Injury severity in blast induced Traumatic Brain Injury (bTBI) increases with blast overpressure (BOP) and impulse in dose-dependent manner. Pure primary blast waves were simulated in compressed gas shock-tubes in discrete increments. Present work demonstrates 24 hour survival of rats in 0–450 kPa (0–800 Pa∙s impulse) range at 10 discrete levels (60, 100, 130, 160, 190, 230, 250, 290, 350 and 420 kPa) and determines the mortality rate as a non-linear function of BOP. Using logistic regression model, predicted mortality rate (PMR) function was calculated, and used to establish TBI severities. We determined a BOP of 145 kPa as upper mild TBI threshold (5% PMR). Also we determined 146–220 kPa and 221–290 kPa levels as moderate and severe TBI based on 35%, and 70% PMR, respectively, while BOP above 290 kPa is lethal. Since there are no standards for animal bTBI injury severity, these thresholds need further refinements using histopathology, immunohistochemistry and behavior. Further, we specifically investigated mild TBI range (0–145 kPa) using physiological (heart rate), pathological (lung injury), immuno-histochemical (oxidative/nitrosative and blood-brain barrier markers) as well as blood borne biomarkers. With these additional data, we conclude that mild bTBI occurs in rats when the BOP is in the range of 85–145 kPa.

Traumatic brain injury (TBI) impacts over 3.17 million Americans. Management of hemorrhage and coagulation caused by vascular disruption after TBI is critical for the recovery of patients. Cerebrovascular pathologies play an important role in the underlying mechanisms of TBI. The objective of this study is to evaluate a novel regenerative medicine for the injured tissue after brain injury. We utilized a recently described synthetic growth factor with angiogenic potential to facilitate vascular growth in situ at the injury site. Previous work has shown how this injectable self-assembling peptide-based hydrogel (SAPH) creates a regenerative microenvironment for neovascularization at the injury site. Supramolecular assembly allows for thixotropy; the injectable drug delivery system provides sustained in vivo efficacy. In this study, a moderate blunt injury model was used to cause physical vascular damage and hemorrhage. The angiogenic SAPH was then applied directly on the injured rat brain. At day 7 post-TBI, significantly more blood vessels were observed than the sham and injury control group, as well as activation of VEGF-receptor 2, demonstrating the robust angiogenic response elicited by the angiogenic SAPH. Vascular markers von-Willebrand factor (vWF) and α-smooth muscle actin (α-SMA) showed a concomitant increase with blood vessel density in response to the angiogenic SAPH. Moreover, blood brain barrier integrity and blood coagulation were also examined as the parameters to indicate wound recovery post TBI. Neuronal rescue examination by NeuN and myelin basic protein staining showed that the angiogenic SAPH may provide and neuroprotective benefit in the long-term recovery.