Dual action of NO synthases on blood flow and infarct volume consecutive to neonatal focal cerebral ischemia
Dual action of NO synthases on blood flow and infarct volume consecutive to neonatal focal cerebral ischemia
复制标题
DOI：
10.1016/j.expneurol.2012.04.001
复制
发表时间：
2012-07-01
影响因子：
5.3
通讯作者：
Charriaut-Marlangue, Christiane
中科院分区：
文献类型：
--
作者：
Bonnin, Philippe;Leger, Pierre-Louis;Charriaut-Marlangue, Christiane
由于缺乏对导致损伤的初始血流动力学机制，特别是NO介导的血管机制的完整了解，阻碍了对新生儿缺血性脑损伤的研究。在一个新生卒中大鼠模型中，我们最近发现侧支循环募集有助于脑梗塞面积的变化。在动脉闭塞(左侧大脑中动脉电凝双侧颈总动脉闭塞50min)大鼠模型中，我们评估了非特异性和选择性的一氧化氮合酶(NOS)抑制对脑血流变化和预后的影响。用超声成像和序列多普勒记录测量颈内动脉和基底动脉干的血流变化。用激光多谱勒血流仪测量皮质血流灌注。我们发现，在两性中，全局抑制一氧化氮合酶显著减少侧支支持和皮质灌流(侧支衰竭)，并加重缺血性损伤。相反，内皮型一氧化氮合酶的抑制增加了男性的血流量，加重了体积损伤，而女性的血流量没有变化，脑梗塞病变明显减少。这些变化分别与男性神经元型一氧化氮合酶在Ser(847)处的磷酸化水平降低和女性在24 h时的磷酸化水平升高有关。神经元型一氧化氮合酶的抑制也增加了雄性幼鼠的血流量，但雌性并没有显著改变梗塞体积。结论：nNOS和eNOS似乎都在脑缺血期间调节动脉血流方面起着关键作用，主要是在雄性幼鼠中，随后对梗塞病变进行了修改。(C)2012 Elsevier Inc.保留所有权利。
Research into neonatal ischemic brain damage is impeded by the lack of a complete understanding of the initial hemodynamic mechanisms resulting in a lesion, particularly that of NO-mediated vascular mechanisms. In a neonatal stroke rat model, we recently show that collateral recruitment contributes to infarct size variability.Non-specific and selective NO synthase (NOS) inhibition was evaluated on cerebral blood-flow changes and outcome in a P7 rat model of arterial occlusion (left middle cerebral artery electrocoagulation with 50 min occlusion of both common carotid arteries). Blood-flow changes were measured by using ultrasound imaging with sequential Doppler recordings in both internal carotid arteries and basilar trunk. Cortical perfusion was measured by using laser Doppler flowmetry. We showed that global NOS inhibition significantly reduced collateral support and cortical perfusion (collateral failure), and worsened the ischemic injury in both gender. Conversely, endothelial NOS inhibition increased blood-flows and aggravated volume lesion in males, whereas in females blood-flows did not change and infarct lesion was significantly reduced. These changes were associated with decreased phosphorylation of neuronal NOS at Ser(847) in males and increased phosphorylation in females at 24 h, respectively. Neuronal NOS inhibition also increased blood-flows in males but not in females, and did not significantly change infarct volumes compared to their respective PBS-treated controls.In conclusion, both nNOS and eNOS appear to play a key role in modulating arterial blood flow during ischemia mainly in male pups with subsequent modifications in infarct lesion. (C) 2012 Elsevier Inc. All rights reserved.