Department of Surgery, University of Cincinnati, Cincinnati, Ohio.
Department of Surgery, University of Cincinnati, Cincinnati, Ohio.
J Surg Res. 2024 Oct;302:106-115. doi: 10.1016/j.jss.2024.07.023. Epub 2024 Aug 1.
Tranexamic acid (TXA) administered early after traumatic brain injury (TBI) can decrease morbidity and mortality. The purpose of this study is to determine if the timing of TXA administration after TBI affects postinjury inflammatory markers or phosphorylated tau (p-tau) levels within the hippocampus.
Male mice (9-11 wk) were split into six groups based on injury and timing of TXA administration (n = 5 per group): Sham, TBI-only, 100 mg/kg TXA-only, TBI + TXA 10 min, TBI + TXA 1 h, and TBI + TXA 6 h. Moderate concussive TBI was induced via weight drop. Serum and brain homogenates were collected at 6 and 24 h postinjury and analyzed for 14 inflammatory cytokines via multiplex enzyme-linked immunosorbent assay. Serum was analyzed for glial fibrillary acidic protein levels. Additional cohorts were survived to 30 d for hippocampal p-tau quantification using immunohistochemistry.
Serum levels of interleukin (IL) 1β (IL-1β), IL-3, IL-12, IL-17, monocyte chemoattractant protein-1, granulocyte-macrophage colony-stimulating factor, and regulated on activation, normal T-cell expressed and secreted were elevated in TBI mice compared to sham mice at 24 h. Levels of IL-1β and monocyte chemoattractant protein-1 were lower in 6-h TXA-treated mice than 1-h TXA-treated mice following TBI. IL-12 and macrophage inflammatory protein-1α levels were decreased in 6-h TXA-treated mice compared to 10-min TXA-treated mice. Administration of TXA at 10 min and 6 h but not 1 h postTBI reduced serum glial fibrillary acidic protein levels compared to TBI-only mice. Hippocampal p-tau accumulation was increased after TBI but not reduced by TXA administration.
Our results demonstrate that neither early nor delayed administration of TXA conveyed significant systemic or cerebral benefit in cytokine levels following TBI. Further research should be conducted to assess blood brain barrier integrity and neurobehavioral recovery following TXA administration postTBI.
创伤性脑损伤（TBI）后早期给予氨甲环酸（TXA）可降低发病率和死亡率。本研究的目的是确定 TBI 后 TXA 给药时间是否会影响损伤后海马内的炎症标志物或磷酸化 tau（p-tau）水平。
根据损伤和 TXA 给药时间将雄性小鼠（9-11 周）分为六组（每组 5 只）：假手术组、TBI 组、100mg/kg TXA 组、TBI+TXA 10min 组、TBI+TXA 1h 组和 TBI+TXA 6h 组。通过重物坠落诱导中度震荡性 TBI。伤后 6 和 24 小时采集血清和脑匀浆，通过多重酶联免疫吸附试验分析 14 种炎症细胞因子。分析血清中神经胶质纤维酸性蛋白的水平。另外的队列存活到 30 天，用于使用免疫组织化学定量海马 p-tau。
与假手术组相比，TBI 小鼠在 24 小时时血清白细胞介素（IL）1β（IL-1β）、IL-3、IL-12、IL-17、单核细胞趋化蛋白-1、粒细胞-巨噬细胞集落刺激因子和调节激活、正常 T 细胞表达和分泌的水平升高。与 1 小时 TXA 治疗的 TBI 小鼠相比，6 小时 TXA 治疗的 TBI 小鼠的 IL-1β 和单核细胞趋化蛋白-1 水平较低。与 10 分钟 TXA 治疗的小鼠相比，6 小时 TXA 治疗的小鼠的 IL-12 和巨噬细胞炎症蛋白-1α 水平降低。与 TBI 仅组相比，TBI 后 10 分钟和 6 小时给予 TXA 治疗而非 1 小时给药可降低血清神经胶质纤维酸性蛋白水平。TBI 后海马内 p-tau 积聚增加，但 TXA 给药不能减少。
我们的结果表明，TBI 后早期或延迟给予 TXA 均不能显著改善细胞因子水平。应进一步研究评估 TBI 后 TXA 给药对血脑屏障完整性和神经行为恢复的影响。
