2. Academic Validation
  3. Benzbromarone improves blood hypercoagulability after TBI by reducing phosphatidylserine externalization through inhibition of TMEM16F expression

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

  • Life Sci. 2025 Apr 1:366-367:123501. doi: 10.1016/j.lfs.2025.123501.
Kaiji Li 1,  Jinchao Wang 1,  Yalong Gao 2,  Xin Chen 1,  Ruilong Peng 2,  Lei Li 1,  Cong Wang 1,  Tuo Li 2,  Shu Zhang 3,  Guili Yang 4,  Jianning Zhang 5
Affiliations

Affiliations

  • 1 Tianjin Neurological Institute, Key Laboratory of Post-Neuro injury, Neuro-repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin, China; Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China.
  • 2 Department of Neurosurgery, Tianjin Huanhu Hospital, Tianjin, China.
  • 3 Tianjin Neurological Institute, Key Laboratory of Post-Neuro injury, Neuro-repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin, China; Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China; State Key Laboratory of Experimental Hematology, Tianjin, China. Electronic address: gloria523@163.com.
  • 4 Tianjin Neurological Institute, Key Laboratory of Post-Neuro injury, Neuro-repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin, China; Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China; State Key Laboratory of Experimental Hematology, Tianjin, China. Electronic address: gyang@tmu.edu.cn.
  • 5 Tianjin Neurological Institute, Key Laboratory of Post-Neuro injury, Neuro-repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin, China; Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China; State Key Laboratory of Experimental Hematology, Tianjin, China. Electronic address: jianningzhang@hotmail.com.
PMID: 39983827 DOI: 10.1016/j.lfs.2025.123501
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.

Keywords

Benzbromarone; Hypercoagulability; Phosphatidylserine; Platelet; TMEM16F; Traumatic brain injury.

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