increased in unmedicated depressed subjects. EJNMMI Res. 2018;8:57.","journal-title":"EJNMMI Res"},{"key":"1804_CR27","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1002\/art.30655","volume":"64","author":"YY Gent","year":"2012","unstructured":"Gent YY, Voskuyl AE, Kloet RW, van Schaardenburg D, Hoekstra OS, Dijkmans BA, et al. Macrophage positron emission tomography imaging as a biomarker for preclinical rheumatoid arthritis: findings of a prospective pilot study. Arthritis Rheum. 2012;64:62\u20136.","journal-title":"Arthritis Rheum"},{"key":"1804_CR28","first-page":"638","volume":"297","author":"SK Paulson","year":"2001","unstructured":"Paulson SK, Vaughn MB, Jessen SM, Lawal Y, Gresk CJ, Yan B, et al. Pharmacokinetics of celecoxib after oral administration in dogs and humans: effect of food and site of absorption. J Pharmacol Exp Ther. 2001;297:638\u201345.","journal-title":"J Pharmacol Exp Ther"},{"key":"1804_CR29","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1007\/s11307-016-0984-3","volume":"19","author":"S Sridharan","year":"2017","unstructured":"Sridharan S, Lepelletier FX, Trigg W, Banister S, Reekie T, Kassiou M, et al. Comparative evaluation of three TSPO PET radiotracers in an LPS-induced model of mild neuroinflammation in rats. Mol Imaging Biol. 2017;19:77\u201389.","journal-title":"Mol Imaging Biol"},{"key":"1804_CR30","doi-asserted-by":"publisher","first-page":"12468","DOI":"10.1073\/pnas.1511003112","volume":"112","author":"CM Sandiego","year":"2015","unstructured":"Sandiego CM, Gallezot JD, Pittman B, Nabulsi N, Lim K, Lin SF, et al. Imaging robust microglial activation after lipopolysaccharide administration in humans with PET. Proc Natl Acad Sci U S A. 2015;112:12468\u201373.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"1804_CR31","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/0006-8993(95)01474-8","volume":"25","author":"CD Breder","year":"1996","unstructured":"Breder CD, Saper CB. Expression of inducible cyclooxygenase mRNA in the mouse brain after systematic administration of bacterial lipopolysaccharide. Brain Res. 1996;25:64\u20139.","journal-title":"Brain Res"},{"key":"1804_CR32","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1002\/jnr.23317","volume":"92","author":"Y An","year":"2014","unstructured":"An Y, Belevych N, Wang Y, Zhang H, Herschman H, Chen Q, et al. Neuronal and nonneuronal COX-2 expression confers neurotoxic and neuroprotective phenotypes in response to excitotoxin challenge. J Neurosci Res. 2014;92:486\u201395.","journal-title":"J Neurosci Res"},{"key":"1804_CR33","doi-asserted-by":"publisher","first-page":"1234","DOI":"10.1111\/epi.14083","volume":"59","author":"DL Nguyen","year":"2018","unstructured":"Nguyen DL, Wimberley C, Truillet C, Jego B, Caille F, Pottier G, et al. Longitudinal positron emission tomography imaging of glial cell activation in a mouse model of mesial temporal lobe epilepsy: toward identification of optimal treatment windows. Epilepsia. 2018;59:1234\u201344.","journal-title":"Epilepsia."},{"key":"1804_CR34","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1016\/j.plipres.2007.01.001","volume":"46","author":"YJ Kang","year":"2007","unstructured":"Kang YJ, Mbonye UR, DeLong CJ, Wada M, Smith WL. Regulation of intracellular cyclooxygenase levels by gene transcription and protein degradation. Prog Lipid Res. 2007;46:108\u201325.","journal-title":"Prog Lipid Res"},{"key":"1804_CR35","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1007\/s12975-012-0152-2","volume":"3","author":"RF Keep","year":"2012","unstructured":"Keep RF, Hua Y, Xi G. Brain water content. A misunderstood measurement? Transl Stroke Res. 2012;3:263\u20135.","journal-title":"Transl Stroke Res"},{"key":"1804_CR36","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1093\/rheumatology\/38.3.202","volume":"38","author":"G Steiner","year":"1999","unstructured":"Steiner G, Tohidast-Akrad M, Witzmann G, Vesely M, Studnicka-Benke A, Gal A, et al. Cytokine production by synovial T cells in rheumatoid arthritis. Rheumatology. 1999;38:202\u201313.","journal-title":"Rheumatology."},{"key":"1804_CR37","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1002\/art.1780400206","volume":"40","author":"PP Tak","year":"1997","unstructured":"Tak PP, Smeets TJ, Daha MR, Kluin PM, Meijers KA, Brand R, et al. Analysis of the synovial cell infiltrate in early rheumatoid synovial tissue in relation to local disease activity. Arthritis Rheum. 