Cerebral and peripheral changes occurring in nitric oxide (NO) synthesis in a rat model of sleeping sickness: identification of brain iNOS expressing cells.
Cerebral and peripheral changes occurring in nitric oxide (NO) synthesis in a rat model of sleeping sickness: identification of brain iNOS expressing cells.
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DOI：
10.1371/journal.pone.0009211
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发表时间：
2010-02-16
期刊：
影响因子：
3.7
通讯作者：
Cespuglio R
中科院分区：
文献类型：
--
作者：
Amrouni D;Gautier-Sauvigné S;Meiller A;Vincendeau P;Bouteille B;Buguet A;Cespuglio R
一氧化氮（NO）在人类非洲锥虫病（HAT）的发展使用的动物模型的影响，进行了检查。感染布氏锥虫的大鼠外周和脑中NO杀锥虫活性受损的方式（T. B.通过以下方式分析：（i）外周（血液）和脑区室中NO浓度发生的变化;（ii）nNOS和iNOS酶的活性;（iii）鉴定其中NO途径在感染的时间过程中特别活跃的脑细胞类型。在感染后的不同天数：D5、D10、D16和D22，在健康和感染动物的中枢（脑）和外周（血液）隔室中测定NO浓度（通过伏安法直接测量）。在两个隔室中观察到相反的变化。从D10（+32%）到D16（+71%），大脑（下丘脑）中的NO产量增加，但从D10（-22%）到D16（-46%）和D22（-60%），血液中的NO产量减少。与NO测量平行，脑iNOS活性增加，并在D16达到峰值（高达+700%）。然而，nNOS活性没有变化。免疫组织化学染色证实了iNOS激活在几个脑区，特别是在下丘脑。在腹腔巨噬细胞中，iNOS活性从D10（-83%）下降到D16（-65%）和D22（-74%），与循环NO相似。在我们的大鼠模型中观察到的NO变化依赖于外周和中央室的iNOS活性。在外周，NO产生减少可能反映了锥虫生长所必需的多胺的脱氢酶介导的合成。在脑中，NO浓度的增加可能是由于神经元和神经胶质细胞中存在的iNOS活性增强所致。它可被视为有害炎症反应的标志物。
The implication of nitric oxide (NO) in the development of human African trypanosomiasis (HAT) using an animal model, was examined. The manner by which the trypanocidal activity of NO is impaired in the periphery and in the brain of rats infected with Trypanosoma brucei brucei (T. b. brucei) was analyzed through: (i) the changes occurring in NO concentration in both peripheral (blood) and cerebral compartments; (ii) the activity of nNOS and iNOS enzymes; (iii) identification of the brain cell types in which the NO-pathways are particularly active during the time-course of the infection. NO concentration (direct measures by voltammetry) was determined in central (brain) and peripheral (blood) compartments in healthy and infected animals at various days post-infection: D5, D10, D16 and D22. Opposite changes were observed in the two compartments. NO production increased in the brain (hypothalamus) from D10 (+32%) to D16 (+71%), but decreased in the blood from D10 (−22%) to D16 (−46%) and D22 (−60%). In parallel with NO measures, cerebral iNOS activity increased and peaked significantly at D16 (up to +700%). However, nNOS activity did not vary. Immunohistochemical staining confirmed iNOS activation in several brain regions, particularly in the hypothalamus. In peritoneal macrophages, iNOS activity decreased from D10 (−83%) to D16 (−65%) and D22 (−74%) similarly to circulating NO. The NO changes observed in our rat model were dependent on iNOS activity in both peripheral and central compartments. In the periphery, the NO production decrease may reflect an arginase-mediated synthesis of polyamines necessary to trypanosome growth. In the brain, the increased NO concentration may result from an enhanced activity of iNOS present in neurons and glial cells. It may be regarded as a marker of deleterious inflammatory reactions.
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影响因子：
4
作者：
De Baetselier, P;Namangala, B;Beschin, A
通讯作者：
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DOI：
10.1152/ajpheart.1998.274.1.h342
发表时间：
1998-01-01
影响因子：
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作者：
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影响因子：
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通讯作者：
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影响因子：
3.2
作者：
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通讯作者：
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影响因子：
3.3
作者：
Clément, P;Sarda, N;Gharib, A
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