Benzbromarone improves blood hypercoagulability after TBI by reducing phosphatidylserine externalization through inhibition of TMEM16F expression

Abstract

Aims

Traumatic brain injury-induced coagulopathy (TBI-IC) frequently occurs after TBI, exacerbating the severity of TBI and affecting patient prognosis. Benzbromarone (BBR) is commonly used to treat hyperuricemia; however, its protective effects against TBI-IC remain unknown. Therefore, we explored whether BBR could improve TBI.

Materials and methods

C57BL/6 wild-type mice were subjected to fluid percussion injury to mimic TBI, and BBR was administered intraperitoneally 30 min after TBI. Magnetic resonance imaging (MRI) and Evans blue dye extravasation were used to assess the prognosis, tail bleeding time, ELISA, and coagulation tests assess coagulation function. We further explored the potential mechanism by which BBR alleviates hypercoagulation after TBI using flow cytometry.

Key findings

The intraperitoneally injected BBR group showed improved survival and neurological severity scores compared to the TBI group. Subsequently, we found that hypercoagulability developed 3 h after TBI and that the administration of BBR improved this hypercoagulability. BBR also reduced the degree of platelet phosphatidylserine (PS) exposure after TBI, platelet activation, and Ca2+ overload, in addition to inhibition of scramblase activity in procoagulant platelets.

Significance

Our findings indicate that BBR reduces PS externalization by inhibiting TMEM16F expression, thereby improving blood hypercoagulability after TBI.