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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Intracerebral VEGF injection highly upregulates AQP4 mRNA and protein in the perivascular space and glia limitans externa.
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Intracerebral VEGF injection highly upregulates AQP4 mRNA and protein in the perivascular space and glia limitans externa.

机译：脑内VEGF注射高度上调血管周间隙和局限神经胶质外层中的AQP4 mRNA和蛋白。

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摘要

Stroke is the third leading cause of death and the leading cause of adult disability in the industrialized nations. One of the consequences of stroke is blood-brain barrier (BBB) leakage and subsequent edema, which is one of the causes of mortality in this pathology. Aquaporin-4 (AQP4) is the most abundant water channel in the brain. Studies in AQP4 knock-out mice have shown a prominent role of this water channel in edema development and resolution after ischemia. Here we have studied changes in AQP4 mRNA and protein expression in response to vascular endothelial growth factor (VEGF), a potent angiogenic factor. VEGF administration highly upregulated AQP4 mRNA and protein in the ventral midbrain. Perfusion of the animals with FITC-albumin prior to sacrifice demonstrated localization of AQP4 protein in close proximity to the VEGF-induced new blood vessels. Expression levels of AQP4 mRNA were maximum 7 days after VEGF injection whereas our previous report showed that BBB leakage is resolved at this time point. Therefore, we speculate a positive role of AQP4 in edema resolution, which may partially explain the previously reported beneficial effects of delayed VEGF administration in ischemic rats. Our results provide new insights into the molecular changes in the edematous brain and may help in future therapeutical directions.
机译：在工业化国家，中风是导致死亡的第三大原因，也是导致成人残疾的主要原因。中风的后果之一是血脑屏障（BBB）渗漏和随后的水肿，这是该病理学导致死亡的原因之一。 Aquaporin-4（AQP4）是大脑中最丰富的水通道。在AQP4敲除小鼠中的研究表明，该水通道在缺血后水肿发展和消退中起着重要作用。在这里，我们研究了AQP4 mRNA和蛋白质表达对血管内皮生长因子（VEGF）（一种有效的血管生成因子）的响应变化。 VEGF给药在腹中脑中高度上调了AQP4 mRNA和蛋白。在处死前用FITC-白蛋白对动物进行灌注证明了AQP4蛋白的定位非常接近VEGF诱导的新血管。 VEGF注射后7天，AQP4 mRNA的表达水平最高，而我们先前的报告显示，此时BBB渗漏得以解决。因此，我们推测AQP4在水肿消退中具有积极作用，这可能部分解释了先前报道的在缺血大鼠中延迟VEGF给药的有益作用。我们的结果为水肿性大脑中分子的变化提供了新的见解，并可能在未来的治疗方向上有所帮助。

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