Giridharan Vijayasree V, Simões Lutiana R, Dagostin Valdemira S, Generoso Jaqueline S, Rezin Gislaine T, Florentino Drielly, Muniz Jhonata P, Collodel Allan, Petronilho Fabricia, Quevedo Joao, Barichello Tatiana
Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX 77054, USA.
Laboratory of Experimental Microbiology, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina (UNESC), Criciúma, SC 88806-000, Brazil.
Neurosci Lett. 2017 Jul 13;653:288-295. doi: 10.1016/j.neulet.2017.06.002. Epub 2017 Jun 3.
Despite advances in antimicrobial therapy and advanced critical care neonatal bacterial meningitis has a mortality rate of over 10% and induces neurological sequelae in 20-50% of cases. Escherichia coli K1 (E. coli K1) is the most common gram-negative organism causing neonatal meningitis and is the second most common cause behind group B streptococcus. We previously reported that an E. coli K1 experimental meningitis infection in neonatal rats resulted in habituation and aversive memory impairment and a significant increase in cytokine levels in adulthood. In this present study, we investigated the oxidative stress profile including malondialdehyde (MDA) levels, carbonyl protein formation, myeloperoxidase activity (MPO) activity, superoxide dismutase (SOD) activity and catalase (CAT) activity 6, 12, 24, 48, 72 and 96h after E. coli K1 experimental meningitis infection. In addition, sulfhydryl groups, nitrite and nitrate levels and activity of the mitochondrial respiratory chain enzymes were also measured in the frontal cortex and hippocampus of neonatal rats. The results from this study demonstrated a significant increase in MDA, protein carbonyls and MPO activity and a simultaneous decrease in SOD activity in the hippocampus of the neonatal meningitis survivors but the same was not observed in frontal cortex. In addition, we also observed a significant increase in complex IV activity in the hippocampus and frontal cortex of meningitis survivor rats. Thus, the results from this study reaffirmed the possible role of oxidative stress, nitric oxide and its related compounds in the complex pathophysiology of E. coli K1-induced bacterial meningitis.
尽管抗菌治疗取得了进展，且有先进的重症监护手段，但新生儿细菌性脑膜炎的死亡率仍超过10%，并且在20%-50%的病例中会引发神经后遗症。大肠杆菌K1（E. coli K1）是引起新生儿脑膜炎最常见的革兰氏阴性菌，是仅次于B族链球菌的第二大常见病因。我们之前报道过，新生大鼠的大肠杆菌K1实验性脑膜炎感染会导致习惯化和厌恶记忆障碍，并使成年期细胞因子水平显著升高。在本研究中，我们调查了大肠杆菌K1实验性脑膜炎感染后6、12、24、48、72和96小时的氧化应激情况，包括丙二醛（MDA）水平、羰基蛋白形成、髓过氧化物酶（MPO）活性、超氧化物歧化酶（SOD）活性和过氧化氢酶（CAT）活性。此外，还测量了新生大鼠额叶皮质和海马体中的巯基、亚硝酸盐和硝酸盐水平以及线粒体呼吸链酶的活性。本研究结果表明，新生儿脑膜炎幸存者海马体中的MDA、蛋白羰基和MPO活性显著增加，同时SOD活性降低，但额叶皮质未观察到同样情况。此外，我们还观察到脑膜炎存活大鼠海马体和额叶皮质中的复合物IV活性显著增加。因此，本研究结果再次证实了氧化应激、一氧化氮及其相关化合物在大肠杆菌K1诱导的细菌性脑膜炎复杂病理生理过程中的可能作用。
