{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T02:30:09Z","timestamp":1790735409420,"version":"4.1.0"},"reference-count":48,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T00:00:00Z","timestamp":1653436800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cerebral small vessel disease (CSVD) is the second most common cause of stroke and a major contributor to dementia. Manifestations of CSVD include cerebral microbleeds, intracerebral hemorrhages (ICH), lacunar infarcts, white matter hyperintensities (WMH) and enlarged perivascular spaces. Chronic hypertensive models have been found to reproduce most key features of the disease. Nevertheless, no animal models have been identified to reflect all different aspects of the human disease. Here, we described a novel model for CSVD using salt-sensitive \u2018Sabra\u2019 hypertension-prone rats (SBH\/y), which display chronic hypertension and enhanced peripheral oxidative stress. SBH\/y rats were either administered deoxycorticosteroid acetate (DOCA) (referred to as SBH\/y-DOCA rats) or sham-operated and provided with 1% NaCl in drinking water. Rats underwent neurological assessment and behavioral testing, followed by ex vivo MRI and biochemical and histological analyses. SBH\/y-DOCA rats show a neurological decline and cognitive impairment and present multiple cerebrovascular pathologies associated with CSVD, such as ICH, lacunes, enlarged perivascular spaces, blood vessel stenosis, BBB permeability and inflammation. Remarkably, SBH\/y-DOCA rats show severe white matter pathology as well as WMH, which are rarely reported in commonly used models. Our model may serve as a novel platform for further understanding the mechanisms underlying CSVD and for testing novel therapeutics.<\/jats:p>","DOI":"10.3390\/ijms23115915","type":"journal-article","created":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T08:41:33Z","timestamp":1653468093000},"page":"5915","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["A Novel Rodent Model of Hypertensive Cerebral Small Vessel Disease with White Matter Hyperintensities and Peripheral Oxidative Stress"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1101-2018","authenticated-orcid":false,"given":"Reut","family":"Guy","sequence":"first","affiliation":[{"name":"Felsenstein Medical Research Center, Department of Human Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rotem","family":"Volkman","sequence":"additional","affiliation":[{"name":"Felsenstein Medical Research Center, Department of Human Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6025-8666","authenticated-orcid":false,"given":"Ella","family":"Wilczynski","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, The Iby and Aladar Fleischman Faculty of Engineering, Tel Aviv University, Tel Aviv 69978, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chana","family":"Yagil","sequence":"additional","affiliation":[{"name":"Israeli Rat Genome Center, Laboratory for Molecular Medicine, Barzilai University Medical Center, Ashkelon 78306, Israel"},{"name":"Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoram","family":"Yagil","sequence":"additional","affiliation":[{"name":"Israeli Rat Genome Center, Laboratory for Molecular Medicine, Barzilai University Medical Center, Ashkelon 78306, Israel"},{"name":"Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Findler","sequence":"additional","affiliation":[{"name":"Felsenstein Medical Research Center, Department of Human Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel"},{"name":"Department of Neurology, Rabin Medical Center, Petah-Tikva 49100, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eitan","family":"Auriel","sequence":"additional","affiliation":[{"name":"Felsenstein Medical Research Center, Department of Human Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel"},{"name":"Department of Neurology, Rabin Medical Center, Petah-Tikva 49100, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uri","family":"Nevo","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, The Iby and Aladar Fleischman Faculty of Engineering, Tel Aviv University, Tel Aviv 69978, Israel"},{"name":"Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1102-4521","authenticated-orcid":false,"given":"Daniel","family":"Offen","sequence":"additional","affiliation":[{"name":"Felsenstein Medical Research Center, Department of Human Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel"},{"name":"Sagol School of Neuroscience, Tel Aviv University, Tel Aviv 69978, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/S1474-4422(13)70060-7","article-title":"Mechanisms of sporadic cerebral small vessel disease: Insights from neuroimaging","volume":"12","author":"Wardlaw","year":"2013","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"109","DOI":"10.3389\/fnagi.2020.00109","article-title":"Clinical Features and Experimental Models of Cerebral Small Vessel Disease","volume":"12","author":"Shindo","year":"2020","journal-title":"Front. 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