Effects of combined treatment of minocycline and methylprednisolone on the expression of tumor necrosis factor alpha and interleukine-6 in experimental spinal cord injury: a light and electron microscopic study

Ultrastruct Pathol. 2020 May 3;44(3):283-299. doi: 10.1080/01913123.2020.1771493. Epub 2020 Jun 22.

Abstract

Spinal cord injury (SCI) is an important health problem, and there is no universal treatment protocol for it today. Following SCI pro-inflammatory mediators such as tumor necrosis factor- alpha (TNF-α) and interleukin-6 (IL-6) increase at the lesion site and play important roles in secondary tissue damage. Methylprednisolone (MP) is a glucocorticoid, and minocycline is a tetracycline-derived antibiotic both with neuroprotective effects on central nervous system trauma. However, there are limited studies on their effects on SCI. In this study, we aimed to evaluate effects of MP+minocycline combined treatment on cellular distribution and localization of TNF-α And IL-6 after SCI. Eighty Wistar rats were divided into three main groups as the intact control group, sham operation group, and experimental control group that received spinal cord compression injury. Following the injury, the experimental control group was subdivided into four groups as control, methylprednisolone treatment, minocycline treatment and, MP+minocycline combined treatment groups. Tissue samples were obtained from all groups at 24 hours and 72 hours after the injury. We found a significant decrease in TNF-α And IL-6 expressions in combined treatment group at 24 hours after injury. Also, there was a significant decrease in MDA and increase in SOD levels in this group. Furthermore, decreased lipid peroxidation and neuronal and glial cell death were also observed in combined treatment group. These results suggest that MP+minocycline combined treatment promotes functional recovery and, it should be considered as an effective treatment protocol following SCI.

Keywords: IL-6; TNF-α; methylprednisolone; minocycline; spinal cord injury; ultrastructure.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Disease Models, Animal
  • Interleukin-6 / biosynthesis
  • Methylprednisolone / pharmacology*
  • Minocycline / pharmacology*
  • Neuroprotective Agents / pharmacology
  • Rats
  • Rats, Wistar
  • Recovery of Function / drug effects
  • Spinal Cord Injuries / metabolism*
  • Spinal Cord Injuries / pathology*
  • Tumor Necrosis Factor-alpha / biosynthesis*

Substances

  • Anti-Inflammatory Agents
  • Interleukin-6
  • Neuroprotective Agents
  • Tumor Necrosis Factor-alpha
  • Minocycline
  • Methylprednisolone