{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T05:59:01Z","timestamp":1770357541755,"version":"3.49.0"},"reference-count":49,"publisher":"S. Karger AG","issue":"9","license":[{"start":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T00:00:00Z","timestamp":1751587200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"},{"start":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T00:00:00Z","timestamp":1751587200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuroendocrinology"],"abstract":"<jats:p>Objective: This study aimed to elucidate the effect and mechanism of hyperoside on blood-brain barrier (BBB) damage in bacterial meningitis (BM) by regulating the microRNA-155 (miR-155)\/brain-derived neurotrophic factor (BDNF) pathway. Methods: A rat model of meningitis was established via intracisternal injection of Streptococcus pneumoniae (SPN), while an in vitro BBB injury model was created by treating human cerebral microvascular endothelial cells (hCMEC\/D3) with lipopolysaccharide (LPS). Hyperoside was administered in both models. Evans blue staining was used to assess BBB permeability in rats. Brain water content was determined using the wet-dry weight method. Transendothelial electrical resistance (TEER) was measured with an endothelial resistance meter. RT-qPCR, Western blotting, and ELISA were conducted to assess the expression of tight junction proteins (ZO-1, Claudin-5, and AQP4) in brain tissues and cell supernatants. ELISA was also used to measure inflammatory cytokines (TNF-\u03b1, IL-1\u03b2, IL-6) in cerebrospinal fluid and cell culture supernatants. Bioinformatics analysis and dual-luciferase reporter assays were employed to predict and validate the regulatory relationship between miR-155 and BDNF. Results: Hyperoside treatment reduced BBB permeability, alleviated brain edema, and suppressed inflammatory cytokine expression in SPN-infected rats. In LPS-induced hCMEC\/D3 cells, hyperoside significantly increased TEER values. Furthermore, hyperoside markedly downregulated miR-155 and upregulated BDNF expression. miR-155 was confirmed to directly target BDNF and negatively regulate its expression in hCMEC\/D3 cells. Importantly, the administration of a miR-155 mimic or BDNF knockdown (sh-BDNF) partially reversed the protective effects of hyperoside on TEER, tight junction protein expression (ZO-1, Claudin-5, AQP4), and inflammatory cytokine levels (TNF-\u03b1, IL-1\u03b2, IL-6) in LPS-induced hCMEC\/D3 cells. Conclusion: Hyperoside mitigates BBB damage in BM via reducing miR-155 expression and upregulating BDNF expression, leading to an increase in tight junction-related protein expression, a reduction in inflammatory factor secretion, and a decrease in BBB permeability. <\/jats:p>","DOI":"10.1159\/000547276","type":"journal-article","created":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T12:17:37Z","timestamp":1751631457000},"page":"704-718","source":"Crossref","is-referenced-by-count":2,"title":["Impact of Hyperoside on the Blood-Brain Barrier in Rats with Bacterial Meningitis through the MicroRNA-155\/Brain-Derived Neurotrophic Factor Pathway"],"prefix":"10.1159","volume":"115","author":[{"given":"Tao","family":"Zhang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Long","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renzhao","family":"Kuang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2025,7,4]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2022.1106596"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2307899120"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics11121843"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2219435120"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24032852"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-022-02651-3"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2021.06.001"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2023.102637"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2024.110276"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.239445"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics15041254"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2023.114317"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-023-02150-4"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01357"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22168946"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2017.05.019"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1186\/s12987-022-00344-w"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.3736\/jcim20060518"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2020.112884"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1080\/13880209.2023.2228379"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-023-01387-8"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-023-01828-z"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2015.3945"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2023.117031"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-019-1716-9"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/120641"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2019.00048"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1007\/s11596-018-1869-2"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.00762"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.1186\/s12987-016-0032-3"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.7150\/thno.71392"},{"key":"ref32","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2016.00009"},{"key":"ref33","doi-asserted-by":"publisher","DOI":"10.1186\/s12887-017-0824-x"},{"key":"ref34","doi-asserted-by":"publisher","DOI":"10.1186\/s13148-023-01573-y"},{"key":"ref35","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-014-1628-x"},{"key":"ref36","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.01065"},{"key":"ref37","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-014-8914-3"},{"key":"ref38","doi-asserted-by":"publisher","DOI":"10.1128\/cmr.00079-21"},{"key":"ref39","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2023-077887"},{"key":"ref40","doi-asserted-by":"publisher","DOI":"10.1038\/d41586-023-00540-0"},{"key":"ref41","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27093009"},{"key":"ref42","doi-asserted-by":"publisher","DOI":"10.1186\/s40779-021-00356-x"},{"key":"ref43","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-021-01374-9"},{"key":"ref44","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2024.156662"},{"key":"ref45","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02751"},{"key":"ref46","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-021-03234-z"},{"key":"ref47","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-018-0599-0"},{"key":"ref48","doi-asserted-by":"publisher","DOI":"10.1016\/j.jphs.2021.02.005"},{"key":"ref49","doi-asserted-by":"publisher","DOI":"10.3389\/pore.2021.629829"}],"container-title":["Neuroendocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/karger.com\/article-pdf\/doi\/10.1159\/000547276","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T16:01:07Z","timestamp":1758556867000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000547276"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,4]]},"references-count":49,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9,22]]},"published-print":{"date-parts":[[2025,9,29]]}},"URL":"https:\/\/doi.org\/10.1159\/000547276","archive":["Portico"],"relation":{},"ISSN":["0028-3835","1423-0194"],"issn-type":[{"value":"0028-3835","type":"print"},{"value":"1423-0194","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,4]]}}}