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

Abstract

<jats:sec> <jats:title>Object</jats:title> <jats:p>Arteriovenous malformations (AVMs) are classically described as congenital static lesions. However, in addition to rupturing, AVMs can undergo growth, remodeling, and regression. These phenomena are directly related to cellular, molecular, and physiological processes. Understanding these relationships is essential to direct future diagnostic and therapeutic strategies. The authors performed a search of the contemporary literature to review current information regarding the molecular and cellular biology of AVMs and how this biology will impact their potential future management.</jats:p></jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>A PubMed search was performed using the key words “genetic,” “molecular,” “brain,” “cerebral,” “arteriovenous,” “malformation,” “rupture,” “management,” “embolization,” and “radiosurgery.” Only English-language papers were considered. The reference lists of all papers selected for full-text assessment were reviewed.</jats:p></jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>Current concepts in genetic polymorphisms, growth factors, angiopoietins, apoptosis, endothelial cells, pathophysiology, clinical syndromes, medical treatment (including tetracycline and microRNA-18a), radiation therapy, endovascular embolization, and surgical treatment as they apply to AVMs are discussed.</jats:p></jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Understanding the complex cellular biology, physiology, hemodynamics, and flow-related phenomena of AVMs is critical for defining and predicting their behavior, developing novel drug treatments, and improving endovascular and surgical therapies.</jats:p></jats:sec>

Development of an angiogenesis animal model featuring brain arteriovenous malformation histological characteristics

“…VEGF is not produced by quiescent brain but it is found in AVMs brain endothelial cells22 and it is highly expressed in children with recurrent AVMs 5. An increase in VEGF receptors has been noticed in syndromic and sporadic bAVM 5. The increase in VEGF receptors in the occlusion group in our model shows an angiogenic process probably triggered by the flow changes induced by occlusion of the CCA–ECA.…”

“…Abnormal angiogenesis has an important role in bAVM genesis and evolution4 and VEGF, in particular, has been shown to interfere at many levels of bAVM formation and evolution 3 4. VEGF is not produced by quiescent brain but it is found in AVMs brain endothelial cells22 and it is highly expressed in children with recurrent AVMs 5. An increase in VEGF receptors has been noticed in syndromic and sporadic bAVM 5.…”

In-room assessment of intravascular velocity from time-resolved rotational angiography in patients with arteriovenous malformation: a pilot study

“…This phenomenon was also observed in transcranial Doppler ultrasound in patients with AVM owing to the low vasculature resistance of the nidus 22. Normalization of velocity and restoration of pulsatile waveforms in the feeders can monitor hemodynamic changes in response to the therapeutic effects of staged surgery, gamma knife radiosurgery and embolization 5 6 20.…”

Integrin β8 Deletion Enhances Vascular Dysplasia and Hemorrhage in the Brain of Adult Alk1 Heterozygous Mice

“…Brain arteriovenous malformation (bAVM) is a vascular disease with tangles of dysplastic, dilated vessels that shunt blood directly from arteries to veins [1, 2]. These abnormal vessels are prone to rupture, causing life-threatening intracranial hemorrhage.…”