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Therapeutic hypothermia (HT) is the only recommended therapy. However, 30% still suffer from neurological deficits. Inflammation is a major hallmark of HI pathophysiology with myeloid cells being key players, participating either in progression or in resolution of injury-induced inflammation. In the present study, we investigated the impact of HT on the temporal and spatial dynamics of microglia\/macrophage polarization after neonatal HI in newborn mice.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Nine-day-old C57BL\/6 mice were exposed to HI through occlusion of the right common carotid artery followed by 1\u00a0h hypoxia. Immediately after HI, animals were cooled for 4\u00a0h or kept at physiological body core temperature. Analyses were performed at 1, 3 and 7\u00a0days post HI. Brain injury, neuronal cell loss, apoptosis and microglia activation were assessed by immunohistochemistry. A broad set of typical genes associated with classical (M1) and alternative (M2) myeloid cell activation was analyzed by real time PCR in ex vivo isolated CD11b<jats:sup>+<\/jats:sup> microglia\/macrophages. Purity and composition of isolated cells was determined by flow cytometry.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Immediate HT significantly reduced HI-induced brain injury and neuronal loss 7\u00a0days post HI, whereas only mild non-significant protection from HI-induced apoptosis and neuronal loss were observed 1 and 3\u00a0days after HI. Microglia activation, i.e., Iba-1 immunoreactivity peaked 3\u00a0days after HI and was not modulated by HT. However, ex vivo isolated CD11b<jats:sup>+<\/jats:sup> cells revealed a strong upregulation of the majority of M1 but also M2 marker genes at day 1, which was significantly reduced by HT and rapidly declined at day 3. HI induced a significant increase in the frequency of peripheral macrophages in sorted CD11b<jats:sup>+<\/jats:sup> cells at day 1, which deteriorated until day 7 and was significantly decreased by HT.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Our data demonstrate that HT-induced neuroprotection is preceded by acute suppression of HI-induced upregulation of inflammatory genes in myeloid cells and decreased infiltration of peripheral macrophages, both representing potential important effector mechanisms of HT.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12974-021-02314-9","type":"journal-article","created":{"date-parts":[[2021,11,13]],"date-time":"2021-11-13T04:41:09Z","timestamp":1636778469000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Hypothermia modulates myeloid cell polarization in neonatal hypoxic\u2013ischemic brain injury"],"prefix":"10.1186","volume":"18","author":[{"given":"Marina","family":"Seitz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"K\u00f6ster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Dzietko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hemmen","family":"Sabir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meray","family":"Serdar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ursula","family":"Felderhoff-M\u00fcser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivo","family":"Bendix","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8132-7459","authenticated-orcid":false,"given":"Josephine","family":"Herz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,11,13]]},"reference":[{"key":"2314_CR1","doi-asserted-by":"publisher","first-page":"67","DOI":"10.5409\/wjcp.v5.i1.67","volume":"5","author":"CE Ahearne","year":"2016","unstructured":"Ahearne CE, Boylan GB, Murray DM. 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