Injectable Hydrogel Containing Tauroursodeoxycholic Acid for Anti-neuroinflammatory Therapy After Spinal Cord Injury in
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Injectable Hydrogel Containing Tauroursodeoxycholic Acid for Anti-neuroinflammatory Therapy After Spinal Cord Injury in Rats Gong Ho Han 1,2 & Seong Jun Kim 1,2 & Wan-Kyu Ko 1,2 & Daye Lee 1,2 & Jae Seo Lee 3 & Haram Nah 3 & In-Bo Han 1 & Seil Sohn 1 Received: 4 March 2020 / Accepted: 1 July 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract We investigate the anti-inflammatory effects of injectable hydrogel containing tauroursodeoxycholic acid (TUDCA) in a spinal cord injury (SCI) model. To this end, TUDCA-hydrogel (TC gel) is created by immersing the synthesized hydrogel in a TUDCA solution for 1 h. A mechanical SCI was imposed on rats, after which we injected the TC gel. After the SCI and injections, motor functions and lesions were significantly improved in the TC gel group compared with those in the saline group. The TC gel significantly decreased pro-inflammatory cytokine levels compared with the saline; TUDCA and glycol chitosan-oxidized hyaluronate were mixed at a ratio of 9:1 (CHA) gel independently. In addition, the TC gel significantly suppressed the phosphorylation of extracellular signal–regulated kinase (p-ERK) and c-Jun N-terminal kinase (p-JNK) in the mitogen-activated protein kinase (MAPK) pathway compared with the saline, TUDCA, and CHA gel independently. It also decreased tumor necrosis factor-α (TNF-α) and glial fibrillary acidic protein (GFAP), inflammatory marker, at the injured sites more than those in the saline, TUDCA, and CHA gel groups. In conclusion, the results of this study demonstrate the neuroinflammatory inhibition effects of TC gel in SCI and suggest that TC gel can be an alternative drug system for SCI cases. Keywords Spinal cord injuries . Neuroinflammation . Tauroursodeoxycholic acid . Hydrogel . Drug delivery systems
Introduction Spinal cord injury (SCI) is a type of severe trauma with poor reversibility and high disability rates. The annual incidence of spinal cord injury worldwide is estimated to be 35 patients per million [1]. SCI provokes a pro-inflammatory response via the secretion of inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and interferon (IFN)-ϒ [2]. Inflammation is involved in a wide range of Gong Ho Han and Seong Jun Kim contributed equally as the first authors. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12035-020-02010-4) contains supplementary material, which is available to authorized users. * Seil Sohn [email protected] 1
Department of Neurosurgery, CHA Bundang Medical Center, CHA University, 59, Yatap-ro, Bundang-gu, Seongnam-si, Gyeonggi-do 13496, Republic of Korea
2
Department of Biomedical Science, CHA University, Seongnam-si, Gyeonggi-do, Republic of Korea
3
Department of Dentistry, Graduate School, Kyung Hee University, Dongdaemun-gu, Seoul 02447, Republic of Korea
events, including glial scar formation and vascular permeability at the injury site [3]. In particular, the glial scar is a major impediment to axon regenera
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