{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T04:49:38Z","timestamp":1782276578979,"version":"3.54.5"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Hemorrhagic transformation (HT) following reperfusion therapy is associated with poor outcomes in patients with acute ischemic stroke. Here, we determined the role of microRNA-383-5p (miR-383-5p) in alleviating HT-associated injury using models of middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation\/reoxygenation (OGD\/R).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Two hundred and five hyperglycemic rats were used to establish a model of HT induced by mechanical recanalization after 5 hours of MCAO, followed by 3 and 6 hours of recanalization; then, miR-383-5p agomir was administered intravenously before recanalization. Analysis involved brain water content; hemorrhage severity; infarct volume; blood-brain barrier (BBB) disruption; neuronal apoptosis, reactive oxygen species (ROS) production; along with the expression levels of miR-383-5p, NADPH oxidase 4 (NOX4), interleukin 1 beta (IL-1\u03b2), and BBB-associated proteins. The expression of miR-383-5p and NOX4 was also evaluated in neurons after OGD\/R, whereas neuronal injury and ROS production were assessed following intervention with miR-383-5p and small interfering RNA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In the MCAO model, intravenous administration of miR-383-5p agomir increased miR-383-5p and suppressed NOX4 upregulation in peri-infarct tissue and in brain microvascular endothelial cells, neurons, and astrocytes, as demonstrated by immunohistochemical fluorescent staining. Increased levels of miR-383-5p alleviated brain edema, infarct volume, and the severity of hemorrhage; reduced ROS overproduction, neuronal apoptosis, and IL-1\u03b2 overexpression in astrocytes; and preserved BBB integrity after mechanical recanalization following ischemia, thereby improving acute neurological outcomes assessed at 3 and 6 hours after recanalization. Following OGD\/R, reduced miR-383-5p and increased NOX4 expression were detected in neurons. Elevated miR-383-5p levels reduced neuronal injury, ROS overproduction, and NOX4 overexpression in OGD\/R-treated neurons. NOX4 was confirmed as a direct target gene of miR-383-5p.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>MiR-383-5p alleviated oxidative stress injury, neuronal apoptosis, inflammation, and preserved BBB integrity by regulating NOX4. Therefore, miR-383-5p represents a potential therapeutic target to reduce HT and improve outcomes during the acute phase of recanalization after endovascular treatment for acute ischemic stroke.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1870493","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T04:43:03Z","timestamp":1782276183000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["MicroRNA-383-5p regulation of NADPH oxidase 4 alleviates hemorrhagic transformation and improves acute outcomes after endovascular recanalization in acute ischemic stroke"],"prefix":"10.3389","volume":"17","author":[{"given":"Qiu-Yi","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University","place":["Guangzhou, China"]},{"name":"RNA Biomedical Institute, Sun Yat-sen Memorial Hospital, Sun Yat-sen University","place":["Guangzhou, China"]},{"name":"Nanhai Translational Innovation Center of Precision Immunology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University","place":["Foshan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wang","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University","place":["Guangzhou, China"]},{"name":"RNA Biomedical Institute, Sun Yat-sen Memorial Hospital, Sun Yat-sen University","place":["Guangzhou, China"]},{"name":"Nanhai Translational Innovation Center of Precision Immunology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University","place":["Foshan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Kun","family":"Zhuang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University","place":["Guangzhou, China"]},{"name":"RNA Biomedical Institute, Sun Yat-sen Memorial Hospital, Sun Yat-sen University","place":["Guangzhou, China"]},{"name":"Nanhai Translational Innovation Center of Precision Immunology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University","place":["Foshan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ze-Xin","family":"Chen","sequence":"additional","affiliation":[{"name":"RNA Biomedical Institute, Sun Yat-sen Memorial Hospital, Sun Yat-sen University","place":["Guangzhou, China"]},{"name":"Nanhai Translational Innovation Center of Precision Immunology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University","place":["Foshan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian-Yu","family":"Chen","sequence":"additional","affiliation":[{"name":"RNA Biomedical Institute, Sun Yat-sen Memorial Hospital, Sun Yat-sen University","place":["Guangzhou, China"]},{"name":"Nanhai Translational Innovation Center of Precision Immunology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University","place":["Foshan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang-Luo","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University","place":["Guangzhou, China"]},{"name":"RNA Biomedical Institute, Sun Yat-sen Memorial Hospital, Sun Yat-sen University","place":["Guangzhou, China"]},{"name":"Nanhai Translational Innovation Center of Precision Immunology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University","place":["Foshan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhong-Song","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University","place":["Guangzhou, China"]},{"name":"RNA Biomedical Institute, Sun Yat-sen Memorial Hospital, Sun Yat-sen University","place":["Guangzhou, China"]},{"name":"Nanhai Translational Innovation Center of Precision Immunology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University","place":["Foshan, China"]},{"name":"Guangdong Province Key Laboratory of Brain Function and Disease, Sun Yat-sen University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1004484","article-title":"Endovascular thrombectomy in acute stroke with a large ischemic core: a systematic review and meta-analysis of randomized controlled trials","volume":"22","author":"Lin","year":"2025","journal-title":"PloS Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-023-01377-1","article-title":"Hemorrhagic conversion of acute ischemic 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