Tauroursodeoxycholic Acid Alleviates Secondary Injury in Spinal Cord Injury Mice Through Reducing Oxidative Stress, Apoptosis, and Inflammatory Response
Abstract Background 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 is aim to investigate the protective effects of TUDCA in SCI mouse model and the related mechanism involved.Methods The primary cortical neurons were isolated from E16.5 C57BL/6 mouse embryos. To evaluate the effect of TUDCA on oxidative stress in vitro, the cortical neurons were treated with H2O2 with or without TUDCA added. Mice were randomly divided into sham, SCI and TUDCA groups. SCI model was induced using a pneumatic impact device at T9-T10 level of vertebra. TUDCA (200 mg/kg) or equal volume of saline was intragastrically administrated daily post injury for 14 days. ResultsWe found that TUDCA reduced reactive oxygen species (ROS) generation, lactate dehydrogenase (LDH) release and restored superoxide dismutase (SOD) activity to protect primary cortical neurons from oxidative stress in vitro. In vivo, TUDCA treatment significantly reduced tissue injury, oxidative stress, inflammatory response, and apoptosis; promoted axon regeneration and remyelination in the lesion site of spinal cord of SCI mice. The functional recovery test revealed that TUDCA treatment significantly ameliorated recovery of limb function.ConclusionsTUDCA treatment can alleviate secondary injury and promote functional recovery through 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.