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Although ARDS primarily affects the lung, many ARDS patients also develop neurocognitive impairments. To investigate the connection between the lung and brain during ARDS and the therapeutic potential of SPMs and its derivatives, fat-1 mice were crossbred with RvE1 receptor knockout mice. ARDS was induced in these mice by intratracheal application of lipopolysaccharide (LPS, 10 \u00b5g). Mice were sacrificed at 0 h, 4 h, 24 h, 72 h, and 120 h post inflammation, and effects on the lung, liver, and brain were assessed by RT-PCR, multiplex, immunohistochemistry, Western blot, and LC-MS\/MS. Protein and mRNA analyses of the lung, liver, and hypothalamus revealed LPS-induced lung inflammation increased inflammatory signaling in the hypothalamus despite low signaling in the periphery. Neutrophil recruitment in different brain structures was determined by immunohistochemical staining. Overall, we showed that immune cell trafficking to the brain contributed to immune-to-brain communication during ARDS rather than cytokines. Deficiency in RvE1 receptors and enhanced omega-3 polyunsaturated fatty acid levels (fat-1 mice) affect lung\u2013brain interaction during ARDS by altering profiles of several inflammatory and lipid mediators and glial activity markers.<\/jats:p>","DOI":"10.3390\/ijms241713524","type":"journal-article","created":{"date-parts":[[2023,8,31]],"date-time":"2023-08-31T09:14:41Z","timestamp":1693473281000},"page":"13524","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["n-3 Polyunsaturated Fatty Acids Modulate LPS-Induced ARDS and the Lung\u2013Brain Axis of Communication in Wild-Type versus Fat-1 Mice Genetically Modified for Leukotriene B4 Receptor 1 or Chemerin Receptor 23 Knockout"],"prefix":"10.3390","volume":"24","author":[{"given":"Jessica","family":"Hernandez","sequence":"first","affiliation":[{"name":"Institute of Veterinary Physiology and Biochemistry, Justus Liebig University Giessen, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Sch\u00e4ffer","sequence":"additional","affiliation":[{"name":"Institute of Veterinary Physiology and Biochemistry, Justus Liebig University Giessen, 35392 Giessen, Germany"},{"name":"Excellence Cluster Cardio-Pulmonary Institute (CPI), Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus Liebig University Giessen, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1858-2267","authenticated-orcid":false,"given":"Christiane","family":"Herden","sequence":"additional","affiliation":[{"name":"Institute of Veterinary Pathology, Justus Liebig University Giessen, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabian Johannes","family":"Pflieger","sequence":"additional","affiliation":[{"name":"Institute of Veterinary Physiology and Biochemistry, Justus Liebig University Giessen, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia","family":"Reiche","sequence":"additional","affiliation":[{"name":"Excellence Cluster Cardio-Pulmonary Institute (CPI), Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus Liebig University Giessen, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svenja","family":"K\u00f6rber","sequence":"additional","affiliation":[{"name":"Institute of Veterinary Pathology, Justus Liebig University Giessen, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromu","family":"Kitagawa","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Osaka Institute of Technology, Omiya, Osaka 535-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joelle","family":"Welter","sequence":"additional","affiliation":[{"name":"Institute of Veterinary Physiology and Biochemistry, Justus Liebig University Giessen, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Michels","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Clinical Pharmacy, Philipps University of Marburg, 35032 Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5121-5015","authenticated-orcid":false,"given":"Carsten","family":"Culmsee","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Clinical Pharmacy, Philipps University of Marburg, 35032 Marburg, Germany"},{"name":"Center for Mind Brain and Behavior, Universities Giessen and Marburg, 35032 Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Bier","sequence":"additional","affiliation":[{"name":"Excellence Cluster Cardio-Pulmonary Institute (CPI), Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus Liebig University Giessen, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natascha","family":"Sommer","sequence":"additional","affiliation":[{"name":"Excellence Cluster Cardio-Pulmonary Institute (CPI), Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus Liebig University Giessen, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing X.","family":"Kang","sequence":"additional","affiliation":[{"name":"Laboratory for Lipid Medicine and Technology, Department of Medicine, Massachusetts General Hospital and Harvard Medical, Boston, MA 02129, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6565-2187","authenticated-orcid":false,"given":"Konstantin","family":"Mayer","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Justus Liebig University Giessen, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Hecker","sequence":"additional","affiliation":[{"name":"Excellence Cluster Cardio-Pulmonary Institute (CPI), Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus Liebig University Giessen, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5457-4390","authenticated-orcid":false,"given":"Christoph","family":"Rummel","sequence":"additional","affiliation":[{"name":"Institute of Veterinary Physiology and Biochemistry, Justus Liebig University Giessen, 35392 Giessen, Germany"},{"name":"Center for Mind Brain and Behavior, Universities Giessen and Marburg, 35032 Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1038\/nrn3820","article-title":"Polyunsaturated fatty acids and their metabolites in brain function and disease","volume":"15","author":"Bazinet","year":"2014","journal-title":"Nat. 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