Dl-3-n-butylphthalide attenuates acute inflammatory activation in rats with spinal cord injury by inhibiting microglial TLR4/NF-κB signalling

J Cell Mol Med. 2017 Nov;21(11):3010-3022. doi: 10.1111/jcmm.13212. Epub 2017 Aug 25.

Abstract

In this study, we examined the neuroprotective effects and anti-inflammatory properties of Dl-3-n-butylphthalide (NBP) in Sprague-Dawley (SD) rats following traumatic spinal cord injury (SCI) as well as microglia activation and inflammatory response both in vivo and in vitro. Our results showed that NBP improved the locomotor recovery of SD rats after SCI an significantly diminished the lesion cavity area of the spinal cord, apoptotic activity in neurons, and the number of TUNEL-positive cells at 7 days post-injury. NBP inhibited activation of microglia, diminished the release of inflammatory mediators, and reduced the upregulation of microglial TLR4/NF-κB expression at 1 day post-injury. In a co-culture system with BV-2 cells and PC12 cells, NBP significantly reduced the cytotoxicity of BV-2 cells following lipopolysaccharide (LPS) stimulation. In addition, NBP reduced the activation of BV-2 cells, diminished the release of inflammatory mediators, and inhibited microglial TLR4/NF-κB expression in BV-2 cells. Our findings demonstrate that NBP may have neuroprotective and anti-inflammatory properties in the treatment of SCI by inhibiting the activation of microglia via TLR4/NF-κB signalling.

Keywords: Dl-3-n-butylphthalide (NBP); inflammatory; microglia; spinal cord injury.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Benzofurans / pharmacology*
  • Cell Line
  • Coculture Techniques
  • Female
  • Gene Expression Regulation
  • Lipopolysaccharides / antagonists & inhibitors
  • Lipopolysaccharides / pharmacology
  • Microglia / cytology
  • Microglia / drug effects*
  • Microglia / metabolism
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / genetics
  • NF-kappa B / immunology
  • Neuroprotective Agents / pharmacology*
  • PC12 Cells
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction
  • Spinal Cord / drug effects
  • Spinal Cord / immunology
  • Spinal Cord / metabolism
  • Spinal Cord / pathology
  • Spinal Cord Injuries / drug therapy*
  • Spinal Cord Injuries / genetics
  • Spinal Cord Injuries / immunology
  • Spinal Cord Injuries / pathology
  • Toll-Like Receptor 4 / antagonists & inhibitors
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / immunology

Substances

  • Anti-Inflammatory Agents
  • Benzofurans
  • Lipopolysaccharides
  • NF-kappa B
  • Neuroprotective Agents
  • Tlr4 protein, rat
  • Toll-Like Receptor 4
  • 3-n-butylphthalide