Related Experiment Video
Updated: Sep 20, 2025
A Mouse Model for Vascular Cognitive Impairment and Dementia Based on Needle-guided Asymmetric Bilateral Common Carotid Artery Stenosis
Published on: November 22, 2024
A Novel Rodent Model of Hypertensive Cerebral Small Vessel Disease with White Matter Hyperintensities and Peripheral
Reut Guy1, Rotem Volkman1, Ella Wilczynski2
1Felsenstein Medical Research Center, Department of Human Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
Insights
A new rat model effectively mimics cerebral small vessel disease (CSVD), a key cause of stroke and dementia. This model displays multiple CSVD pathologies, offering a platform for therapeutic development.
Area of Science:
- Neuroscience
- Vascular Biology
- Animal Models
Background:
- Cerebral small vessel disease (CSVD) is a leading cause of stroke and dementia.
- Existing animal models fail to replicate all facets of human CSVD.
- Hypertension and oxidative stress are implicated in CSVD pathogenesis.
Purpose of the Study:
- To develop and characterize a novel animal model for CSVD.
- To investigate the utility of salt-sensitive 'Sabra' hypertension-prone rats (SBH/y) for CSVD research.
- To assess the capacity of this model to recapitulate key human CSVD features.
Main Methods:
- SBH/y rats were treated with deoxycorticosterone acetate (DOCA) and high salt to induce hypertension.
- Neurological, behavioral, MRI, biochemical, and histological assessments were performed.
- Comparison of SBH/y-DOCA rats with sham-operated controls.
Main Results:
- SBH/y-DOCA rats exhibited neurological decline and cognitive impairment.
- The model displayed multiple CSVD pathologies including intracerebral hemorrhages (ICH), lacunes, enlarged perivascular spaces, and stenosis.
- Significant white matter hyperintensities (WMH) and inflammation were observed, features rarely seen in other models.
- Increased blood-brain barrier (BBB) permeability was noted.
Conclusions:
- The SBH/y-DOCA rat is a novel and comprehensive model for CSVD.
- This model recapitulates key cerebrovascular pathologies, including severe white matter damage.
- It provides a valuable platform for studying CSVD mechanisms and testing new therapies.
Abstract:
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.
