Oxidative stress in brain during experimental bacterial meningitis:: Differential effects of α-phenyl-tert-butyl nitrone and N-acetylcysteine treatment
Oxidative stress in brain during experimental bacterial meningitis:: Differential effects of α-phenyl-tert-butyl nitrone and N-acetylcysteine treatment
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DOI：
10.1016/s0891-5849(01)00642-6
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发表时间：
2001-09-15
影响因子：
7.4
通讯作者：
Täuber, MG
中科院分区：
文献类型：
--
作者：
Christen, S;Schaper, M;Täuber, MG
抗氧化剂治疗先前已被证明对实验性细菌性脑膜炎具有神经保护作用。为了获得这种疾病中氧化应激的定量证据，我们测量了感染肺炎链球菌的幼鼠皮质中主要的脑抗氧化剂抗坏血酸和还原型谷胱甘肽，以及脂质过氧化终产物丙二醛。感染22小时后，当动物病情严重时，这两种抗氧化剂的皮质水平显着下降。皮质中的总吡啶核苷酸水平没有改变，表明两种抗氧化剂的损失不是由于细胞坏死。细菌性脑膜炎伴有皮质丙二醛中度显着增加。虽然用抗氧化剂α-苯基叔丁基硝酮或N-乙酰半胱氨酸处理显着抑制了这种增加，但只有前者减弱了内源抗氧化剂的损失。感染后18小时脑脊液细菌滴度、亚硝酸盐和硝酸盐水平以及髓过氧化物酶活性不受抗氧化剂治疗的影响，表明它们通过调节炎症以外的机制发挥作用。结果表明，细菌性脑膜炎伴有脑实质氧化应激。此外，皮质脂质过氧化的增加似乎并不是实质氧化应激的结果，因为它被 NAC 阻止，而 NAC 对大脑抗氧化剂的损失没有影响。 (C) 2001 爱思唯尔科学公司。
Antioxidant treatment has previously been shown to be neuroprotective in experimental bacterial meningitis. To obtain quantitative evidence for oxidative stress in this disease, we measured the major brain antioxidants ascorbate and reduced glutathione, and the lipid peroxidation endproduct malondialdehyde in the cortex of infant rats infected with Streptococcus pneumoniae. Cortical levels of the two antioxidants were markedly decreased 22 h after infection, when animals were severely ill. Total pyridine nucleotide levels in the cortex were unaltered, suggesting that the loss of the two antioxidants was not due to cell necrosis. Bacterial meningitis was accompanied by a moderate, significant increase in cortical malondialdehyde. While treatment with either of the antioxidants alpha -phenyl-tert-butyl nitrone or N-acetylcysteine significantly inhibited this increase, only the former attenuated the loss of endogenous antioxidants. Cerebro-spinal fluid bacterial titer, nitrite and nitrate levels, and myeloperoxidase activity at 18 h after infection were unaffected by antioxidant treatment, suggesting that they acted by mechanisms other than modulation of inflammation. The results demonstrate that bacterial meningitis is accompanied by oxidative stress in the brain parenchyma. Furthermore, increased cortical lipid peroxidation does not appear to be the result of parenchymal oxidative stress, because it was prevented by NAC, which had no effect on the loss of brain antioxidants. (C) 2001 Elsevier Science Inc.