The effect of bevacizumab and 5-Fluorouracil combination on epidural fibrosis in a rat laminectomy model.
OBJECTIVE
An animal model of laminectomy in rats was used to study scar tissue formation around the spinal cord. Bevacizumab (BV) [a recombinant, humanized, monoclonal antibody targeting vascular endothelial growth factor], 5-Fluorouracil (5-FU) and BV+5-FU was tested in this system for its ability to decrease fibrous tissue formation.


METHODS
Twenty-eight Sprague Dawley rats were used in this sudy. Rats were divided into four groups; a control group, a BV group, a 5-FU group and a BV+5-FU group. L1-2 laminectomies were performed on the rats. The medicated groups were treated with topical drug administration. After 6 weeks, the rats were sacrified and histologic sections prepared from the spines were examined and graded by a pathologist. Epidural fibrosis and fibroblast density were evaluated under light microscope.


RESULTS
BV (Avastin: Genentech, San Francisco, CA, USA) significantly reduced the density of the scar tissue undermining the laminas (p < 0.005). Monotherapy with 5-FU did not change the scar formation in the back (p = 0.317). Combination of 5-FU and BV was more effective on reducing the epidural fibrosis after laminectomy on rats (p < 0.001).


CONCLUSIONS
Bevacizumab reduced the spinal epidural fibrosis significantly that developed in rats after laminectomy and 5-Fluorouracil combination had a synergic effect. Further investigations under the light of these findings may help to reduce epidural fibrosis formation after laminectomy.
Department of Neurosurgery, Dumlupinar University Medical Faculty, Kütahya, Turkey. arifosun@yahoo.com.
U
U
Ozkan
A
A
Osun
A
A
Samancioglu
S
S
Ercan
U
U
Firat
S
S
Kemaloglu
D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000068258:Bevacizumab; D004359:Drug Therapy, Combination; D004824:Epidural Space / Q000187:drug effects / Q000473:pathology*; D005355:Fibrosis; D005472:Fluorouracil / Q000627:therapeutic use*; D007796:Laminectomy / Q000009:adverse effects*; D008159:Lumbar Vertebrae / Q000601:surgery; D008297:Male; D011183:Postoperative Complications / Q000188:drug therapy*; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D005472:Fluorouracil