Protective effect of albumin on VEGF and brain edema in acute ischemia in rats

Vascular endothelial growth factor (VEGF) is known to be an important stroke-related pathogenic factor for the formation of brain edema. We examined the therapeutic effect of human serum albumin on VEGF expression in acute ischemic stroke. Adult male Sprague-Dawley (SD) rats were subjected to Middle Cerebral Artery Occlusion (MCAO), the suture was withdrawn 2 h later, and 25% albumin (1.25 g/kg) or saline (5 ml/kg) was administered intravenously after reperfusion. The model was evaluated by 2,3,5-triphenyl-tetrazolium chloride (TTC) staining, neurological deficits and brain water content. Serum albumin level was determined. VEGF expression was studied by enzyme linked immunosorbent assay (ELISA), quantitative real-time PCR and immunohistochemistry. We demonstrated that albumin administration maintained the serum albumin at a higher level than the sham group at 6 h, 1 d, 2 d and 3d after MCAO, and significantly improved the neurological deficits and decreased the brain water content. In addition, the strong up-regulation of VEGF expression at 6 h and 1 d after MCAO can be attenuated by albumin administration. However, albumin administration had no significant depressing effect on VEGF expression at 2 d, 3d and 5 d after MCAO in the cortex and hippocampus. Strong up-regulation of VEGF immunoreactivity was noted in the saline group in the blood-brain barrier (BBB), and in neurons surrounding the pen-infarct area and periventricular area at 24h after MCAO. The expression of VEGF in the albumin group was much weaker. Furthermore, there were high correlations between the brain water content with the serum albumin level, with serum VEGF protein level, and with brain VEGF mRNA expression at 24 h after MCAO. In conclusion, maintaining the serum albumin at a higher level, and attenuating endogenous VEGF expression at 6 h and 1 d, but not 2 d, 3d, or 5 d after MCAO, may partially contribute to the protective effects of albumin on reduction of brain edema in the early stage of ischemia. (C) 2010 Elsevier Ireland Ltd. All rights reserved.