Neuroprotective Effects of Direct Intrathecal Administration of Granulocyte Colony-Stimulating Factor in Rats with Spinal Cord Injury

CNS Neurosci Ther. 2015 Sep;21(9):698-707. doi: 10.1111/cns.12429. Epub 2015 Jul 20.

Abstract

Aims: To date, no reliable methods have proven effective for treating spinal cord injury (SCI). Even systemic administration of methylprednisolone (MP) remains controversial. We previously reported that intrathecal (i.t.) administration of granulocyte colony-stimulating factor (G-CSF) improves outcome after experimental spinal cord ischemic insults in rats. The present study aimed to examine the neuroprotective efficacy of i.t. G-CSF or MP in rats with SCI.

Methods: Female rats were subjected to spinal cord contusion injury at T10 using NYU impactor. We i.t. administered G-CSF (10 μg) or MP (one bolus of 100 μg, followed by 18 μg/h infusion for 23 h) immediately after SCI.

Results: Both G-CSF and MP significantly improved the rats' motor function after SCI. Immunofluorescence staining revealed suppressed expression of transforming growth factor-beta 1 (TGF-β1), chondroitin sulfate proteoglycans (neurocan and phosphacan), OX-42 and tumor necrosis factor alpha after i.t. G-CSF, but not MP, in rats with SCI. In addition, G-CSF significantly decreased the expression of astrocytic TGF-β1 and glial fibrillary acidic protein around the injury site. Furthermore, rats with G-CSF treatment showed increased neurofilament expression beyond the glial scars.

Conclusion: Direct i.t. administration of G-CSF provides a promising therapeutic option for SCI or related spinal diseases.

Keywords: G-CSF; Intrathecal; Methylprednisolone; Spinal cord injury; Transforming growth factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / drug effects
  • Astrocytes / metabolism
  • Astrocytes / pathology
  • Axons / drug effects
  • Axons / metabolism
  • Axons / pathology
  • Chondroitin Sulfate Proteoglycans / metabolism
  • Disease Models, Animal
  • Female
  • Granulocyte Colony-Stimulating Factor / administration & dosage*
  • Injections, Spinal
  • Intermediate Filaments / metabolism
  • Microglia / drug effects
  • Microglia / metabolism
  • Microglia / pathology
  • Motor Activity / drug effects
  • Neurocan
  • Neuroprotective Agents / administration & dosage*
  • Rats, Wistar
  • Receptor-Like Protein Tyrosine Phosphatases, Class 5 / metabolism
  • Recovery of Function / drug effects
  • Spinal Cord / drug effects*
  • Spinal Cord / metabolism
  • Spinal Cord / pathology
  • Spinal Cord Injuries / drug therapy*
  • Spinal Cord Injuries / pathology
  • Spinal Cord Injuries / physiopathology
  • Transforming Growth Factor beta1 / metabolism
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Chondroitin Sulfate Proteoglycans
  • Ncan protein, rat
  • Neurocan
  • Neuroprotective Agents
  • Transforming Growth Factor beta1
  • Tumor Necrosis Factor-alpha
  • Granulocyte Colony-Stimulating Factor
  • Receptor-Like Protein Tyrosine Phosphatases, Class 5