{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T02:28:54Z","timestamp":1793413734604,"version":"4.5.0"},"reference-count":82,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:p>JOURNAL\/nrgr\/04.03\/01300535-202502000-00029\/figure1\/v\/2026-05-04T143158Z\/r\/image-tiff<\/jats:p>\n                  <jats:p>Cerebral edema caused by blood\u2013brain barrier injury after intracerebral hemorrhage is an important factor leading to poor prognosis. Human-induced pluripotent stem cell\u2013derived neural stem cell exosomes (hiPSC\u2013NSC\u2013Exos) have shown potential for brain injury repair in central nervous system diseases. In this study, we explored the impact of hiPSC\u2013NSC\u2013Exos on blood\u2013brain barrier preservation and the underlying mechanism. Our results indicated that intranasal delivery of hiPSC\u2013NSC\u2013Exos mitigated neurological deficits, enhanced blood\u2013brain barrier integrity, and reduced leukocyte infiltration in a mouse model of intracerebral hemorrhage. Additionally, hiPSC\u2013NSC\u2013Exos decreased immune cell infiltration, activated astrocytes, and decreased the secretion of inflammatory cytokines like monocyte chemoattractant protein-1, macrophage inflammatory protein-1\u03b1, and tumor necrosis factor-\u03b1 post\u2013intracerebral hemorrhage, thereby improving the inflammatory microenvironment. RNA sequencing indicated that hiPSC\u2013NSC\u2013Exo activated the PI3K\/AKT signaling pathway in astrocytes and decreased monocyte chemoattractant protein-1 secretion, thereby improving blood\u2013brain barrier integrity. Treatment with the PI3K\/AKT inhibitor LY294002 or the monocyte chemoattractant protein-1 neutralizing agent C1142 abolished these effects. In summary, our findings suggest that hiPSC-NSC-Exos maintains blood\u2013brain barrier integrity, in part by downregulating monocyte chemoattractant protein-1 secretion through activation of the PI3K\/AKT signaling pathway in astrocytes.<\/jats:p>","DOI":"10.4103\/nrr.nrr-d-23-01889","type":"journal-article","created":{"date-parts":[[2024,4,24]],"date-time":"2024-04-24T08:00:33Z","timestamp":1713945633000},"page":"518-532","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":44,"title":["Human-induced pluripotent stem cell\u2013derived neural stem cell exosomes improve blood\u2013brain barrier function after intracerebral hemorrhage by activating astrocytes via PI3K\/AKT\/MCP-1 axis"],"prefix":"10.4103","volume":"20","author":[{"given":"Conglin","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangyuan","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoli","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan","family":"Liao","sequence":"additional","affiliation":[{"name":"School of Medicine, Nankai University, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyu","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xintong","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dai","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongrong","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Tianjin Neurological Institute, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanglian","family":"Chen","sequence":"additional","affiliation":[{"name":"Tianjin Neurological Institute, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8410-7715","authenticated-orcid":false,"given":"Ping","family":"Lei","sequence":"additional","affiliation":[{"name":"Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2024,4,16]]},"reference":[{"key":"R1-20260504","doi-asserted-by":"crossref","first-page":"100118","DOI":"10.1074\/jbc.RA120.015389","article-title":"An endogenous PI3K interactome promoting astrocyte-mediated neuroprotection identifies a novel association with RNA-binding protein ZC3H14","volume":"296","author":"Alqawlaq","year":"2021","journal-title":"J Biol Chem"},{"key":"R2-20260504","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1189\/jlb.68.4.545","article-title":"Monocyte:astrocyte interactions regulate MCP-1 expression in both cell types","volume":"68","author":"Andjelkovic","year":"2000","journal-title":"J Leukoc Biol"},{"key":"R3-20260504","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1002\/jnr.22256","article-title":"Astrocytes protect oligodendrocyte precursor cells via MEK\/ERK and PI3K\/Akt signaling","volume":"88","author":"Arai","year":"2010","journal-title":"J Neurosci Res"},{"key":"R4-20260504","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene ontology: tool for the unification of biology. 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