{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T02:42:00Z","timestamp":1790563320874,"version":"4.1.0"},"reference-count":39,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Emerging evidence highlighted vascular injury in aggravating radiation-induced brain injury (RIBI), a common complication of radiotherapy. This study aimed to delineate the pathological feature of cerebral small vessel and investigate the functional roles of Notch signaling in RIBI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Brain tissue and functional MRI from RIBI patients were collected and analyzed for radiation-induced vasculopathy. A RIBI mouse model was induced by a single dose of 30-Gy cranial irradiation. Vascular morphology, pulsatility, and reactivity to pharmacological interventions, such as nimodipine and 20-hydroxyeicosa-6(Z),15(Z)-dienoic acid, were monitored by 2-photon imaging in mice at 6 weeks postirradiation. Western blot, real-time quantitative PCR, immunofluorescence staining, and behavioral tests were performed. The effect of N-[N-(3, 5-difluorophenacetyl)-l-alanyl]-s-phenylglycinet-butyl ester, a Notch inhibitor, was used to investigate the vascular pathogenesis of RIBI mouse model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Morphologically, radiation resulted in vascular malformation featured by focal contractile rings together with general stenosis. Functionally, radiation also led to hypoperfusion, attenuated vascular pulsatility, and decreased dilation to nimodipine and 20-hydroxyeicosa-6(Z),15(Z)-dienoic acid. Mechanically, Notch activation and increased expression of \u03b1-SMA protein were found in both surgical specimens of RIBI patients and the irradiated mice. Importantly, Notch inhibition by N-[N-(3, 5-difluorophenacetyl)-l-alanyl]-s-phenylglycinet-butyl ester significantly alleviated cerebral hypoperfusion, vasculopathy, and cognitive deficits in the RIBI mouse model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Radiation-induced cerebral vasculopathy showed bead-like shape and increased contractile state. Inhibition of Notch signaling by N-[N-(3, 5-difluorophenacetyl)-l-alanyl]-s-phenylglycinet-butyl ester effectively attenuated vasculopathy and relieved cognitive impairment, suggesting Notch signaling as a therapeutic target for the treatment of RIBI.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/strokeaha.122.040697","type":"journal-article","created":{"date-parts":[[2022,10,28]],"date-time":"2022-10-28T05:02:14Z","timestamp":1666933334000},"page":"3751-3762","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":16,"title":["Notch Signaling Mediates Radiation-Induced Smooth Muscle Cell Hypermuscularization and Cerebral Vasculopathy"],"prefix":"10.1161","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5590-8348","authenticated-orcid":true,"given":"Yuhua","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat\u2011sen University, Guangzhou, China (Y.Y., H.L., Y.X., J.X., Q.L., Z.S., J.H., J.C., Siqi Chen, Sitai Chen, X.Z., S.L., Z.Z., J.C., B.H., Q.S., Y.L., Y.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honghong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat\u2011sen University, Guangzhou, China (Y.Y., H.L., Y.X., J.X., Q.L., Z.S., J.H., J.C., Siqi Chen, Sitai Chen, X.Z., S.L., Z.Z., J.C., B.H., Q.S., Y.L., Y.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongteng","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat\u2011sen University, Guangzhou, China (Y.Y., H.L., Y.X., J.X., Q.L., Z.S., J.H., J.C., Siqi Chen, Sitai Chen, X.Z., S.L., Z.Z., J.C., B.H., Q.S., Y.L., Y.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiatian","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat\u2011sen University, Guangzhou, China (Y.Y., H.L., Y.X., J.X., Q.L., Z.S., J.H., J.C., Siqi Chen, Sitai Chen, X.Z., S.L., Z.Z., J.C., B.H., Q.S., Y.L., Y.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat\u2011sen University, Guangzhou, China (Y.Y., H.L., Y.X., J.X., Q.L., Z.S., J.H., J.C., Siqi Chen, Sitai Chen, X.Z., S.L., Z.Z., J.C., B.H., Q.S., Y.L., Y.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5802-7332","authenticated-orcid":true,"given":"Zhongshan","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat\u2011sen University, Guangzhou, China (Y.Y., H.L., Y.X., J.X., Q.L., Z.S., J.H., J.C., Siqi Chen, Sitai Chen, X.Z., S.L., Z.Z., J.C., B.H., Q.S., Y.L., Y.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialin","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat\u2011sen University, Guangzhou, China (Y.Y., H.L., Y.X., J.X., Q.L., Z.S., J.H., J.C., Siqi Chen, Sitai Chen, X.Z., S.L., Z.Z., J.C., B.H., Q.S., Y.L., Y.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinping","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat\u2011sen University, Guangzhou, China (Y.Y., H.L., Y.X., J.X., Q.L., Z.S., J.H., J.C., Siqi Chen, Sitai Chen, X.Z., S.L., Z.Z., J.C., B.H., Q.S., Y.L., Y.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siqi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat\u2011sen University, Guangzhou, China (Y.Y., H.L., Y.X., J.X., Q.L., Z.S., J.H., J.C., Siqi Chen, Sitai Chen, X.Z., S.L., Z.Z., J.C., B.H., Q.S., Y.L., Y.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sitai","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat\u2011sen University, Guangzhou, China (Y.Y., H.L., Y.X., J.X., Q.L., Z.S., J.H., J.C., Siqi Chen, Sitai Chen, X.Z., S.L., Z.Z., J.C., B.H., Q.S., Y.L., Y.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat\u2011sen University, Guangzhou, China (Y.Y., H.L., Y.X., J.X., Q.L., Z.S., 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Yat-sen University, Guangzhou, China (W.- J.L., Q.S., Y.L., Y.T.)."},{"name":"Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China and Guangdong Province Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China (W.-J.L., Y.T.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingyu","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat\u2011sen University, Guangzhou, China (Y.Y., H.L., Y.X., J.X., Q.L., Z.S., J.H., J.C., Siqi Chen, Sitai Chen, X.Z., S.L., Z.Z., J.C., B.H., Q.S., Y.L., Y.T.)."},{"name":"Brain Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China (W.- J.L., Q.S., Y.L., 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