Cerebral Metabolic Changes Related to Oxidative Metabolism in a Model of Bacterial Meningitis Induced by Lipopolysaccharide

We studied causative pathogens, clinical characteristics, and outcome of adult community-acquired bacterial meningitis after the introduction of adjunctive dexamethasone treatment and nationwide implementation of paediatric conjugate vaccines.

In experimental studies, the outcome of bacterial meningitis has been related to the severity of inflammation in the subarachnoid space. Corticosteroids reduce this inflammatory response.

Lipopolysaccharide (LPS) administration may be used to induce an in vivo model for neuroinflammation or neurodegeneration. We examined the regional distribution of inflammatory markers induced by LPS in the brain of young mice. Criteria for inflammation included measures of cytokines and microglial activation. Levels of IL-1β mRNA increased in the frontal cortex, parietal cortex, hippocampus, and striatum following systemic treatment with LPS. Levels of SRA mRNA increased in the frontal cortex and striatum and levels of TLR2 and TLR4 mRNAs increased in the frontal cortex and cerebellum. Iba1-positive microglial cells increased in the striatum, medial septum, frontal cortex, and hippocampus after LPS treatment. In addition, glutathione (GSH) levels decreased and mitochondrial complex II/III activities increased after systemic LPS injection. Although LPS treatment did not significantly alter cellular ATP levels, these levels correlated with levels of IL-1β and TLR4 in the LPS-treated mice. The region-specific inflammatory response to LPS in the brain may serve to create a model for studies of neurodegenerative disease. Copyright © 2014 Elsevier Ltd. All rights reserved.