Exogenous nitric oxide decreases brain vascular inflammation, leakage and venular resistance during Plasmodium berghei ANKA infection in mice.
Exogenous nitric oxide decreases brain vascular inflammation, leakage and venular resistance during Plasmodium berghei ANKA infection in mice.
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外源一氧化氮减少小鼠疟原虫在Anka感染期间脑血管炎症，泄漏和静脉电阻。
DOI：
10.1186/1742-2094-8-66
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发表时间：
2011-06-07
影响因子：
9.3
通讯作者：
Carvalho LJ
中科院分区：
文献类型：
--
作者：
Zanini GM;Cabrales P;Barkho W;Frangos JA;Carvalho LJ
脑型疟疾（CM）是恶性疟原虫感染的致命并发症。在伯氏疟原虫ANKA（PbA）鼠模型中，CM与显著的脑炎症、内皮细胞粘附分子表达增加以及脑血管中白细胞和血小板积聚相关，导致血管闭塞和血流量减少，损伤内皮并导致血脑屏障破坏、渗漏和破裂。外源性一氧化氮（NO）的管理在很大程度上防止综合征。在这里，我们评估了NO预防小鼠CM的作用机制是否与其抗炎特性和内皮保护有关。用生理盐水或二亚丙基三胺NONOate（DPTA-NO）每天两次处理感染PbA的C57 B1/6小鼠。免疫印迹法检测两组感染第6天脑组织中内皮细胞粘附分子（ICAM-1，VCAM，E-和P-选择素）的表达。对于活体显微镜研究，在感染第6天，用白蛋白-FITC、抗-CD 45-TxR和抗-CD 41-FITC抗体注射先前植入闭合颅窗的DPTA-NO处理和盐水处理的小鼠，以定量软脑膜血管中的白蛋白渗漏、白细胞和血小板粘附。与盐水处理的小鼠相比，用NO供体DPTA-NO处理的PbA感染的小鼠显示脑中ICAM-1和P-选择素的表达降低，但VCAM-1没有。DPTA-NO处理还减少了软脑膜血管中粘附的白细胞和血小板的数量，特别是在直径为30-50 μm的小静脉中，降低了炎性血管阻力，并防止了在盐水处理的PbA感染小鼠中观察到的小动脉和小静脉白蛋白渗漏的发生，如通过活体显微镜所评估的。这些结果表明，外源性NO对小鼠CM的保护作用与脑血管炎性标志物的表达减少有关，从而导致内皮连接损伤减弱并促进血流。
Cerebral malaria (CM) is a lethal complication of Plasmodium falciparum infections. In the Plasmodium berghei ANKA (PbA) murine model, CM is associated with marked brain inflammation, increased expression of endothelial cell adhesion molecules and leukocyte and platelet accumulation in brain vessels, causing vascular occlusion and decreased blood flow, damaging the endothelium and leading to blood-brain barrier breakdown, leakage and hemorrhages. Exogenous nitric oxide (NO) administration largely prevents the syndrome. Here we evaluated whether the mechanism of action of NO in preventing murine CM is related to its anti-inflammatory properties and to protection of the endothelium. C57Bl/6 mice infected with PbA were treated twice a day with saline or dipropylenetriamineNONOate (DPTA-NO). Endothelial cell adhesion molecule (ICAM-1, VCAM, E- and P-selectin) expression in brain tissue on day 6 of infection was assessed in both groups by western blot. For intravital microscopy studies, DPTA-NO-treated and saline-treated mice with a previously implanted closed cranial window were injected with albumin-FITC, anti-CD45-TxR and anti-CD41-FITC antibodies on day 6 of infection for quantification of albumin leakage, leukocyte and platelet adherence in pial vessels. PbA-infected mice treated with the NO-donor DPTA-NO showed decreased expression of ICAM-1 and P-selectin, but not VCAM-1, in the brain, compared to saline-treated mice. DPTA-NO treatment also decreased the number of adherent leukocytes and platelets in pial vessels, particularly in venules 30-50 μm in diameter, decreased inflammatory vascular resistance and prevented the occurrence of arteriolar and venular albumin leakage observed in saline-treated PbA-infected mice, as assessed by intravital microscopy. These results indicate that the protective effect of exogenous NO on murine CM is associated with decreased brain vascular expression of inflammatory markers resulting in attenuated endothelial junction damage and facilitating blood flow.
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影响因子：
82.9
作者：
Gramaglia, Irene;Sobolewski, Peter;van der Heyde, Henri C.
通讯作者：
van der Heyde, Henri C.
影响因子：
5
作者：
Lackner, P.;Burger, C.;Beer, R.
通讯作者：
Beer, R.
DOI：
10.3791/2184
发表时间：
2010-11-18
期刊：
Journal of visualized experiments : JoVE
影响因子：
--
作者：
Cabrales, Pedro;Carvalho, Leonardo J M
通讯作者：
Carvalho, Leonardo J M
影响因子：
20.1
作者：
KUROSE, I;KUBES, P;GRANGER, DN
通讯作者：
GRANGER, DN
影响因子：
4.4
作者：
Belnoue, E;Kayibanda, M;Rénia, L
通讯作者：
Rénia, L