Beneficial effects of thymosin β4 on spinal cord injury in the rat

Neuropharmacology. 2014 Oct:85:408-16. doi: 10.1016/j.neuropharm.2014.06.004. Epub 2014 Jun 14.

Abstract

Thymosin β4 (Tβ4) has many physiological functions that are highly relevant to spinal cord injury (SCI), including neuronal survival, anti-inflammation, wound repair promotion, and angiogenesis. The present study investigated the therapeutic value of Tβ4 in SCI, with a focus on its neuroprotective, anti-inflammatory, and vasculoprotective properties. Tβ4 or a saline control was administered by intraperitoneal injection 30 min, 3 days, or 5 days after SCI with mild compression in rat. Locomotor recovery was tested with the Basso-Beattie-Bresnahan scale and a footprint analysis. All behavioral assessments were markedly improved with Tβ4 treatment. Histological examination at 7 days post injury showed that the numbers of surviving neurons and oligodendrocytes were significantly increased in Tβ4-treated animals compared to saline-treated controls. Levels of myelin basic protein, a marker of mature oligodendrocytes, in Tβ4-treated rats were 57.8% greater than those in saline-treated controls. The expression of ED1, a marker of activated microglia/macrophages, was reduced by 36.9% in the Tβ4-treated group compared to that of the saline-treated group. Tβ4 treatment after SCI was also associated with a significant decrease in pro-inflammatory cytokine gene expression and a significant increase in the mRNA levels of IL-10 compared to the control. Moreover, the size of lesion cavity delineated by astrocyte scar in the injured spinal cord was markedly reduced in Tβ4-treated animals compared to saline-treated controls. Given the known safety of Tβ4 in clinical trials and its beneficial effects on SCI recovery, the results of this study suggested that Tβ4 is a good candidate for SCI treatment in humans.

Keywords: Neuroprotection; Rat; Spinal cord injury; Thymosin β4.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Cytokines / metabolism
  • Disease Models, Animal
  • Interleukin-10 / metabolism
  • Macrophages / drug effects
  • Macrophages / physiology
  • Male
  • Microglia / drug effects
  • Microglia / physiology
  • Myelin Basic Protein / metabolism
  • Neuroimmunomodulation / drug effects
  • Neuroimmunomodulation / physiology
  • Neurons / drug effects
  • Neurons / pathology
  • Neurons / physiology
  • Neuroprotective Agents / pharmacology*
  • Oligodendroglia / drug effects
  • Oligodendroglia / pathology
  • Oligodendroglia / physiology
  • Random Allocation
  • Rats, Sprague-Dawley
  • Recovery of Function / drug effects*
  • Recovery of Function / physiology
  • Spinal Cord / drug effects*
  • Spinal Cord / pathology
  • Spinal Cord / physiopathology
  • Spinal Cord Injuries / drug therapy*
  • Spinal Cord Injuries / pathology
  • Spinal Cord Injuries / physiopathology
  • Thymosin / pharmacology*
  • Time Factors

Substances

  • Cytokines
  • Mbp protein, rat
  • Myelin Basic Protein
  • Neuroprotective Agents
  • Interleukin-10
  • thymosin beta(4)
  • Thymosin