Neurovascular Unit and the Effects of Dosage in VEGF Toxicity: Role for Oxidative Stress and Thrombin

摘要: Bidirectional communication between neurons and vascular cells is important to the maintenance of central nervous system (CNS) milieu. Vascular endothelial growth factor (VEGF), through its ability affect both neuronal cells, likely a key protein in this process. Despite considerable literature documenting neuroprotective function for VEGF, overexpression has also been shown wide variety CNS diseases, including Alzheimer's disease (AD). Increased oxidative stress elevated thrombin levels have documented AD, specifically microvasculature. The aim current study examine vitro determine effects on VEGF release as well low high dose viability. data show that microvessels isolated from AD patients secrete significantly higher compared control-derived vessels. Exposure brain (sodium nitroprusside, menadione, or hydrogen peroxide) increases expression. cultured expression thrombin. Treating rat cortical with (≥500 ng/ml) decreases survival anti-apoptotic Bcl-2 while increasing proapoptic proteins caspase 3 phosphorylated p38 MAPK. High negates decrease amyloid-β evoked by VEGF. These results suggest despite supporting protein, caution warranted prior implementation therapeutic brain.