Erythropoietin prevents cognitive impairment and oxidative parameters in Wistar rats subjected to pneumococcal meningitis
Erythropoietin prevents cognitive impairment and oxidative parameters in Wistar rats subjected to pneumococcal meningitis
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DOI：
10.1016/j.trsl.2013.12.008
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发表时间：
2014-05-01
影响因子：
7.8
通讯作者：
Quevedo, Joao
中科院分区：
文献类型：
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作者：
Barichello, Tatiana;Simoes, Lutiana R.;Quevedo, Joao
肺炎球菌脑膜炎的特征是在蛛网膜下腔和脑室空间中的严重炎症反应，血脑屏障破坏，听力损失，以及多达27%的存活患者的神经系统后遗症。几项实验研究表明，促红细胞生成素（EPO）及其受体在中枢神经系统中表达，并通过抑制细胞凋亡以及抗炎、抗氧化、血管生成和神经营养作用具有神经保护特性。在目前的研究中，我们证明了促红细胞生成素（EPO）对脂质过氧化，蛋白质羰基化，超氧化物歧化酶（SOD），过氧化氢酶（CAT），髓过氧化物酶（MPO），和行为参数的影响与肺炎球菌脑膜炎大鼠。EPO降低脂质过氧化和蛋白质羰基化，并防止海马和额叶皮质中的蛋白质降解。肺炎球菌脑膜炎诱导后6 h内MPO活性降低，SOD和CAT活性均升高。脑膜炎组的新物体识别记忆受损;然而，EPO辅助治疗可预防短期和长期保留测试中的记忆受损。脑膜炎组在旷场任务的训练和测试阶段之间的运动和探索活动没有差异，这表明习惯性记忆受损;然而，EPO辅助治疗可预防习惯性记忆受损。尽管肺炎球菌脑膜炎动物模型存在一些局限性，但本研究表明，EPO辅助治疗有助于降低氧化应激并预防认知障碍。
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.