Erythrocyte Coupled tPA Improves Outcomes of Percussion Brain Trauma in Rats.

Coupling tissue plasminogen activator (tPA) to carrier red blood cells (RBC): i) restricts tPA’s permeation into tissues and pre-existing hemostatic clots, minimizing hemorrhage; ii) protects it from plasma inhibitors; and iii) prolongs its circulation, permitting incorporation into nascent clots and their lysis from within. These features support the thromboprophylactic utility of RBC coupled tPA (RBC/tPA). In this study we explored the utility of RBC/tPA in traumatic brain injury (TBI), a disorder in which both cerebral thrombosis leading to cerebral ischemia and intracerebral hemorrhage (ICH) have been implicated. Eleven male, Sprague-Dawley rats (340–400g) were subjected to a moderate (avg. peak pressure 2.6atm) lateral fluid percussion injury to the left hemisphere. Rats were given a single intravenous dose of RBC/tPA (0.05mg/Kg, n=5) or vehicle (n=4), 15 min post-injury. Animals were sacrificed 48h later for histopathology and staining for fibrin. The lesions in control animals occupied 8.3 ± 2.8% (mean±SD) of the hemispheric volume. Animals treated with RBC/tPA had a significant decrease in mean lesion volume (1.4±0.7%; p