Tauroursodeoxycholic acid (TUDCA) is a hydrophilic bile acid derivative, which has been demonstrated to have neuroprotective effects in different neurological disease models. However, the effect and underlying mechanism of TUDCA on spinal cord injury (SCI) have not been fully elucidated. This study aims to investigate the protective effects of TUDCA in the SCI mouse model and the related mechanism involved. The primary cortical neurons were isolated from E16.5 C57BL/6 mouse embryos. To evaluate the effect of TUDCA on axon degeneration induced by oxidative stress in vitro, the cortical neurons were treated with H2O2 with or without TUDCA added and immunostained with Tuj1. Mice were randomly divided into sham, SCI, and SCI+TUDCA groups. SCI model was induced using a pneumatic impact device at T9-T10 level of the vertebra. TUDCA (200 mg/kg) or an equal volume of saline was intragastrically administrated daily post-injury for 14 days. We found that TUDCA attenuated axon degeneration induced by H2O2 treatment and protected primary cortical neurons from oxidative stress in vitro. In vivo, TUDCA treatment significantly reduced tissue injury, oxidative stress, inflammatory response, and apoptosis and promoted axon regeneration and remyelination in the lesion site of the spinal cord of SCI mice. The functional recovery test revealed that TUDCA treatment significantly ameliorated the recovery of limb function. TUDCA treatment can alleviate secondary injury and promote functional recovery by reducing oxidative stress, inflammatory response, and apoptosis induced by primary injury, and promote axon regeneration and remyelination, which could be used as a potential therapy for human SCI recovery.

中文翻译：

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牛磺熊去氧胆酸通过减少氧化应激、细胞凋亡和炎症反应减轻脊髓损伤小鼠的继发性损伤

牛磺熊去氧胆酸 (TUDCA) 是一种亲水性胆汁酸衍生物，已被证明在不同的神经疾病模型中具有神经保护作用。然而，TUDCA 对脊髓损伤 (SCI) 的影响和潜在机制尚未完全阐明。本研究旨在探讨TUDCA在SCI小鼠模型中的保护作用及其相关机制。从 E16.5 C57BL/6 小鼠胚胎中分离出初级皮层神经元。为了评估 TUDCA 对体外氧化应激诱导的轴突变性的影响，用添加或不添加 TUDCA 的 H2O2 处理皮质神经元，并用 Tuj1 进行免疫染色。将小鼠随机分为假手术组、SCI组和SCI+TUDCA组。使用气动冲击装置在椎骨 T9-T10 水平诱导 SCI 模型。受伤后每天灌胃 TUDCA (200 mg/kg) 或等体积的盐水，持续 14 天。我们发现 TUDCA 减弱了 H2O2 处理诱导的轴突变性，并在体外保护初级皮层神经元免受氧化应激。在体内，TUDCA 治疗显着减少了 SCI 小鼠脊髓损伤部位的组织损伤、氧化应激、炎症反应和细胞凋亡，并促进了轴突再生和髓鞘再生。功能恢复测试显示，TUDCA 治疗显着改善了肢体功能的恢复。TUDCA 治疗可通过减少原发性损伤引起的氧化应激、炎症反应和细胞凋亡，促进轴突再生和髓鞘再生，从而减轻继发性损伤，促进功能恢复，