ArticleJournal of neuroinflammation2011
Exacerbation of CNS inflammation and neurodegeneration by systemic LPS treatment is independent of circulating IL-1β and IL-6.
Article in Journal of neuroinflammation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 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
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
58 citing papers in PubMed, 1 synthesis or guideline pooled it, 97 citations in OpenAlex.
- Systemic inflammation and microglial activation: systematic review of animal experiments.Journal of neuroinflammation · 2015Pooled it
- Systemic Inflammation Aggravates Retinal Ganglion Cell Vulnerability to Optic Nerve Trauma in Adult Rats.International journal of molecular sciences · 2026Article
- A modified hot phenol-based protocol for high-purity Escherichia coli lipopolysaccharide extraction: Biochemical validation, stem cell cytotoxicity, and dose dependent multi-organ inflammation in a rat model.Biotechnology reports (Amsterdam, Netherlands) · 2025Article
- Acute particulate matter exposure diminishes executive cognitive functioning after four hours regardless of inhalation pathway.Nature communications · 2025Article
- Enantiomeric Agonists of the Type 2 Cannabinoid Receptor Reduce Retinal Damage during Proliferative Vitreoretinopathy and Inhibit Hyperactive MicrogliaACS pharmacology & translational science · 2024Article
- JAK1/2 Regulates Synergy Between Interferon Gamma and Lipopolysaccharides in Microglia.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2024Article
- Effect of isolated intracranial hypertension on cerebral perfusion within the phase of primary disturbances after subarachnoid hemorrhage in rats.Frontiers in cellular neuroscience · 2023Article
- Mechanism of lily bulb and Rehmannia decoction in the treatment of lipopolysaccharide-induced depression-like rats based on metabolomics study and network pharmacology.Pharmaceutical biology · 2022Article
- Unique brain endothelial profiles activated by social stress promote cell adhesion, prostaglandin E2 signaling, hypothalamic-pituitary-adrenal axis modulation, and anxiety.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022Article
- Long-term cognitive performance and its relation to anti-inflammatory therapy in a cohort of survivors of severe COVID-19.Brain, behavior, & immunity - health · 2022Article
- Microbial pathogens induce neurodegeneration in Alzheimer's disease mice: protection by microglial regulation.Journal of neuroinflammation · 2022Article
- Microglial Priming in Infections and Its Risk to Neurodegenerative Diseases.Frontiers in cellular neuroscience · 2022Review
- Inflammation-Induced Histamine Impairs the Capacity of Escitalopram to Increase Hippocampal Extracellular Serotonin.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Systemic Inflammation Accelerates Changes in Microglial and Synaptic Markers in an Experimental Model of Chronic Neurodegeneration.Frontiers in neuroscience · 2021Article
- Prevalence and Predictors of Prolonged Cognitive and Psychological Symptoms Following COVID-19 in the United States.Frontiers in aging neuroscience · 2021Article
- Novel Neuroprotective Potential of Crocin in Neurodegenerative Disorders: An Illustrated Mechanistic Review.Neurochemical research · 2020Review
- Wild-type huntingtin regulates human macrophage function.Scientific reports · 2020Article
- Acute Inflammation Alters Brain Energy Metabolism in Mice and Humans: Role in Suppressed Spontaneous Activity, Impaired Cognition, and Delirium.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Phyllanthus amarus prevents LPS-mediated BV2 microglial activation via MyD88 and NF-κB signaling pathways.BMC complementary medicine and therapies · 2020Article
- Sex-specific hippocampal metabolic signatures at the onset of systemic inflammation with lipopolysaccharide in the APPswe/PS1dE9 mouse model of Alzheimer's disease.Brain, behavior, and immunity · 2020Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
backgroundChronic neurodegeneration comprises an inflammatory response but its contribution to the progression of disease remains unclear. We have previously shown that microglial cells are primed by chronic neurodegeneration, induced by the ME7 strain of prion disease, to synthesize limited pro-inflammatory cytokines but to produce exaggerated responses to subsequent systemic inflammatory insults. The consequences of this primed response include exaggerated hypothermic and sickness behavioural responses, acute neuronal death and accelerated progression of disease. Here we investigated whether inhibition of systemic cytokine synthesis using the anti-inflammatory steroid dexamethasone-21-phosphate was sufficient to block any or all of these responses.
methodsME7 animals, at 18-19 weeks post-inoculation, were challenged with LPS (500 μg/kg) in the presence or absence of dexamethasone-21-phosphate (2 mg/kg) and effects on core-body temperature and systemic and CNS cytokine production and apoptosis were examined.
resultsLPS induced hypothermia and decreased exploratory activity. Dexamethasone-21-phosphate prevented this hypothermia, markedly suppressed systemic IL-1β and IL-6 secretion but did not prevent decreased exploration. Furthermore, robust transcription of cytokine mRNA occurred in the hippocampus of both ME7 and NBH (normal brain homogenate) control animals despite the effective blocking of systemic cytokine synthesis. Microglia primed by neurodegeneration were not blocked from the robust synthesis of IL-1β protein and endothelial COX-2 was also robustly synthesized. We injected biotinylated LPS at 100 μg/kg and even at this lower dose this could be detected in blood plasma. Apoptosis was acutely induced by LPS, despite the inhibition of the systemic cytokine response.
conclusionsThese data suggest that LPS can directly activate the brain endothelium even at relatively low doses, obviating the need for systemic cytokine stimulation to transduce systemic inflammatory signals into the brain or to exacerbate existing pathology.
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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.