RAT-BRAIN VEGF EXPRESSION IN ALVEOLAR HYPOXIA - POSSIBLE ROLE IN HIGH-ALTITUDE CEREBRAL EDEMA

The mechanism by which hypoxia causes high-altitude cerebral edema (HA CE) is unknown. Tissue hypoxia triggers angiogenesis, initially by exp ressing vascular endothelial growth factor (VEGF), which has been show n to increase extracerebral capillary permeability. This study investi gated brain VEGF expression in 32 rats exposed to progressively severe normobaric hypoxia (9-6% O-2) for 0 (control), 3, 6, or 12 h or 1, 2, 3, or 6 days. O-2 concentration was adjusted intermittently to the li mit of tolerance by activity and intake, but no attempt was made to de tect HACE. Northern blot analysis demonstrated that two molecular band s of transcribed VEGF mRNA(similar to 3.9 and 4.7 kb) were upregulated in cortex and cerebellum after as little as 3 h of hypoxia, with a th reefold increase peaking at 12-24 h. Western blot revealed that VEGF p rotein was increased after 12 h of hypoxia, reaching a maximum in simi lar to 2 days. The expression of flt-1 mRNA was enhanced after 3 days of hypoxia. We conclude that VEGF production in hypoxia is consistent with the hypothesis that angiogenesis may be involved in HACE.