Locomotor activity of rats with SCI is improved by dexmedetomidine by targeting the expression of inflammatory factors

Mol Med Rep. 2018 Jul;18(1):415-420. doi: 10.3892/mmr.2018.8930. Epub 2018 Apr 26.

Abstract

Dexmedetomidine, a well‑known selective α‑2 adrenoceptor agonist, inhibits the apoptosis of neurons and protects other organs from oxidative damage. In the present study, the effect of dexmedetomidine on spinal cord injury (SCI) in a rat model was investigated. The SCI rat model was prepared using the weight‑drop method, and the effect of dexmedetomidine on locomotor activity was analyzed using the Basso, Beattie and Bresnahan (BBB) rating scale. Western blot analysis was used to observe changes in the expression of apoptosis‑related proteins, including B‑cell lymphoma 2 (Bcl‑2) and Bcl‑2‑associated X protein (Bax). The results revealed that treatment of the SCI rats with dexmedetomidine at a dose of 50 mg/kg significantly prevented the formation of edema in the tissues of the spinal cord. Dexmedetomidine also inhibited the SCI‑induced accumulation of neutrophils in the spinal cord. The BBB scores were significantly increased (P<0.05) in the rats with SCI treated with dexmedetomidine after 10 days. The results of grid walking test revealed a marked decrease in the number of missteps following 10 days of dexmedetomidine treatment. The expression levels of tumor necrosis factor (TNF)‑α and interleukin (IL)‑1β were significantly reduced (P<0.05) in the spinal cord tissues of the dexmedetomidine group, compared with those in the control group of rats. Dexmedetomidine treatment following SCI exerted an inhibitory effect on the SCI‑induced increase in the expression of Bax. The expression of Bcl‑2 was increased in the dexmedetomidine treated rats, compared with that in the control group. Taken together, dexmedetomidine improved the locomotor activity of the rats through the inhibition of edema, reduction in the expression levels of TNF‑α and IL‑1β, and inhibition of the induction of apoptosis. Therefore, dexmedetomidine may be of therapeutic importance for patients with SCI.

MeSH terms

  • Animals
  • Dexmedetomidine / pharmacology*
  • Gene Expression Regulation / drug effects*
  • Inflammation Mediators / metabolism*
  • Interleukin-1beta / biosynthesis*
  • Locomotion / drug effects*
  • Male
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Cord Injuries / drug therapy
  • Spinal Cord Injuries / metabolism*
  • Spinal Cord Injuries / pathology
  • Spinal Cord Injuries / physiopathology
  • Tumor Necrosis Factor-alpha / biosynthesis*

Substances

  • Bcl2 protein, rat
  • IL1B protein, rat
  • Inflammation Mediators
  • Interleukin-1beta
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Necrosis Factor-alpha
  • Dexmedetomidine