Ursodeoxycholic Acid Inhibits Inflammatory Responses and Promotes Functional Recovery After Spinal Cord Injury in Rats.
Wan-Kyu KoSeong Jun KimMin-Jae JoHyemin ChoiDonghyun LeeIl Keun KwonSoo-Hong LeeIn-Bo HanSeil SohnPublished in: Molecular neurobiology (2018)
The aim of this study was to investigate the anti-inflammatory effects by ursodeoxycholic acid (UDCA) in rats with a spinal cord injury (SCI). A moderate mechanical compression injury was imposed on adult Sprague-Dawley (SD) rats. The post-injury locomotor functions were assessed using the Basso, Beattie, and Bresnahan (BBB) locomotor scale and the tissue volume of the injured region was analyzed using hematoxylin and eosin staining. The pro-inflammatory factors were evaluated by immunofluorescence (IF) staining, a quantitative real-time polymerase chain reaction (qRT-PCR), and enzyme-linked immunosorbent assay (ELISA). The phosphorylation of the extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 in mitogen-activated protein kinase (MAPK) signaling pathways related to inflammatory responses were measured by Western blot assays. UDCA improved the BBB scores and promoted the recovery of the spinal cord lesions. UDCA inhibited the expression of glial fibrillary acidic protein (GFAP), tumor necrosis factor-α (TNF-α), ionized calcium-binding adapter molecule 1 (iba1), and inducible nitric oxide synthase (iNOS). UDCA decreased the pro-inflammatory cytokines of TNF-α, interleukin 1-β (IL-1β), and interleukin 6 (IL-6) in the mRNA and protein levels. UDCA increased the anti-inflammatory cytokine interleukin 10 (IL-10) in the mRNA and protein levels. UDCA suppressed the phosphorylation of ERK, JNK, and the p38 signals. UDCA reduces pro-inflammatory responses and promotes functional recovery in SCI in rats. These results suggest that UDCA is a potential therapeutic drug for SCI.
Keyphrases
- spinal cord injury
- spinal cord
- signaling pathway
- neuropathic pain
- binding protein
- nitric oxide synthase
- anti inflammatory
- protein kinase
- pi k akt
- rheumatoid arthritis
- blood brain barrier
- nitric oxide
- induced apoptosis
- cell death
- tyrosine kinase
- protein protein
- epithelial mesenchymal transition
- amino acid
- oxidative stress
- south africa
- ionic liquid
- high intensity
- young adults
- emergency department
- high throughput
- endoplasmic reticulum stress
- drug induced
- real time pcr