The cerebrovasculature is essential to maintaining health of the brain;​ however, traumatic brain injuries (TBI) can injure or cause dysfunction of the vasculature, putting neural tissue at risk. While dysfunction is a known consequence of the post-trauma biochemical cascade, stretch-induced structural damage to the vascular extracellular matrix (ECM) may also contribute. The objective of the present work is to characterize potentially treatable damage to the cerebrovascular ECM in TBI. Three in vitro studies characterize mechanical and structural alterations of isolated ovine middle cerebral arteries following a single overstretch. Results serve to guide a subsequent in vivo investigation of vascular damage in closed-head injury. In the first in vitro study, mechanical testing revealed a significant increase in axial and circumferential compliance of the arterial wall following axial overstretch. Biaxial data were subsequently fit with a microstructurally-motivated constitutive model of damage. A second study employed a recently developed collagen hybridizing peptide (CHP) to characterize molecular-level collagen damage, the first ever such study in blood vessels. Imaging and quantification of CHP showed that overstretch produced damage among fibers aligned with the direction of loading, that damage increased with overstretch severity, and that damage initiated just after the vessel reached maximum stiffness. These findings held true for both axial and circumferential overload. A third study investigated subfailure disruption of the intima as this has been implicated in the increased risk of stroke following blunt trauma. As with collagen, intimal disruption occurred just after reaching maximum stiffness. Additional analysis showed that disruption included failure of both the internal elastic lamina (IEL) and endothelium. The threshold of failure did not change over four stages of development. In a final study, preliminary in vivo investigations were conducted to detect structural damage to the vascular wall in an ovine closed-head injury model. After significant refinement of procedures, cortical hemorrhage in the absence of skull fracture was successfully achieved by a left temporal blow with a captive bolt stunner. Neither collagen nor elastin damage was found among neighboring cortical vessels;​ however, investigations were limited. The combined in vitro studies of this dissertation elucidate the mechanical and microstructural changes to the vascular wall that may occur in head trauma. Additional work is needed to better detect and characterize the contribution of such damage in in vivo trauma.