MECHANISMS OF COGNITIVE IMPAIRMENT DEVELOPMENT IN AGED HYPERTENSIVE RATS: FOCUS ON MACROPHAGES

Abstract

Stroke survivors have an increased risk of developing long-term disability and dementia. Hypertension and aging are major contributing factors to vascular dementia, stroke, and the development of PSCI. Most animal models fail to capture the complex interplay between these pathophysiologic processes. The purpose of this dissertation is to investigate the impact of aging and hypertension on cognitive function, prior to, and following stroke. We utilized aged hypertensive rats to study the trajectory of vascular cognitive impairment, and to investigate the impact of delayed and chronic stimulation of Angiotensin II type 2 receptor on stroke outcomes. Sixty SHRs were housed (in pairs) for 18 months with cognitive assessments every six months and post-surgery. Multiple MRI scans were performed at baseline and throughout the study. At day 3 after stroke, rats were randomized to receive either an angiotensin receptor agonist, Compound 21, or plain drinking water and followed up for 8 weeks. Additionally, we examined the ability of C21 to mediate anti- inflammatory and neurotrophic effects in mouse microglial cell line, C8-B4, and RAW 264.7 macrophages.