Protective effects of the calcium-channel blocker flunarizine on crush injury of sciatic nerves in a rat model

Neurol India. 2010 Jul-Aug;58(4):530-6. doi: 10.4103/0028-3886.68665.

Abstract

Background: Neural damage can be mitigated by calcium-channel blockers (CCBs). However, the mechanism of action of CCBs is not yet fully understood. Objective : To investigate the mechanism of action and efficacy of CCB, flunarizine in restoring neural function after crush injury to the nerves.

Materials and methods: The sciatic nerves of rats were crushed using pincers to establish the model for crush injury. Two hundred and eighty-eight Sprague-Dawley (SD) rats were randomly divided into sham-operated, saline, and low-dose flunarizine and high-dose flunarizine (FI and FII) groups. The expression of the protein c-fos in the dorsal root ganglia (DRG) after crush injury to the sciatic nerves was investigated by using reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. The effect of flunarizine on c-fos expression and its efficacy in restoring neural function was evaluated.

Results: The c-fos messenger ribonucleic acid (mRNA) and protein expression in FI and FII groups was significantly lower than in the saline group and was the least in the FII group. Nerve-conduction velocity was increased in the order of: saline < FI< FII< sham-operated. There was no significant difference in the nerve-conduction velocity in the sham-operated and FII groups (P>.05).

Conclusions: When administered after crush injury to peripheral nerves, flunarizine may protect neurons with lesions from further damage and improve neural function by downregulating c-fos expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Channel Blockers / therapeutic use*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Female
  • Flunarizine / therapeutic use*
  • Ganglia, Spinal / drug effects
  • Ganglia, Spinal / metabolism
  • Gene Expression Regulation / drug effects
  • Male
  • Neural Conduction / drug effects
  • Proto-Oncogene Proteins c-fos / genetics
  • Proto-Oncogene Proteins c-fos / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Sciatic Nerve / drug effects
  • Sciatic Neuropathy / etiology
  • Sciatic Neuropathy / pathology
  • Sciatic Neuropathy / prevention & control*
  • Statistics, Nonparametric

Substances

  • Calcium Channel Blockers
  • Proto-Oncogene Proteins c-fos
  • RNA, Messenger
  • Flunarizine