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A NOVEL MODEL OF CEREBRAL SMALL VESSEL DISEASE WITH WHITE MATTER HYPERINTENSITIES AND PERIPHERAL OXIDATIVE STRESS USING THE SABRA RATS
Abstract
Aims
Cerebral small vessel disease (CSVD) is the second most common cause of stroke and a major contributor to dementia. CSVD manifests in a variety of pathological mechanisms including cerebral microbleeds, intracerebral hemorrhages (ICH), lacunar infarcts, white matter hyperintensities (WMH) and enlarged perivascular spaces. Chronic hypertensive models were found to resemble most key features of the disease. Nevertheless, no animal models have been identified to reflect all different aspects of the human disease. We designed experiments for characterizing a novel model for CSVD, using salt-sensitive ‘Sabra’ hypertension-prone rats (SBH/y) which display chronic hypertension and enhanced peripheral oxidative stress.
Methods
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, biochemical and histological analyses.
Results
SBH/y-DOCA rats show 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.
Conclusions
Our model may serve as a novel platform for further understanding the mechanisms underlying CSVD and for discovery of novel therapies for this disease.