Expression of VEGF and neural repair after alprostadil treatment in a rat model of sciatic nerve crush injury.
BACKGROUND
Vasoactive drug alprostadil improves microcirculation and can be effective in treating disorders of peripheral nerves. Vascular endothelial growth factor (VEGF) has been shown to have protective action in cerebral ischemia, disorders of spinal cord, and also peripheral nerves. However, the mechanism of action of VEGF in peripheral nerve injuries is uncertain.


OBJECTIVE
To study the effect of application of alprostadil on the pathological and functional repair of crush nerve injuries and also the expression of VEGF.


METHODS
Rat sciatic nerves were crushed by pincers to establish the model of crush injury. All of the 400 sprague dawley (SD) rats were randomly divided into: Control; saline; saline+VEGF-antibody; alprostadil; and alprostadil+VEGF antibody groups. The SPSS 11.5 software was used for statistical analysis. The expression of VEGF in dorsal root ganglia (DRGs), following crush injury to sciatic nerves, was studied by reverse transcribed-polymerase chain reaction (RT-PCR), immunohistochemistry, electromicroscope, and electrophysiology. The effects of alprostadil on expression of VEGF, repair of neural pathology, and recovery of neural function were also evaluated.


RESULTS
We found that VEGF messenger ribonucleic acid (mRNA) was significantly increased in alprostadil and alprostadil+VEGF-antibody groups, compared to the saline and saline+VEGF antibody groups. The number of VEGF-positive neurons was significantly increased in the alprostadil group, compared to the saline, saline+VEGF antibody, and alprostadil+VEGF antibody groups. Besides, addition of this drug also caused less pathological changes in DRGs, better improvement of nerve conduction velocities of sciatic nerves, and more increase of toe spaces of right hind limbs of rats.


CONCLUSIONS
The vasoactive agent alprostadil may reduce the pathological lesion of peripheral nerves and improve the rehabilitation of the neural function, which may relate to upregulation of the expression of VEGF, following crush injury to the peripheral nerves.
Tang
Jinrong
J
Department of Neurology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210 029, China.
Hua
Ye
Y
Su
Jianhua
J
Zhang
Ping
P
Zhu
Xuejiang
X
Wu
Le
L
Niu
Qi
Q
Xiao
Hang
H
Ding
Xinsheng
X
D000527:Alprostadil / Q000494:pharmacology* / Q000627:therapeutic use*; D000704:Analysis of Variance; D000818:Animals; D000906:Antibodies / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D005343:Fibrinolytic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D005727:Ganglia, Spinal / Q000378:metabolism / Q000648:ultrastructure; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D016253:Microscopy, Immunoelectron / Q000379:methods; D009416:Nerve Regeneration / Q000187:drug effects*; D009431:Neural Conduction / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020426:Sciatic Neuropathy / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D000906:Antibodies; D005343:Fibrinolytic Agents; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D000527:Alprostadil