From the Division of Traumatology, Surgical Critical Care and Emergency Surgery, Department of Surgery (M.C.C., M.C., P.B., A.T., C.J., P.S., L.J.K., J.L.P.), and Center for Brain Injury and Repair, Department of Neurosurgery (M.C.C., M.C., P.B., A.T., A.P.G., E.A., K.D.B., C.J., P.S., L.J.K., D.F.M., D.H.S., J.L.P.), Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
J Trauma Acute Care Surg. 2024 Jan 1;96(1):26-34. doi: 10.1097/TA.0000000000004155. Epub 2023 Oct 19.
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 postinjury. We hypothesized that early (1 hour post-TBI) but not late (24 hours post-TBI) TXA administration improves cognitive recovery for 14 days.
CD1 male mice (n = 25) were randomized to severe TBI (injury [I], by controlled cortical impact) or sham craniotomy (S) followed by intravenous saline at 1 hour (placebo [P1]) or 30 mg/kg TXA at 1 hour (TXA1) or 24 hours (TXA24). Daily body weights, Garcia Neurological Test scores, brain/lung water content, and Morris water maze exercises quantifying swimming traffic in the platform quadrant (zone [Z] 1) and platform area (Z5) were recorded for up to 14 days.
Among injured groups, I-TXA1 demonstrated fastest weight gain for 14 days and only I-TXA1 showed rapid (day 1) normalization of Garcia Neurological Test ( p = 0.01 vs. I-P1, I-TXA24). In cumulative spatial trials, compared with I-TXA1, I-TXA24 hindered learning (distance to Z5 and % time in Z1, p < 0.05). Compared with I-TXA1, I-TXA24 showed poorer memory with less Z5 time (0.51 vs. 0.16 seconds, p < 0.01) and Z5 crossing frequency. Unexpectedly, TXA in uninjured animals (S-TXA1) displayed faster weight gain but inferior learning and memory.
Early TXA appears beneficial for cognitive and behavioral outcomes following TBI, although administration 24 hours postinjury consistently impairs cognitive recovery. Tranexamic acid in sham animals may lead to adverse effects on cognition.
在 TBI 后早期（而非晚期）使用氨甲环酸（TXA）可保持血脑屏障的完整性，但尚不清楚剂量时机是否以及如何影响受伤后数小时的认知恢复。我们假设早期（TBI 后 1 小时）而非晚期（TBI 后 24 小时）给予 TXA 可改善 14 天的认知恢复。
CD1 雄性小鼠（n=25）随机分为严重 TBI（损伤[I]，通过皮质冲击控制）或假手术（S），然后在 1 小时时静脉注射生理盐水（安慰剂[P1]）或 1 小时时 30mg/kg TXA（TXA1）或 24 小时时 TXA24）。记录每日体重、加西亚神经功能测试评分、脑/肺含水量以及 Morris 水迷宫实验（用于量化平台象限（Z1）和平台区域（Z5）的游泳流量），持续 14 天。
在受伤组中，I-TXA1 在 14 天内体重增长最快，只有 I-TXA1 在第 1 天迅速恢复加西亚神经功能测试（与 I-P1、I-TXA24 相比，p=0.01）。在累积空间试验中，与 I-TXA1 相比，I-TXA24 阻碍了学习（到达 Z5 的距离和 Z1 中的时间百分比，p<0.05）。与 I-TXA1 相比，I-TXA24 在 Z5 时间（0.51 秒对 0.16 秒，p<0.01）和 Z5 穿越频率上表现出较差的记忆。出乎意料的是，未受伤动物（S-TXA1）中的 TXA 表现出更快的体重增加，但学习和记忆能力更差。
TBI 后早期使用 TXA 似乎对认知和行为结果有益，尽管损伤后 24 小时给药会持续损害认知恢复。假手术动物中的氨甲环酸可能对认知产生不利影响。
