The effect of bevacizumab and 5-Fluorouracil combination on epidural fibrosis in a rat laminectomy model

U. Ozkan, A. Osun, A. Samancioglu, S. Ercan, U. Firat, S. Kemaloglu

Department of Neurosurgery, Dumlupinar University Medical Faculty, Kütahya, Turkey. arifosun@yahoo.com

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• Neurology

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.

MATERIALS AND 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.

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