Integrative roles of the sympathetic nervous system and the endothelium in cerebrovascular physiology

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OVERVIEW: My research program aims to better understand the control of blood flow as it relates to organ function. The goal of this work is to better understand brain blood vessel physiology with respect to the sympathetic nervous system (often called the fight-or-flight response) and the endothelium (a tissue that lines the inside blood vessels in the brain). Specifically, exploring how the sympathetic nervous system influences the control of blood flow in the brain and whether the level of sympathetic control is influenced by the endothelium. The role of the sympathetic nervous system and how interactions with the endothelium influence brain blood vessel function is not clear. The central hypothesis of this work is that sympathetic and endothelial inputs exert competing influences. That is, the effect of the sympathetic nerves to cause blood vessels to get smaller (vasoconstrict) is masked by the release of substances by the endothelium that cause blood vessels to get wider (vasodilate). Further, these sympathetic-endothelial interactions are not uniform across all brain blood vessels. The specific objectives to address this hypothesis are as follows: OBJECTIVES: 1)Identify the different types and number of sympathetic nerves and primary dilator substances in brain blood vessels throughout the brain at the molecular level 2)Characterize the actions of sympathetic nerve receptor activation with and without the endothelial dilator substances present using a blood vessel function test. 3)Determine whether sympathetic nerve and endothelial functions interact and jointly regulate brain blood flow under living conditions. SCIENTIFIC APPROACH: This work utilizes a pig model and combines molecular, single blood vessel and brain blood flow vascular imaging techniques to advance our understanding of mammalian brain blood vessel physiology. Objectives 1 and 2 will focus on biochemical characterization of brain blood vessels and matching functional tests of single blood vessels using an isolated vessel preparation. These analyses will be performed in blood vessels from different brain regions. This is an ideal approach to study brain blood vessel physiology under controlled conditions. Objective 3 will focus on the regulation of blood flow in the brain in live animals under dynamic conditions. This will help interpret and understand the physiological significance of findings from the Objectives 1 and 2. IMPACT: The fundamental  processes being studied are influenced by sex, age, environmental stress, injury and pathology and they affect brain function and behaviour. Thus, findings from this work will broadly influence biological sciences, human and veterinary sciences and agricultural industries. This research will lay the foundation for future work examining the relationship between brain blood flow, brain metabolism and cognition and provides excellent training opportunities for young scientists and students interested in integrative physiology.