{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T06:36:00Z","timestamp":1775284560479,"version":"3.50.1"},"reference-count":42,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T00:00:00Z","timestamp":1706745600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T00:00:00Z","timestamp":1706745600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,12,30]],"date-time":"2023-12-30T00:00:00Z","timestamp":1703894400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["2020.04442"],"award-info":[{"award-number":["2020.04442"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["2021.06135"],"award-info":[{"award-number":["2021.06135"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002809","name":"Generalitat de Catalunya","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["PID2021-122473OA-I00"],"award-info":[{"award-number":["PID2021-122473OA-I00"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["SAF2017-84283-R"],"award-info":[{"award-number":["SAF2017-84283-R"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100015496","name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas","doi-asserted-by":"publisher","award":["CB06\/05\/2004"],"award-info":[{"award-number":["CB06\/05\/2004"]}],"id":[{"id":"10.13039\/501100015496","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["International Immunopharmacology"],"published-print":{"date-parts":[[2024,2]]},"DOI":"10.1016\/j.intimp.2023.111471","type":"journal-article","created":{"date-parts":[[2024,1,9]],"date-time":"2024-01-09T06:14:10Z","timestamp":1704780850000},"page":"111471","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":16,"special_numbering":"C","title":["Intranasal irbesartan reverts cognitive decline and activates the PI3K\/AKT pathway in an LPS-induced neuroinflammation mice model"],"prefix":"10.1016","volume":"128","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4859-375X","authenticated-orcid":false,"given":"Filipa","family":"Gouveia","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3320-9658","authenticated-orcid":false,"given":"Carla","family":"Fonseca","sequence":"additional","affiliation":[]},{"given":"Ana","family":"Silva","sequence":"additional","affiliation":[]},{"given":"Antoni","family":"Camins","sequence":"additional","affiliation":[]},{"given":"M.","family":"Teresa Cruz","sequence":"additional","affiliation":[]},{"given":"Miren","family":"Ettcheto","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6981-6639","authenticated-orcid":false,"given":"Ana","family":"Fortuna","sequence":"additional","affiliation":[]}],"member":"78","reference":[{"key":"10.1016\/j.intimp.2023.111471_b0005","doi-asserted-by":"crossref","DOI":"10.3390\/ijms23115938","article-title":"An overview of oxidative stress, neuroinflammation and neurodegenerative diseases","volume":"23","author":"Teleanu","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.intimp.2023.111471_b0010","first-page":"1","article-title":"Neuroinflammation in Alzheimer\u2019s disease: current evidence and future directions","author":"Calsolaro","year":"2016","journal-title":"Alzheimer\u2019s Dement"},{"key":"10.1016\/j.intimp.2023.111471_b0015","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1038\/s41380-022-01878-z","article-title":"Neuroinflammation is independently associated with brain network dysfunction in Alzheimer\u2019s disease","volume":"28","author":"Leng","year":"2023","journal-title":"Mol. Psychiatry"},{"key":"10.1016\/j.intimp.2023.111471_b0020","doi-asserted-by":"crossref","DOI":"10.1016\/j.arr.2022.101612","article-title":"Targeting brain renin-angiotensin system for the prevention and treatment of Alzheimer\u2019s disease: past, present and future","volume":"77","author":"Gouveia","year":"2022","journal-title":"Ageing Res. Rev."},{"key":"10.1016\/j.intimp.2023.111471_b0025","doi-asserted-by":"crossref","first-page":"508","DOI":"10.2174\/1570159X15666170720095240","article-title":"Microglia and astrocytes in Alzheimer\u2019s disease: implications for therapy","volume":"16","author":"Fakhoury","year":"2018","journal-title":"Curr. Neuropharmacol."