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Tamoxifen-dependent conditional depletion of TAK1 in microglial cells was induced in\n                      <jats:italic>Cx3cr1<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>creER<\/jats:italic>\n                      <\/jats:sup>\n                      <jats:italic>-Tak1<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>fl\/fl<\/jats:italic>\n                      <\/jats:sup>\n                      mice. The\n                      <jats:italic>cre<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>ER<\/jats:italic>\n                      <\/jats:sup>\n                      -negative\n                      <jats:italic>Tak1<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>fl\/fl<\/jats:italic>\n                      <\/jats:sup>\n                      mice and vehicle-treated (corn oil) mice served as control groups. A transient intraluminal middle cerebral artery occlusion of 30\u00a0min followed by 6\u00a0h and 72\u00a0h of reperfusion was performed in male mice. Oxygen-glucose-deprivation (OGD) was performed with primary cortical glial cell cultures to examine the effect of microglial-specific and general (5Z-7-Oxozeaenol) TAK1 inhibition after different reperfusion times (1\u00a0h, 6\u00a0h, and 72\u00a0h).\n                      <jats:italic>Cx3cr1<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>creER<\/jats:italic>\n                      <\/jats:sup>\n                      <jats:italic>-Tak1<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>fl\/fl<\/jats:italic>\n                      <\/jats:sup>\n                      mice showed reduced infarct sizes and improved neurological outcomes compared to the control group. The mRNA and protein levels of pro-inflammatory\n                      <jats:italic>Il1b<\/jats:italic>\n                      \/IL-1\u03b2 and\n                      <jats:italic>Tnf<\/jats:italic>\n                      \/TNF-\u03b1 in the peri-infarct zones of microglial-specific TAK1-depleted mice were significantly reduced. Furthermore, TAK1 depletion in vitro led to reduced cell death rates after OGD. Moreover, hypoxia-mediated activation of TAK1 and its downstream signalling proteins, JNK and p38, were dampened by microglial TAK1 depletion. In contrast, 5Z-7-Oxozeaenol-induced pharmacological inhibition of TAK1 completely diminished MAPK-signalling including the kinases JNK and p38 in all cells. Microglial TAK1 depletion abrogates post-ischemic neuroinflammation and apoptosis in the acute phase, hence might be considered as a potential target in the treatment of cerebral hypoxia.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key messages<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>\n                            TAK1 is activated after cerebral ischemia and induces MAP kinases p38 and JNK\n                            <jats:italic>.<\/jats:italic>\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Activated TAK1 increases apoptosis rate and the level pro-inflammatory cytokines IL-1\u03b2 and TNF-\u03b1.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Microglial cells seem to be the main source of TAK1-mediated post-ischemic neuroinflammation.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Microglial-specific TAK1-depletion mediates sustainable neuroprotective effects, which might be superior to global TAK1 inhibition.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00109-020-01916-9","type":"journal-article","created":{"date-parts":[[2020,5,7]],"date-time":"2020-05-07T15:02:38Z","timestamp":1588863758000},"page":"833-847","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Microglial-specific depletion of TAK1 is neuroprotective in the acute phase after ischemic stroke"],"prefix":"10.1007","volume":"98","author":[{"given":"Thomas","family":"Zeyen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rozina","family":"Noristani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahin","family":"Habib","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ole","family":"Heinisch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Slowik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Huber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rg B.","family":"Schulz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arno","family":"Reich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5771-216X","authenticated-orcid":false,"given":"Pardes","family":"Habib","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,5,7]]},"reference":[{"issue":"5","key":"1916_CR1","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1038\/nrneurol.2010.36","volume":"6","author":"R-L Chen","year":"2010","unstructured":"Chen R-L, Balami JS, Esiri MM, Chen L-K, Buchan AM (2010) Ischemic stroke in the elderly: an overview of evidence. 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