1997;40:217\u201325.","journal-title":"Arthritis Rheum"},{"key":"1804_CR38","doi-asserted-by":"publisher","first-page":"3350","DOI":"10.1002\/art.23955","volume":"58","author":"CJ van der Laken","year":"2008","unstructured":"van der Laken CJ, Elzinga EH, Kropholler MA, Molthoff CF, van der Heijden JW, Maruyama K, et al. Noninvasive imaging of macrophages in rheumatoid synovitis using 11C-(R)-PK11195 and positron emission tomography. Arthritis Rheum. 2008;58:3350\u20135.","journal-title":"Arthritis Rheum"},{"key":"1804_CR39","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.2967\/jnumed.117.202200","volume":"59","author":"RK Narayan","year":"2018","unstructured":"Narayan RK, Owen DR, Mandhair H, Smyth E, Carlucci F, Saleem A, et al. Translocator protein as an imaging marker of macrophage and stromal activation in rheumatoid arthritis pannus. J Nucl Med. 2018;59:1125\u201332.","journal-title":"J Nucl Med"},{"key":"1804_CR40","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1073\/pnas.1517642113","volume":"113","author":"NS Kirkby","year":"2016","unstructured":"Kirkby NS, Chan MV, Zaiss AK, Garcia-Vaz E, Jiao J, Berglund LM, et al. Systematic study of constitutive cyclooxygenase expression: role of NF-kB and NFAT transcriptional pathways. Proc Natl Acad Sci U S A. 2016;113:434\u20139.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"1804_CR41","doi-asserted-by":"publisher","first-page":"3743","DOI":"10.1111\/j.1582-4934.2008.00430.x","volume":"13","author":"N Zidar","year":"2009","unstructured":"Zidar N, Odar K, Glavac D, Jerse M, Zupanc T, Stajer D. Cyclooxygenase in normal human tissues\u2014is COX-1 really a constitutive isoform, and COX-2 an inducible isoform. J Cell Mol Med. 2009;13:3743\u201363.","journal-title":"J Cell Mol Med"},{"key":"1804_CR42","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1006\/bbrc.1998.9981","volume":"254","author":"Y Kitamura","year":"1999","unstructured":"Kitamura Y, Shimohama S, Koike H, Kakimura J, Matsuoka Y, Nomura Y, et al. Increased expression of cyclooxygenases and peroxisome proliferator-activated receptor-gamma in Alzheimer\u2019s disease brains. Biochem Biophys Res Commun. 1999;254:582\u20136.","journal-title":"Biochem Biophys Res Commun"},{"key":"1804_CR43","doi-asserted-by":"publisher","first-page":"577000","DOI":"10.1016\/j.jneuroim.2019.577000","volume":"334","author":"A Forsberg","year":"2019","unstructured":"Forsberg A, Lampa J, Estelius J, Cervenka S, Farde L, Halldin C, et al. Disease activity in rheumatoid arthritis is inversely related to cerebral TSPO binding assessed by [11C]PBR28 positron emission tomography. J Neuroimmunol. 2019;334:577000.","journal-title":"J Neuroimmunol"},{"key":"1804_CR44","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1038\/nn.4475","volume":"20","author":"M Prinz","year":"2017","unstructured":"Prinz M, Priller J. The role of peripheral immune cells in the CNS in steady state and disease. Nat Neurosci. 2017;20:136\u201344.","journal-title":"Nat Neurosci"}],"container-title":["Journal of Neuroinflammation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-020-01804-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12974-020-01804-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-020-01804-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,5,3]],"date-time":"2021-05-03T13:12:19Z","timestamp":1620047539000},"score":1,"resource":{"primary":{"URL":"https:\/\/jneuroinflammation.biomedcentral.com\/articles\/10.1186\/s12974-020-01804-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,2]]},"references-count":44,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["1804"],"URL":"https:\/\/doi.org\/10.1186\/s12974-020-01804-6","relation":{},"ISSN":["1742-2094"],"issn-type":[{"value":"1742-2094","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,2]]},"assertion":[{"value":"16 January 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 April 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 May 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Written informed consent was obtained from all participants, in accordance with the National Institutes of Health (NIH) Institutional Review Board (Protocol 19-M-0079 and NCT03912428). All procedures involving animals were approved by the NIMH Animal Care and Use Committee and complied with the Institute of Medicine Guide for the Care and Use of Laboratory Animals. This information is stated in the Methods section of the paper.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Consent was obtained from all participants and the investigators have retained copies of all consent forms.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"140"}}