Differential Left and Right Carotid Artery Blood Flow and Altered Hippocampal Mitochondrial Function After Transverse Aortic Constriction in Aging Rats.

Abstract

BACKGROUND: The hippocampus is a key brain structure that has been implicated in vascular dementia cause and is highly sensitive to changes in cerebral blood flow. Brain hypoperfusion in cardiovascular disease may facilitate neurodegeneration in the hippocampus by limiting substrate transport and metabolism. Although most animal studies have relied on artery occlusion to lower brain blood flow, brain hypoperfusion can also stem from mechanical damage resulting from high blood flow velocity and pulsatility. This study assessed, within the same rodent, whether high and low cerebral blood flow differentially affected hippocampal glucose transport protein expression, mitochondrial fuel oxidation, and expression of mitochondrial quality control proteins. METHODS: Four-week-old male and female Sprague-Dawley rats underwent transverse aortic constriction (n=13) or control (n=18) surgeries. Bilateral carotid artery diameter and blood flow were measured 20, 30, and 40&#x2009;weeks postsurgery. Right and left hippocampal mitochondrial respiration and expression of glucose transporters and mitochondrial quality control proteins were measured 40&#x2009;weeks postsurgery. RESULTS: Right carotid blood flow velocity and pulsatility were highest in the right and lowest in the left carotid of transverse aortic constriction animals (<0.05). Complex I (=0.057), complex I&II (<0.05), and complex II uncoupled (<0.05) respiration rates were lower in the right hippocampus of transverse aortic constriction animals when compared with the left, and markers of mitochondrial fusion were upregulated in transverse aortic constriction animals compared with controls (<0.05). CONCLUSIONS: Although both limited and pulsatile blood flow alter mitochondrial fusion markers, only pulsatile flow impairs mitochondrial respiration, suggesting turbulent hemodynamics may drive metabolic dysfunction in vascular dementia.