{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:46:03Z","timestamp":1786977963116,"version":"build-2736575974"},"reference-count":32,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T00:00:00Z","timestamp":1757289600000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Blood\u2010Brain Barrier (BBB) dysfunction acts as a key mediator of ischemic brain injury, contributing to brain edema, inflammatory cell infiltration, and neuronal damage. The integrity of the BBB is largely maintained by tight junction proteins, such as Claudin\u20105, and its disruption exacerbates neurological deficits. Neurokinin B (NKB), a neuropeptide that belongs to the tachykinin family, has been implicated in various physiological processes, including neuroinflammation and vascular function. However, the precise effects of NKB on BBB integrity during ischemic stroke have not been thoroughly investigated. Herein, we explore the role of NKB and its receptor, NKB receptor 3 (NK3R), in the context of ischemic stroke. Our results show a significant increase in both NKB and NK3R levels in the infarcted hemisphere of middle cerebral artery occlusion (MCAO)\u2010operated mice. When we experimentally reduced NKB levels, we observed a notable decrease in infarct volume, improved neurological function, and better BBB permeability. Additionally, we found that inhibiting NKB restored the expression of Claudin\u20105, which in turn reduced endothelial permeability in both in vivo and in vitro experiments. We additionally recognized early growth response protein 1 (Egr\u20101) as a critical downstream target of NKB, which plays a key role in compromising the endothelial barrier. Silencing Egr\u20101 effectively reversed the increase in endothelial permeability and the decrease in Claudin\u20105 caused by NKB, highlighting an important regulatory pathway. These findings emphasize the involvement of NKB in the disruption of the BBB during ischemic stroke, primarily through the upregulation of Egr\u20101, which leads to reduced Claudin\u20105 expression. Therefore, targeting NKB could be a promising therapeutic strategy for maintaining BBB integrity and reducing neuronal damage after ischemic stroke.<\/jats:p>","DOI":"10.1002\/jbt.70483","type":"journal-article","created":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T11:07:48Z","timestamp":1757329668000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Neurokinin B Inhibition Preserves BBB Integrity in Ischemic Stroke via Suppression of Egr\u20101\u2010Mediated Claudin\u20105 Downregulation"],"prefix":"10.1002","volume":"39","author":[{"given":"Jijing","family":"Fu","sequence":"first","affiliation":[{"name":"Department of Intensive Care Medicine Hebei Engineering University Affiliated Hospital Handan Hebei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihua","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Cardiology Hebei Engineering University Affiliated Hospital Handan Hebei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumin","family":"Ping","sequence":"additional","affiliation":[{"name":"Department of Surgical Hebei Engineering University Affiliated Hospital Handan Hebei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Emergency Hebei Engineering University Affiliated Hospital Handan Hebei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Medicine Hebei Engineering University Affiliated Hospital Handan Hebei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Medicine Hebei Engineering University Affiliated Hospital Handan Hebei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6604-2612","authenticated-orcid":false,"given":"Suli","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine Hebei Engineering University Affiliated Hospital Handan Hebei China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,8]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/ane.12457"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2013.242"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0369-12.2012"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00095.2018"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jpcb.5b09977"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.meegid.2014.07.022"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-019-00770-9"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2016.02.035"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jstrokecerebrovasdis.2020.105255"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.5483\/BMBRep.2021.54.11.089"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2010.08.059"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1210\/endocr\/bqaa013"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0893-133X(02)00305-6"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2006.05.041"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yhbeh.2012.04.007"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.16282"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.etap.2016.01.020"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.2769-2795.2021.tb00068.x"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-012-9570-2"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-023-03259-1"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1213\/ANE.0b013e31821a9fbe"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1955"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12020376"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2023.114479"},{"key":"e_1_2_10_26_1","first-page":"5993","article-title":"[Research Progress in Mechanism of Puerarin in Treating Vascular Dementia]","volume":"48","author":"Qi D. 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