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.

败血症由于感染引起器官功能障碍，并可能影响中枢神经系统。脓毒症后神经炎症和氧化应激与脑功能障碍有关。这两个过程都会影响小胶质细胞的激活，神经营养蛋白的产生和长期的认知。鱼油（FO）是一种抗炎化合物，硫辛酸（LA）是一种通用的抗氧化剂。当单独给药时，它们发挥神经保护作用。我们旨在确定败血症后FO + LA组合对小胶质细胞活化和脑功能障碍的影响。将新生幼仔的小胶质细胞与脂多糖（LPS）和FO或LA单独或联合处理24小时。测量细胞因子水平。威士达通过盲肠结扎和穿孔（CLP）对大鼠进行脓毒症治疗，并用FO，LA或FO + LA口服治疗。手术后24小时，获得海马，前额叶皮层和总皮层，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）的水平。手术后第10天，测定脑源性神经营养因子（BDNF）水平并进行行为测试。该组合降低了促炎细胞因子的体外水平。该组合降低了皮层中的TNF-α，前额皮层中的IL-1β以及MPO活性，并减少了所有结构中蛋白质羰基的形成。该组合增强了前额叶皮层和海马中的过氧化氢酶活性，提高了所有结构中的BDNF水平，并防止行为受损。总之，该组合通过减少神经炎症和氧化应激以及增加BDNF水平，可有效预防认知损害。