{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T11:42:50Z","timestamp":1761824570831,"version":"build-2065373602"},"reference-count":44,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T00:00:00Z","timestamp":1759104000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Exp Pharma Physio"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The integrity of the Blood\u2010Brain Barrier (BBB) is crucial in the pathophysiological progression of acute ischemic stroke (AIS). However, the potential of Kisspeptin\u201010 (Kp\u201010), with its antioxidant and anti\u2010inflammatory properties, has not been explored experimentally in the context of stroke management. This study aimed to investigate the neurovascular protective effects of Kp\u201010 following cerebral ischemia using both in\u00a0vivo and in\u00a0vitro models. A middle cerebral artery occlusion (MCAO) model was established in C57BL\/6 mice, followed by Kp\u201010 administration. Neurological deficits (Longa score), infarct volume (TTC staining), BBB permeability (14C\u2010Sucrose), and Claudin\u201010 expression (qRT\u2010PCR and immunohistochemistry) were assessed to evaluate the therapeutic effects of Kp\u201010. Human brain microvascular endothelial cells (HBMVECs) were subjected to oxygen\u2013glucose deprivation\/reoxygenation (OGD\/R) to mimic ischemic conditions. Endothelial permeability, oxidative stress (OS), and nuclear factor erythroid 2\u2010related factor 2 (Nrf2) levels were evaluated. Nrf2 silencing was performed to validate its role in Kp\u201010\u2010mediated protection. Initially, we observed a significant reduction in Kp\u201010 expression within the cortical tissue of mice subjected to MCAO. Subsequent administration of Kp\u201010 not only alleviated neurological deficits but also significantly mitigated blood\u2013brain barrier (BBB) dysfunction following stroke induction, as evidenced by reduced 14C\u2010sucrose leakage. Furthermore, Kp\u201010 treatment led to an upregulation of Claudin\u201010 expression in the post\u2010stroke cortical region. In our in\u00a0vitro experiments, we employed HBMVECs exposed to OGD\/R to simulate ischemic conditions. We found that Kp\u201010 effectively reduced OGD\/R\u2010induced endothelial permeability by enhancing Claudin\u201010 expression. Additionally, Kp\u201010 exhibited antioxidant capabilities by decreasing mitochondrial reactive oxygen species (ROS) levels, increasing superoxide dismutase (SOD) activity, and upregulating nuclear factor erythroid 2\u2010related factor 2 (Nrf2) expression. Notably, when Nrf2 was knocked down in HBMVECs, the protective effects of Kp\u201010 on endothelial permeability and Claudin\u201010 expression were abolished, indicating that the beneficial actions of Kp\u201010 are mediated through the Nrf2 pathway. In conclusion, our findings suggest that Kp\u201010 holds promise as a therapeutic strategy to preserve BBB integrity and promote neuroprotection following stroke, acting primarily via the Nrf2 signalling pathway. These findings suggest that Kp\u201010 may represent a promising therapeutic strategy for preserving BBB integrity following ischemic stroke.<\/jats:p>","DOI":"10.1111\/1440-1681.70079","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T02:59:06Z","timestamp":1759201146000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Kisspeptin\u201010 Preserves the Blood\u2010Brain Barrier's Integrity Post\u2010Stroke by Augmenting Claudin\u201010 Expression"],"prefix":"10.1111","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-9523-0455","authenticated-orcid":false,"given":"Liming","family":"Li","sequence":"first","affiliation":[{"name":"College of Life and Health Sciences, Northeastern University  Shenyang China"},{"name":"Key Laboratory of Bioresource Research and Development of Liaoning Province  Shenyang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunlong","family":"Guo","sequence":"additional","affiliation":[{"name":"College of Life and Health Sciences, Northeastern University  Shenyang China"},{"name":"Key Laboratory of Bioresource Research and Development of Liaoning Province  Shenyang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaijie","family":"Zhao","sequence":"additional","affiliation":[{"name":"College of Life and Health Sciences, Northeastern University  Shenyang China"},{"name":"Key Laboratory of Bioresource Research and Development of Liaoning Province  Shenyang China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,9,29]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2021.07.027"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00095.2018"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-017-0091-7"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-021-04379-z"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-022-02761-2"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-022-00991-z"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X221078065"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20190062"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jstrokecerebrovasdis.2021.106160"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2009.07.030"},{"issue":"4","key":"e_1_2_8_12_1","first-page":"R277","article-title":"Blood\u2010Brain Interfaces in Vertebrates: A Comparative Approach","volume":"246","author":"Cserr H. 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