ArticleJournal of neuroinflammation2012
Long-term impact of systemic bacterial infection on the cerebral vasculature and microglia.
Article in Journal of neuroinflammation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
93 citing papers in PubMed, 1 synthesis or guideline pooled it, 161 citations in OpenAlex.
- Systemic inflammation and microglial activation: systematic review of animal experiments.Journal of neuroinflammation · 2015Pooled it
- Microglial Innate Immune Memory: Implications and Research Advances in Central Nervous System Disorders.Current issues in molecular biology · 2026Review
- Short-Chain Fatty Acids Regulate Poultry Feed Intake via the Hypothalamus: Receptor-Mediated and Epigenetic Mechanisms.Animals : an open access journal from MDPI · 2026Review
- Interactions between Innate Immune Memory and the Central Nervous System.Neuroimmunomodulation · 2026Review
- Review
- Early-life IL-4 administration induces long-term changes in microglia in the cerebellum and prefrontal cortex.Journal of neurochemistry · 2025Article
- Synthesis and Antimicrobial Activity of Silver/Copper Oxide/Clay Hybrid Nanocomposites Against Gram-Positive and Gram-Negative Bacteria.Current drug metabolism · 2025Article
- Mild Systemic Inflammation Increases Erythrocyte Fragility.International journal of molecular sciences · 2024Article
- Contribution of CNS and extra-CNS infections to neurodegeneration: a narrative review.Journal of neuroinflammation · 2024Review
- Microglia at the blood brain barrier in health and disease.Frontiers in cellular neuroscience · 2024Review
- Association of intestinal dysbiosis with susceptibility to multiple sclerosis: Evidence from different population studies (Review).Biomedical reports · 2023Review
- Naïve Huntington's disease microglia mount a normal response to inflammatory stimuli but display a partially impaired development of innate immune tolerance that can be counteracted by ganglioside GM1.Journal of neuroinflammation · 2023Article
- Transcriptional and epigenetic decoding of the microglial aging process.Nature aging · 2023Article
- Determinants of urinary tract infection in hospitalized patients with acute ischemic stroke.BMC neurology · 2023Article
- CARD9 attenuates Aβ pathology and modifies microglial responses in an Alzheimer's disease mouse model.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Pro-Inflammatory Priming of the Brain: The Underlying Cause of Parkinson's Disease.International journal of molecular sciences · 2023Article
- Endothelial Toll-like receptor 4 is required for microglia activation in the murine retina after systemic lipopolysaccharide exposure.Journal of neuroinflammation · 2023Article
- A review of cytokine-based pathophysiology of Long COVID symptoms.Frontiers in medicine · 2023Article
- Gliosis, misfolded protein aggregation, and neuronal loss in a guinea pig model of pulmonary tuberculosis.Frontiers in neuroscience · 2023Article
- Latroeggtoxin-VI protects nerve cells and prevents depression by inhibiting NF-κB signaling pathway activation and excessive inflammation.Frontiers in immunology · 2023Article
33 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundSystemic infection leads to generation of inflammatory mediators that result in metabolic and behavioural changes. Repeated or chronic systemic inflammation leads to a state of innate immune tolerance: a protective mechanism against overactivity of the immune system. In this study, we investigated the immune adaptation of microglia and brain vascular endothelial cells in response to systemic inflammation or bacterial infection.
methodsMice were given repeated doses of lipopolysaccharide (LPS) or a single injection of live Salmonella typhimurium. Inflammatory cytokines were measured in serum, spleen and brain, and microglial phenotype studied by immunohistochemistry. To assess priming of the innate immune response in the brain, mice were infected with Salmonella typhimurium and subsequently challenged with a focal unilateral intracerebral injection of LPS.
resultsRepeated systemic LPS challenges resulted in increased brain IL-1β, TNF-α and IL-12 levels, despite attenuated systemic cytokine production. Each LPS challenge induced significant changes in burrowing behaviour. In contrast, brain IL-1β and IL-12 levels in Salmonella typhimurium-infected mice increased over three weeks, with high interferon-γ levels in the circulation. Behavioural changes were only observed during the acute phase of the infection. Microglia and cerebral vasculature display an activated phenotype, and focal intracerebral injection of LPS four weeks after infection results in an exaggerated local inflammatory response when compared to non-infected mice.
conclusionsThese studies reveal that the innate immune cells in the brain do not become tolerant to systemic infection, but are primed instead. This may lead to prolonged and damaging cytokine production that may have a profound effect on the onset and/or progression of pre-existing neurodegenerative disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.