ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2005
Toll-like receptor 4 on nonhematopoietic cells sustains CNS inflammation during endotoxemia, independent of systemic cytokines.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 191 papers, 1 of them a synthesis that pooled it.
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Who cites it
191 citing papers in PubMed, 1 synthesis or guideline pooled it, 399 citations in OpenAlex.
- The Key Drivers of Brain Injury by Systemic Inflammatory Responses after Sepsis: Microglia and Neuroinflammation.Molecular neurobiology · 2023Pooled it
- Systemic inflammation alters the neuroinflammatory response: a prospective clinical trial in traumatic brain injury.Journal of neuroinflammation · 2021Trial
- Spatially resolved transcriptomics identifies intercellular signaling post-ischemic stroke that controls neural stem cell proliferation.Stem cell reports · 2026Article
- Postoperative neurocognitive disorder: migration and crosstalk of inflammation in the peripheral and central nervous system.Perioperative medicine (London, England) · 2026Review
- Changes in Artemin Correlate with Anxiety- and Depression-like Behaviors in a Lipopolysaccharide-Induced Rat Neuroinflammation Model.Biomolecules · 2025Article
- The influence of the choroid plexus on brain function: beyond its role in cerebrospinal fluid production.Inflammation and regeneration · 2025Review
- Partial depletion of circulating neutrophil granulocytes in mice exacerbates the inflammatory response and hypothermia during LPS induced severe systemic inflammation.Frontiers in immunology · 2025Article
- The immunology of sickness metabolism.Cellular & molecular immunology · 2024Review
- Electroacupuncture Reduces Fibromyalgia Pain via Neuronal/Microglial Inactivation and Toll-like Receptor 4 in the Mouse Brain: Precise Interpretation of Chemogenetics.Biomedicines · 2024Article
- Paclitaxel triggers molecular and cellular changes in the choroid plexus.Frontiers in pain research (Lausanne, Switzerland) · 2024Article
- Extracellular vesicles from hiPSC-NSCs can prevent peripheral inflammation-induced cognitive dysfunction with inflammasome inhibition and improved neurogenesis in the hippocampus.Journal of neuroinflammation · 2023Article
- Polyomavirus Wakes Up and Chooses Neurovirulence.Viruses · 2023Review
- Effect of Systemic Inflammation in the CNS: A Silent History of Neuronal Damage.International journal of molecular sciences · 2023Review
- The Endotoxin Hypothesis of Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2023Review
- Electroacupuncture Attenuates Fibromyalgia Pain via Toll-like Receptor 4 in the Mouse Brain.Life (Basel, Switzerland) · 2023Article
- LPS Triggers Acute Neuroinflammation and Parkinsonism Involving NLRP3 Inflammasome Pathway and Mitochondrial CI Dysfunction in the Rat.International journal of molecular sciences · 2023Article
- Exploring the Connectivity of Neurodegenerative Diseases: Microglia as the Center.Journal of inflammation research · 2023Review
- The gastrointestinal tract and Parkinson's disease.Frontiers in cellular and infection microbiology · 2023Review
- Therapeutic strategies to recover ependymal barrier after inflammatory damage: relevance for recovering neurogenesis during development.Frontiers in neuroscience · 2023Review
- Review
131 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Inflammatory agonists such as lipopolysaccharide (LPS) induce robust systemic as well as CNS responses after peripheral administration. Responses in the innate immune system require triggering of toll-like receptor 4 (TLR4), but the origin of CNS sequelas has been controversial. We demonstrate expression of TLR4 transcripts in mouse brain in the meninges, ventricular ependyma, circumventricular organs, along the vasculature, and in parenchymal microglia. The contribution of TLR4 expressed in CNS resident versus hematopoietic cells to the development of CNS inflammation was examined using chimeric mice. Reciprocal bone marrow chimeras between wild-type and TLR4 mutant mice show that TLR4 on CNS resident cells is critically required for sustained inflammation in the brain after systemic LPS administration. Hematopoietic TLR4 alone supported the systemic release of acute phase cytokines, but transcription of proinflammatory genes in the CNS was reduced in duration. In contrast, TLR4 function in radiation-resistant cells was sufficient for inflammatory progression in the brains of chimeric mice, despite the striking absence of cytokine elevations in serum. Surprisingly, a temporal rise in serum corticosterone was also dependent on TLR4 signaling in nonhematopoietic cells. Our findings demonstrate a requirement for TLR4 function in CNS-resident cells, independent of systemic cytokine effects, for sustained CNS-specific inflammation and corticosterone rise during endotoxemia.
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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.