Expression of angiogenic factors in cerebral arteriovenous malformations

BACKGROUND： In the process of vascularization, vascular endothelial growth factor （VEGF）, angiopoietin-2 and Tie2 are involved in the migration, differentiation and proliferation of vascular endothelial cells, and stimulate the rapid angiogenesis; Tiel and angiopoietin-1 play important roles in facilitating the formation of vascular lumen and maintaining the integrity of vascular wall. Thus the distributions and expressions may be associated with the occurrence of cerebral arteriovenous malformation. OBJECTIVE： To observe the biological effects of angiogenic factors in the occurrence and development of cerebral arteriovenous malformation. DESIGN： An observational comparative experiment. SETTINGS： Department of Neurosurgery, General Hospital of Shenyang Military Area Command of Chinese PLA; Department of Neurosurgery, General Hospital of Tianjin Medical University. PARTICIPANTS： Fresh samples of complete cerebral arteriovenous malformations resected in 47 patients were collected from the Department of Neurosurgery, General Hospital of Tianjin Medical University from August 1999 to May 2001, including 22 males and 25 females, the mean age was 34.5 years. Informed consents were obtained from all the patients or their relatives. The initial symptom was hemorrhage in 28 cases. All the patients were classified according to the clinical imaging data and Spetzler-Martin grading standard, including 11 cases of grade Ⅰ, 17 cases of grade Ⅱ, 11 cases of grade Ⅲ, and 8 cases of grade Ⅳ - Ⅴ. Normal brain tissues resected by decompression due to trauma were taken from 8 patients as controls, including 5 males and 3 females, aging 12 - 65 years. METHODS： ① The expressions of VEGF, Tie receptors, angiopoietin-1, angiopoietin-2, proto-oncogene c-myc and proliferating cell nuclear antigen（PCNA） in the samples of cerebral arteriovenous malformation were detected with immunohistochemical method. Under light microscope, the positively stained rat-anti-human factor Ⅷ-related antigens （specific marker of vascular endothelial cells） were counted, then the immuno-positive cells of the other antibodies in the visual field of neighboring section which was in ＂mirror＂ relation were counted, and the percentage of the latter to the former was considered as the labeling index of positive cells. The immunostaining intensity was classified negative （ - ）： no positive cells; positive （＋）： number of positive cells 〈 20%; moderately positive （＋＋）： number of positive cells 20% - 50%; strongly positive （＋＋＋）： number of positive cells 〉 50%. ② The differences of the enumeration data were compared with chi-squam test, and the correlation were analyzed with the linear correlation analysis. MAIN OUTCOME MEASURES： Expressions and distributions of VEGF, Tie 1 and Tie2 receptors, angiopoietin-1, angiopoietin-2, PCNA and c-myc in the samples of cerebral arteriovenons malformation and normal brain tissue. RESULTS： ① Expressions of angiogenic factors in the control group and cerebral arteriovenons malformation groups of each grade： The positive rates of VEGF, Tie2, angiopoietin-2, c-myc and PCNA expressions in the control group were significantly different from those in the cerebral arteriovenous malformation groups of each grade （ x^2=21.09 - 34.23, P 〈 0.05）, whereas the positive rates of Tiel and angiopoietin-1 expressions were close （ x^2=3.43 - 3.869, P 〉 0.05）. ② Expressions of angiogenic factors in hemorrhage group and non-hemorrhage group： The expressions of VEGF, angiopoietin-2 and PCNA in the hemorrhage group were significantly lower than those in the non-hemorrhage group （ x^2= 16.22 - 26.56, P 〈 0.05）. There ware no obvious differences in the expressions of Tiel and angiopoietin-1 expressions between the hemorrhage group and non-hemorrhage group （ x^2=3.22 - 3.78, P 〉 0.05）.The VEGF was positively correlated with the expressions of c-myc and PCNA （r = 0.728, 0.916, P 〈 0.05）. CONCLUSION： ①The expressions of angiogenic factors and related receptors may be involved in the process of cerebral arteriovenous malformation, and had important correlation the its clinical grading. ② Angiogenic factors may induce the expression of endothelial cell c-myc in cerebral arteriovenous malformation, and then interfere the cell proliferation and apoptosis.

