Qiquan Zhou1, 2, Chang’e Liu3, Jing Wang4, Yunli Wang4, Bo Zhou5

1Department of High Altitude Disease, College of High Altitude Military Medicine, Third Military Medical University of Chinese PLA, Chongqing   400038, China
2Key Laboratory of High Altitude Medicine, Ministry of Education, and Key Laboratory of High Altitude Physiology and High Altitude Disease of Chinese PLA, Chongqing  400038, China
3Department of Animal Science, College of Basic Medicine, Third Military Medical University of Chinese PLA, Chongqing  400038, China
4Department of Pathology and Pathophysiology, Chengdu Medical College, Chengdu  610083, Sichuan Province, China
5Clinical Laboratory, the 25 Hospital of Chinese PLA, Jiuquan  735000, Gansu Province, China

the Tackle Key Problem in Science and Technology during the “11th Five-Year Plan” Period of Chinese PLA, No. 06G030*

Abstract
BACKGROUND: Many studies have evaluated the role of vascular endothelial growth factor (VEGF) in traumatic brain edema and hemorrhagic brain edema.
OBJECTIVE: To observe the effects of VEGF expression on permeability of the blood-brain barrier (BBB) during high-altitude and hypoxia exposure, and to investigate the correlation between VEGF expression and BBB permeability with regard to Evans blue staining and brain edema during high-altitude exposure.
DESIGN, TIME AND SETTING: The randomized, controlled, animal study was performed at the Tanggula Etape, Central Laboratory of Chengdu Medical College, and Central Laboratory of General Hospital of Chengdu Military Area Command of Chinese PLA, China, from July 2003 to November 2004.
MATERIALS: Quantitative RT-PCR kit (Sigma, USA), VEGF ELISA kit (Biosource, USA), and Evans blue (Jingchun, China) were acquired for this study.
METHODS: A total of 180 Wistar rats were equally and randomly assigned to 15 groups: low-altitude (500 m), middle-altitude (2 880 m), high-altitude (4 200 m), super-high-altitude (5 000 m), 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, and 21 days of super high-altitude exposure. Wistar rats were exposed to various altitude gradients to establish a hypoxia model.
MAIN OUTCOME MEASURES: Brain water content was calculated according to the wet-to-dry weight ratio. BBB permeability to Evans blue was determined by colorimetric method. VEGF mRNA and protein levels in brain tissues were detected using RT-PCR and double-antibody sandwich ELISA.
RESULTS: Brain water content, BBB permeability to Evans blue, and VEGF mRNA and protein levels in brain tissues increased with increasing altitude and prolonged exposure to altitude. The greatest increase was determined on day 9 upon ascending 5 000 m. Simultaneously, VEGF expression positively correlated to BBB permeability of Evans blue and brain water content (r = 0.975, 0.917, P < 0.01).
CONCLUSION: Increased VEGF protein and mRNA expression was responsible for increased BBB permeability, which may be an important mechanism underlying brain edema during high-altitude exposure.

Key Words: high-altitude; blood-brain barrier; permeability; vascular endothelial growth factor

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