Laboratory of Neurobiology of Inflammatory and Metabolic Processes, Graduate Program in Health Sciences, University of South Santa Catarina, Tubarão, SC, Brazil.
Experimental Neuroscience Laboratory (LaNEx), Postgraduate Program in Health Sciences, University of Southern Santa Catarina, Palhoça, Santa Catarina, Brazil.
Mol Neurobiol. 2020 Nov;57(11):4451-4466. doi: 10.1007/s12035-020-02032-y. Epub 2020 Aug 2.
Sepsis causes organ dysfunction due to an infection, and it may impact the central nervous system. Neuroinflammation and oxidative stress are related to brain dysfunction after sepsis. Both processes affect microglia activation, neurotrophin production, and long-term cognition. Fish oil (FO) is an anti-inflammatory compound, and lipoic acid (LA) is a universal antioxidant substance. They exert neuroprotective roles when administered alone. We aimed at determining the effect of FO+LA combination on microglia activation and brain dysfunction after sepsis. Microglia cells from neonatal pups were co-treated with lipopolysaccharide (LPS) and FO or LA, alone or combined, for 24 h. Cytokine levels were measured. Wistar rats were subjected to sepsis by cecal ligation and perforation (CLP) and treated orally with FO, LA, or FO+LA. At 24 h after surgery, the hippocampus, prefrontal cortex, and total cortex were obtained and assayed for levels of cytokines, myeloperoxidase (MPO) activity, protein carbonyls, superoxide dismutase (SOD), and catalase (CAT) activity. At 10 days after surgery, brain-derived neurotrophic factor (BDNF) levels were determined and behavioral tests were performed. The combination diminished in vitro levels of pro-inflammatory cytokines. The combination reduced TNF-α in the cortex, IL-1β in the prefrontal cortex, as well as MPO activity, and decreased protein carbonyls formation in all structures. The combination enhanced catalase activity in the prefrontal cortex and hippocampus, elevated BDNF levels in all structures, and prevented behavioral impairment. In summary, the combination was effective in preventing cognitive damage by reducing neuroinflammation and oxidative stress and increasing BDNF levels.
败血症会因感染导致器官功能障碍，并且可能会影响中枢神经系统。神经炎症和氧化应激与败血症后大脑功能障碍有关。这两个过程都会影响小胶质细胞的激活、神经营养因子的产生和长期认知。鱼油（FO）是一种抗炎化合物，硫辛酸（LA）是一种通用的抗氧化物质。当单独使用时，它们都具有神经保护作用。我们旨在确定 FO+LA 联合使用对败血症后小胶质细胞激活和大脑功能障碍的影响。将新生幼鼠的小胶质细胞与脂多糖（LPS）单独或联合用 FO 或 LA 共同处理 24 小时。测量细胞因子水平。将 Wistar 大鼠通过盲肠结扎和穿孔（CLP）引发败血症，并通过口服给予 FO、LA 或 FO+LA 进行治疗。手术后 24 小时，取出海马体、前额叶皮层和全皮层，并测定细胞因子、髓过氧化物酶（MPO）活性、蛋白羰基、超氧化物歧化酶（SOD）和过氧化氢酶（CAT）活性。手术后 10 天，测定脑源性神经营养因子（BDNF）水平并进行行为测试。联合用药降低了体外促炎细胞因子的水平。该联合用药降低了皮质中的 TNF-α、前额叶皮层中的 IL-1β以及 MPO 活性，并减少了所有结构中的蛋白羰基形成。该联合用药增加了前额叶皮层和海马体中的过氧化氢酶活性，提高了所有结构中的 BDNF 水平，并预防了行为障碍。总之，该联合用药通过降低神经炎症和氧化应激以及增加 BDNF 水平，有效预防了认知损伤。