Endovascular treatment of cerebral arteriovenous malformations with Onyx embolization

Background In the past 5 years, new treatment materials and techniques offering a different concept in endovascular treatment have been described for cerebral arteriovenous malformations （CAVMs）. The aim of this study was to assess the endovascular treatment of CAVMs by using a liquid embolic material, Onyx （ Micro Therapeutics. Inc. , Irvine, CA, USA）. Methods From September 2003 to September 2004, Onyx was used to treat 22 patients with CAVMs. Ten AVMS were located in functional areas, 8 in deep cerebral areas, and 4 in the cerebellar hemisphere. The size of CAVMs was about 3 cm in diameter in 5 patients, 3 -6 cm in 11, and more than 6 cm in 6. Results In the 22 patients, Onyx embolization was successful. Nidus occlusion was complete in 3 patients, 〉 90% in 8, 〉 80% and 〈 90% in 6, and 〉 50% and 〈 80% in 5. Complications included transient neurological deficits in 2 patients, and adherence of microcatheter to the site of injection in 2. Conclusions Being non-adhesiveness, Onyx is a safe and satisfactory embolic material in the treatment of CAVMs. But its long-term efficacy awaits further follow-up.

Clinical and pathological changes in cerebral arteriovenous malformations after stereotactic radiosurgery failure

Background Stereotactic radiosurgery is an altemative to resection of intracranial cerebral arteriovenous malformations （AVMs）, while it will fail in some cases. This study aimed to evaluate the changes after stereotactic radiosurgery for AVMs.Methods Nineteen cases with cerebral AVMs had failure after stereotactic radiosurgery therapy. The symptoms and angiography were assessed. All patients underwent microsurgery. Pathologic examination was performed for all cases and electron microscopic examination was carried out in 6 patients.Results Seven cases had hemorrhage from 12 to 98 months after stereotactic radiosurgery, 5 had headache, 4 had refractory encephalon edema, 2 had epilepsy as a new symptom and 1 had a pressure cyst 5 years after radiosurgery. Angiography in 18 cases, 8-98 months after radiation therapy, demonstrated no significant changes in 5 cases, slight reduction in 9, near complete obliteration in 1 and complete obliteration in 3. An abnormal vessel was found on pathologic examination in 17 cases, even one case had obliterated in angiography. Electron microscopy examination showed vessel wall weakness, but the vessels remained open and blood circulated. One case died because of a moribund state before surgery. The other 18 cases had no new neurological deficiencies, seizure control and no hemorrhage occurred after microsurgery at an average follow-up of 3 years.Conclusion Stereotactic radiotherapy for AVMs should have a long period follow-up. If serious complications occur, microsurgery can be performed as salvage treatment.

A low-grade cerebral arteriovenous malformation suspected of being a metastatic tumor:A case report and literature review

Cases of low-grade cerebral arteriovenous malformations(c AVMs)showing dynamic changes and large areas of brain edema on short-term MRI follow-up have rarely been reported.This report describes an incidentally discovered and initially misdiagnosed c AVM in a patient with malignancies.The presence of abnormal signals surrounded by large areas of brain edema combined with tortuous or dilated vessels indicates the possibility of an AVM,especially in young people.

Analysis of the Expression of Angioarchitecture-related Factors in Patients with Cerebral Arteriovenous Malformation

Background： Cerebral arteriovenous malformation （cAVM） is a type of vascular malformation associated with vascular remodeling, hemodynamic imbalance, and inflammation. We detected four angioarchitecture-related cytokines to make a better understanding of the potential aberrant signaling in the pathogenesis of cAVM and found useful proteins in predicting the risk of cerebral hemorrhage. Methods： lmmunohistochemical analysis was conducted on specimens from twenty patients with cAVM diagnosed via magnetic resonance imaging and digital subtraction angiography and twenty primary epilepsy controls using antibodies against vascular endothelial growth factor receptor-2 （VEGFR-2）, matrix metalloproteinase-9 （MMP-9）, vascular cell adhesion molecule （VCAM- 1 ）, and endothelial nitric oxide synthase （eNOS）. Western blotting and real-time fluorescent quantitative polymerase chain reaction （PCR） were performed to determine protein and mRNA expression levels. Student＇s t-test was used for statistical analysis. Results： VEGFR-2, MMP-9, VCAM-1, and eNOS expression levels increased in patients with cAVM compared with those in normal cerebral vascular tissue, as determined by immunohistochemical analysis. In addition, Western blotting and real-time PCR showed that the protein and mRNA expression levels ofVEGFR-2, MMP-9, VCAM-1, and eNOS were higher in the cAVM group than in the control group, all the differences mentioned were statistically significant （P 〈 0,05）. Conclusions： VEGFR-2, MMP-9, VCAM-1, and eNOS are upregulated in patients with cAVM and might play important roles in angiogenesis, vascular remodeling, and migration in patients with cAVM. MMP-9, VEGFR-2, VCAM-1, and eNOS might be potential excellent group proteins in predicting the risk of cerebral hemorrhage at arteriovenous malformation.