Recent Translational Research Models of Intracranial Atherosclerotic Disease

Intracranial atherosclerotic disease (ICAD) is a leading cause of ischemic stroke worldwide. However, research on the pathophysiology of ICAD is scarce due to the relative inaccessibility of histology samples and the lack of comprehensive experimental models. As a result, much of the current understanding of ICAD relies on research on extracranial atherosclerosis. This approach is problematic as intracranial and extracranial arteries are anatomically, structurally, physiologically, and metabolically distinct, indicating that intracranial and extracranial atherosclerosis likely develop through different biologic pathways. The current standard of care for ICAD treatment relies predominantly on therapeutics developed to treat extracranial atherosclerosis and is insufficient given the alarmingly high risk of stroke. To provide a definitive treatment for the disease, a deeper understanding of the pathophysiology underlying ICAD is specifically required. True mechanistic understanding of disease pathogenesis is only possible using robust experimental models. In this review, we aim to identify the advantages and limitations of the existing in vivo and in vitro models of ICAD and basic atherosclerotic processes, which may be used to inform better models of ICAD in the future and drive new therapeutic strategies to reduce stroke risk.