Poulet Roberta, Gentile Maria T, Vecchione Carmine, Distaso Maria, Aretini Alessandra, Fratta Luigi, Russo Giovanni, Echart Cinara, Maffei Angelo, De Simoni Maria G, Lembo Giuseppe
Department of Angio-Cardio-Neurology, IRCCS Neuromed, Pozzilli (IS), Italy.
J Cereb Blood Flow Metab. 2006 Feb;26(2):253-62. doi: 10.1038/sj.jcbfm.9600188.
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.
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,还与较轻形式的脑损伤有关。神经退行性变的主要原因之一是活性氧(ROS)增加,这也是高血压状态的一个共同特征,因此表明这种机制可能在高血压诱发的脑损伤发病中也起作用。为了研究这个问题,我们探讨了急性诱导的高血压状态对脑氧化应激的影响。为此,我们建立了一种在两条颈动脉之间进行横向主动脉缩窄(TAC)的小鼠模型,该模型会使右脑半球的血压急剧升高。我们的结果表明,主动脉缩窄急性诱导的高血压通过过度灌注导致血脑屏障(BBB)破坏和反应性星形胶质细胞增生,并引发神经退行性变的触发因素,如氧化应激和炎症,这与脑灌注不足时观察到的情况相似。此外,由此产生的脑损伤主要局限于控制认知功能的特定脑区,如皮质和海马体,并且可能是血脑屏障通透性缺陷的结果。值得强调的是,即使这些后期事件不足以产生缺血/出血性损伤,它们也能够改变维持正常脑功能的基本机制,如蛋白质合成,而蛋白质合成在记忆形成和皮质可塑性方面具有重要作用。