Delivery of a fibrin-binding hemostatic polymer ameliorates neurovascular damage and neural tissue loss after traumatic brain injury.

Abstract

Traumatic brain injury (TBI) often induces blood leakage into brain tissues, which causes further tissue loss after the initial injury. To mitigate this secondary injury, we hypothesized that delivery of a fibrin-binding hemostatic polymer, PolySTAT, would act as a molecular patch and ameliorate brain vessel damage following TBI. We developed a three-dimensional (3D) pathology and analysis workflow to quantify the effects of PolySTAT versus a control polymer, PolySCRM, on neurovascular networks and neural tissue in whole mouse brains. Using a panel of fluorescent probes, our 3D pathology pipeline revealed that PolySTAT treatment preserves neurovascular density and function, reduces hypoxia and blood extravasation, and reduces brain tissue loss after TBI. To further corroborate the 3D microscopy-based findings, gene expression analyses show that PolySTAT attenuates the expression of inflammation and reactive gliosis biomarkers. These findings support future translational investigation of intravenous PolySTAT as an early post-injury therapy to mitigate neural tissue loss after TBI.