Characterizing Infiltrating Macrophages in Intracranial Aneurysm with IA Animal Models and Spatial Transcriptomics.

Abstract

Intracranial aneurysm (IA) prevalence in the general population can be as high as 3%. Most IAs are asymptomatic and diagnosed incidentally. However, IAs can cause subarachnoid hemorrhage (SAH), which is responsible for high mortality and morbidity. No effective medical therapy is currently available to control the IA and reduce the SAH risk. Understanding IA pathophysiology to identify potential targets is, therefore, an essential clinical objective. IAs typically form at arterial bifurcations and are characterized by macrophage infiltration. Macrophages are innate immune cells that present antigens to adaptive immune cells and promote inflammation. The potential role of macrophages in IA was demonstrated when inhibiting the macrophage recruitment contained aneurysm formation or growth. Recent advances in spatial transcriptomics enable the study of infiltrating macrophages within the aneurysmal lesion and the identification of pathogenic changes that were previously challenging to probe. While sample availability may limit the use of spatial transcriptomics, judicious use of IA animal models will enable translational research to address unmet clinical needs. With spatial insights and refined animal models, researchers can identify key characteristics of infiltrating macrophages, including their ontogeny, transcriptomic profiles, and interactions with other cell subsets. This review article summarizes the current understanding of infiltrating macrophages in IAs and introduces available animal models of IA and spatial transcriptomics approaches for studying macrophage infiltration.