부산대학교 도서관

BACKGROUND: Early but not late tranexamic acid (TXA) after TBI preserves blood-brain-barrier integrity, but it is unclear if and how dose timing affects cognitive recovery beyond hours post-injury. We hypothesized that early (1 h post-TBI) but not late (24 h post-TBI) TXA administration improves cognitive recovery for 14 days. METHODS: CD1 male mice (n = 25) were randomized to severe TBI (Injury, [I] by controlled cortical impact) or sham craniotomy (S) followed by IV saline at 1 h (placebo, P1) or 30 mg/kg TXA at 1 h or 24 h (TXA1, TXA24). Daily body weights, Garcia Neurological Test (GNT) scores, brain/lung water content and Morris water maze exercises quantifying swimming traffic in the platform quadrant (Z1) & platform area (Z5) were recorded for up to 14 days. RESULTS: Among injured groups, I + TXA1 demonstrated fastest weight gain for 14 days and only I + TXA1 showed rapid (day 1) normalization of GNT (p = 0.01 vs. I + P1, I + TXA24). In cumulative spatial trials, compared to I + TXA1, I + TXA24 hindered learning (distance to Z5 and % time in Z1: p < 0.05). Compared to I + TXA1, I + TXA24 showed poorer memory with less Z5 time (0.51 vs 0.16 s, p < 0.01) and Z5 crossing frequency. Unexpectedly, TXA in uninjured animals (S + TXA1) displayed faster weight gain, but inferior learning and memory. CONCLUSION: Early TXA appears beneficial for cognitive and behavioral outcomes following TBI, though administration 24 h post-injury consistently impairs cognitive recovery. TXA in sham animals may lead to adverse effects on cognition.