Cognitive impairment, blood-brain barrier breakdown, and pro-inflammatory mediators in neonatal Escherichia coli K1 meningitis.

Abstract

Abstract Neonatal Escherichia coli meningitis is an important cause of mortality and morbidity in newborns. We evaluated cytokines, oxidative damage/enzymatic defense, BDNF levels, blood-brain barrier (BBB) integrity in the hippocampus of neonatal Wistar rats following E. coli K1 meningitis and subsequent behavioral parameters in adulthood. Neonatal male rats received an intracisternal injection of placebo or E. coli K1 suspension. First: at 6, 12, 24, 48, and 96 h were evaluated cytokines, oxidative damage/enzymatic defense, BDNF levels, and BBB integrity. TNF-α, IL-4, IL-6, IL-10, BDNF, and protein carbonylation were produced mainly in the first 6 to 96 h. Myeloperoxidase, thiobarbituric acid reactive-substances, nitrate/nitrite, and sulfhydryl group were produced at 24 h. Superoxide dismutase decrease in the first 6 h, catalase activity levels did not change and the BBB breakdown at 12 h after meningitis induction. Second: sixty days after meningitis were evaluated behavioural parameters (neonatal rats received antibiotic treatment): habituation to the open-field, step-down inhibitory avoidance, and continuous multiple-trials step down inhibitory avoidance tasks. In the habituation to the open-field and in the step-down inhibitory avoidance tasks there were no differences between training and test session in the meningitis group, demonstrating memory impairment. In the continuous multiple-trials step-down inhibitory avoidance task, there was a significant increase in the number of training trials required to reach the acquisition criterion in the meningitis group when compared to the control group, indicating a learning impairment. Neonatal E. coli K1 meningitis causes learning and memory impairments in adulthood.