A Novel Rodent Model of Hypertensive Cerebral Small Vessel Disease with White Matter Hyperintensities and Peripheral Oxidative Stress

• Published in: International journal of molecular sciences Vol. 23; no. 11; p. 5915
• Main Authors: Guy, Reut, Volkman, Rotem, Wilczynski, Ella, Yagil, Chana, Yagil, Yoram, Findler, Michael, Auriel, Eitan, Nevo, Uri, Offen, Daniel
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 25-05-2022; MDPI
• Subjects: Acetic acid; Animal models; Blood vessels; Brain; cerebral small vessel disease; Dementia disorders; Drinking water; Edema; Hemorrhage; Hypertension; Inflammation; Magnetic resonance imaging; Membrane permeability; Morphology; Neurological complications; Neutrophils; Oxidative stress; Pathogenesis; Pathology; Permeability; Sodium chloride; Stenosis; stroke; Substantia alba; Vascular diseases; white matter hyperintensity; cerebral small vessel disease; hypertension; stroke; oxidative stress; white matter hyperintensity
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23115915

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 'Sabra' 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.