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

Overview

Journal Mol Neurobiol

Specialties Molecular Biology
Neurology

Date 2018 Apr 26

PMID 29691718

Citations 34

Authors

Wan-Kyu Ko

Seong Jun Kim

Min-Jae Jo

Hyemin Choi

Donghyun Lee

Il Keun Kwon

Soo-Hong Lee

In-Bo Han

Seil Sohn

Affiliations

Soon will be listed here.

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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References

Sweitzer S, Colburn R, Rutkowski M, DeLeo J . Acute peripheral inflammation induces moderate glial activation and spinal IL-1beta expression that correlates with pain behavior in the rat. Brain Res. 1999; 829(1-2):209-21. DOI: 10.1016/s0006-8993(99)01326-8. View

Cheng Y, Tauschel H, Nilsson A, Duan R . Ursodeoxycholic acid increases the activities of alkaline sphingomyelinase and caspase-3 in the rat colon. Scand J Gastroenterol. 1999; 34(9):915-20. DOI: 10.1080/003655299750025408. View

Bethea J, Nagashima H, Acosta M, Briceno C, Gomez F, Marcillo A . Systemically administered interleukin-10 reduces tumor necrosis factor-alpha production and significantly improves functional recovery following traumatic spinal cord injury in rats. J Neurotrauma. 1999; 16(10):851-63. DOI: 10.1089/neu.1999.16.851. View

Hayashi M, Ueyama T, Nemoto K, Tamaki T, Senba E . Sequential mRNA expression for immediate early genes, cytokines, and neurotrophins in spinal cord injury. J Neurotrauma. 2000; 17(3):203-18. DOI: 10.1089/neu.2000.17.203. View

Kim G, Ahmed S, Xu J, Yan P, Xu X, Hsu C . Glucocorticoid receptor-mediated suppression of activator protein-1 activation and matrix metalloproteinase expression after spinal cord injury. J Neurosci. 2001; 21(1):92-7. PMC: 6762457. View

Lazaridis K, Gores G, Lindor K . Ursodeoxycholic acid 'mechanisms of action and clinical use in hepatobiliary disorders'. J Hepatol. 2001; 35(1):134-46. DOI: 10.1016/s0168-8278(01)00092-7. View

Noble L, Donovan F, Igarashi T, Goussev S, Werb Z . Matrix metalloproteinases limit functional recovery after spinal cord injury by modulation of early vascular events. J Neurosci. 2002; 22(17):7526-35. PMC: 2792199. View

Hausmann O . Post-traumatic inflammation following spinal cord injury. Spinal Cord. 2003; 41(7):369-78. DOI: 10.1038/sj.sc.3101483. View

Bareyre F, Schwab M . Inflammation, degeneration and regeneration in the injured spinal cord: insights from DNA microarrays. Trends Neurosci. 2003; 26(10):555-63. DOI: 10.1016/j.tins.2003.08.004. View

10.

Qian T, Guo X, Levi A, Vanni S, Shebert R, Sipski M . High-dose methylprednisolone may cause myopathy in acute spinal cord injury patients. Spinal Cord. 2004; 43(4):199-203. DOI: 10.1038/sj.sc.3101681. View

11.

Beattie M . Inflammation and apoptosis: linked therapeutic targets in spinal cord injury. Trends Mol Med. 2004; 10(12):580-3. DOI: 10.1016/j.molmed.2004.10.006. View

12.

Thuret S, Moon L, Gage F . Therapeutic interventions after spinal cord injury. Nat Rev Neurosci. 2006; 7(8):628-43. DOI: 10.1038/nrn1955. View

13.

Fleming J, Norenberg M, Ramsay D, Dekaban G, Marcillo A, Saenz A . The cellular inflammatory response in human spinal cords after injury. Brain. 2006; 129(Pt 12):3249-69. DOI: 10.1093/brain/awl296. View

14.

Donnelly D, Popovich P . Inflammation and its role in neuroprotection, axonal regeneration and functional recovery after spinal cord injury. Exp Neurol. 2007; 209(2):378-88. PMC: 2692462. DOI: 10.1016/j.expneurol.2007.06.009. View

15.

Collins T . ImageJ for microscopy. Biotechniques. 2007; 43(1 Suppl):25-30. DOI: 10.2144/000112517. View

16.

Genovese T, Esposito E, Mazzon E, Muia C, Di Paola R, Meli R . Evidence for the role of mitogen-activated protein kinase signaling pathways in the development of spinal cord injury. J Pharmacol Exp Ther. 2008; 325(1):100-14. DOI: 10.1124/jpet.107.131060. View

17.

Schmittgen T, Livak K . Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 2008; 3(6):1101-8. DOI: 10.1038/nprot.2008.73. View

18.

Beck K, Nguyen H, Galvan M, Salazar D, Woodruff T, Anderson A . Quantitative analysis of cellular inflammation after traumatic spinal cord injury: evidence for a multiphasic inflammatory response in the acute to chronic environment. Brain. 2010; 133(Pt 2):433-47. PMC: 2858013. DOI: 10.1093/brain/awp322. View

19.

Qiao F, Atkinson C, Kindy M, Shunmugavel A, Morgan B, Song H . The alternative and terminal pathways of complement mediate post-traumatic spinal cord inflammation and injury. Am J Pathol. 2010; 177(6):3061-70. PMC: 2993269. DOI: 10.2353/ajpath.2010.100158. View

20.

Yin X, Yin Y, Cao F, Chen Y, Peng Y, Hou W . Tanshinone IIA attenuates the inflammatory response and apoptosis after traumatic injury of the spinal cord in adult rats. PLoS One. 2012; 7(6):e38381. PMC: 3365897. DOI: 10.1371/journal.pone.0038381. View