Laboratory of Experimental Microbiology and National Institute for Translational Medicine (INCT-TM), Postgraduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, 88806-000, Criciúma, SC, Brazil.
Metab Brain Dis. 2012 Dec;27(4):587-93. doi: 10.1007/s11011-012-9315-9. Epub 2012 May 17.
Pneumococcal meningitis is associated with the highest fatality case ratios in the world. Most of patients that survive present neurologic sequelae at later times as well as biochemicals alterations such as oxidative stress in both earlier and later times after central nervous system infection. In this context, we evaluated the effect of antioxidant treatment on memory and oxidative parameters in the hippocampus of meningitis survivor rats 10 days after infection. To this aim, the animals underwent a magna cistern tap receiving either 10 μL sterile saline as a placebo or an equivalent volume of a Streptococcus pneumoniae suspension at the concentration 5x10(9) cfu/mL. The animals submitted to meningitis were divided into the following groups: 1) treated with antibiotic, 2) treated with basic support plus N-acetylcysteine, 3) treated with basic support plus deferoxamine, 4) treated with basic support plus N-acetylcysteine and deferoxamine, or 5) treated with N-acetylcysteine plus deferoxamine. Ten days after meningitis, the animals underwent inhibitory avoidance and habituation to an open field tasks and, immediately after, were assessed for oxidative damage in the hippocampus and cortex. The meningitis group showed significantly decreased performance in latency retention compared with the sham group in the inhibitory avoidance task. In the open-field task, the meningitis group presented memory impairment after meningitis. All these memory impairments were prevented by N-acetylcysteine plus deferoxamine with or without basic support and its isolate use. In addition, there was an increase of lipid phosphorylation in cortex and hippocampus and all the combined antioxidants attenuated lipid phosphorylation in both structures. On the other hand, there was an increase of protein phosphorylation in cortex and N-acetylcysteine plus deferoxamine with or without basic support prevented it. Thus, we hypothesize that oxidative stress may be related to cognitive impairment in pneumococcal meningitis.
肺炎球菌性脑膜炎与全球病死率最高的病例有关。大多数存活的患者在中枢神经系统感染后早期和晚期都会出现神经后遗症以及生化改变，如氧化应激。在这种情况下，我们评估了抗氧化治疗对感染后 10 天脑膜炎幸存者大鼠海马记忆和氧化参数的影响。为此，动物接受了经枕骨大孔穿刺术，接受了 10μL 无菌生理盐水作为安慰剂或相当于 5x10(9)cfu/mL 肺炎链球菌混悬液的等体积。接受脑膜炎的动物分为以下几组：1) 接受抗生素治疗，2) 接受基础支持加 N-乙酰半胱氨酸治疗，3) 接受基础支持加去铁胺治疗，4) 接受基础支持加 N-乙酰半胱氨酸和去铁胺治疗，或 5) 接受 N-乙酰半胱氨酸加去铁胺治疗。脑膜炎后 10 天，动物进行了抑制性回避和习惯化到开阔场任务，之后立即评估了海马体和皮质的氧化损伤。与假手术组相比，脑膜炎组在抑制性回避任务中的潜伏期保留表现明显降低。在开阔场任务中，脑膜炎组在脑膜炎后表现出记忆障碍。所有这些记忆损伤都被 N-乙酰半胱氨酸加去铁胺加或不加基础支持以及其单独使用所预防。此外，皮质和海马体中的脂质磷酸化增加，所有联合抗氧化剂都减轻了这两种结构中的脂质磷酸化。另一方面，皮质和 N-乙酰半胱氨酸加去铁胺加或不加基础支持中都存在蛋白质磷酸化增加，并且 N-乙酰半胱氨酸加去铁胺加或不加基础支持可预防这种增加。因此，我们假设氧化应激可能与肺炎球菌性脑膜炎的认知障碍有关。
