Rapamycin plays a neuroprotective effect after spinal cord injury via anti-inflammatory effects

J Biochem Mol Toxicol. 2015 Jan;29(1):29-34. doi: 10.1002/jbt.21603. Epub 2014 Aug 29.

Abstract

Whether rapamycin has neuroprotective effects in spinal cord injury remains controversial. The present study shows that rapamycin protects neurons from death after spinal cord injury by inhibiting the secondary inflammatory response. The effects of rapamycin were tested using a myeloperoxidase assay, Western blotting, immunohistochemistry, and the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The experimental results showed that after spinal cord injury, rapamycin reduced the numbers of activated microglia and neutrophils in the damage zone, lowered the expression levels of TNF-α and IL-1β, reduced the apoptotic cells, and increased the survival of neurons. The above data proved that rapamycin diminishes inflammatory cell activation and proliferation, downregulates the expression of inflammatory factors, reduces the microenvironmental damage effects on neurons in the acute injury phase, and thus promotes the survival of neurons. Therefore, we believe that rapamycin has neuroprotective effects in spinal cord injury.

Keywords: Inflammation; Neuron protection; Rapamycin; Rat; Secondary damage; Spinal cord injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Survival / drug effects
  • Down-Regulation / drug effects
  • Female
  • Immunosuppressive Agents / pharmacology
  • Interleukin-1beta / biosynthesis
  • Microglia / metabolism
  • Microglia / pathology
  • Neurons / metabolism
  • Neurons / pathology
  • Neuroprotective Agents / pharmacology*
  • Rats
  • Rats, Wistar
  • Sirolimus / pharmacology*
  • Spinal Cord Injuries* / drug therapy
  • Spinal Cord Injuries* / metabolism
  • Spinal Cord Injuries* / pathology
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • Anti-Inflammatory Agents
  • IL1B protein, rat
  • Immunosuppressive Agents
  • Interleukin-1beta
  • Neuroprotective Agents
  • Tumor Necrosis Factor-alpha
  • Sirolimus