Focal neurons: another source of vascular endothelial growth factor in brain arteriovenous malformation tissues?

Abstract

Background Brain arteriovenous malformations (bAVMs) are devastating, hemorrhage-prone, cerebrovascular entities characterized by well-defined feeding arteries, draining veins, and the absence of a capillary bed. The endothelial cells that comprise bAVMs exhibit a loss of arterial and venous specification. The role of abnormal angiogenesis in the formation and progression of bAVMs is still unclear. This study aimed to investigate the expression of vascular endothelial growth factor (VEGF) in neurons and glial cells in bAVMs to try to uncover the multiple cell origin of VEGF. Methods A total of 25 bAVM specimens and 25 control tissues were obtained. Western blot and immunohistochemical analyses were used to evaluate the expression of VEGF. The distribution of VEGF in neurons and glial cells in these bAVMs were observed by double-label immunofluorescence staining and subsequent imaging. Results Western blot analysis revealed a significant overexpression of VEGF in bAVM tissues (P < 0.05). Immunohistochemistry showed that the amount of cells that overexpressed VEGF in bAVM tissues was significantly greater compared to that in normal tissues (P < 0.05). Double-label immunofluorescence staining showed no significant difference between the mean amounts of VEGF-positive cells in astrocytes and in neurons (P < 0.05). Conclusions The formation and progression of bAVMs is related to the local overexpression of VEGF. Similar levels of VEGF overexpression are found in astrocytes, neurons, and vascular endothelial cells, which suggest that VEGF may be derived from astrocytes and neurons. It implied that focal neurons may play a certain role in the pathophysical process of bAVMs, however, identification of the production and functional mechanisms of VEGF in the neurons still requires further investigation.

Keywords: Brain arteriovenous malformation; astrocyte; neuron; vascular endothelial growth factor.