Laboratório de Microbiologia Experimental, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil; Center for Experimental Models in Psychiatry, Department of Psychiatry and Behavioral Sciences, The University of Texas Medical School at Houston, Houston, TX, USA.
Laboratório de Microbiologia Experimental, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
Transl Res. 2014 May;163(5):503-13. doi: 10.1016/j.trsl.2013.12.008. Epub 2013 Dec 25.
Pneumococcal meningitis is characterized by a severe inflammatory reaction in the subarachnoid and ventricular space of the brain, disruption of the blood-brain barrier, hearing loss, and neurologic sequelae in as many as 27% of surviving patients. Several experimental studies have shown that erythropoietin (EPO) and its receptor are expressed in the central nervous system and have neuroprotective properties through the inhibition of apoptosis, as well as anti-inflammatory, antioxidant, angiogenic, and neurotrophic effects. In the current study, we demonstrated the effect of erythropoietin (EPO) on lipid peroxidation, protein carbonylation, superoxide dismutase (SOD), catalase (CAT), myeloperoxidase (MPO), and behavioral parameters in rats with pneumococcal meningitis. EPO decreased lipid peroxidation and protein carbonylation, and it prevented protein degradation in the hippocampus and frontal cortex. MPO activity was decreased, and both SOD and CAT activity were increased in the first 6 hours after pneumococcal meningitis induction. Novel object recognition memory was impaired in the meningitis group; however, adjuvant treatment with EPO prevented memory impairment during both the short- and long-term retention tests. The meningitis group showed no difference in motor and exploratory activity between training and test sessions in the open-field task, which indicates that habituation memory was impaired; however, adjuvant treatment with EPO prevented habituation memory impairment. Although there are some limitations with respect to the animal model of pneumococcal meningitis, this study suggests that adjuvant treatment with EPO contributed to decreased oxidative stress and prevented cognitive impairment.
肺炎球菌性脑膜炎的特征是大脑蛛网膜下腔和脑室空间发生严重的炎症反应，血脑屏障被破坏，多达 27%的幸存患者出现听力损失和神经后遗症。多项实验研究表明，促红细胞生成素（EPO）及其受体在中枢神经系统中表达，具有神经保护作用，可通过抑制细胞凋亡以及发挥抗炎、抗氧化、血管生成和神经营养作用。在本研究中，我们证明了促红细胞生成素（EPO）对肺炎球菌性脑膜炎大鼠脂质过氧化、蛋白羰基化、超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、髓过氧化物酶（MPO）和行为参数的影响。EPO 降低了脂质过氧化和蛋白羰基化水平，防止了海马体和额叶皮质中的蛋白质降解。在诱导肺炎球菌性脑膜炎后 6 小时内，MPO 活性降低，SOD 和 CAT 活性增加。新物体识别记忆在脑膜炎组受损；然而，EPO 的辅助治疗在短期和长期保留测试中均防止了记忆损伤。脑膜炎组在旷场任务的训练和测试会话之间的运动和探索性活动没有差异，这表明习惯记忆受损；然而，EPO 的辅助治疗防止了习惯记忆损伤。尽管肺炎球菌性脑膜炎的动物模型存在一些局限性，但本研究表明，EPO 的辅助治疗有助于降低氧化应激并预防认知障碍。
