Doctor of Philosophy

Abstract

dissertationThe cerebrovasculature is vital in maintaining health in the brain, but can be damaged by traumatic brain injury (TBI). Even in cases without hemorrhage, vessels are deformed with the surrounding tissue. Subfailure deformation could result in altered mechanical properties and dysfunction of these vessels. This dissertation aims to provide a better understanding of the biaxial mechanical properties of cerebral arteries, as well as determine mechanical stretch thresholds which produce ultimate failure and subfailure alteration of mechanical properties or vessel function. Three in vitro studies were undertaken. Passive biaxial mechanical properties under physiological loading, as well as failure properties of rat middle cerebral arteries (MCAs), were measured and compared to those of human pial arteries. Best fit parameters for a Fung type strain energy function are provided for the biaxial mechanical properties. Rat MCAs are stiffer in the axial direction than the circumferential, but less stiff in both directions than human arteries. Rat MCAs also exhibit a lower ultimate failure stress but higher failure stretch. The effect of subfailure axial overstretch on the contractile behavior of smooth muscle cells (SMCs) in rat MCAs was investigated. Potassium dose response tests were conducted before and after a single axial overstretch, with varying magnitude and strain rate. Overstretches beyond a threshold of both magnitude and strain rate significantly reduced SMC contraction relative to time-matched controls, mirrored by an increase in potassium concentration required to evoke the half maximal contraction. The effect of subfailure axial overstretch on passive mechanical properties in sheep MCAs was investigated. Axial response was measured before and after a single quasi-static overstretch of various magnitudes. Post-overstretch, samples showed persistent softening (lower stress values at a given level of stretch). Softening was only observed above an overstretch threshold, and then increased with overstretch severity until a second threshold was reached, above which softening did not increase until failure. This dissertation provides improved understanding of cerebrovascular mechanics and relationships between such data acquired from animals and humans. It also provides insight into the potential role of subfailure cerebrovascular damage in disease states associated with TBI, such as second impact syndrome and strok