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We investigated whether astrocytic extracellular vesicles (AEVs) regulated by microglia modulate glial scars and improve stroke recovery. We found that peri-infarct glial scars comprised reactive astrocytes with proliferating C3d and decreased S100A10 expression in chronic stroke. In cultured astrocytes, microglia-conditioned media and treatment with P2Y\n                    <jats:sub>1<\/jats:sub>\n                    receptor antagonists increased and reduced the area of S100A10- and C3d-expressing reactive astrocytes, respectively, by suppressing mitogen-activated protein kinase\/nuclear factor-\u03ba\u03b2 (NF-\u03baB)\/tumor necrosis factor-\u03b1 (TNF-\u03b1)\/interleukin-1\u03b2 signaling after oxygen\u2013glucose deprivation. Intracerebral administrations of AEVs enriched miR-146a-5p, downregulated NF-\u03baB, and suppressed TNF-\u03b1 expressions, by transforming reactive astrocytes to those with S100A10 preponderance, causing functional recovery in rats subjected to middle cerebral artery occlusion. Modulating neuroinflammation in post-stroke glial scars could permit axonal outgrowth, thus providing a basis for stroke recovery with neuroprotective AEVs.\n                  <\/jats:p>","DOI":"10.1007\/s12035-023-03629-9","type":"journal-article","created":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T04:02:27Z","timestamp":1694059347000},"page":"1002-1021","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Astrocytic Extracellular Vesicles Regulated by Microglial Inflammatory Responses Improve Stroke Recovery"],"prefix":"10.1007","volume":"61","author":[{"given":"Chikage","family":"Kijima","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiki","family":"Inaba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichiro","family":"Hira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobukazu","family":"Miyamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuo","family":"Yamashiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takao","family":"Urabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobutaka","family":"Hattori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8617-3695","authenticated-orcid":false,"given":"Yuji","family":"Ueno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,9,7]]},"reference":[{"issue":"1","key":"3629_CR1","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1159\/000047856","volume":"169","author":"J Gao","year":"2001","unstructured":"Gao J, Dennis JE, Muzic RF, Lundberg M, Caplan AI (2001) The dynamic in vivo distribution of bone marrow-derived mesenchymal stem cells after infusion. 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