Compensatory Neovascularization After Cauda Equina Compression in Rats

Abstract

An experimental study of compensatory neovascularization after cauda equina compression in rats. To explore the possibility that cauda equina compression induces compensatory neovascularization accompanied by an increase in the expression of vascular endothelial growth factor (VEGF). VEGF is a potent promoter of neovascularization that follows ischemia. Studies suggest that compression of the cauda equina causes ischemic changes that in turn cause an increase in VEGF expression that induces neovascularization. The mechanisms by which neovascularization develops in a compressed cauda equina are unknown. Two rectangular-solid pieces of silicone rubber were implanted in the fourth and sixth epidural spaces of rats (1 piece in each space); in the sham control group, no rubber was implanted. VEGF expression in the compressed cauda equina was assessed by immunohistochemistry and Western blotting. Ischemia and neovascularization of the cauda equina were assessed by immunostaining for hypoxia-inducible factor-1 alpha (HIF-1 alpha) and 5-bromodeoxyuridine (BrdU). The unpaired Student t test was used for statistical analysis (P < 0.05). At 14 and 21 days after surgery, ischemic changes were observed, as indicated by expression of HIF-1 alpha. In the compression group at 21 and 28 days after surgery, Western blot analysis showed a significant increase in VEGF expression (P < 0.05). VEGF was localized to pericytes, Schwann cells, and macrophages. In the compression group at 21 days after surgery, neovascularization was observed, as indicated by an increase in the number of proliferating endothelial cells (which stained positive for BrdU). Cauda equina compression seems to induce compensatory neovascularization of the cauda equina accompanied by an increase in VEGF expression.