Dual antiplatelet therapy increases intracerebral hemorrhage and edema after controlled cortical impact and can be partially encountered by 12/15-lipoxygenase inhibition

Traumatic brain injury (TBI) is increasingly prevalent in older age groups, many of whom receive dual antiplatelet therapy (DAPT). The impact of DAPT on post-traumatic intracranial hemorrhage (ICH) and mortality remains controversial. This study investigates ICH in a mouse TBI model under DAPT and explores the potential protective effects of 12/15-lipoxygenase (LOX) inhibition. Male C57BL6 mice received aspirin and clopidogrel in drinking water for 3 days before TBI induction via controlled cortical impact (CCI). The 12/15-LOX inhibitor BPN-27332 was administered i.p. 1 h after CCI. ICH and edema volumes were quantified 24 h post-injury, functional outcomes were assessed over 7 days, and lesion volumes were analyzed on day 7. DAPT significantly increased ICH (36.56 ± 7.1 vs 6.72 ± 2.12 mm2, p = 0.0004) and edema (21.86% ± 2.0% vs 5.94% ± 2.04%, p = 0.0002). BPN-27332 reduced ICH (29.03 ± 4.97 vs 43.99 ± 4.54 mm2, p = 0.038) and edema (7.98% ± 4.61% vs 26.11% ± 3.76%, p = 0.0064) in mice under DAPT. No significant functional differences were observed. Lesion volumes tended to be smaller in the BPN-27332 treated mice. DAPT exacerbates ICH risk in experimental TBI, while 12/15-LOX inhibition may help reduce post-traumatic ICH and edema.