A novel hypertensive rat model of cerebral small vessel disease: Pathological, cognitive, and neuroimaging implications

Cerebral small vessel disease (CSVD) is a major cause of stroke and dementia yet its mechanisms remain poorly understood due to the lack of reliable animal models. This study aimed to develop a novel rat model that replicates human CSVD pathology by combining a 2-kidney 2-clip hypertensive procedure with a high-salt diet. High-salt diet stroke-prone renovascular hypertensive (RHRsp) rats exhibited sustained hypertension, cerebral small artery remodeling, cognitive impairments, and lacunar infarcts, closely mimicking human sporadic CSVD. This model overcomes limitations of existing approaches by accelerating pathological changes and providing a comprehensive representation of CSVD features. The results demonstrate that the high-salt diet RHRsp rat is a promising model for studying hypertension-associated CSVD, offering a robust platform for investigating disease mechanisms and testing therapeutic interventions. This advancement enhances our understanding of CSVD pathology and supports the development of targeted treatments.