},{"key":"10.1016\/j.intimp.2023.111471_b0030","doi-asserted-by":"crossref","first-page":"3458","DOI":"10.1016\/j.neuron.2022.10.020","article-title":"Microglia states and nomenclature: a field at its crossroads","volume":"110","author":"Paolicelli","year":"2022","journal-title":"Neuron"},{"key":"10.1016\/j.intimp.2023.111471_b0035","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.jneuroim.2009.06.022","article-title":"Systemic lipopolysaccharide (LPS)-induced microglial activation results in different temporal reduction of CD200 and CD200 receptor gene expression in the brain","volume":"214","author":"Masocha","year":"2009","journal-title":"J. Neuroimmunol."},{"key":"10.1016\/j.intimp.2023.111471_b0040","doi-asserted-by":"crossref","first-page":"S91","DOI":"10.3233\/JAD-201106","article-title":"Pharmacological strategies to improve dendritic spines in Alzheimer\u2019s disease","volume":"82","author":"Ettcheto","year":"2021","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"10.1016\/j.intimp.2023.111471_b0045","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1038\/nrn3114","article-title":"Neurovascular pathways to neurodegeneration in Alzheimer\u2019s disease and other disorders","volume":"12","author":"Zlokovic","year":"2012","journal-title":"Nat. Rev. Neurosci."},{"key":"10.1016\/j.intimp.2023.111471_b0050","first-page":"6","article-title":"Cognitive impairment in an experimental model of Parkinson \u0301 s disease","volume":"101","author":"Merlini","year":"2019","journal-title":"Neuron"},{"key":"10.1016\/j.intimp.2023.111471_b0055","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12974-015-0238-3","article-title":"Deferoxamine attenuates lipopolysaccharide-induced neuroinflammation and memory impairment in mice","volume":"12","author":"Zhang","year":"2015","journal-title":"J. Neuroinflammation"},{"key":"10.1016\/j.intimp.2023.111471_b0060","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.neuroscience.2012.04.050","article-title":"Age-dependent neuroinflammatory responses and deficits in long-term potentiation in the hippocampus during systemic inflammation","volume":"216","author":"Liu","year":"2012","journal-title":"Neuroscience"},{"key":"10.1016\/j.intimp.2023.111471_b0065","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1007\/s12035-021-02611-7","article-title":"Implications of phosphoinositide 3-kinase-akt (PI3K-Akt) pathway in the pathogenesis of Alzheimer\u2019s disease","volume":"59","author":"Kumar","year":"2022","journal-title":"Mol. Neurobiol."},{"key":"10.1016\/j.intimp.2023.111471_b0070","doi-asserted-by":"crossref","first-page":"699","DOI":"10.3233\/JAD-2010-091555","article-title":"Vascular risk factors: imaging and neuropathologic correlates","volume":"20","author":"Knopman","year":"2010","journal-title":"J. Alzheimers Dis."},{"key":"10.1016\/j.intimp.2023.111471_b0075","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/S0197-4580(00)00259-1","article-title":"Cortical alterations of angiotensin converting enzyme, angiotensin II and AT1 receptor in Alzheimer\u2019 s dementia","volume":"22","author":"Savaskan","year":"2001","journal-title":"Neurobiol. Aging"},{"key":"10.1016\/j.intimp.2023.111471_b0080","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0206705","article-title":"The association of multiple anti-hypertensive medication classes with Alzheimer\u2019s disease incidence across sex, race, and ethnicity","volume":"13","author":"Barthold","year":"2018","journal-title":"PLoS One"},{"key":"10.1016\/j.intimp.2023.111471_b0085","doi-asserted-by":"crossref","first-page":"943","DOI":"10.3233\/JAD-215231","article-title":"Chronic renin-angiotensin system activation induced neuroinflammation: common mechanisms underlying hypertension and dementia?","volume":"85","author":"Tran","year":"2022","journal-title":"J. Alzheimar\u2019s Dis."},{"key":"10.1016\/j.intimp.2023.111471_b0090","first-page":"6950","article-title":"Angiotensin receptor blockade modulates NF \u03ba B and STAT3 signaling and inhibits glial activation and neuroinflammation better than angiotensin-converting enzyme inhibition","volume":"53","author":"Bhat","year":"2016","journal-title":"Mol Ne."