Comparison of an animal model of arteriovenous malformation with human arteriovenous malformation

Tu, Jian; Karunanayaka, Athula; Windsor, Apsara; Stoodley, Marcus A.

doi:10.1016/j.jocn.2009.02.044

Cited by 43 publications

(26 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…62 Radiosurgically induced AVM vaso-occlusion could occur shortly after irradiation or as late as 5 years, or it may never occur by the end of the follow-up period. 49 Studies suggest that radiosurgery-related vasculopathy in AVMs includes stenosis and thrombosis, 62 altered gene expression of endoglin and endothelial nitric oxide synthase, 31 and inflammation. 22,61 However, the mechanism remains a mystery.…”

Section: Discussionmentioning

confidence: 99%

Radiosurgery inhibition of the Notch signaling pathway in a rat model of arteriovenous malformations

Hu³

et al. 2014

JNS

Self Cite

View full text Add to dashboard Cite

R adiosuRgeRy has been used to manage patients with cerebral arteriovenous malformations (AVMs) for more than 4 decades. 56 It offers an important option for patients with AVMs that are unsuitable for resection or embolization. 47,54 Studies reveal that radiosurgery induces thrombosis in AVM vessels, and by 2-3 years approximately 75% of AVM vessels are completely obliterated. 37,48,63 Although overexpression of endothelial adhesion and inflammatory and thrombotic molecules has been reported in irradiated endothelial cells in an AVM model in rats, 22,57,61 Department of Electromagnetic and Laser Biology, Beijing Institute of Radiation Medicine, Beijing, ChinaObject. Notch signaling has been suggested to promote the development and maintenance of arteriovenous malformations (AVMs), but whether radiosurgery inhibits Notch signaling pathways in AVMs is unknown. The aim of this study was to examine molecular changes of Notch signaling pathways following radiosurgery and to explore mechanisms of radiosurgical obliteration of "nidus" vessels in a rat model of AVMs.Methods. One hundred eleven rats received common carotid artery-to-external jugular vein anastomosis to form an arteriovenous fistula (AVF) model. Six weeks postoperatively, dilated small vessels and capillaries formed a nidus. The rats with AVFs received 25-Gy radiosurgery. The expression of Notch1 and Notch4 receptors and their ligands, Delta-like1 and Delta-like4, Jagged1, Notch downstream gene target HES1, and an apoptotic marker caspase-3 in nidus vessels in the AVF rats was examined immunohistochemically and was quantified using LAS-AF software at 7 time points over a period of 42 days postradiosurgery. The interaction events between Notch1 receptor and Jagged1, as well as Notch4 receptor and Jagged1, were quantified in nidus vessels in the AVF rats using proximity ligation assay at different time points over 42 days postradiosurgery.Results. The expression of Notch1 and Notch4 receptors, Delta-like1, Delta-like4, Jagged1, and HES1 was observed in nidus vessels in the AVF rats pre-and postradiosurgery. Radiosurgery enhanced apoptotic activity (p < 0.05) and inhibited the expression of Notch1 and Notch4 receptors and Jagged1 in the endothelial cells of nidus vessels in the AVF rats at 1, 2, 3, 7, 21, 28, and 42 days postradiosurgery (p < 0.05). Radiosurgery suppressed the interaction events between Notch1 receptor and Jagged1 (p < 0.001) as well as Notch4 receptor and Jagged1 (p < 0.001) in the endothelial cells of nidus vessels in the AVF rats over a period of 42 days postradiosurgery. Radiosurgery induced thrombotic occlusion of nidus vessels in the AVF rats. There was a positive correlation between the percentage of fully obliterated nidus vessels and time after radiosurgery (r = 0.9324, p < 0.001).Conclusions. Radiosurgery inhibits endothelial Notch1 and Notch4 signaling pathways in nidus vessels while inducing thrombotic occlusion of nidus vessels in a rat model of AVMs. The underlying mechanisms of radiosurgeryinduced AVM shrinkage could be a c...

show abstract

Section: Discussionmentioning

confidence: 99%

Radiosurgery inhibition of the Notch signaling pathway in a rat model of arteriovenous malformations

Hu³

et al. 2014

JNS

Self Cite

View full text Add to dashboard Cite

show abstract

“…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. 51 Over the last 2 decades, new genetic, molecular, and cellular factors have been demonstrated to be involved in the process of formation, growth, and rupture of AVMs. The goal of this work was to compile and analyze new evidence regarding these processes and investigate consequent potential future therapeutic alternatives.…”

