Date of Award
Master of Science
Rodney A. Swain
Karyn M. Frick, Fred J. Helmstetter
Angiogenesis, Cerebrovasculature, Exercise, Hypoxia, Plasticity, Vasoflexibility
Vascular pathologies represent the leading causes of mortality worldwide, accounting for 31% of all deaths in 2012. Cerebral hypoxia is a condition that often manifests as a result of these medical conditions. Remarkably, the nervous system has evolved mechanisms to compensate for oxygen deprivation. The dilation of existing vessels and the growth of new blood vessels are two prominent physiological responses to hypoxia, both of which play a critical role in maintaining cerebral homeostasis. More recently, exercise has been shown to induce a mild state of hypoxia in the brain, leading to several robust morphological changes within the cerebrovascular system (e.g., angiogenesis, vasodilation). Thus, exercise serves as a viable model for investigating hypoxia-induced adaptations. The present study introduces spectral domain optical coherence tomography (SD-OCT) as a novel technique for examining these micro-level changes in the rat motor cortex. SD-OCT produces high resolution, three-dimensional angiograms, and allows for moderately invasive imaging within the same animal at multiple time points. The independent effect of exercise training on cerebrovascular structure and function has never been explored using SD-OCT. Thus, the primary goal of this study was to determine the relative efficacy of SD-OCT utility. To validate this novel technology, we employed SD-OCT in the examination of exercise-dependent blood vessel growth, as well as real-time capillary dilation in response to a laboratory-induced condition of hypoxia (i.e., 10% oxygen). In addition, histology data was collected to provide comparative measures for statistical analyses. At the start of this investigation, animals were pseudo-randomly assigned to one of two groups: 26-week voluntary exercise (VX), or an inactive control (IC). Upon completing the exercise treatment, animals were anesthetized and prepared for imaging. Vascular anatomy and blood velocity data was captured during three experimental conditions:  normal oxygen baseline,  hypoxia – 10% oxygen, and  normoxia, return to baseline. A two-way analysis of variance revealed a significant difference in total blood vessel density between treatment groups, independent of condition. That is, VX animals had a greater density of blood vessels in the scanned region of interest when compared to IC. These findings were confirmed using unbiased stereology techniques to analyze tissue in the scanned region of interest. Furthermore, statistical analyses revealed a significant increase in small arteriole diameter in both VX and IC animals. However, the dilation captured by SD-OCT was significantly greater in VX animals when compared to IC. In sum, exercise induces potent adaptations that promote greater flexibility during hypoxia. Moreover, these micro-level changes can be effectively probed using SD-OCT.
Kay, Jacob James Michael, "Spectral Domain-optical Coherence Tomography for the Assessment of Cerebrovascular Plasticity" (2016). Theses and Dissertations. 1280.