Brain Arteriovenous Malformation Modeling, Pathogenesis, and Novel Therapeutic Targets

Chen, Wanqiu; Choi, Eun‐Jung; McDougall, Cameron M.; Su, Hua

doi:10.1007/s12975-014-0343-0

Cited by 65 publications

(72 citation statements)

References 157 publications

(203 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In contrast, the loss of both alleles of any HHT causative gene is embryonically lethal in mice [34, 35], and conditional (tissue/time-specific) homozygous deletion of Eng [32] or Alk1 [36, 37] results in striking vascular malformations resembling the AVMs found in HHT. This has also been demonstrated in our previous studies in modeling bAVM in mice [23, 38–40]. AVM development in an HHT gene-deficient mouse model is influenced by mouse strains, which have various levels of plasma TGF-β1 [41].…”

Section: Discussionsupporting

confidence: 69%

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

Shen

Jun

et al. 2016

Transl. Stroke Res.

Self Cite

View full text Add to dashboard Cite

Brain arteriovenous malformation (bAVM), characterized by tangled dysplastic vessels, is an important cause of intracranial hemorrhage in young adults, and its pathogenesis and progression are not fully understood. Patients with haploinsufficiency of transforming growth factor-β (TGF-β) receptors, activin receptor-like kinase 1 (ALK1) or endoglin (ENG) have a higher incidence of bAVM than the general population. However, bAVM does not develop effectively in mice with the same haploinsufficiency. The expression of integrin β8 subunit (ITGB8), another member in the TGF-β superfamily, is reduced in sporadic human bAVM. Brain angiogenic stimulation results at the capillary level of vascular malformation in adult Alk1 haploinsufficient (Alk1+/−) mice. We hypothesized that deletion of Itgb8 enhances bAVM development in adult Alk1+/− mice. An adenoviral vector expressing Cre recombinase (Ad-Cre) was co-injected with an adeno-associated viral vector expressing vascular endothelial growth factor (AAV-VEGF) into the brain of Alk1+/−;Itgb8-floxed mice to induce focal itgb8 gene deletion and angiogenesis. We showed that compared with Alk+/− mice (4.75±1.38/mm2), the Alk1+/−;Itgb8-deficient mice had more dysplastic vessels in the angiogenic foci (7.14±0.68/mm2, P=0.003). More severe hemorrhage was associated with dysplastic vessels in the brain of Itgb8-deleted Alk1+/−, as evidenced by larger Prussian blue-positive areas (1278±373 pixels/mm2 vs. Alk1+/−: 320±104/mm2; P=0.028). These data indicate that both Itgb8 and Alk1 are important in maintaining normal cerebral angiogenesis in response to VEGF. Itgb8 deficiency enhances the formation of dysplastic vessels and hemorrhage in Alk1+/− mice.

show abstract

Section: Discussionsupporting

confidence: 69%

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

Shen

Jun

et al. 2016

Transl. Stroke Res.

Self Cite

View full text Add to dashboard Cite

show abstract

“…An AVM is a collection of arteries and veins that form without an intervening capillary bed (22). However, a DVA is usually a collection of radiating veins that converge on a large and centrally located draining vein (23).…”

Section: Discussionmentioning

confidence: 99%

Hybrid surgery for an arteriovenous malformation fed by an accessory middle cerebral artery and drained by a developmental venous anomaly: A case report and literature review

Guo

et al. 2018

Exp Ther Med

View full text Add to dashboard Cite

An accessory middle cerebral artery (AMCA), which mainly acts in the collateral circulation of the middle cerebral artery (MCA), is a rare anatomic malformation. Similar to other intracranial vessels, cerebrovascular disease can occur in the AMCA. However, the development of an arteriovenous malformation (AVM) in the AMCA is very rare, especially in conjuction with developmental venous anomalies (DVAs). Here, a rare case of an AMCA combined with an AVM and a DVA was reported. The patient was a 47-year-old female with intracranial hemorrhage at symptom onset. CT and MRI showed lesions in the left Sylvian fissure and insula accompanied by hemorrhage. DSA suggested a left AMCA; an AVM of the AMCA was located in the deep Sylvian fissure. The AVM was diffusely developed and drained into the DVA. The operation was performed in a hybrid operating room. The major feeding artery of the AVM, which was derived from the AMCA, was clipped, then the AVM and DVA were subsequently removed. Intraoperative DSA showed that the AVM and DVA were radically removed. A pathological examination confirmed the presence of an AVM. The patient recovered well and was discharged. Therefore, as highlighted in this case report, rare AVMs can be found in AMCAs and can even occur simultaneously with a DVA. Hybrid surgical treatment can be used to remove AVMs and can lead to an improved prognosis.

show abstract

“…Bevacizumab normalized cardiac output in HHT patients harboring liver AVMs,[7] and was effective in the treatment of severe epistaxis caused by hemorrhage from small mucosal AVMs (telangiectasias). [6] Based on this, a phase I study on the efficacy and safety of bevacizumab in brain AVM patients is about to start (NCT02314377). A common angiogenesis pathway may, thus, explain radiological similarities between these two pathologies.…”

Section: Discussionmentioning

confidence: 99%

Hypervascular glioblastoma multiforme or arteriovenous malformation associated Glioma? A diagnostic and therapeutic challenge: A case report

et al. 2016

View full text Add to dashboard Cite

Background:Simultaneous presentation of arteriovenous malformation (AVM) and glioblastoma multiforme (GBM) is rarely reported in the literature and needs to be differentiated from “angioglioma”, a highly vascular glioma and other differential diagnosis such as hypervascular glioblastoma. Incorporating critical features of both, malignant glioma and AVM, such lesions lack a standard algorithm for diagnosis and therapy due to their rare incidence as well as their complex radiological and highly individualized clinical presentation.Case Description:We present a case of a 71-year-old female with newly developing motor deficits and radiographic findings of a heterogeneously contrast enhancing right-sided thalamic lesion with highly prominent vasculature. While computed tomography angiogram and cerebral digital subtraction angiography supported the diagnosis of AVM, contrast-enhancing magnetic resonance imaging (MRI) and MR-spectroscopy was suggestive of malignant glioma. A stereotactic biopsy revealed the diagnosis of a GBM (WHO IV) and the patient was treated accordingly.Conclusion:The coincidental presentation of vascular lesions such as AVM and malignant glioma is rare and presents a major challenge when establishing a diagnosis. The respective treatment decision is complicated by the fact that available treatment modalities (e.g. radiosurgery and/or open resection) carry disease specific complications for each entity. Finding a suitable solution for such cases requires standardization of early diagnostic and therapeutic management.

show abstract

Brain Arteriovenous Malformation Modeling, Pathogenesis, and Novel Therapeutic Targets

Cited by 65 publications

References 157 publications

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

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

Hybrid surgery for an arteriovenous malformation fed by an accessory middle cerebral artery and drained by a developmental venous anomaly: A case report and literature review

Hypervascular glioblastoma multiforme or arteriovenous malformation associated Glioma? A diagnostic and therapeutic challenge: A case report

Contact Info

Product

Resources

About