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public welfare research institutes","award":["CI2023C023YL"],"award-info":[{"award-number":["CI2023C023YL"]}]},{"name":"Fundamental Research Funds for the Central public welfare research institutes","award":["CI2021B015"],"award-info":[{"award-number":["CI2021B015"]}]},{"name":"Fundamental Research Funds for the Central public welfare research institutes","award":["82474114"],"award-info":[{"award-number":["82474114"]}]},{"name":"Fundamental Research Funds for the Central public welfare research institutes","award":["82274181"],"award-info":[{"award-number":["82274181"]}]},{"name":"Fundamental Research Funds for the Central public welfare research institutes","award":["Z2021203-22"],"award-info":[{"award-number":["Z2021203-22"]}]},{"name":"Fundamental Research Funds for the Central public welfare research institutes","award":["ZZ13-YQ-100"],"award-info":[{"award-number":["ZZ13-YQ-100"]}]},{"name":"Fundamental Research Funds for the Central public welfare research institutes","award":["ZZ16-ND-10-01"],"award-info":[{"award-number":["ZZ16-ND-10-01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Artesunate (AS) and tetramethylpyrazine (TMP) have been proven to have therapeutic potential in ischemic stroke. Nevertheless, their synergistic treatment mechanisms and effectiveness remain unclear. A rat MCAO model was induced, and AS, combined with TMP, was administered intranasally to rats once a day for 3 days. The neurological severity scores, TTC staining, and H&amp;E staining were implemented to analyze tissue injuries. Evans blue staining and immunohistochemistry of ZO-1, occludin, MMP-9, and TIMP-1 were implemented to evaluate the integrity of the blood\u2013brain barrier (BBB). ELISA was used to detect the expression levels of inflammatory factors TNF-\u03b1 and IL-10. TUNEL staining and the protein expression of Bax and Bcl-2 were used to evaluate the apoptosis of brain tissue cells. The core targets were predicted by network pharmacology and verified by the OGD\/R cell model and siRNA in vitro. Results showed that nasal administration of AS and TMP significantly ameliorated ischemic-stroke-induced neurological dysfunction, BBB disruption, and cortical neuronal apoptosis. The protective mechanisms mainly included adjusting the expression and ratio of tight junction proteins TIMP-1 and MMP-9 in brain tissue, regulating the HIF-1\u03b1-VEGF pathway, and anti-inflammatory effects. This study provides experimental support for the further development and application of AS and TMP nasal combinations and provides the foundation for expanding the practical-application value of artemisinin and its derivatives.<\/jats:p>","DOI":"10.3390\/ijms26167979","type":"journal-article","created":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T16:22:33Z","timestamp":1755534153000},"page":"7979","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Synergistic Neuroprotection of Artesunate and Tetramethylpyrazine in Ischemic Stroke, Mechanisms of Blood\u2013Brain Barrier Preservation"],"prefix":"10.3390","volume":"26","author":[{"given":"Yan","family":"Liang","sequence":"first","affiliation":[{"name":"State Key Laboratory for Qualty Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Dongcheng District, Beijing 100700, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuoqiu","family":"Deng","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Qualty Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Dongcheng District, Beijing 100700, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Qualty Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Dongcheng District, Beijing 100700, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuiqing","family":"Qu","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Qualty Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Dongcheng District, Beijing 100700, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chengcheng","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Qualty Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Dongcheng District, Beijing 100700, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luqi","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Qualty Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Dongcheng District, Beijing 100700, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lina","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Qualty Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Dongcheng District, Beijing 100700, China"},{"name":"Artemisinin Research Center, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tuo","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Qualty Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Dongcheng District, Beijing 100700, China"},{"name":"Artemisinin Research Center, China Academy of Chinese Medical Sciences, Beijing 100700, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2359-2673","authenticated-orcid":false,"given":"Yujie","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Qualty Ensurance and Sustainable Use of Dao-di Herbs, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Dongcheng District, Beijing 100700, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2820","DOI":"10.1016\/S0140-6736(24)00642-1","article-title":"Stroke","volume":"403","author":"Hilkens","year":"2024","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1038\/nrneurol.2016.107","article-title":"Prevention of stroke, a strategic global imperative","volume":"12","author":"Feigin","year":"2016","journal-title":"Nat. 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