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Ursodeoxycholic Acid Inhibits Inflammatory Responses and Promotes Functional Recovery After Spinal Cord Injury in Rats

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Abstract

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.

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Funding

This work was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT, and future Planning (NRF-2016M3A9E8941668).

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Authors and Affiliations

  1. Department of Neurosurgery, CHA Bundang Medical Center, CHA University, 59, Yatap-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, 13496, Republic of Korea

    Wan-Kyu Ko, Seong Jun Kim, Min-Jae Jo, Hyemin Choi, In-Bo Han & Seil Sohn

  2. Department of Dentistry, Graduate School, Kyung Hee University, Dongdaemun-gu, Seoul, 02447, Republic of Korea

    Donghyun Lee

  3. Department of Dental Materials, School of Dentistry, Kyung Hee University, Dongdaemun-gu, Seoul, 02447, Republic of Korea

    Il Keun Kwon

  4. Department of Biomedical Science, CHA University, Seongnam-si, Gyeonggi-do, 13488, Republic of Korea

    Soo-Hong Lee

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  1. Wan-Kyu Ko
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  2. Seong Jun Kim
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Correspondence to In-Bo Han or Seil Sohn.

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Electronic Supplementary Material

Fig. S1

Quantification of GFAP and TNF-α in injured spinal cords. (A) Quantitative analysis of the fluorescence intensity for GFAP. (B) Analysis of the quantitative fluorescence intensity for TNF-α. Results are the mean ± SEM: *p < 0.05 and **p < 0.01, significant differences among three groups were demonstrated. (GIF 18 kb)

High resolution image (TIFF 2700 kb)

Fig. S2

Quantification of iba1 and iNOS in injured spinal cords. (A) Quantitative analysis of the fluorescence intensity for iba1. (B) Analysis of the quantitative fluorescence intensity for iNOS. Results are the mean ± SEM: *p < 0.05 and **p < 0.01, significant differences among three groups were demonstrated. (GIF 15 kb)

High resolution image (TIFF 2700 kb)

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Ko, WK., Kim, S.J., Jo, MJ. et al. Ursodeoxycholic Acid Inhibits Inflammatory Responses and Promotes Functional Recovery After Spinal Cord Injury in Rats. Mol Neurobiol 56, 267–277 (2019). https://doi.org/10.1007/s12035-018-0994-z

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  • DOI: https://doi.org/10.1007/s12035-018-0994-z

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