Acute hypertension induces oxidative stress in brain tissues
Acute hypertension induces oxidative stress in brain tissues
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DOI：
10.1038/sj.jcbfm.9600188
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发表时间：
2006-02-01
影响因子：
6.3
通讯作者：
Lembo, G
中科院分区：
文献类型：
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作者：
Poulet, R;Gentile, MT;Lembo, G
动脉高血压不仅是脑血管意外（如中风和脑出血）的主要危险因素，而且还与轻度脑损伤有关。神经退行性变的主要原因之一是活性氧（ROS）的增加，这也是高血压疾病的常见特征，因此表明这种机制甚至在高血压诱发的脑损伤的发病中也可以发挥作用。为了研究这个问题，我们探讨了急性高血压对脑氧化应激的影响。为此，我们已经开发了一个小鼠模型的横向主动脉缩窄（TAC）之间的两个颈动脉，急性对右脑半球的血压急剧增加。我们的研究结果表明，高血压急性引起的主动脉缩窄引起的血脑屏障（BBB）的破坏和反应性星形胶质细胞增生，通过过度灌注，并引起神经退行性变的触发因素，如氧化应激和炎症，类似于脑灌注不足。此外，衍生的脑损伤主要位于控制认知功能的选定脑区，如皮质和海马，并且可能是BBB通透性缺陷的结果。值得强调的是，即使这些后一种事件不足以产生缺血性/出血性损伤，它们也能够改变维持正常脑功能的基本机制，例如蛋白质合成，其对记忆形成和皮质可塑性具有突出作用。
Arterial hypertension is not only a major risk factor for cerebrovascular accidents, such as stroke and cerebral hemorrhage, but is also associated to milder forms of brain injury. One of the main causes of neurodegeneration is the increase in reactive oxygen species (ROS) that is also a common trait of hypertensive conditions, thus suggesting that such a mechanism could play a role even in the onset of hypertension-evoked brain injury. To investigate this issue, we have explored the effect of acute-induced hypertensive conditions on cerebral oxidative stress. To this aim, we have developed a mouse model of transverse aortic coarctation (TAC) between the two carotid arteries, which imposes acutely on the right brain hemisphere a dramatic increase in blood pressure. Our results show that hypertension acutely induced by aortic coarctation induces a breaking of the blood-brain barrier (BBB) and reactive astrocytosis through hyperperfusion, and evokes trigger factors of neurodegeneration such as oxidative stress and inflammation, similar to that observed in cerebral hypoperfusion. Moreover, the derived brain injury is mainly localized in selected brain areas controlling cognitive functions, such as the cortex and hippocampus, and could be a consequence of a defect in the BBB permeability. It is noteworthy to emphasize that, even if these latter events are not enough to produce ischemic/hemorrhagic injury, they are able to alter mechanisms fundamental for maintaining normal brain function, such as protein synthesis, which has a prominent role for memory formation and cortical plasticity.