},{"key":"10.1016\/j.intimp.2023.111471_b0095","first-page":"462","article-title":"Analysis of cell viability by the alamarblue assay","volume":"2018","author":"Kumar","year":"2018","journal-title":"Cold Spring Harb Protoc"},{"key":"10.1016\/j.intimp.2023.111471_b0100","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1046\/j.1440-1711.2001.01041.x","article-title":"Granulocyte-macrophage colony-stimulating factor activates the transcription of nuclear factor kappa B and induces the expression of nitric oxide synthase in a skin dendritic cell line","volume":"79","author":"Cruz","year":"2001","journal-title":"Immunol. Cell Biol."},{"key":"10.1016\/j.intimp.2023.111471_b0105","doi-asserted-by":"crossref","first-page":"2531","DOI":"10.1038\/nprot.2013.155","article-title":"Object recognition test in mice","volume":"8","author":"Leger","year":"2013","journal-title":"Nat. Protoc."},{"key":"10.1016\/j.intimp.2023.111471_b0110","first-page":"1","article-title":"The forced swim test as a model of depressive-like behavior","volume":"2015","author":"Yankelevitch-Yahav","year":"2015","journal-title":"J. Vis. Exp."},{"key":"10.1016\/j.intimp.2023.111471_b0115","first-page":"1863","article-title":"Neurotensin downregulates the pro-inflammatory properties of skin dendritic cells and increases epidermal growth factor expression","volume":"2011","author":"da Silva","year":"1813","journal-title":"Biochim. Biophys. Acta - Mol. Cell Res."},{"key":"10.1016\/j.intimp.2023.111471_b0120","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.beproc.2014.05.001","article-title":"Persistence of behaviours in the Forced Swim Test in 3xTg-AD mice at advanced stages of disease","volume":"106","author":"Torres-Lista","year":"2014","journal-title":"Behav. Process."},{"key":"10.1016\/j.intimp.2023.111471_b0125","first-page":"327","article-title":"Behavioral despair in mice: a primary screening test for antidepressants","volume":"229","author":"Porsolt","year":"1977","journal-title":"Arch. Int. Pharmacodyn. Ther."},{"key":"10.1016\/j.intimp.2023.111471_b0130","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1002\/glia.20467","article-title":"Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration","volume":"55","author":"Qin","year":"2007","journal-title":"Glia"},{"key":"10.1016\/j.intimp.2023.111471_b0135","article-title":"Angiotensin AT2 receptor protects against cerebral ischemia-induced neuronal injury","volume":"1\u201325","author":"Li","year":"2005","journal-title":"FASEB J."},{"key":"10.1016\/j.intimp.2023.111471_b0140","doi-asserted-by":"crossref","first-page":"699","DOI":"10.3233\/JAD-2011-110347","article-title":"Associations of anti-hypertensive treatments with Alzheimer\u2019 s disease, vascular dementia, and other dementias","volume":"26","author":"Davies","year":"2014","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"10.1016\/j.intimp.2023.111471_b0145","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.3233\/JAD-150868","article-title":"Enalapril alone or co-administered with losartan rescues cerebrovascular dysfunction, but not mnemonic deficits or amyloidosis in a mouse model of Alzheimer\u2019 s disease","volume":"51","author":"Ongali","year":"2016","journal-title":"J. Alzheimar\u2019s Dis."},{"key":"10.1016\/j.intimp.2023.111471_b0150","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.brainres.2010.07.006","article-title":"Effect of a centrally active angiotensin-converting enzyme inhibitor, perindopril, on cognitive performance in a mouse model of Alzheimer \u2019 s disease","volume":"1352","author":"Yamada","year":"2010","journal-title":"Brain Res."},{"key":"10.1016\/j.intimp.2023.111471_b0155","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/S1474-4422(21)00263-5","article-title":"Safety and efficacy of losartan for the reduction of brain atrophy in clinically diagnosed Alzheimer\u2019s disease (the RADAR trial): a double-blind, randomised, placebo-controlled, phase 2 trial","volume":"20","author":"Kehoe","year":"2021","journal-title":"Lancet Neurol."},{"key":"10.1016\/j.intimp.2023.111471_b0160","doi-asserted-by":"crossref","DOI":"10.1016\/j.intimp.2021.107834","article-title":"Irbesartan suppresses lipopolysaccharide (LPS)-induced blood\u2013brain barrier (BBB) dysfunction by inhibiting the activation of MLCK\/MLC","volume":"98","author":"Yang","year":"2021","journal-title":"Int. Immunopharmacol."