| Objective: To investigate the angiogenic effect and protective effect on cognitive dysfunction of exogenous acid fibroblast growth factor (aFGF) following hypoxic-ischemic brain damage in neonatal rats.Methods: the neonatal Sprague-Dawley rats model of hypoxic-ischemic brain damage (HIBD) were made by ligating the left carotid and breathing the 8% oxygen. The HIBD model rats were divided into two groups randomly, one was the aFGF trail group, the other was the NS control group. The other rats were taken into the pseudo operation group. The expression of VEGF messenger ribonucleic acid (mRNA) and protein in rat brain were analyzed with semiquantitative reverse transcriptase-polymerase chain reaction and immunohistochemical techniques, respectively. Immunohistochemical techniques were used to evaluate VEGF protein localization with mouse monoclonal anti-rat VEGF, microvessel with rabbit polyclonal anti-rat PECAM-1. Each group's spatial cognitive capability was evaluated by using the Morris water maze.Results: VEGF mRNA were observed in every group. VEGF mRNA levels were significantly increased in the aFGF trail group brains at 1st day postoperatively compared with the control group(0.97 + 0.09 vs. 0.72 + 0.14, p<0.05), peaked by 1 st day. It returned to the control group levels but also higher than the pseudo operation group(0.92 0.19 vs. 0.58 + 0.13, p<0.05) by 3rd day after operation. At 7th day it returned to the pseudo operation group levels. VEGF protein expression, as measured in immunohistochemical techniques, was also increased in rat brains in the afgf trail group at 1st day to 3rd day postoperatively. It was significantly increased in the afgf trail group at 3rd day (168.50 + 47.40 vs. 90.83 + 23.69), p<0.01 . There was no statistical difference among three groups at 7th day. Microvessel in the rat brains began to increase significantly at 1st day after operation in the trail group compared with control group, (14.50 + 4.04 vs. 6.83 + 3.66, p<0.01). as assessed immunohistochemically, and the increase was maintained for 3 days (12.33 + 6.50 vs. 5.33 + 3.08, p<0.05). Microvesselin the trail group was more than that in pseudo operation group even at 7th day(6.33 0.52 vs. 0.50 + 0.55, p<0.01). In Morris water maze trail, the latency to find the hidden platform in control group(53.64 47.30s) was longer than that in trail group(27.15 30.82s) and the pseudo operation group(28.36 29.98s), /?<0.01, and there was no statistical difference between trail group and the pseudo operation group. The frequency of pass through the platform in control group(2.4 2.72) was less than that in trail group(6.3 3.71) and pseudo group(7.2 3.65), p<0.05, and there was no statistical difference between trail group and the pseudo operation group.Conclusion: These results demonstrated that aFGF could induce sustained up-regulation of VEGF mRNA and protein expression in rat brain, which was correlated with angiogenesis. The early treatment with exogenous aFGF can improve the attenuate learning and memory dysfunction following HIBD. |
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