Vascular Endothelial Growth Factor Expression In Intracranial Aneurysms And Arteriovenous Malformations

Objective: The mechanism of intracranial aneurysmal and AVM's (Arteriovenous Malformation) etiology, development and rupture has not yet been clearly elucidated. There have been many reports about the close relationship between vascular growth factors and cerebral vascular diseases, and one of them - VEGF (Vascular Endothelial Growth Factor) plays more important role in the etiology of cerebral vascular diseases. The objective of this study is to characterize the expression of VEGF in intracranial aneurysms and AVMs; at the same time, the relationship between VEGF expression and clinical features will also be investigated. This study will provide useful information for better understanding of prognosis and etiology of intracranial aneurysm and AVMs.Methods: All cases were chosen from department of neurosurgery in Tianjin Huanhu Hospital, which were confirmed by operation and pathology from Jan., 1993 to Dec., 2002. Three specimens of Willis' circle arteries obtained from autopsy in 1999 at the same hospital served as aneurysms' control and 4 pieces of normal brain tissue obtained from cranial decompression operation as AVMs' control. VEGF and bFGF (basic Fibroblast Growth Factor) expression were performed on 5 11 m paraffin embeded section by immunohistochemistry. All the stained sections were observed under light microscope recording the positive site and intensity. SPSS 10.0 statistical software was used to analyze the relationship between VEGF positive index (PI) and some clinical features, including patients' age, aneurysmal and AVMs' size, aneurysm's Hunt&Hess gradation and bFGF expression, as well as AVM's Spetzler's gradation.Results: Three specimens of Willis circle vessels and 4 pieces of normal brain tissue showed negative immunohistochemistry staining. AVM and aneurysm had the same positive rate at 89% (16/18 and 25/28). Media and adventitia layers of vessels had significantly higher positive rate than endothelium layer (x² =9.94, P<0.05); There was no correlation between VEGF expression and patient's age, the size of aneurysm, and Hunt&Hess gradation. VEGF expression in the arterialized veins of AVM was higher than that of arteries x²=4.77, P <0.05 ). VEGF expression in AVM had no significant relationship with patient's age, AVM's size and Spetzler gradation. The positive rate of VEGF expression was significantly higher than that of bFGF expression in all cases of aneurismal and AVMs' x²=4.9%5, P<0.05 and x²=9.091, P<0.05, respectively) .Conclusion: From the result which the positive rate of media and adventitia layers of vessels had significantly higher positive rate than endothelium layer as the same comparative rate of VEGF with bFGF indicated that VEGF may play effective role in development and maintenance of intracranial aneurysm and AVM. The etiology of aneurysm should be a more complicated process. VEGF can't be considered as the only responsible factor for that which can be deduced from negative relationship between VEGF expression and patient's age, aneurysmal size and Hunt&Hess gradation. Higher VEGF expression in the arterialized veins of AVM than that of arteries proved that VEGF maybe influence this arterialized process. VEGF can't be used as the clinical prognosis index of intracranial aneurysm and AVM, because there is no correlation between VEGF expression and aneurysmal Hunt&Hess gradation and AVM's Spetzler gradation.