Rat brain VEGF expression in alveolar hypoxia: possible role in high-altitude cerebral edema.
The mechanism by which hypoxia causes high-altitude cerebral edema (HACE) is unknown. Tissue hypoxia triggers angiogenesis, initially by expressing vascular endothelial growth factor (VEGF), which has been shown to increase extracerebral capillary permeability. This study investigated brain VEGF expression in 32 rats exposed to progressively severe normobaric hypoxia (9-6% O2) for 0 (control), 3, 6, or 12 h or 1, 2, 3, or 6 days. O2 concentration was adjusted intermittently to the limit of tolerance by activity and intake, but no attempt was made to detect HACE. Northern blot analysis demonstrated that two molecular bands of transcribed VEGF mRNA (approximately 3.9 and 4.7 kb) were upregulated in cortex and cerebellum after as little as 3 h of hypoxia, with a threefold increase peaking at 12-24 h. Western blot revealed that VEGF protein was increased after 12 h of hypoxia, reaching a maximum in approximately 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.
Xu
F
F
Department of Anesthesia, University of California Medical School, San Francisco, California 94143-0542, USA.
Severinghaus
J W
JW
D000532:Altitude Sickness / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D015153:Blotting, Western; D001923:Brain Chemistry / Q000502:physiology*; D001929:Brain Edema / Q000378:metabolism* / Q000503:physiopathology; D016228:Endothelial Growth Factors / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology; D008222:Lymphokines / Q000096:biosynthesis*; D008297:Male; D011650:Pulmonary Alveoli / Q000503:physiopathology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors