From the Division of Traumatology, Surgical Critical Care and Emergency Surgery, Department of Surgery (M.C.C., P.B., A.J.L., G.N., C.L.J., L.J.K., J.L.P.), and Center for Brain Injury and Repair, Department of Neurosurgery (M.C.C., P.B., A.P.G., A.J.L., G.N., C.L.J., H.S., V.E.J., L.J.K., D.H.S., J.L.P.), Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
J Trauma Acute Care Surg. 2023 Jul 1;95(1):47-54. doi: 10.1097/TA.0000000000003971. Epub 2023 Apr 11.
Tranexamic acid (TXA) given early, but not late, after traumatic brain injury (TBI) appears to improve survival. This may be partly related to TXA-driven profibrinolysis and increased leukocyte (LEU)-mediated inflammation when administered late post-injury. We hypothesized that early TXA (1 hour post-TBI), blunts penumbral, blood-brain barrier (BBB) leukocyte-endothelial cell (LEU-EC) interactions and microvascular permeability, in vivo when compared with late administration (24 hours post-TBI).
CD1 male mice (n = 35) were randomized to severe TBI (injury by controlled cortical impact; injury: velocity, 6 m/s; depth, 1 mm; diameter, 3 mm) or sham craniotomy followed by intravenous saline (placebo) at 1 hour, or TXA (30 mg/kg) at 1 hour or 24 hours. At 48 hours, in vivo pial intravital microscopy visualized live penumbral LEU-EC interactions and BBB microvascular fluorescent albumin leakage. Neuroclinical recovery was assessed by the Garcia Neurological Test (motor, sensory, reflex, and balance assessments) and body weight loss recovery at 1 and 2 days after injury. Analysis of variance with Bonferroni correction assessed intergroup differences ( p < 0.05).
One-hour, but not 24-hour, TXA improved Garcia Neurological Test performance on day 1 post-TBI compared with placebo. Both 1 hour and 24 hours TXA similarly improved day 1 weight loss recovery, but only 1 hour TXA significantly improved weight loss recovery on day 2 compared with placebo ( p = 0.04). No intergroup differences were found in LEU rolling or adhesion between injured animal groups. Compared with untreated injured animals, only TXA at 1 hour reduced BBB permeability.
Only early post-TBI TXA consistently improves murine neurological recovery. Tranexamic acid preserves BBB integrity but only when administered early. This effect appears independent of LEU-EC interactions and demonstrates a time-sensitive effect that supports only early TXA administration.
创伤性脑损伤（TBI）后早期给予氨甲环酸（TXA）似乎可提高生存率。这可能部分与 TXA 诱导的纤维蛋白溶解和受伤后晚期给药时白细胞（LEU）介导的炎症增加有关。我们假设，与晚期给药（TBI 后 24 小时）相比，早期 TXA（TBI 后 1 小时）可减轻半影区、血脑屏障（BBB）白细胞-内皮细胞（LEU-EC）相互作用和微血管通透性，从而减轻半影区、血脑屏障（BBB）白细胞-内皮细胞（LEU-EC）相互作用和微血管通透性。
CD1 雄性小鼠（n = 35）随机分为严重 TBI（通过皮质控制冲击造成损伤；损伤速度为 6 m/s，深度为 1 mm，直径为 3 mm）或假手术颅骨切开术，随后在 1 小时静脉内给予生理盐水（安慰剂）或 TXA（30 mg/kg），分别在 1 小时或 24 小时后给药。在 48 小时时，通过活体大脑皮层微血管内活细胞显微镜观察活半影区 LEU-EC 相互作用和 BBB 微血管荧光白蛋白渗漏。通过 Garcia 神经学测试（运动、感觉、反射和平衡评估）和损伤后 1 天和 2 天的体重减轻恢复情况评估神经临床恢复情况。采用方差分析和 Bonferroni 校正评估组间差异（p < 0.05）。
与安慰剂相比，TXA 可在 TBI 后 1 天改善 Garcia 神经学测试表现，但仅在 1 小时时才有改善。1 小时和 24 小时 TXA 均可改善第 1 天的体重减轻恢复，但仅 1 小时 TXA 与安慰剂相比可显著改善第 2 天的体重减轻恢复（p = 0.04）。与未治疗的受伤动物组相比，各组之间的 LEU 滚动或黏附均无差异。与未治疗的受伤动物相比，只有 TXA 在 1 小时时可降低 BBB 通透性。
只有 TBI 后早期给予 TXA 才可一致改善小鼠神经恢复。TXA 可维持 BBB 完整性，但仅在早期给药时有效。这种作用似乎与 LEU-EC 相互作用无关，并证明了一种时间敏感的作用，仅支持早期 TXA 给药。
