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Here, we interrogated the relevance of stress\u2010related activities of SorCS2 in the brain by exploring its role in ischemic stroke in mouse models and in patients. Although primarily seen in neurons in the healthy brain, expression of SorCS2 was massively induced in astrocytes surrounding the ischemic core in mice following stroke. Post\u2010stroke induction was likely a result of increased levels of transforming growth factor \u03b21 in damaged brain tissue, inducing\n                    <jats:italic>Sorcs2<\/jats:italic>\n                    gene transcription in astrocytes but not neurons. Induced astrocytic expression of SorCS2 was also seen in stroke patients, substantiating the clinical relevance of this observation. In astrocytes in vitro and in the mouse brain in vivo, SorCS2 specifically controlled release of endostatin, a factor linked to post\u2010stroke angiogenesis. The ability of astrocytes to release endostatin acutely after stroke was lost in mice deficient for SorCS2, resulting in a blunted endostatin response which coincided with impaired vascularization of the ischemic brain. Our findings identified activated astrocytes as a source for endostatin in modulation of post\u2010stroke angiogenesis, and the importance of the sorting receptor SorCS2 in this brain stress response.\n                  <\/jats:p>","DOI":"10.1002\/glia.23778","type":"journal-article","created":{"date-parts":[[2020,1,3]],"date-time":"2020-01-03T05:58:31Z","timestamp":1578031111000},"page":"1304-1316","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["SorCS2 facilitates release of endostatin from astrocytes and controls post\u2010stroke angiogenesis"],"prefix":"10.1002","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7732-0756","authenticated-orcid":false,"given":"Anna R.","family":"Malik","sequence":"first","affiliation":[{"name":"Max\u2010Delbrueck\u2010Center for Molecular Medicine  Berlin Germany"},{"name":"Nencki Institute of Experimental Biology Polish Academy of Sciences  Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet","family":"Lips","sequence":"additional","affiliation":[{"name":"Department of Experimental Neurology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin and Berlin Institute of Health Neurocure Cluster of Excellence  Berlin Germany"},{"name":"Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin Center for Stroke Research Berlin  Berlin Germany"},{"name":"Berlin Institute of Health QUEST Centre for Transforming Biomedical Research  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malgorzata","family":"Gorniak\u2010Walas","sequence":"additional","affiliation":[{"name":"Max\u2010Delbrueck\u2010Center for Molecular Medicine  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diede W. 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