Evidences has suggested that in the early life the innate immune system presents plasticity and the time and dose-adequate stimuli in this phase may program long-lasting immunological responses that persist until adulthood. We aimed to evaluate whether LPS challenge in early childhood period may modulate brain alterations after sepsis in adult life. Experiments were performed to evaluate the LPS challenge in early childhood or adult period on acute and long-term brain alterations after model of sepsis by cecal ligation and perforation (CLP) in adult life. Wistar rats were divided in saline+sham, LPS+sham, saline+CLP and LPS+CLP groups to determine cytokine levels and nitrite/nitrate concentration in cerebrospinal fluid (CSF); oxidative damage, activity of antioxidant enzymes (superoxide dismutase-SOD and catalase-CAT); blood brain barrier (BBB) permeability; myeloperoxidase (MPO) and epigenetic enzymes activities in the hippocampus and prefrontal cortex (at 24 hours after CLP) and cognitive function, survival and brain-derived neurotrophic factor (BDNF) level (at ten days after CLP). LPS-preconditioning in early life could lead to decreased levels of TNF-α and IL-6 and oxidative damage parameters in the brain after CLP in adult rats. In addition, LPS-preconditioning in early life increase CAT activity, attenuates the BBB permeability and epigenetic enzymes alterations and in long term, improves the memory, BDNF levels and survival. In conclusion, rats submitted to CLP in adulthood displayed acute neuroinflammation, neurochemical and epigenetic alteration improvement accompanied in long term by an increase in survival, neurotrophin level and memory performance when preconditioned with LPS in the early life.

中文翻译：

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早期生活中的神经免疫攻击可在成年大鼠败血症后保护大脑。

有证据表明，在生命的早期，先天免疫系统具有可塑性，在此阶段，时间和剂量充足的刺激可能会导致持久的免疫反应，持续到成年。我们旨在评估儿童期LPS挑战是否可以调节成年败血症后的大脑变化。进行实验以评估在成年后通过盲肠结扎和穿孔（CLP）败血症模型对成年后急性和长期脑部改变的LPS挑战，对儿童的早期或成年期的LPS挑战。将Wistar大鼠分成盐水+假手术，LPS +假手术，盐水+ CLP和LPS + CLP组，以确定细胞因子水平和脑脊液（CSF）中的亚硝酸盐/硝酸盐浓度。氧化损伤，抗氧化酶的活性（超氧化物歧化酶-SOD和过氧化氢酶-CAT）；血脑屏障（BBB）渗透性；海马和前额叶皮层中的髓过氧化物酶（MPO）和表观遗传酶活性（CLP后24小时）以及认知功能，存活率和脑源性神经营养因子（BDNF）水平（CLP后10天）。早年进行LPS预处理可导致成年大鼠CLP后脑中TNF-α和IL-6水平降低以及脑部氧化损伤参数降低。此外，LPS的早期调节可提高CAT活性，减弱BBB的通透性和表观遗传酶的变化，从长远来看，可提高记忆力，BDNF水平和存活率。总之，成年后提交给CLP的大鼠表现出急性神经炎症，神经化学和表观遗传学改变的改善，并伴随长期生存率的提高，