Differential effects of chronic hypertension and sex on vascular density along the septotemporal axis of the hippocampus in a rat model of VCID

Abstract

Background: Chronic hypertension is a major modifiable risk factor for vascular contributions to cognitive impairment and dementia (VCID), yet vascular changes that precede cognitive dysfunction remain poorly understood. This is particularly relevant for the hippocampus, a deep brain structure critical to memory function, which differs along its septotemporal axis functionally and in its susceptibility to hypoxic/ischemic injury. The impacts of hypertension and sex on hippocampal vascularization remains unclear and could contribute to the development/progression of VCID. Methods: In this study, adult male and female Wistar and spontaneously hypertensive rats (SHR) were used at 5 months old, an age before memory impairments. Vascular density and morphometric parameters in dorsal and ventral hippocampus were quantified using high-resolution confocal microscopy and 3D vascular reconstruction. Results: In SHR, vascular density was increased in the dorsal hippocampus in males and across dorsal and ventral hippocampus in females compared to normotensive rats. Diameter and length of the microvasculature shifted to be smaller and longer during hypertension in males, but not females. Conclusions: These findings demonstrate chronic hypertension increases vascular density differentially by sex along the septotemporal axis of the hippocampus in mid adulthood that may increase vascular resistance and potentiate perfusion deficits or increase sites of blood-brain barrier disruption and contribute to VCID.