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


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.
Su
Jian-Hua
JH
Department of Neurology, the First Affiliated Hospital of Nanjing Medical University, Nanjing- 210 029, China.
Chen
Yu-Fang
YF
Tang
Jin-Rong
JR
Wu
Le
L
Zhang
Ping
P
Yu
Long-Bin
LB
Niu
Qi
Q
Xiao
Hang
H
D000818:Animals; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005444:Flunarizine / Q000627:therapeutic use*; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D009431:Neural Conduction / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects; D020426:Sciatic Neuropathy / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D018709:Statistics, Nonparametric
D002121:Calcium Channel Blockers; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D005444:Flunarizine