Date: Thursday, August 25, 2016
Parenchymal arterioles (PAs) regulate blood flow to the brain parenchyma. Unlike the large cerebral arteries, the structural and functional features of PAs in physiological and pathological models remain largely unexplored. Even though, epidemiological studies highlight PA dysfunction as a key driver of cerebral small vessel disease, a leading cause of vascular cognitive impairment (VCI). Chronic cerebral hypoperfusion (CCH) and hypertension are major risk factors of VCI. Understanding the combined effects of these co-morbidities on PA structure and functions could provide mechanistic insight into the progression of VCI. This study shows, for the first time, an association between impaired PA functions and cognitive deficits. Epoxyeicosatrienoic acids (EETs) are potent vasodilators in the microcirculation. Enhancing EET levels by inhibiting its metabolizing enzyme, soluble epoxide hydrolase (sEH), could have potential therapeutic effects in VCI models. This dissertation work is the first to demonstrate that chronic pharmacological inhibition of sEH prevents CCH-induced memory deficits, and impaired dilation in PAs from hypertensive rats.