Injectable Hydrogel Containing Tauroursodeoxycholic Acid for Anti-neuroinflammatory Therapy After Spinal Cord Injury in Rats

Mol Neurobiol. 2020 Oct;57(10):4007-4017. doi: 10.1007/s12035-020-02010-4. Epub 2020 Jul 9.

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: Drug delivery systems; Hydrogel; Neuroinflammation; Spinal cord injuries; Tauroursodeoxycholic acid.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Apoptosis / drug effects
  • Behavior, Animal
  • Chitosan / chemistry
  • Cytokines / metabolism
  • Glial Fibrillary Acidic Protein / metabolism
  • Hyaluronic Acid / chemistry
  • Hydrogels / chemistry*
  • Inflammation Mediators / metabolism
  • Injections*
  • MAP Kinase Signaling System / drug effects
  • Motor Activity / drug effects
  • Neuraminidase / metabolism
  • Phosphorylation / drug effects
  • Rats, Sprague-Dawley
  • Recovery of Function / drug effects
  • Spinal Cord Injuries / drug therapy*
  • Spinal Cord Injuries / enzymology
  • Spinal Cord Injuries / physiopathology
  • Taurochenodeoxycholic Acid / pharmacology
  • Taurochenodeoxycholic Acid / therapeutic use*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Glial Fibrillary Acidic Protein
  • Hydrogels
  • Inflammation Mediators
  • Tumor Necrosis Factor-alpha
  • Taurochenodeoxycholic Acid
  • ursodoxicoltaurine
  • Hyaluronic Acid
  • Chitosan
  • Neuraminidase