Biology of Cerebral Arteriovenous Malformations with a Focus on Inflammation

Abstract

Cerebral arteriovenous malformations (AVMs) entail a significant risk of intracerebral hemorrhage owing to the direct shunting of arterial blood into the venous vasculature without the dissipation of the arterial blood pressure. The mechanisms involved in the growth, progression and rupture of AVMs are not clearly understood, but a number of studies point to inflammation as a major contributor to their pathogenesis. The upregulation of proinflammatory cytokines induces the overexpression of cell adhesion molecules in AVM endothelial cells, resulting in enhanced recruitment of leukocytes. The increased leukocyte-derived release of metalloproteinase-9 is known to damage AVM walls and lead to rupture. Inflammation is also involved in altering the AVM angioarchitecture via the upregulation of angiogenic factors that affect endothelial cell proliferation, migration and apoptosis. The effects of inflammation on AVM pathogenesis are potentiated by certain single-nucleotide polymorphisms in the genes of proinflammatory cytokines, increasing their protein levels in the AVM tissue. Furthermore, studies on metalloproteinase-9 inhibitors and on the involvement of Notch signaling in AVMs provide promising data for a potential basis for pharmacological treatment of AVMs. Potential therapeutic targets and areas requiring further investigation are highlighted.

Cerebral Arteriovenous Malformations and Epilepsy, Part 2: Predictors of Seizure Outcomes Following Radiosurgery

“…While prior literature has suggested that hemosiderin deposition may promote epileptogenesis, many of these observations were in patients with cerebral cavernous malformations rather than AVMs (33). Absorption of hemosiderin over time following AVM rupture and differences in the pathobiology and natural history between cavernous malformations and AVMs may sufficiently account for the disparity between our findings and previous theories (41).…”

The emerging role of adiponectin in cerebrovascular and neurodegenerative diseases

“…To date, no studies have investigated the impact of hypoadiponectinemia on the CNS. Neurological disorders have complex pathophysiologies [80][81][82]. Previous studies have demonstrated that adiponectin may perform a neuroprotective function in the CNS via mechanisms that remain to be elucidated.…”

Radiosurgery for Cerebral Arteriovenous Malformations in A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA)-Eligible Patients

“…Either complete and incomplete surgical resection or embolization can result in postoperative hemorrhage because of cerebral vasomotor dysregulation or bleeding from a residual AVM. [43][44][45][46] However, if treatment-related hemorrhage was the sole contributor, one would expect the Kaplan-Meier plot for the interventional arm to flatten over time. Because this does not occur, one can assume that any delayed hemorrhage is because of incomplete AVM occlusion.…”