{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:20:37Z","timestamp":1785410437039,"version":"3.56.0"},"reference-count":64,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,4,19]],"date-time":"2024-04-19T00:00:00Z","timestamp":1713484800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82074525"],"award-info":[{"award-number":["82074525"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82274639"],"award-info":[{"award-number":["82274639"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["KYCX23_2157"],"award-info":[{"award-number":["KYCX23_2157"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Postgraduate Research &amp; Practice Innovation Program of Jiangsu Province","award":["82074525"],"award-info":[{"award-number":["82074525"]}]},{"name":"Postgraduate Research &amp; Practice Innovation Program of Jiangsu Province","award":["82274639"],"award-info":[{"award-number":["82274639"]}]},{"name":"Postgraduate Research &amp; Practice Innovation Program of Jiangsu Province","award":["KYCX23_2157"],"award-info":[{"award-number":["KYCX23_2157"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Background: Ischemic stroke (IS) is one of the leading causes of death and disability worldwide. The narrow therapeutic window (within 4.5 h) and severe hemorrhagic potential limits therapeutic efficacy of recombinant tissue type plasminogen activator (rt-PA) intravenous thrombolysis for patients. Xingnao Kaiqiao (XNKQ) acupuncture is an integral part of traditional Chinese medicine, specifically designed to address acute ischemic stroke by targeting key acupoints such as Shuigou (GV26) and Neiguan (PC6). In this study, we explored the therapeutic potential of XNKQ acupuncture in extending the time window for thrombolysis and interrogated the molecular mechanisms responsible for this effect. Methods: The effect of extending the thrombolysis window by acupuncture was evaluated via TTC staining, neuronal score evaluation, hemorrhagic transformation assay, and H&amp;E staining. RNA sequencing (RNA-seq) technology was performed to identify the therapeutic targets and intervention mechanisms of acupuncture. Evans blue staining and transmission electron microscopy were used to assess blood\u2013brain barrier (BBB) integrity. Immunofluorescence staining and co-immunoprecipitation were performed to evaluate the level of autophagy and apoptosis and validate their interactions with BBB endothelial cells. Results: Acupuncture alleviated infarction and neurological deficits and extended the thrombolysis window to 6 h. The RNA-seq revealed 16 potential therapeutic predictors for acupuncture intervention, which related to suppressing inflammation and restoring the function of BBB and blood vessels. Furthermore, acupuncture suppressed BBB leakage and preserved tight junction protein expression. The protective effect was associated with regulation of the autophagy\u2013apoptosis balance in BBB endothelial cells. Acupuncture intervention dissociated the Beclin1\/Bcl-2 complex, thereby promoting autophagy and reducing apoptosis. Conclusion: XNKQ acupuncture could serve as an adjunctive therapy for rt-PA thrombolysis, aiming to extend the therapeutic time window and mitigate ischemia\u2013reperfusion injury. Acupuncture suppressed BBB disruption by regulating the autophagy\u2013apoptosis balance, which in turn extended the therapeutic window of rt-PA in IS. These findings provide a rationale for further exploration of acupuncture as a complementary candidate co-administered with rt-PA.<\/jats:p>","DOI":"10.3390\/brainsci14040399","type":"journal-article","created":{"date-parts":[[2024,4,19]],"date-time":"2024-04-19T06:28:09Z","timestamp":1713508089000},"page":"399","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Acupuncture Extended the Thrombolysis Window by Suppressing Blood\u2013Brain Barrier Disruption and Regulating Autophagy\u2013Apoptosis Balance after Ischemic Stroke"],"prefix":"10.3390","volume":"14","author":[{"given":"Zhihui","family":"Zhang","sequence":"first","affiliation":[{"name":"College of Acupuncture-Moxibustion and Tuina, Nanjing University of Chinese Medicine, No. 138 Xianlin Avenue, Qixia District, Nanjing 210023, China"},{"name":"Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, No. 138 Xianlin Avenue, Qixia District, Nanjing 210023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianliang","family":"Lu","sequence":"additional","affiliation":[{"name":"College of Acupuncture-Moxibustion and Tuina, Nanjing University of Chinese Medicine, No. 138 Xianlin Avenue, Qixia District, Nanjing 210023, China"},{"name":"Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, No. 138 Xianlin Avenue, Qixia District, Nanjing 210023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanshan","family":"Li","sequence":"additional","affiliation":[{"name":"College of Acupuncture-Moxibustion and Tuina, Nanjing University of Chinese Medicine, No. 138 Xianlin Avenue, Qixia District, Nanjing 210023, China"},{"name":"Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, No. 138 Xianlin Avenue, Qixia District, Nanjing 210023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruyu","family":"Zhao","sequence":"additional","affiliation":[{"name":"College of Acupuncture-Moxibustion and Tuina, Nanjing University of Chinese Medicine, No. 138 Xianlin Avenue, Qixia District, Nanjing 210023, China"},{"name":"Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, No. 138 Xianlin Avenue, Qixia District, Nanjing 210023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honglei","family":"Li","sequence":"additional","affiliation":[{"name":"College of Acupuncture-Moxibustion and Tuina, Nanjing University of Chinese Medicine, No. 138 Xianlin Avenue, Qixia District, Nanjing 210023, China"},{"name":"Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, No. 138 Xianlin Avenue, Qixia District, Nanjing 210023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinchang","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Acupuncture-Moxibustion and Tuina, Nanjing University of Chinese Medicine, No. 138 Xianlin Avenue, Qixia District, Nanjing 210023, China"},{"name":"Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, No. 138 Xianlin Avenue, Qixia District, Nanjing 210023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyang","family":"Li","sequence":"additional","affiliation":[{"name":"College of Acupuncture-Moxibustion and Tuina, Nanjing University of Chinese Medicine, No. 138 Xianlin Avenue, Qixia District, Nanjing 210023, China"},{"name":"Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, No. 138 Xianlin Avenue, Qixia District, Nanjing 210023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yawen","family":"Xia","sequence":"additional","affiliation":[{"name":"College of Acupuncture-Moxibustion and Tuina, Nanjing University of Chinese Medicine, No. 138 Xianlin Avenue, Qixia District, Nanjing 210023, China"},{"name":"Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, No. 138 Xianlin Avenue, Qixia District, Nanjing 210023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangxia","family":"Ni","sequence":"additional","affiliation":[{"name":"College of Acupuncture-Moxibustion and Tuina, Nanjing University of Chinese Medicine, No. 138 Xianlin Avenue, Qixia District, Nanjing 210023, China"},{"name":"Key Laboratory of Acupuncture and Medicine Research of Ministry of Education, Nanjing University of Chinese Medicine, No. 138 Xianlin Avenue, Qixia District, Nanjing 210023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e231455","DOI":"10.1001\/jamanetworkopen.2023.1455","article-title":"Estimated Burden of Stroke in China in 2020","volume":"6","author":"Tu","year":"2023","journal-title":"JAMA Netw. 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