{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T20:22:41Z","timestamp":1790108561503,"version":"4.0.1"},"reference-count":62,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T00:00:00Z","timestamp":1656460800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Multicellular crosstalk within the brain tissue has been suggested to play a critical role in maintaining cerebral vascular homeostasis. Exosomes (EXs) mediated cell\u2013cell communication, but its role in cerebral ischemic injury is largely unknown. Rab27a is one of the major genes controlling EX release. Here, we explored the role of Rab27a in regulating brain EXs secretion, and the effects of Rab27a\u2010mediated EXs on ischemia evoked cerebral vascular disruption and brain injury.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Cerebral ischemia was induced in Rab27a knockout (Rab27a<jats:sup>\u2212\/\u2212<\/jats:sup>) and wide type (WT) mice by transient middle cerebral artery occlusion (tMCAO). Differential gene expression analysis was performed in ischemic brain tissue by using mRNA sequencing. EXs isolated from brain tissue of Rab27a<jats:sup>\u2212\/\u2212<\/jats:sup> and WT mice (EX<jats:sup>WT<\/jats:sup> or EX<jats:sup>Rab27a\u2212\/\u2212<\/jats:sup>) were pre\u2010administrated into tMCAO operated Rab27a<jats:sup>\u2212\/\u2212<\/jats:sup> mice or oxygen and glucose deprivation (OGD) treated primary brain vascular endothelial cells (ECs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We demonstrated that Rab27a expression in the peri\u2010infarct area of brain was significantly elevated, which was associated with local elevation in EXs secretion. Rab27a deficiency dramatically decreased the level of EXs in brain tissue of normal and tMCAO\u2010treated mice, and Rab27a<jats:sup>\u2212\/\u2212<\/jats:sup> mice displayed an increase in infarct volume and NDS, and a decrease in cMVD and CBF following tMCAO. Pre\u2010infusion of EX<jats:sup>WT<\/jats:sup> increased the brain EXs levels in the tMCAO operated Rab27a<jats:sup>\u2212\/\u2212<\/jats:sup> mice, accompanied with an increase in cMVD and CBF, and a decrease in infarct volume, NDS, ROS production, and apoptosis. The effects of EX<jats:sup>Rab27a\u2212\/\u2212<\/jats:sup> infusion were much diminished although in a dose\u2010dependent manner. In OGD\u2010treated ECs, EX<jats:sup>Rab27a\u2212\/\u2212<\/jats:sup> showed less effectivity than EX<jats:sup>WT<\/jats:sup> in decreasing ROS overproduction and apoptosis, paralleling with down\u2010regulated expression of NOX2 and cleaved caspase\u20103.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study demonstrates that Rab27a controls brain EXs secretion and functions, contributing to cerebral vascular protection from ischemic insult by preventing oxidative stress and apoptosis via down\u2010regulating NOX2 and cleaved caspase\u20103 expression.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.13902","type":"journal-article","created":{"date-parts":[[2022,6,30]],"date-time":"2022-06-30T06:40:28Z","timestamp":1656571228000},"page":"1596-1612","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Rab27a\u2010dependent exosomes protect against cerebral ischemic injury by reducing 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