New insight into DAVF pathology—Clues from meningeal immunity

Abstract

In recent years, with the current access in techniques, studies have significantly advanced the knowledge on meningeal immunity, revealing that the central nervous system (CNS) border acts as an immune landscape. The latest concept of meningeal immune system is a tertiary structure, which is a comprehensive overview of the meningeal immune system from macro to micro. We comprehensively reviewed recent advances in meningeal immunity, particularly the new understanding of the dural sinus and meningeal lymphatics. Moreover, based on the clues from the meningeal immunity, new insights were proposed into the dural arteriovenous fistula (DAVF) pathology, aiming to provide novel ideas for DAVF understanding.

Peripheral macrophages in the development and progression of structural cerebrovascular pathologies

“…168 The abnormal vascular anastomoses characterizing dAVFs may reflect compensatory consequences of immune surveillance throughout the meningeal immune system. 15 While these findings suggest that macrophage involvement in dAVFs may have been overlooked and that timepoint-specific investigations are warranted, it is unlikely that macrophages serve a central role in these lesions as is seen in IAs, CCMs, and bAVMs, especially given the heterogeneous etiologies of dAVFs. Further studies in this area are necessary to distinguish intrinsic CNS macrophage involvement in these lesions from peripheral macrophages.…”

“…157,167 Another line of evidence that has brought the inflammatory hypothesis of dAVF development to the fore of discussion is the influence of the meningeal immune system. 15 Now recognized as an essential tertiary structure heavily involved in CNS disease, the role of this complex immune landscape is contingent upon innate populations of CNS macrophages and communications with peripheral immune cells. 168 The abnormal vascular anastomoses characterizing dAVFs may reflect compensatory consequences of immune surveillance throughout the meningeal immune system.…”

“…14 Though bAVMs, CCMs, IAs, and dAVFs each carry unique risk factors, mounting evidence implicates inflammation and immune cell infiltration as contributors to their pathogenesis, shifting our understanding of these conditions from diseases of genetic abnormalities and artifacts of hemodynamic stress to diseases with pathology-promoting microenvironments rich with complex cellular interactions. [15][16][17][18] Macrophages in particular play a critical role in the pathophysiology of these diseases and have significant therapeutic potential. 19 In-vivo animal studies have implicated macrophages in upregulation of proteinases (including major metalloproteinases, MMPs), extracellular matrix (ECM) degradation, hemoglobin phagocytosis, leukocyte recruitment, angiogenesis, vascular permeability regulation, and induction of pro-inflammatory cytokines in the behavior of vascular abnormalities and malformations.…”