Injury from explosive blast is a growing public health threat worldwide with complex mechanisms and limited treatment and prevention pathways. Blastrelated traumatic brain injury (bTBI) is a multimodal injury event in which cerebral blood vessels play a central role in both the mechanical and physiological response to blast loading. This dissertation seeks to define the nature of vessel injury from primary blast loading by measuring injury thresholds for vasculature in bTBI by assessing blood-brain barrier (BBB) integrity and disruption, examining which types of vessels are affected, and mapping the distribution of injury in the brain. To assess the consequences of vascular injury, we measured inflammatory changes in glial cell activity with immunohistological techniques, and evaluated changes in behavior in a rodent model of bTBI. The importance of overpressure duration and impulse are examined by performing matched assays with two distinct blast tube devices capable of producing a wide range of blast wave characteristics. Exploration in measuring changes in cerebral blood flow, blood oxygen levels, and cerebral hemorrhage is described. Our primary findings include the presence of focal deposits of IgG in the parenchymal brain tissue indicating an elevated permeability of the blood-brain barrier, a heterogeneous distribution of these lesions among various brain structures, changes in astrocyte glial fibrillary acidic protein (GFAP) expression at lesion locations, and decrease in nociception and pedal withdrawal reflex following primary blast exposure. Changes in macrophage and neural cell populations were observed using markers for IBA1, CD68, and NeuN. Injury levels between devices were broadly similar;​ however, some differences in both histology and behavior were seen following high-impulse blast testing. Blast injury research remains an important topic with many unanswered questions, and further effort will provide help to those afflicted and preventative protection for those at risk.