Electronic Thesis and Dissertation Repository

Thesis Format

Monograph

Degree

Master of Science

Program

Medical Biophysics

Supervisor

Frisbee, Jefferson C.

Abstract

Metabolic syndrome is associated with cerebrovascular disease and cognitive impairment. We determined vascular reactivity in middle cerebral arteries (MCA), and performed cognitive testing using an operant conditioning chamber (OCC) and Morris Water Maze (MWM). Male obese Zucker rats (OZR) were used to test the hypothesis that the pro-inflammatory environment present in the OZR impairs cerebrovascular tone regulation and is associated with neuroinflammation of the white matter and cognitive impairment. Dilation of MCA following challenge with acetylcholine was blunted, whereas constrictor responses were enhanced. Learning was impaired in the MWM and a shift in swim strategy towards increased allocentric navigation was observed. Few impairments were detected in the OCC tests or when white matter regions were examined for markers of neuroinflammation. These results suggest that the reactivity of MCA in OZR is altered with MetS, and that this impairment is associated mild cognitive dysfunction in the absence of white matter inflammation.

Summary for Lay Audience

Metabolic syndrome is a cluster of conditions including increased blood pressure, high blood sugar, excess body fat around the waist, and abnormal cholesterol or triglycerides. It is a prevalent public health concern associated with elevated cardiovascular disease risk throughout the body. Impairments associated with this disease are particularly problematic when they affect the brain and lead to problems such as stroke (a blockage in an artery that supplies blood to the brain). Even in the absence of an acute event such as stroke, metabolic syndrome is strongly associated with impaired cognitive function and decreased quality of life. The work presented in this thesis aims to describe some of the changes occurring to the ability of blood vessels in the brain to alter their diameter which has implications in regulating blood flow. It also investigated if these changes are associated with cognitive impairment and inflammation in the brain using a rodent model of metabolic syndrome. Understanding these risk factors allows for better implementation of targeted therapeutic strategies aimed at ameliorating the regulation of blood flow in the brain and has the potential to improve current negative outcomes associated with metabolic syndrome.

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