Investigating exacerbation of traumatic brain injury under warfarin anticoagulation in male C57BL/6J mice

STUDY PURPOSE: This study aimed to clarify how warfarin treatment exacerbates traumatic brain injury (TBI) and to assess the impact of TBI on the anticoagulant effects of warfarin. DATA COLLECTED: TBI was induced in male C57BL/6J mice after pre-treatment with oral warfarin (low dose: 0.35 mg/kg/24 h; high dose: 0.70 mg/kg/24 h). A cortical contusion (CCI model) was induced in the injury group, centered 3.5 mm posterior to the coronal suture and 3.5 mm lateral to the sagittal suture over the left parietal cortex, while the sham group underwent either scalp incision alone or with bone window formation. The injury group received cerebral contusions, while the sham group underwent either scalp incision alone or with bone window formation. Key measures, including prothrombin time-international normalized ratio (PT-INR), brain hemorrhage volume, blood levels of warfarin and 7-hydroxywarfarin (measured using LC-MS/MS), and cytochrome P450 2C9 (CYP2C9) protein expression (analyzed via capillary-based Western blot), were assessed at post-injury hours (PIHs) 2, 24, and 72.
Warfarin increased PT-INR and brain hemorrhage on the first day after injury, with higher warfarin and 7-hydroxywarfarin levels. CYP2C9 expression showed no significant difference between groups. DATA USAGE NOTES: