Early life neuroimmune challenge protects the brain after sepsis in adult rats

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 h 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.