Mouse Models of Intracranial Aneurysm

Abstract

Subarachnoid hemorrhage secondary to rupture of an intracranial aneurysm is a highly lethal medical condition. Current management strategies for unruptured intracranial aneurysms involve radiological surveillance and neurosurgical or endovascular interventions. There is no pharmacological treatment available to decrease the risk of aneurysm rupture and subsequent subarachnoid hemorrhage. There is growing interest in the pathogenesis of intracranial aneurysm focused on the development of drug therapies to decrease the incidence of aneurysm rupture. The study of rodent models of intracranial aneurysms has the potential to improve our understanding of intracranial aneurysm development and progression. This review summarizes current mouse models of intact and ruptured intracranial aneurysms and discusses the relevance of these models to human intracranial aneurysms. The article also reviews the importance of these models in investigating the molecular mechanisms involved in the disease. Finally, potential pharmaceutical targets for intracranial aneurysm suggested by previous studies are discussed. Examples of potential drug targets include matrix metalloproteinases, stromal cell-derived factor-1, tumor necrosis factor-α, the renin-angiotensin system and the β-estrogen receptor. An agreed clear, precise and reproducible definition of what constitutes an aneurysm in the models would assist in their use to better understand the pathology of intracranial aneurysm and applying findings to patients.

Angiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology

“…While several animal models are available for intracranial aneurysm (1126), there is a model of this disease in mice with injection of elastase into the cerebrospinal fluid at the right basal cistern combined with systemic ANG II infusion (760). This model and others have been employed in the effort to elucidate potential signaling mechanisms by which ANG II may contribute to intracranial aneurysm development and rupture.…”

Polymorphisms of Inflammatory Cytokine Genes and Risk for Intracranial Aneurysm: A Systematic Review and Meta-Analysis

“…32 Increased TNF-α protein can promote inflammation and subsequent apoptosis in vessels, thereby weakening vessel walls, destroying the integrity thereof, and increasing the risk of IA. 33 However, few studies have investigated the mechanism of TNF-α polymorphism in relation to IA. It is not clear whether rs1800629 polymorphism can affect the occurrence of IA by regulating the expression levels of TNF-α, because in the studies that are available, participants did not undergo measurement of TNF-α levels for the mutant and wild-type allele.…”

Biology of Saccular Cerebral Aneurysms: A Review of Current Understanding and Future Directions

“…Intracranial aneurysms are common abnormalities of the brain ( 1 – 30 ). The reported prevalence was 3.2% in a homogeneous Finnish population and up to 5% in others ( 31 , 32 ).…”