Tauroursodeoxycholic acid alleviates secondary injury in spinal cord injury mice by 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 aims to investigate the protective effects of TUDCA in the 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 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. Results 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. Conclusions 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.

Selenium nanoparticles derived from Proteus mirabilis YC801 alleviate oxidative stress and inflammatory response to promote nerve repair in rats with spinal cord injury

“…After SCI, a high amount of MDA and ROS was produced in the injury site. Over time, GSH-Px and SOD are produced to remove the free radicals and scavenge ROS-induced lipid peroxides to protect the tissue function [ 35 ]. To evaluate the inhibitory effects of SeNPs at different concentrations on the oxidative stress of the SCI rats in vivo , the expressions of MDA, ROS, SOD, and GSH-Px were detected ( Fig.…”

Comparative Analysis of Urso- and Tauroursodeoxycholic Acid Neuroprotective Effects on Retinal Degeneration Models

“…In this experiment, TUDCA was more efficacious than UDCA in reducing microglial activation. One study reported the comparative efficacy of TUDCA and UDCA in a laser-induced choroidal neovascularization (CNV) model, showing similar effects in terms of CNV suppression [ 13 ]. However, only TUDCA was associated with early inhibition of VEGF in the retina after laser injury, which indicates that other mechanisms might be involved in the suppression of CNV by UDCA.…”

“…Anti-inflammatory and antioxidant effects have been reported for TUDCA in photoreceptor degeneration models [ 8 , 9 , 12 ]. Additionally, TUDCA showed beneficial effects on axonal regeneration and amyloid-beta synaptic toxicity in a spinal cord injury model and in cortical neurons [ 12 , 13 ]. The neuroprotective effect of UDCA also has been demonstrated, although in a limited number of animal models [ 14 , 15 ].…”

Evaluation of neuroprotective and immunomodulatory properties of mesenchymal stem cells in an ex vivo retinal explant model

“…It allows clearance of debris, restores tissue homeostasis, and promotes tissue repair by inhibiting inflammation through the production of anti-inflammatory, neurotrophic factors, and chemokine receptors [ 14 – 16 , 18 ]. Several M2 phenotype markers characterize this M2 state, e.g., the enzyme Arginase 1 (ARG1), a marker of microglia involved in tissue repair and phagocytosis, the receptor CD163, a marker of microglia implicated in the anti-inflammatory process and healing, IL-10, an anti-inflammatory cytokine used by the M2 subtype to antagonize the pro-inflammatory phase and healing, and TNFα-stimulated gene-6 (TSG-6/TNFAIP6), which is a key anti-inflammatory factor produced by MSCs [ 19 – 22 ]. Reducing the pro-inflammatory M1 phenotype or inducing M2 microglial polarization might represent a potential and promising therapeutic option to treat neuroinflammatory degenerative diseases such as glaucoma [ 9 , 23 – 25 ].…”