More severe vascular remodeling in deep brain regions caused by hemodynamic differences is a potential mechanism of hypertensive cerebral small vessel disease.

In hypertension-associated arteriolosclerosis cerebral small vessel disease (CSVD), various studies have shown that MRI-detected lesions-such as lacunes, white matter hyperintensities, enlarged perivascular spaces, and cerebral microbleeds-are more prevalent in deep brain regions (DBR) than in the cortex. However, the underlying mechanisms remain poorly understood. We propose that differential vascular remodeling between DBR small vessels and superficial cortical branches contributes to this heterogeneity. Using a stroke-prone renovascular hypertensive rat (RHRsp) model, we observed pronounced changes in vessel density, diameter, extracellular matrix deposition, and smooth muscle cell alterations in DBR small arteries compared to that of the cortex. These findings were further confirmed in human brain tissue of our study. Additionally, our mathematical modeling indicated greater hemodynamic alterations in DBR vessels, with increased shear and circumferential stress under hypertension conditions. Overall, our study highlights more severe vascular remodeling and hemodynamic changes in the deep brain regions, where CSVD-associated MRI lesions are frequently detected.