Insulin-Like Growth Factor (IGF)-I Modulates Endothelial Blood-Brain Barrier Function in Ischemic Middle-Aged Female Rats
Insulin-Like Growth Factor (IGF)-I Modulates Endothelial Blood-Brain Barrier Function in Ischemic Middle-Aged Female Rats
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DOI：
10.1210/en.2015-1840
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发表时间：
2016-01-01
期刊：
影响因子：
4.8
通讯作者：
Sohrabji, Farida
中科院分区：
文献类型：
--
作者：
Bake, Shameena;Okoreeh, Andre K.;Sohrabji, Farida
与年轻雌性相比，中年雌性大鼠中风后脑梗死更严重，功能恢复更差。中年女性较差的中风结果与年龄相关的igf - 1水平降低有关。脑卒中后igf - 1治疗可减少老年女性梗死体积，并降低缺血半球细胞因子的表达。igf - 1也减少了埃文斯蓝染料向大脑的转移，这表明这种肽也可能促进血脑屏障功能。为了验证igf - 1在缺血性卒中中可能作用于血脑屏障的假设，采用了两种方法。在第一种方法中，中年雌性大鼠大脑中动脉闭塞，再灌注后用IGF-I处理。对缺血半球的单个核细胞进行CD4染色或CD4/CD25/FoxP3三重标记，并进行血流分析。与对照组相比，igf - i处理动物的两组细胞均显著减少。免疫细胞运输到缺血部位的减少表明，在igf - i治疗的动物中，血脑屏障的完整性得到了更好的维持。第二种方法是直接检测igf - 1对衰老内皮细胞屏障功能的影响。因此，我们在体外培养中年雌性大鼠的脑微血管内皮细胞并使其缺血（缺氧-葡萄糖剥夺）。与载体处理的培养物相比，IGF-I处理显著减少了荧光标记的BSA在内皮单层的转移，以及异硫氰酸荧光素BSA的细胞内化。总的来说，这些数据支持了IGF-I改善中年女性血脑屏障功能的假设。
In comparison with young females, middle-aged female rats sustain greater cerebral infarction and worse functional recovery after stroke. These poorer stroke outcomes in middle-aged females are associated with an age-related reduction in IGF-I levels. Poststroke IGF-I treatment decreases infarct volume in older females and lowers the expression of cytokines in the ischemic hemisphere. IGF-I also reduces transfer of Evans blue dye to the brain, suggesting that this peptide may also promote blood-brain barrier function. To test the hypothesis that IGF-I may act at the blood-brain barrier in ischemic stroke, 2 approaches were used. In the first approach, middle-aged female rats were subjected to middle cerebral artery occlusion and treated with IGF-I after reperfusion. Mononuclear cells from the ischemic hemisphere were stained for CD4 or triple-labeled for CD4/CD25/FoxP3 and subjected to flow analyses. Both cohorts of cells were significantly reduced in IGF-I-treated animals compared with those in vehicle controls. Reduced trafficking of immune cells to the ischemic site suggests that blood-brain barrier integrity is better maintained in IGF-I-treated animals. The second approach directly tested the effect of IGF-I on barrier function of aging endothelial cells. Accordingly, brain microvascular endothelial cells from middle-aged female rats were cultured ex vivo and subjected to ischemic conditions (oxygen-glucose deprivation). IGF-I treatment significantly reduced the transfer of fluorescently labeled BSA across the endothelial monolayer as well as cellular internalization of fluorescein isothiocyanate-BSA compared with those in vehicle-treated cultures, Collectively, these data support the hypothesis that IGF-I improves blood-brain barrier function in middle-aged females.