Preclinical Intracranial Aneurysm Models: A Systematic Review.

Intracranial aneurysms (IA) are characterized by weakened cerebral vessel walls that may lead to rupture and subarachnoid hemorrhage. The mechanisms behind their formation and progression are yet unclear and warrant preclinical studies. This systematic review aims to provide a comprehensive, systematic overview of available animal models for the study of IA pathobiology. We conducted a systematic literature search using the PubMed database to identify preclinical studies employing IA animal models. Suitable articles were selected based on predefined eligibility criteria following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Included studies were reviewed and categorized according to the experimental animal and aneurysm model. Of 4266 returned results, 3930 articles were excluded based on the title and/or abstract and further articles after screening the full text, leaving 123 studies for detailed analysis. A total of 20 different models were found in rats (nine), mice (five), rabbits (four), and dogs (two). Rat models constituted the most frequently employed intracranial experimental aneurysm model (79 studies), followed by mice (31 studies), rabbits (12 studies), and two studies in dogs. The most common techniques to induce cerebral aneurysms were surgical ligation of the common carotid artery with subsequent induction of hypertension by ligation of the renal arteries, followed by elastase-induced creation of IAs in combination with corticosterone- or angiotensin-induced hypertension. This review provides a comprehensive summary of the multitude of available IA models to study various aspects of aneurysm formation, growth, and rupture. It will serve as a useful reference for researchers by facilitating the selection of the most appropriate model and technique to answer their scientific question

Fluorescence Angiography for Evaluation of Aneurysm Perfusion and Parent Artery Patency in Rat and Rabbit Aneurysm Models.

Brain aneurysm treatment focuses on achieving complete occlusion, as well as preserving blood flow in the parent artery. Fluorescein sodium and indocyanine green are used to enable the observation of blood flow and vessel perfusion status, respectively. The aim of this study is to apply FVA to verify real-time blood flow, vessel perfusion status and occlusion of aneurysms after induction of sidewall aneurysms in rabbits and rats, as well as to validate the procedure in these species. Twenty sidewall aneurysms were created in 10 rabbits by suturing a decellularized arterial vessel pouch on the carotid artery of a donor rabbit. In addition, 48 microsurgical sidewall aneurysms were created in 48 rats. During follow-up at one month after creation, the parent artery/aneurysm complex was dissected and FVA was performed using an intravenous fluorescein (10%, 1 mL) injection via an ear vein catheterization in rabbits and a femoral vein catherization in rats. Aneurysms were then harvested, and patency was evaluated macroscopically. Macroscopically, 14 out of 16 aneurysms in rabbits indicated no residual parent artery perfusion with totally occluded luminae, however 11 (79%) were detected by FVA. Four aneurysms were excluded due to technical problems. In rats, residual aneurysm perfusion was macroscopically observed in 25 out of 48 cases. Of the 23 without macroscopic evidence of perfusion, FVA confirmed the incidence of 22 aneurysms (96%). There were no adverse events associated with FVA. Fluorescein is easily applicable and no special equipment is needed. It is a safe and extremely effective method for evaluating parent artery integrity and aneurysm patency/residual perfusion in an experimental setting with rabbits and rats. FVA using fluorescein as a contrast agent appears to be effective in controlling patency of aneurysms and the underlying vessel and can even be adapted to bypass surgery

Anatomical Variations of the Common Carotid Arteries and Neck Structures of the New Zealand White Rabbit and Their Implications for the Development of Preclinical Extracranial Aneurysm Models

Background: Rabbit models involving neck arteries are of growing importance for the development of preclinical aneurysm models. An optimal understanding of the anatomy is primordial to allow the conception of models while minimizing mortality and morbidity. The aim of this study is to give reliable anatomical landmarks to allow a standardized approach to the neck vessels. Methods: We performed a necropsy on nine specimens from ongoing experimental studies. We measured the distance between the origins of the right and left common carotid artery (rCCA/lCCA) and between the rCCA and the manubrium sterni (MS). The structures at risk were described. Results: Female New Zealand White rabbits (NZWR) weighing 3.7 ± 0.3 kg and aged 25 ± 5 weeks were included. The rCCA origin was located 9.6 ± 1.2 mm laterally and 10.1 ± 3.3 mm caudally to the MS. In all specimens, the lCCA originated from the aortic arch, together with the brachiocephalic trunk (BCT), and 6.2 ± 3.1 mm proximally to the rCCA origin. The external and internal jugular veins, trachea and laryngeal nerve were the main structures at risk. Conclusions: The data help to localize both CCAs and their origin to guide surgical approaches with the manubrium sterni as a main landmark. Special attention has to be paid to the trachea, jugular veins and laryngeal nerves

Anatomical Variations of the Common Carotid Arteries and Neck Structures of the New Zealand White Rabbit and Their Implications for the Development of Preclinical Extracranial Aneurysm Models.

BACKGROUND Rabbit models involving neck arteries are of growing importance for the development of preclinical aneurysm models. An optimal understanding of the anatomy is primordial to allow the conception of models while minimizing mortality and morbidity. The aim of this study is to give reliable anatomical landmarks to allow a standardized approach to the neck vessels. METHODS We performed a necropsy on nine specimens from ongoing experimental studies. We measured the distance between the origins of the right and left common carotid artery (rCCA/lCCA) and between the rCCA and the manubrium sterni (MS). The structures at risk were described. RESULTS Female New Zealand White rabbits (NZWR) weighing 3.7 ± 0.3 kg and aged 25 ± 5 weeks were included. The rCCA origin was located 9.6 ± 1.2 mm laterally and 10.1 ± 3.3 mm caudally to the MS. In all specimens, the lCCA originated from the aortic arch, together with the brachiocephalic trunk (BCT), and 6.2 ± 3.1 mm proximally to the rCCA origin. The external and internal jugular veins, trachea and laryngeal nerve were the main structures at risk. CONCLUSIONS The data help to localize both CCAs and their origin to guide surgical approaches with the manubrium sterni as a main landmark. Special attention has to be paid to the trachea, jugular veins and laryngeal nerves