},{"key":"10.1016\/j.intimp.2023.111471_b0165","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1742-2094-5-37","article-title":"Neuro-inflammation induced by lipopolysaccharide causes cognitive impairment through enhancement of beta-amyloid generation","volume":"5","author":"Lee","year":"2008","journal-title":"J. Neuroinflammation"},{"key":"10.1016\/j.intimp.2023.111471_b0170","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1161\/HYPERTENSIONAHA.121.17049","article-title":"Blood-brain barrier crossing renin-angiotensin drugs and cognition in the elderly: a meta-analysis","volume":"78","author":"Ho","year":"2021","journal-title":"Hypertension"},{"key":"10.1016\/j.intimp.2023.111471_b0175","doi-asserted-by":"crossref","first-page":"2475","DOI":"10.1007\/s11095-012-0915-1","article-title":"Intranasal treatment of central nervous system dysfunction in humans","volume":"30","author":"Chapman","year":"2013","journal-title":"Pharm. Res."},{"key":"10.1016\/j.intimp.2023.111471_b0180","doi-asserted-by":"crossref","DOI":"10.1016\/j.ijpharm.2019.04.047","article-title":"Nose-to-brain delivery of levetiracetam after intranasal administration to mice","volume":"564","author":"Gon\u00e7alves","year":"2019","journal-title":"Int. J. Pharm."},{"key":"10.1016\/j.intimp.2023.111471_b0185","doi-asserted-by":"crossref","unstructured":"C. Fonseca, M. Ettcheto, J. Bicker, M. Jos, A. Fortuna, Under the umbrella of depression and Alzheimer\u2019s disease physiopathology\u00a0: Can cannabinoids be a dual-pleiotropic therapy\u00a0? \u2606, 90 (2023).","DOI":"10.1016\/j.arr.2023.101998"},{"key":"10.1016\/j.intimp.2023.111471_b0190","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.nbd.2014.04.018","article-title":"Neurobiology of Disease Angiotensin II type 1 receptor blocker losartan prevents and rescues cerebrovascular, neuropathological and cognitive deficits in an Alzheimer disease model","volume":"68","author":"Ongali","year":"2014","journal-title":"Neurobiol. Dis."},{"key":"10.1016\/j.intimp.2023.111471_b0195","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1179\/1743132813Y.0000000295","article-title":"The effects of valsartan on cognitive deficits induced by aluminum trichloride and D -galactose in mice","volume":"36","author":"Yang","year":"2014","journal-title":"Neurol. Res."},{"key":"10.1016\/j.intimp.2023.111471_b0200","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.bbi.2005.04.005","article-title":"Peripheral immune activation by lipopolysaccharide decreases neurotrophins in the cortex and hippocampus in rats","volume":"20","author":"Guan","year":"2006","journal-title":"Brain Behav. Immun."},{"key":"10.1016\/j.intimp.2023.111471_b0205","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fcell.2021.655731","article-title":"The mTOR\u2013autophagy axis and the control of metabolism","volume":"9","author":"Deleyto-Seldas","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"10.1016\/j.intimp.2023.111471_b0210","doi-asserted-by":"crossref","DOI":"10.1016\/j.bbi.2017.04.001","article-title":"Intranasal telmisartan ameliorates brain pathology in five familial Alzheimer\u2019s disease mice","author":"Torika","year":"2017","journal-title":"Brain Behav. Immun."}],"container-title":["International Immunopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1567576923017988?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1567576923017988?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T18:13:03Z","timestamp":1761588783000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1567576923017988"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2]]},"references-count":42,"alternative-id":["S1567576923017988"],"URL":"https:\/\/doi.org\/10.1016\/j.intimp.2023.111471","relation":{},"ISSN":["1567-5769"],"issn-type":[{"value":"1567-5769","type":"print"}],"subject":[],"published":{"date-parts":[[2024,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Intranasal irbesartan reverts cognitive decline and activates the PI3K\/AKT pathway in an LPS-induced neuroinflammation mice model","name":"articletitle","label":"Article Title"},{"value":"International Immunopharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.intimp.2023.111471","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 The Author(s). Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"111471"}}