Summary Blast-related traumatic brain injury (TBI) is associated with the development of neuropsychiatric injuries (including post-traumatic stress disorder [PTSD] and major depression) among soldiers in the war theaters of Iraq and Afghanistan. Treatment for blast-related TBI is currently limited to counseling and palliative care. We have explored the effects of 74.5-kPa blast exposures that mimic mild TBI (mTBI) in a rat model. Blast- exposed rats exhibit a variety of PTSD-like behavioral traits, including increased anxiety, enhanced acoustic startle, altered responses to a predator scent, and altered cued fear responses. Further experimental evidence indicates that the cerebral vasculature is a main target for blast waves, as acute and chronic vascular degenerative processes develop after blast-exposures. Previous research has shown that fibroblast growth factor 1 (FGF1) is a strong angiogenic factor that can induce neovascularization, capillary branching, and vascular remodeling. We have published evidence indicating that FGF signaling is essential for endothelial cell homeostasis and survival. The overall goal of the proposed research is to test whether intranasal administration of FGF1 can reverse the established cerebrovascular and cognitive degenerative processes present in our rat model of blast-induced mTBI. We propose to administer recombinant FGF1 into blast-exposed rats (3 × 74.5 kPa) once they have developed the chronic PTSD phenotype (6 months post-blast exposure) to test whether this treatment improves the cognitive deficits and vascular alterations associated with these diseases. We will test for memory (Morris Water Maze), contextual and cued fear conditioning, and novel object recognition. Using X- ray CT, immunohistochemical and stereological methods we will analyze alterations in large vessels and in the microvasculature, including the presence of abnormal vasculature and changes in vascular density, length, and volume. Biochemical analyses will identify any molecular structural changes in the microvasculature induced by FGF1 treatment. Collectively, the proposed studies will explore the potential therapeutic benefits of FGF1 for the treatment of blast-induced PTSD. These studies may uncover new therapeutic options for the treatment of active duty military personnel and veterans affected by this devastating condition.