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As a linkage between innate and adaptive immunity, interleukin-17\u2009A (IL-17\u2009A) secreted from gamma delta (\u03b3\u03b4) T cells has detrimental roles in the pathogenesis of acute ischemic stroke. However, to date, the long-term actions of IL-17\u2009A after stroke have not been investigated. Here, we found that IL-17\u2009A showed two distinct peaks of expression in the ischemic hemisphere: the first occurring within 3 days and the second on day 28 after stroke. Our data also showed that astrocyte was the major cellular source of IL-17\u2009A that maintained and augmented subventricular zone (SVZ) neural precursor cells (NPCs) survival, neuronal differentiation, and subsequent synaptogenesis and functional recovery after stroke. IL-17\u2009A also promoted neuronal differentiation in cultured NPCs from the ischemic SVZ. Furthermore, our <jats:italic>in vitro<\/jats:italic> data revealed that in primary astrocyte cultures activated astrocytes released IL-17\u2009A via p38 mitogen-activated protein kinase (MAPK). Culture media from reactive astrocytes increased neuronal differentiation of NSCs <jats:italic>in vitro<\/jats:italic>. Blockade of IL-17\u2009A with neutralizing antibody prevented this effect. In addition, after screening for multiple signaling pathways, we revealed that the p38 MAPK\/calpain 1 signaling pathway was involved in IL-17\u2009A-mediated neurogenesis <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic>. Thus, our results reveal a previously uncharacterized property of astrocytic IL-17\u2009A in the maintenance and augment of survival and neuronal differentiation of NPCs, and subsequent synaptogenesis and spontaneous recovery after ischemic stroke.<\/jats:p>","DOI":"10.1038\/cddis.2015.284","type":"journal-article","created":{"date-parts":[[2016,6,24]],"date-time":"2016-06-24T14:24:17Z","timestamp":1466778257000},"page":"e2273-e2273","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":101,"title":["Critical role of astrocytic interleukin-17\u2009A in post-stroke survival and neuronal differentiation of neural precursor cells in adult mice"],"prefix":"10.1038","volume":"7","author":[{"given":"Y","family":"Lin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J-C","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C-Y","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A F","family":"Abdelgawad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S-L","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S-Y","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,6,23]]},"reference":[{"key":"BFcddis2015284_CR1","doi-asserted-by":"crossref","first-page":"1612","DOI":"10.1016\/S0140-6736(08)60694-7","volume":"371","author":"GA Donnan","year":"2008","unstructured":"Donnan GA, Fisher M, Macleod M, Davis SM . 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