{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T23:46:53Z","timestamp":1792194413956,"version":"4.4.0"},"reference-count":185,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Frequently underestimated, encephalopathy or delirium are common neurological manifestations associated with sepsis. Brain dysfunction occurs in up to 80% of cases and is directly associated with increased mortality and long-term neurocognitive consequences. Although the central nervous system (CNS) has been classically viewed as an immune-privileged system, neuroinflammation is emerging as a central mechanism of brain dysfunction in sepsis. Microglial cells are major players in this setting. Here, we aimed to discuss the current knowledge on how the brain is affected by peripheral immune activation in sepsis and the role of microglia in these processes. This review focused on the molecular pathways of microglial activity in sepsis, its regulatory mechanisms, and their interaction with other CNS cells, especially with neuronal cells and circuits.<\/jats:p>","DOI":"10.3390\/ph14050416","type":"journal-article","created":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T21:35:39Z","timestamp":1619904939000},"page":"416","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":92,"title":["Neuroinflammation in Sepsis: Molecular Pathways of Microglia Activation"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6170-2485","authenticated-orcid":false,"given":"Carolina","family":"Moraes","sequence":"first","affiliation":[{"name":"Immunopharmacology Lab, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21045-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila","family":"Zaverucha-do-Valle","sequence":"additional","affiliation":[{"name":"National Institute of Infectious Disease Evandro Chagas, Oswaldo Cruz Foundation, Ministry of Health, Rio de Janeiro 21040-360, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2274-3393","authenticated-orcid":false,"given":"Renaud","family":"Fleurance","sequence":"additional","affiliation":[{"name":"UCB Biopharma SRL, 1420 Braine L\u2019Alleud, Belgium"},{"name":"Experimental Neuropathology, Infection, and Epidemiology Department, Institut Pasteur, 75015 Paris, France"},{"name":"Universit\u00e9 de Paris Sciences et Lettres, 75006 Paris Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarek","family":"Sharshar","sequence":"additional","affiliation":[{"name":"Experimental Neuropathology, Infection, and Epidemiology Department, Institut Pasteur, 75015 Paris, France"},{"name":"Neuro-Anesthesiology and Intensive Care Medicine, Sainte-Anne Hospital, Paris-Descartes University, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4878-0256","authenticated-orcid":false,"given":"Fernando","family":"Bozza","sequence":"additional","affiliation":[{"name":"National Institute of Infectious Disease Evandro Chagas, Oswaldo Cruz Foundation, Ministry of Health, Rio de Janeiro 21040-360, Brazil"},{"name":"D\u2019Or Institute for Research and Education, Rio de Janeiro 22281-100, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2045-0813","authenticated-orcid":false,"given":"Joana","family":"d\u2019Avila","sequence":"additional","affiliation":[{"name":"Immunopharmacology Lab, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21045-900, Brazil"},{"name":"School of Medicine, Universidade Igua\u00e7u, Rio de Janeiro 26260-045, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1001\/jama.2016.0287","article-title":"The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/S0140-6736(19)32989-7","article-title":"Global, Regional, and National Sepsis Incidence and Mortality, 1990\u20132017: Analysis for the Global Burden of Disease Study","volume":"395","author":"Rudd","year":"2020","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.brainres.2010.07.049","article-title":"Alterations in the Brain Electrical Activity in a Rat Model of Sepsis-Associated Encephalopathy","volume":"1354","author":"Kafa","year":"2010","journal-title":"Brain Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/s12028-019-00703-w","article-title":"Continuous EEG Monitoring in a Consecutive Patient Cohort with Sepsis and Delirium","volume":"32","author":"Nielsen","year":"2020","journal-title":"Neurocrit. 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