Histopathologic and immunohistochemical comparison of human, rabbit, and swine aneurysms embolized with platinum coils

Abstract

Background and purpose: The purpose of this study was to clarify the cellular mechanisms of aneurysmal healing by comparing histologic and immunohistochemical findings in experimental rabbit and swine aneurysms to a human aneurysm embolized with platinum coils.

Methods: Swine sidewall aneurysms (n = 5, harvested at 12 weeks) and elastase-induced rabbit aneurysms (n = 6, harvested at 24 weeks) were created and embolized. A single human aneurysm, embolized 6 years before death, was harvested following autopsy. All specimens were processed by using a modified paraffin embedding technique. Tissue was sectioned and stained with hematoxylin and eosin and Masson trichrome. Immunohistochemistry and immunofluorescence were performed with multiple antibodies, including alpha smooth muscle actin, myosin heavy chain, desmin, vimentin, and CD31.

Results: The human aneurysm's dome was filled with loose, hypocellular, amorphous tissue. The aneurysm's neck was completely covered with a thin layer of hypocellular tissue. Collagen and myofibroblasts were sparse in both the dome and neck. Rabbit aneurysms' domes were also filled with a loose, hypocellular tissue, amorphous matrix. In 5 of 6 aneurysms, a thin layer of hypocellular tissue ran along the neck. Collagen and myofibroblasts were sparse in the dome. Swine aneurysms were filled with densely infiltrated tissue, including chronic inflammatory tissue and extensive, attenuated collagen fiber bundles associated with myofibroblasts. Thick layers of myofibroblasts entirely bridged the necks.

Conclusions: Absence of collagen deposition and scant myofibroblastic reaction to platinum coil embolization are seen in the rabbit model but not in swine aneurysms. The elastase-induced aneurysm model in rabbits is more suitable than sidewall swine aneurysms for testing of modified devices aimed at improving intra-aneurysmal fibrosis.

Fig 1.

Human vertebrobasilar aneurysm embolized with platinum coils. A, Gross photograph showing thin membranous tissue at the neck with coil loops that are visible through the membrane. B, Section of the vertebrobasilar aneurysm stained with H&E (magnification 100×). The photomicrograph shows hypocellular, amorphous tissue in the dome. C, Section of the aneurysm stained with H&E (magnification 60×). This photomicrograph shows a large area of poorly organized thrombus in the aneurysm dome. D, Section stained with H&E (magnification 20×). A photomicrograph showing a thin layer of hypocellular tissue covering the neck of aneurysm. E, Immunofluorescent double stain of the vertebrobasilar aneurysm, with antibodies for SMA (red) and vimentin (green) (magnification 20×; oil). This photomicrograph shows scattered, sparse cells within the aneurysm dome, which are positive for vimentin, but negative for SMA. F, Stained with Masson trichrome (magnification 60×). It reveals that collagen deposition was absent in the aneurysm.

Fig 2.

Rabbit aneurysm embolized with platinum coils. A, Gross photograph showing a thin, translucent membranous tissue at the neck, through which coils loops are visible. B, Section of the rabbit aneurysm stained with H&E (magnification 60×). The photomicrograph shows loose, hypocellular, amorphous tissue in the dome. C, Section stained with H&E (magnification 60×). The photomicrograph illustrates the thin layer of tissue along the entire neck. D, Masson trichrome stain (magnification 60×). The photomicrograph reveals no collagen deposition within the aneurysm dome’s loose tissue. E, Immunofluorescent double stain with antibodies for SMA (red) and vimentin (green) (magnification 20×; oil). This photomicrograph reveals that the scattered cells within the aneurysm dome are positive for vimentin and negative for SMA. In addition, the cells lining the thin neovessels were shown to be positive for SMA and vimentin.

Fig 3.

Swine aneurysm embolized with platinum coils. A, Gross photograph showing a smooth, thick membrane completely covering the neck. Coil loops are not visible through this membrane. B, Section of the swine aneurysm stained with H&E (magnification 60×). The photomicrograph shows diffuse, attenuated chronic inflammatory tissue within the aneurysm dome. C, Stained with H&E (magnification 60×). This photomicrograph shows extensive, attenuated, fibrous tissue within the dome, which is associated with rich neovessels. D, Section stained with Masson trichrome (magnification 60×). A photomicrograph shows diffuse, attenuated, abundant, collagen fibers within the aneurysm dome. E, Section stained with H&E (magnification 40×). A photomicrograph of this stained section shows a thick layer of hypercellular tissue along aneurysm neck. F, Immunofluorescent double stain with antibodies for SMA (red) and vimentin (green) (magnification = 20×; oil). This photomicrograph reveals the attenuated cells at neck of aneurysm are positive for both SMA and vimentin, which indicates classic neointimal formation.