Blood brain barrier (BBB) dysfunction associated with increased expression of tissue and urokinase plasminogen activators following peripheral thermal injury

Emerging data suggests the serine proteases, tissue plasminogen activator (tPA), and urokinase plasminogen activator (uPA), may play a detrimental role in traumatic states leading to compromise of the blood brain barrier (BBB). The purpose of our study was to define the role of endogenous tPA and uPA on the BBB following peripheral burn injuries. Adult male Sprague-Dawley rats (n = 46) were studied in control and thermal injury groups. Rats were anesthetized and submerged in 100 °C water for 6 s producing a third degree burn affecting 60-70% of the total body surface area. BBB dysfunction was then evaluated by measuring the amount of Evans blue and by calculating the water content in the brain. Levels of tPA and uPA mRNA in the brain were determined with real-time polymerase chain reaction (PCR) at 3 and 7 h post-injury. Results showed an increase in the brain water content and the presence of Evans blue in the brain tissue of thermally injured rats, temporally associated with an increased expression of endogenous tPA and uPA. Our study demonstrates that peripheral thermal injury does induce an increase in the permeability of the BBB. A possible mechanism may be an increased expression of tPA and uPA.