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Aging influences in the blood-brain barrier permeability and cerebral oxidative stress in sepsis.
Experimental Gerontology ( IF 3.3 ) Pub Date : 2020-08-19 , DOI: 10.1016/j.exger.2020.111063
Willian Margotti 1 , Amanda Della Giustina 1 , Mariana Pereira de Souza Goldim 1 , Marcos Hubner 1 , Thainá Cidreira 1 , Taís Luise Denicol 1 , Larissa Joaquim 1 , Raquel Jaconi De Carli 1 , Lucinéia Gainski Danielski 1 , Kiuanne Lino Lobo Metzker 1 , Sandra Bonfante 1 , Tatiana Barichello 2 , Fabricia Petronilho 1
Affiliation  

Sepsis is a set of serious manifestations throughout the body produced by an infection, leading to changes that compromise cellular homeostasis and can result in dysfunction of the central nervous system. The elderly have a higher risk of developing sepsis than younger peoples. Under the influence of inflammatory mediators and oxidizing agents released in the periphery as a result of the infectious stimulus, changes occur in the blood-brain barrier (BBB) permeability, with neutrophil infiltration, the passage of toxic compounds, activation of microglia and production of reactive species that results in potentiation of neuroimmune response, with the progression of neuronal damage and neuroinflammation. The objective of this study is to compare BBB permeability and the development of oxidative stress in the hippocampus and prefrontal cortex of young and old rats submitted to polymicrobial sepsis induction. Male Wistar rats grouped into sham (60d), sham (210d), cecal ligation and perforation (CLP) (60d) and CLP (210d) with n = 16 per experimental group were evaluated using the CLP technique to induce sepsis. The brain regions were collected at 24 h after sepsis induction to determine BBB permeability, myeloperoxidase (MPO) activity as marker of neutrophil activation, nitrite/nitrate (N/N) levels as marker of reactive nitrogen species, thiobarbituric acid reactive substances as marker of lipid peroxidation, protein carbonylation as marker of protein oxidation, and activity of antioxidant enzyme catalase (CAT). There was an increase in the BBB permeability in the CLP groups, and this was enhanced with aging in both brain region. MPO activity in the brain regions increased in the CLP groups, along with a hippocampal increase in the CLP 210d group compared to the 60d group. The concentration of N/N in the brain region was increased in the CLP groups. The damage to lipids and proteins in the two structures was enhanced in the CLP groups, while only lipid peroxidation was higher in the prefrontal cortex of the CLP 210d group compared to the 60d. CAT activity in the hippocampus was decreased in both CLP groups, and this was also influenced by age, whereas in the prefrontal cortex there was only a decrease in CAT in the CLP 60d group compared to the sham 60d. These findings indicate that aging potentiated BBB permeability in sepsis, which possibly triggered an increase in neutrophil infiltration and, consequently, an increase in oxidative stress.



中文翻译:


衰老对脓毒症中血脑屏障通透性和脑氧化应激的影响。



脓毒症是感染引起的一系列严重的全身症状,会导致细胞稳态发生变化,并可能导致中枢神经系统功能障碍。老年人比年轻人患败血症的风险更高。在感染刺激导致外周释放的炎症介质和氧化剂的影响下,血脑屏障(BBB)通透性发生变化,出现中性粒细胞浸润、有毒化合物通过、小胶质细胞激活和产生随着神经元损伤和神经炎症的进展,导致神经免疫反应增强的反应性物种。本研究的目的是比较接受多种微生物败血症诱导的年轻和年老大鼠的血脑屏障通透性以及海马和前额皮质氧化应激的发展。将雄性Wistar大鼠分为假手术(60天)、假手术(210天)、盲肠结扎穿孔(CLP)(60天)和CLP(210天),每个实验组n = 16,使用CLP技术诱导败血症进行评估。败血症诱导后 24 小时收集脑区域,测定 BBB 通透性、髓过氧化物酶 (MPO) 活性作为中性粒细胞活化的标记、亚硝酸盐/硝酸盐 (N/N) 水平作为活性氮物种的标记、硫代巴比妥酸反应物质作为中性粒细胞活化的标记。脂质过氧化、作为蛋白质氧化标记的蛋白质羰基化以及抗氧化酶过氧化氢酶 (CAT) 的活性。 CLP 组的 BBB 通透性增加,并且随着两个大脑区域的衰老而增强。 与 60 天组相比,CLP 210 天组的大脑区域 MPO 活性有所增加,同时 CLP 210 天组的海马体活性也有所增加。 CLP 组脑区 N/N 浓度增加。 CLP组中两种结构中脂质和蛋白质的损伤均增强,而CLP 210d组的前额叶皮层仅脂质过氧化程度高于60d。两个CLP组的海马CAT活性均下降,这也受到年龄的影响,而在前额皮质中,与假手术60d相比,CLP 60d组的CAT活性仅下降。这些发现表明,衰老会增强脓毒症中的血脑屏障通透性,这可能引发中性粒细胞浸润增加,从而导致氧化应激增加。

更新日期:2020-08-26
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