Cáceres Eder, Salazar Pascal, Torbey Michel T, Wilson Colin M, Bragin Denis E, Selwyn Reed G, Divani Afshin A
Unisabana Center for Translational Science, School of Medicine, Universidad de La Sabana, Chía, Colombia; Bioscience PhD. School of Engineering, Universidad de La Sabana, Chía, Colombia; Department of Critical Care, Clínica Universidad de La Sabana, Chía, Colombia.
Canon Medical Informatics, Inc., Minnetonka, MN, USA.
Brain Res. 2025 Sep 15;1863:149773. doi: 10.1016/j.brainres.2025.149773. Epub 2025 Jun 7.
Traumatic brain injury (TBI) continues to be a major cause of death and disability worldwide. Effective treatment options are limited, and randomized clinical data has been futile.
In this study, we assessed the efficacy of tauroursodeoxycholic acid (TUDCA) in treating TBI using a controlled cortical impact injury model in male Wistar rats.
Animals were randomized into two experimental groups: 1) TBI with sham treatment (Control, n = 12) and 2) TBI treated with intravenous infusion of 300 mg/kg TUDCA (TUDCA-treated group, n = 10) 30 min post-injury. Anxiety levels and magnetic resonance imaging studies were performed on days 1 and 7 post-injury. Animals were euthanized on day 7 for histopathological assessments.
On days 1 and 7, we observed a smaller brain lesion volume in the TUDCA-treated group compared with the Control group and greater cytotoxic edema on day 1 in the Control group. Elevated plus maze revealed a lower anxiety index for the TUDCA-treated group on day 7.
Our study showed that TBI rats treated with TUDCA at a hyperacute stage had a statistically significant reduction in lesion volume and improved levels of anxiety. However, a dose-response relationship and ideal therapeutic window still need to be determined. Future studies should consider a multiday therapy paradigm to identify the optimum intervention frequency in a mixed-gender.
创伤性脑损伤（TBI）仍然是全球范围内死亡和残疾的主要原因。有效的治疗选择有限，随机临床试验数据也未取得成效。
在本研究中，我们使用雄性Wistar大鼠的控制性皮质撞击损伤模型评估了牛磺熊去氧胆酸（TUDCA）治疗TBI的疗效。
将动物随机分为两个实验组：1）创伤性脑损伤并接受假治疗（对照组，n = 12）和2）创伤性脑损伤并在损伤后30分钟静脉输注300 mg/kg TUDCA进行治疗（TUDCA治疗组，n = 10）。在损伤后第1天和第7天进行焦虑水平评估和磁共振成像研究。在第7天对动物实施安乐死以进行组织病理学评估。
在第1天和第7天，我们观察到TUDCA治疗组的脑损伤体积小于对照组，且对照组在第1天出现更严重的细胞毒性水肿。高架十字迷宫实验显示，TUDCA治疗组在第7天的焦虑指数较低。
我们的研究表明，超急性期接受TUDCA治疗的TBI大鼠的损伤体积在统计学上显著减小，焦虑水平得到改善。然而，仍需确定剂量反应关系和理想的治疗窗。未来的研究应考虑采用多日治疗模式，以确定在混合性别中的最佳干预频率。
