A Dried Platelet-Derived Biologic for Blood-Brain Barrier Repair and Hemorrhage Control Following TBI in Mice

Traumatic Brain Injury (TBI) is the leading cause of death in children and adults aged 18-44. Despite its high prevalence and devastating consequences, there are currently few effective therapies that target the acute, life-threatening complications of TBI - particularly cerebral edema and intracranial hemorrhage (ICH). The blood-brain barrier (BBB) and regulation of vascular stability following injury are emerging as critical therapeutic targets. In this study, we evaluate the therapeutic potential of a first-in-class, freeze-dried platelet-derived biologic (FDPlts) in a murine model of TBI. FDPlt transfusion significantly reduces post-TBI ICH and restores cerebral vascular perfusion. Additionally, FDPlts attenuate BBB permeability, suppress intravascular leukocytosis, and mitigate neuroinflammation evidenced by decreased microglial activation, astrocyte reactivity, and macrophage infiltration. Transcriptomic profiling of cortical and hippocampal tissues reveals that FDPlts downregulate gene networks associated with inflammation and fibrosis, suggesting a role for FDPlts in the modulation of post-injury repair. Mechanistically, FDPlts are enriched in Angiopoietin-1, a key bioactive protein that signals through the Tie2 receptor pathway, a central regulator of endothelial stability. Inhibition of Tie2 exacerbates BBB permeability after TBI, an effect attenuated by FDPlt administration; implicating Ang-1 as a key mediator of FDPlts mediated BBB protection in TBI. The BBB plays a vital role in maintaining cerebral homeostasis, and its breakdown after TBI initiates harmful cascades of edema, inflammation, and neuronal injury. Our findings demonstrate, for the first time, that a dried, platelet-derived biologic can promote vascular repair and neuroprotection in TBI.