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As a potential mechanism, surplus salt intake primes macrophages towards a proinflammatory phenotype. In this study, whether HSD could blunt the efferocytic capability of macrophages after ischemic stroke, thus exacerbating post-stroke neural inflammation, was investigated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Wild-type male C57BL\/6 mice were fed with fodder containing 8% sodium chloride for 4 weeks and subjected to transient middle cerebral occlusion (tMCAO). Disease severity, macrophage polarization as well as efferocytic capability were evaluated. Bone marrow-derived macrophages were cultured in vitro, and the impact of high salinity on their efferocytic activity, as well as their expression of phagocytic molecules, were analyzed. The relationships among sodium concentration, macrophage phenotype, and disease severity in AIS patients were explored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>HSD-fed mice displayed increased infarct volume and aggravated neurological deficiency. Mice fed with HSD suffered exacerbated neural inflammation as shown by higher inflammatory mediator expression and immune cell infiltration levels. Infiltrated macrophages within stroke lesions in HSD-fed mice exhibited a shift towards proinflammatory phenotype and impaired efferocytic capability. As assessed with a PCR array, the expression of triggering receptor expressed on myeloid cells 2 (TREM2), a receptor relevant to phagocytosis, was downregulated in high-salt-treated bone marrow-derived macrophages. Enhancement of TREM2 signaling restored the efferocytic capacity and cellular inflammation resolution of macrophages in a high salinity environment in vitro and in vivo. A high concentration of urine sodium in AIS patients was found to be correlated with lower TREM2 expression and detrimental stroke outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>HSD inhibited the efferocytic capacity of macrophages by downregulating TREM2 expression, thus impeding inflammation resolution after ischemic stroke. Enhancing TREM2 signaling in monocytes\/macrophages could be a promising therapeutic strategy to enhance efferocytosis and promote post-stroke inflammation resolution.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12974-021-02144-9","type":"journal-article","created":{"date-parts":[[2021,4,12]],"date-time":"2021-04-12T07:03:22Z","timestamp":1618211002000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["High-salt diet downregulates TREM2 expression and blunts efferocytosis of macrophages after acute ischemic stroke"],"prefix":"10.1186","volume":"18","author":[{"given":"Mengyan","family":"Hu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinyao","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuejiao","family":"Men","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shisi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobo","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danli","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanxin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingjun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2118-0368","authenticated-orcid":false,"given":"Zhengqi","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,4,12]]},"reference":[{"issue":"2","key":"2144_CR1","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1159\/000352052","volume":"36","author":"Y Kono","year":"2013","unstructured":"Kono Y, Yamada S, Yamaguchi J, Hagiwara Y, Iritani N, Ishida S, et al. 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All participants had signed the informed consent according to the principles illustrated in the Declaration of Helsinki. All animal experiments were approved by The Third Affiliated Hospital of Sun Yat-sen University and performed following the Guide for the Care and Use of Laboratory Animals and Stroke Treatment.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"We have obtained consent to publish from the participant to report individual patient data.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"90"}}