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.

Autophagy exerts a protective role in cervical spinal cord injury by microglia inhibition through the nuclear factor kappa-B pathway

“…Animal procedures were approved by The First Affiliated Hospital of Hebei North University and this study was approved by the Ethics Committee of The First Affiliated Hospital of Hebei North University. To probe the property of autophagy in SCI and uncover the regulatory relationship between autophagy and microglial polarization in SCI, 10 male C57BL/6 mice (26-30 g) frequently used in the construction of SCI models [11,14,21] were anesthetized with 1% isoflurane. As described before, contusion SCI was performed (n = 5) [35].…”

Screening and evaluation of metabolites binding PRAS40 from Erxian decoction used to treat spinal cord injury

“…Therefore, research on effective SCI treatment is necessary. Previous studies have reported that SCI pathogenesis comprises multiple cellular and biochemical processes, including free radical formation (Hou et al, 2021), posttraumatic inflammatory response , autophagy (Ko et al, 2020), vascular ischemia (Ahn et al, 2020), apoptosis (Wang et al, 2019), and genetically programmed cell death (Xu et al, 2021). Autophagy is a cellular self-defense mechanism that prevents cell damage, promotes cell survival in the presence of nutrient deficiencies, and responds to cytotoxic stimuli (Klionsky et al, 2021).…”

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 in ammation through the production of anti-in ammatory, neurotrophic factors and chemokine receptors [14][15][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-in ammatory process and healing, IL-10, an anti-in ammatory cytokine used by the M2 subtype to antagonize the pro-in ammatory phase and healing, and TNFα-stimulated gene-6 (TSG-6), which is a key anti-in ammatory factor produced by MSCs [19][20][21][22]. Reducing the proin ammatory M1 phenotype or inducing M2 microglial polarization might represent a potential and promising therapeutic option to treat neuroin ammatory degenerative diseases such as glaucoma [12,[23][24][25].…”