Abstract
BackgroundTauroursodeoxycholic 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.MethodsThe 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.ResultsWe 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.ConclusionsTUDCA 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.
Highlights
Spinal cord injury (SCI) refers to complete or incomplete spinal motor and sensory dysfunction caused by injury to the spinal cord
We found that Tauroursodeoxycholic acid (TUDCA) protected mouse cortical neurons from oxidative stress by reducing reactive oxygen species (ROS) generation and Lactate dehydrogenase (LDH) release caused by H2O2 treatment and restoring Superoxide dismutase (SOD) activity (Figure S1)
We found that TUDCA was nontoxic to mouse cortical neurons
Summary
Spinal cord injury (SCI) refers to complete or incomplete spinal motor and sensory dysfunction caused by injury to the spinal cord. The pathophysiological process of SCI includes primary and secondary injuries [1,2,3]. The primary injury is caused by initial mechanical damage to the spinal cord which is an irreversible process [4, 5]. Inhibiting the progression of the second injury timely through attenuating oxidative stress and inflammation will benefit to reduce neuronal cell death and promote axon regeneration after primary injury, which could be an effective strategy to alleviate the neurological impairment of SCI [8, 9]. 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
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