[Changes of VEGF and AQPs gene and protein expression in rat brain tissue during hypoxic encephaledema].

Zhongguo Ying Yong Sheng Li Xue Za Zhi

Department of Military High Altitude Medicine, Institute of Health and Environmental Medicine, Academy of Military Medical Sciences, Tianjin 300050, China.

Published: February 2011

Objective: To explore the changes of vascular endothelial growth factor(VEGF), aquaporin (AQP) gene and protein expression during hypoxic encephaledema so as to provide the basis for elucidating the brain injury caused by acute hypoxic exposure and pathogenesis of the encephaledema.

Methods: Wistar rats were randomly divided into 4 groups, i.e. control group, hypoxia 4 000 m group, hypoxia 6 000 m group and hypoxia 8 000 m group. Rats in hypoxic groups were exposed to hypoxia at simulated altitude of 4 000 m, 6 000 m and 8 000 m above sea level for 8 hours respectively in order to establish hypoxic encephaledema model. The water content in brain was determined by dry-weight method. The changes in morphology of brains were observed under optical microscope. The changes in expression of VEGF, AQP1 and AQP4 genes and protein were determined by RT-PCR and immunohistochemistry.

Results: (1) The results determined by dry-weight method indicated that water content of rats brain increased markedly after rats were exposed to a simulated altitude at 6 000 m, 8 000 m. (2) The results determined by microscopy indicated that during the rats exposed to hypoxia, nerve cells, vascular endothelial cells and astrocyte foot processes swelled lightly, transudate occurred in tissues at 4 000 m. The swelling of vascular endothelial cell (VEC) and astrocyte foot processes aggravated, interspace between vessels and tissues enlarged, and transudate in tissue increased at 6 000 m. The swelling of VEC and astrocyte foot processes went from bad to worse, interspace between vessels and tissues enlarged further, and transudate in tissue increased evidently at 8 000 m. (3) During hypoxic encephaledema, the expression of VEGF, AQP1 and AQP4 mRNA increased, AQP1 was abnormally expressed on the surface of VEC, and the expressive level of VEGF and AQP1 on VEC and AQP4 on astrocyte foot processes increased.

Conclusion: The changes in expression and distribution of VEGF, AQP1 and AQP4 during encephaledema caused by hypoxic exposure may induce blood-brain barrier injury, and may be one of the pathogenesis of hypoxic encephaledema.

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