Preclinical extracranial aneurysm models for the study and treatment of brain aneurysms: A systematic review

Abstract

Animal models make an important contribution to our basic understanding of the pathobiology of human brain aneurysms, are indispensable in testing novel treatment approaches, and are essential for training interventional neuroradiologists and neurosurgeons. Researchers are confronted with a broad diversity of models and techniques in various species. This systematic review aims to summarize and categorize extracranial aneurysm models and their characteristics, discuss advantages and disadvantages, and suggest the best use of each model. We searched the electronical Medline/PubMed database between 1950 and 2020 to identify main models and their refinements and technical modifications for creation of extracranial aneurysms. Each study included was assessed for aneurysm-specific characteristics, technical details of aneurysm creation, and histological findings. Among more than 4000 titles and abstracts screened, 473 studies underwent full-text analysis. From those, 68 different techniques/models in five different species were identified, analyzed in detail, and then grouped into one of the five main groups of experimental models as sidewall, terminal, stump, bifurcation, or complex aneurysm models. This systematic review provides a compact guide for investigators in selecting the most appropriate model from a range of techniques to best suit their experimental goals, practical considerations, and laboratory environment.

Keywords: Aneurysm; animal model; endovascular therapy; intracranial aneurysm; saccular.

Figure 1.

PRISMA flowchart of PubMed search strategy and selection process. Among more than 4000 titles and abstracts screened, 473 studies underwent detailed full-text analysis. From those, 68 models, including refinements and technical modifications, were identified in five different species.

Figure 2.

Main groups of extracranial aneurysm models. Preclinical extracranial aneurysm models in different species can be categorized into one of the five main groups. Top form left to right: (1) sidewall aneurysm models, (2) bifurcation stump aneurysm models, and (3) terminal aneurysm models. Down from left to right: (4) natural and artificial bifurcation aneurysm models and (5) complex aneurysm models.

Figure 3.

Anatomical locations of extracranial aneurysm models. Green circle: modified pouch; blue circle: venous pouch; red circle: arterial pouch. AAA: abdominal aortic artery; CCA: common carotid artery; CIA: common iliac artery; ECA: external carotid artery; FA: femoral artery; IA: iliac artery bifurcation; ICA: internal carotid artery; IIA: internal iliac artery; LA: lingual artery; RA: renal artery; SA: subclavian artery; STA: superior thyroid artery; VA: vertebral artery.

Figure 4.

Sidewall, stump, and terminal aneurysm models. Sidewall aneurysms are created by suturing either a venous (A1) or arterial (A2) unmodified pouch onto a parent artery. Stump aneurysms are created by endovascular occlusion, ligature, or flap construction of a branching artery (B1–B5). Modification of the aneurysm wall (green) allows for growth of the stump into a more saccular shape. The tail artery stump represents a unique true arterial bifurcation model (B6). Terminal aneurysm models are designed to simulate flow conditions similar to human basilar and internal carotid artery bifurcation aneurysms (C1–C4).

Figure 5.

Bifurcation and complex aneurysm models. Bifurcation aneurysms are created by suturing a venous pouch into an artificially created bifurcation (D1 and D2). A natural bifurcation aneurysm model is created when a venous pouch is sutured into an already existing bifurcation (D3 and D4). Complex aneurysm models comprise a heterogenous group of microsurgically created aneurysms that mimic rare forms of intracranial aneurysms such as confluence (E1 and E2), giant sized (E3), multilobulated (E4), fusiform (E5 and E6), curved (E7), or aneurysms with a side branch (E8).