Section: Abstract • Molecular • Cellular Biology • Arteriovenous Malmentioning

confidence: 99%

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

Rangel-Castilla¹,

Russin²,

Martinez-del-Campo³

et al. 2014

FOC

View full text Add to dashboard Cite

Object 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. Methods 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. Results 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. Conclusions 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.

show abstract

“…20 We also developed a method to treat the model AVM with LINAC radiosurgery and studied changes in adhesion molecules after irradiation. 19 The feasibility of the proposed thrombotic treatment was demonstrated using LINAC as the radiosurgery priming method.…”

Section: Discussionmentioning

confidence: 99%

“…We have developed an animal model that shares hemodynamic, structural, and molecular characteristics with human AVMs. 6,20 These characteristics make this model suitable for studying the early molecular responses of the AVM endothelial phenotype to radiation. However, before studying the molecular responses, one must understand the morphological, hemodynamic, and histological changes that occur after radiation treatment.…”

mentioning

confidence: 99%

Angiographic, hemodynamic, and histological changes in an animal model of brain arteriovenous malformations treated with Gamma Knife radiosurgery

Kashba

Patel

Grace

et al. 2015

JNS

View full text Add to dashboard Cite

B rain arteriovenous malformations (AVMs) are a major cause of stroke in children and young adults. Surgical excision of an AVM offers immediate protection from hemorrhage and is suitable for small and superficial lesions. Approximately 70% of small AVMs (< 3 cm in diameter) are completely obliterated by 2-3 years after Gamma Knife surgery (GKS).1,3,23 However, patients treated with GKS remain at risk for suffering hemorrhage during the latent period before AVM occlusion. 9,15 A large number of patients who have large and/or deeply located AVMs cannot be treated using current methods.9 An improved method of treating AVMs is required for these patients.One potential new treatment is to induce thrombosis in abbreviatioNs AVM = arteriovenous malformation; GKS = Gamma Knife surgery; LCCA = left common carotid artery; LEJV = left external jugular vein; LINAC = linear accelerator. obJect Brain arteriovenous malformations (AVMs) are a major cause of stroke. Many AVMs are effectively obliterated by stereotactic radiosurgery, but such treatment for lesions larger than 3 cm is not as effective. Understanding the responses to radiosurgery may lead to new biological enhancements to this treatment modality. The aim of the present study was to investigate the hemodynamic, morphological, and histological effects of Gamma Knife surgery (GKS) in an animal model of brain AVM. methods An arteriovenous fistula was created by anastomosing the left external jugular vein to the side of the common carotid artery in 64 male Sprague-Dawley rats (weight 345 ± 8.8 g). Six weeks after AVM creation, 32 rats were treated with a single dose of GKS (20 Gy); 32 animals received sham radiation. Eight irradiated and 8 control animals were studied at each specified time point (1, 3, 6, and 12 weeks) for hemodynamic, morphological, and histological characterization. results Two AVMs showed partial angiographic obliteration at 6 weeks. Angiography revealed complete obliteration in 3 irradiated rats at 12 weeks. Blood flow in the ipsilateral proximal carotid artery (p < 0.001) and arterialized jugular vein (p < 0.05) was significantly lower in the irradiated group than in the control group. The arterialized vein's external diameter was significantly smaller in GKS-treated animals at 6 (p < 0.05) and 12 (p < 0.001) weeks. Histological changes included subendothelial cellular proliferation and luminal narrowing in GKS-treated animals. Neither luminal obliteration nor thrombus formation was identified at any of the time points in either irradiated or nonirradiated animals. coNclusioNs GKS produced morphological, angiographic, and histological changes in the model of AVM as early as 6 weeks after treatment. These results support the use of this model for studying methods to enhance radiation response in AVMs.

show abstract

Comparison of an animal model of arteriovenous malformation with human arteriovenous malformation

Cited by 43 publications

References 14 publications

Radiosurgery inhibition of the Notch signaling pathway in a rat model of arteriovenous malformations

Radiosurgery inhibition of the Notch signaling pathway in a rat model of arteriovenous malformations

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

Angiographic, hemodynamic, and histological changes in an animal model of brain arteriovenous malformations treated with Gamma Knife radiosurgery

Contact Info

Product

Resources

About