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. 2001 Aug;22(7):1410-7.

Delivery of human vascular endothelial growth factor with platinum coils enhances wall thickening and coil impregnation in a rat aneurysm model

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Delivery of human vascular endothelial growth factor with platinum coils enhances wall thickening and coil impregnation in a rat aneurysm model

J M Abrahams et al. AJNR Am J Neuroradiol. 2001 Aug.

Abstract

Background and purpose: Histopathologic studies indicate that aneurysms treated with Guglielmi detachable coils (GDCs) have avascular centers with fibrosis mostly at the aneurysm periphery. We hypothesized that vascular endothelial growth factor (VEGF) released from a coil promotes clot organization, hyperplasia, and endothelial proliferation to facilitate closure of the aneurysm neck.

Methods: GDC segments were inserted into ligated common carotid arteries (CCAs) of adult male rats for 14 days. Coil segments (4-mm) were unmodified, modified with type I collagen (2.4 mg/mL), or modified with type I collagen and recombinant human VEGF-165 (rhVEGF; 500 microg/mL). CCA segments were harvested and coils removed for scanning electron microscopy (SEM).

Results: Collagen/rhVEGF coils (n = 11) resulted in marked reductions in CCA lumen area (0.03 mm(2)) compared with coils (n = 9, 0.21 mm(2), P <.001) and collagen coils (n = 5, 0.13 mm(2), P <.001). Collagen/rhVEGF coils (n = 11) also resulted in marked reductions in CCA diameter (0.19 mm) compared with coils (n = 9, 0.50 mm, P <.001) and collagen coils (n = 5, 0.40 mm, P <.001). Wall thickness was greater for the collagen/rhVEGF coil segments (0.22 mm) compared with coils (0.09 mm, P <.001), and the collagen coils (0.15 mm, P =.06). CCA segments containing collagen/rhVEGF coils also displayed Factor VIII positivity and were completely encapsulated in fibrotic tissue, while the unmodified and collagen coils were essentially smooth, as seen by SEM.

Conclusion: These results suggest that rhVEGF may be beneficial in promoting endothelialization, clot organization, and tissue integration of the coils. This is the first study to hypothesize that rhVEGF may be useful as a surface modification to GDCs for enhancing their therapeutic effects in the treatment of cerebral aneurysms.

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Figures

<sc>fig</sc> 1.
fig 1.
A, Exposure of the CCA showing the temporary proximal and permanent distal ligatures. B, The coil has been inserted into the CCA, a permanent ligature has been placed proximal to the arteriotomy, and the temporary ligature has been released.
<sc>fig</sc> 2.
fig 2.
Histopathologic findings (stained with H&E) in the CCA segments for each group after 14 day coil implantation (original magnification ×20). A, Contralateral control. B, Coil. C, Coil + collagen. D, Coil + collagen/rhVEGF.
<sc>fig</sc> 3.
fig 3.
Bar graphs comparing the results of the quantitative analysis. A, Lumen area. B, Lumen diameter. C, Vessel wall thickness.
<sc>fig</sc> 4.
fig 4.
Immunohistochemical staining for Factor VIII. A, Control CCA section showing positive staining along the endothelium (original magnification ×40). B, CCA section from coil coated with collagen/rhVEGF with positive staining in areas of neovascularization (original magnification ×40).
<sc>fig</sc> 5.
fig 5.
SEMs of the surfaces of coil segments from different groups. A, Unmodified coil (original magnification ×200). B, Coil + collagen (original magnification ×200). C, Coil + collagen/rhVEGF (original magnification ×150). Note the intense cellular reaction with coil + collagen/rhVEGF.

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