Cerebral arteriovenous malformations. Part 2: physiology

Abstract

<jats:sec><jats:title>Object</jats:title><jats:p>The scientific understanding of the nature of arteriovenous malformations (AVMs) in the brain is evolving. It is clear from current work that AVMs can undergo a variety of phenomena, including growth, remodeling, and/or regression—and the responsible processes are both molecular and physiological. A review of these complex processes is critical to directing future therapeutic approaches. The authors performed a comprehensive review of the literature to evaluate current information regarding the genetics, pathophysiology, and behavior of AVMs.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>A comprehensive literature review was conducted using PubMed to reveal the angioarchitecture and cerebral hemodynamics of AVMS as they relate to lesion development.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Feeding artery pressures, brain AVM compartmentalization, venous drainage, flow phenomena, and vascular steal are discussed.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>The dynamic nature of brain AVMs is at least in part attributable to hemodynamic and flow-related phenomena. These forces acting on an evolving structure are critical to understanding the challenges in endovascular and surgical therapy. As knowledge in this field continues to progress, the natural history and predicted behavior of these AVMs will become more clearly elucidated.</jats:p></jats:sec>

Molecular and cellular biology of cerebral arteriovenous malformations: a review of current concepts and future trends in treatment

“…13 Other diagnoses less frequently associated with AVMs include ataxia telangiectasia, Sturge-Weber syndrome, and cerebral autosomaldominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). 33,46 While these represent a variety of associations with AVM formation, they do not yet define a common pathway.…”

“…32,33,50,54 Microscopic animal models have shown that cerebral AVMs have a number of pathological changes present in nidal vessels. These changes include heterogeneously thickened vessel walls, splitting of the elastic lamina, thickened endothelial layers, endothelial cushions, lack of tight and adherent junctions, loss of endothelial continuity, and filopodia (microspikes) directed into the lumen.…”

“…However, it is believed that to develop a cerebral AVM, ANG2 and VEGF work synergistically and both must be overexpressed. 21,33 Genes, molecules, and structural proteins located in BECs are believed to be intimately associated with the development of cerebral AVMs. Neurogenic locus Notch4 is a member of a family of transmembrane proteins with repeats of extracellular endothelial growth factor (EGF).…”

“…35,48 More than 860 genes are now known to be upregulated (300) and downregulated (560) in cerebral AVMs. 33 Single nucleotide polymorphisms (SNPs) are DNA sequence variations that differ between members of the same species. SNPs of certain angiogenic factors were first associated with sporadic cerebral AVMs and subsequently with their risk of rupture.…”

“…SNPs of certain angiogenic factors were first associated with sporadic cerebral AVMs and subsequently with their risk of rupture. 37 Some specific molecules affected by SNPs are TGF-b, an extracellular glycosylated protein that suppresses the effects of interleukins and is critical in de novo AVM formation; 32 brain-derived neurotrophic factor (BDNF), a protein that supports survival, development, and function of neurons; 55 interleukin-6 (IL-6), which contributes to vascular wall instability by stimulating the release of MMP; 32,33,38 and angiopoietin-like 4 (ANGPTL4), a glycoprotein believed to be involved in angiogenesis (Table 1). 31 Vascular endothelial growth factor is a critical signaling molecule that regulates angiogenesis and is typically suppressed in normal adult vasculature.…”