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Mol. Life Sci."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Disruption of the blood-brain barrier (BBB) is a key event in the onset of ischemic stroke (IS), primarily driven by endothelial cytoskeletal rearrangement. The interaction between non-muscle myosin heavy chain IIA (NMMHC IIA) and actin, along with the ROCK\/MLC pathway, is central to this cytoskeletal reorganization. While our previous studies have shown that the Caspase-3\/ROCK1\/MLC\/NMMHC IIA-actin positive feedback loop mediates H\n                      <jats:sub>2<\/jats:sub>\n                      O\n                      <jats:sub>2<\/jats:sub>\n                      -induced neuronal apoptosis, its role in cerebral ischemia-reperfusion (I\/R) injury and BBB disruption remains unclear.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In vivo, we used endothelial-specific NMMHC IIA conditional knockdown mice, NMMHC IIA-inducible endothelial conditional knock-in mice and C57BL\/6J to establish a middle cerebral artery occlusion\/reperfusion model. In vitro, we employed brain microvascular endothelial cells in an oxygen-glucose deprivation\/reoxygenation model. The effects of the NMMHC IIA inhibitor blebbistatin, the ROCK1 inhibitor Y-27632, and the actin depolymerizer cytochalasin D were assessed for their impact on I\/R-induced activation of the ROCK\/MLC\/NMMHC IIA-actin pathway, tight junction proteins (TJs) degradation, and brain damage.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Inhibition of NMMHC IIA expression and stress fiber depolymerization significantly reduced NMMHC IIA-actin interactions, suppressed the ROCK\/MLC pathway, decreased TJs degradation, and alleviated cerebral I\/R injury. Conversely, overexpression of NMMHC IIA further exacerbated cerebral I\/R injury and BBB disruption and amplified activation of the ROCK1\/MLC pathway. Y-27632 inhibited the ROCK\/MLC\/NMMHC IIA-actin pathway, mitigating I\/R-induced BBB disruption.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study reveals that the ROCK1\/MLC\/NMMHC IIA-actin pathway is implicated in I\/R-induced BBB disruption and operates as a positive feedback loop. These findings offer a promising therapeutic strategy for the treatment of IS and BBB damage.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00018-025-05808-4","type":"journal-article","created":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T13:47:38Z","timestamp":1761832058000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The role of ROCK1\/MLC\/NMMHC IIA-actin signaling in ischemic stroke-induced blood-brain barrier disruption: implications for therapeutic intervention"],"prefix":"10.1007","volume":"82","author":[{"given":"Liangying","family":"Bao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanhao","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchuan","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujie","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junhe","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuaishuai","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8377-915X","authenticated-orcid":false,"given":"Junping","family":"Kou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,30]]},"reference":[{"issue":"10","key":"5808_CR1","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1016\/S1474-4422(21)00252-0","volume":"20","author":"GBD 2019 Stroke Collaborators","year":"2021","unstructured":"GBD 2019 Stroke Collaborators (2021) Global, regional, and National burden of stroke and its risk factors, 1990\u20132019: a systematic analysis for the global burden of disease study 2019. 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