{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T10:08:43Z","timestamp":1778407723991,"version":"3.51.4"},"reference-count":24,"publisher":"Brieflands","issue":"1","license":[{"start":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T00:00:00Z","timestamp":1772496000000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["brieflands.com"],"crossmark-restriction":false},"short-container-title":["Iran J Pharm Res"],"abstract":"<jats:p>Background: Ischemic stroke triggers a strong neuroinflammatory response involving cytokines, which are fundamentally involved in tissue damage and repair. Objectives: The present study was designed to investigate the therapeutic potential of miR-146a-enriched extracellular vesicles derived from bone marrow mesenchymal stem cells (BMSC-EVs) in a rat model of middle cerebral artery occlusion (MCAO). Methods: miR-146a was transfected into BMSCs using Lipofectamine 3000. Extracellular vesicles (EVs) were isolated from transfected BMSCs using ultracentrifugation. Thirty rats were randomly assigned to three groups (n = 10 per group): (1) Control (received FBS), (2) miR-control EVs (miR-NC), and (3) miR-146a-enriched EVs, administered intravenously post-ischemia. Neurological deficits were evaluated with the Bederson score, and cytokine levels, including tumor necrosis factor-\u03b1 (TNF-\u03b1), interferon-\u03b3 (IFN-\u03b3), interleukin (IL)-6, IL-10, as well as transforming growth factor \u03b2 (TGF-\u03b2), were measured in splenocyte culture and brain tissues using enzyme-linked immunoassay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR), respectively. The expression of Interleukin-1 Receptor-Associated Kinase 1 (IRAK1), Tumor Necrosis Factor Receptor-Associated Factor 6 (TRAF6), and nuclear factor kappa B (NF-\u03baB) was also measured using RT-PCR. Results: Results showed that EVs enriched in miR-146a significantly decreased pro-inflammatory cytokines, TNF-\u03b1, IFN-\u03b3, and IL-6, and increased anti-inflammatory markers, IL-10 and TGF-\u03b2, when compared with miR-control EVs and FBS-treated groups. miR-146a-EV-treated rats also displayed better Bederson scores, which reflected better neurological recovery. Results also demonstrated that miR-146a-enriched EVs downregulated IRAK1, TRAF6, and NF-\u03baB signaling in ischemic brain tissue. Conclusions: These results indicate that miR-146a overexpression in BMSC-EVs can significantly inhibit neuroinflammation and promote functional improvement in ischemic stroke models, supporting its targeted therapeutic potential.<\/jats:p>","DOI":"10.5812\/ijpr-167245","type":"journal-article","created":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T09:44:30Z","timestamp":1778406270000},"update-policy":"https:\/\/doi.org\/10.5812\/crossmark_update_policy","source":"Crossref","is-referenced-by-count":0,"title":["miR-146a-Enriched Extracellular Vesicles Attenuate Neuroinflammation and Promote Recovery After Ischemic Stroke"],"prefix":"10.5812","volume":"25","author":[{"given":"Nana","family":"Hao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"FuHua","family":"Gong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"3819","published-online":{"date-parts":[[2026,4,15]]},"reference":[{"key":"key-A167245REF1-1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.l6983"},{"key":"key-A167245REF2-2","doi-asserted-by":"publisher","DOI":"10.1177\/2165079916665400"},{"key":"key-A167245REF3-3","doi-asserted-by":"publisher","DOI":"10.1159\/000525822"},{"key":"key-A167245REF4-4","doi-asserted-by":"publisher","DOI":"10.1007\/s11910-023-01282-2"},{"key":"key-A167245REF5-5","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines9060667"},{"key":"key-A167245REF6-6","doi-asserted-by":"publisher","DOI":"10.1016\/j.jddst.2024.105430"},{"key":"key-A167245REF7-7","doi-asserted-by":"publisher","DOI":"10.1007\/s13346-019-00645-y"},{"key":"key-A167245REF8-8","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12071852"},{"key":"key-A167245REF9-9","doi-asserted-by":"publisher","DOI":"10.1186\/s41544-019-0024-y"},{"key":"key-A167245REF10-10","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2020.00311"},{"key":"key-A167245REF11-11","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-022-02985-y"},{"key":"key-A167245REF12-12","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-022-03100-x"},{"key":"key-A167245REF13-13","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.391194"},{"key":"key-A167245REF14-14","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-023-03375-8"},{"key":"key-A167245REF15-15","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2016.11.011"},{"key":"key-A167245REF16-16","doi-asserted-by":"publisher","DOI":"10.1161\/01.str.20.1.84"},{"key":"key-A167245REF17-17","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.29721"},{"key":"key-A167245REF18-18","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2018.00845"},{"key":"key-A167245REF19-19","doi-asserted-by":"publisher","DOI":"10.1161\/01.str.17.3.472"},{"key":"key-A167245REF20-20","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2019.00712"},{"key":"key-A167245REF21-21","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01912"},{"key":"key-A167245REF22-22","doi-asserted-by":"publisher","DOI":"10.4252\/wjsc.v12.i12.1474"},{"key":"key-A167245REF23-23","doi-asserted-by":"publisher","DOI":"10.4172\/2167-0501.1000213"},{"key":"key-A167245REF24-24","doi-asserted-by":"publisher","DOI":"10.1186\/s12987-018-0104-7"}],"container-title":["Iranian Journal of Pharmaceutical Research"],"original-title":[],"link":[{"URL":"https:\/\/brieflands.com\/journals\/ijpr\/articles\/167245","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/brieflands.com\/journals\/ijpr\/articles\/167245","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T09:44:31Z","timestamp":1778406271000},"score":1,"resource":{"primary":{"URL":"https:\/\/brieflands.com\/journals\/ijpr\/articles\/167245"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,15]]},"references-count":24,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,4,15]]}},"alternative-id":["0cd370512436d56987cd8076e4bbf3a479d19b1e"],"URL":"https:\/\/doi.org\/10.5812\/ijpr-167245","relation":{},"ISSN":["1726-6890"],"issn-type":[{"value":"1726-6890","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,15]]}}}