ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
Lipopolysaccharide-induced microglial activation and neuroprotection against experimental brain injury is independent of hematogenous TLR4.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 244 papers.
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Who cites it
244 citing papers in PubMed, 450 citations in OpenAlex.
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- SARS-CoV-2 Spike Protein S1 Subunit Induces Neuroinflammation Via Microglial Kv1.3 Channel.Biological psychiatry global open science · 2026Article
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- Disentangling neuroimmune landscapes across peripheral activation paradigms resolves divergent glial state programs.Research square · 2026Article
- Macrostructural, microstructural, and cellular effects of neuroinflammation on the mouse brain.Brain, behavior, & immunity - health · 2026Article
- Gut-Brain Inflammation and Disrupted Homeostasis Due to Activation of Mast Cells and Microglia.International journal of molecular sciences · 2026Review
- Synaptic aging and neurodegeneration: the role of synaptic vesicle dynamics and neurotransmitter imbalance.Biogerontology · 2026Review
- IL-27, a metabolic regulator secreted by astrocytes in response to GLP-1RA OHP2, modulates microglial reprogramming in Alzheimer's disease by regulating cGAS lactylation.Journal of neuroinflammation · 2026Article
- Neuroinflammatory stress preferentially impacts synaptic MAPK signaling and mitochondria in excitatory neurons.Molecular neurodegeneration advances · 2026Article
- Interactions between Innate Immune Memory and the Central Nervous System.Neuroimmunomodulation · 2026Review
- LPS-Induced Inflammation and Preconditioning in Rainbow Trout: Markers of Innate Immunity and Oxidative Stress.Animals : an open access journal from MDPI · 2025Article
- Histologic Chorioamnionitis and Neurodevelopment in Preterm Infants.JAMA network open · 2025Article
- Electroacupuncture Pretreatment Alleviates Myocardial Ischemia-Reperfusion Injury by Inhibiting Engulfment by Microglia in the Lateral Hypothalamus.CNS neuroscience & therapeutics · 2025Article
- Local microglial activation induced and labeled in the retina in a novel subretinal hemorrhage mouse model.Scientific reports · 2025Article
- Development and characterization of in vitro inducible immortalization of a murine microglia cell line for high throughput studies.Scientific reports · 2025Article
- Brain-derived neurotrophic factor prevents LPS-induced dysregulation of GABAergic interneuron markers in mouse hippocampus.Frontiers in cellular neuroscience · 2025Article
- Article
- Astrocyte-Derived Interleukin 11 Modulates Astrocyte-Microglia Crosstalk via Nuclear Factor-κB Signaling Pathway in Sepsis-Associated Encephalopathy.Research (Washington, D.C.) · 2025Article
- Neuroinflammation: targeting microglia for neuroprotection and repair after spinal cord injury.Frontiers in immunology · 2025Review
184 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Intraperitoneal injection of the Gram-negative bacterial endotoxin lipopolysaccharide (LPS) elicits a rapid innate immune response. While this systemic inflammatory response can be destructive, tolerable low doses of LPS render the brain transiently resistant to subsequent injuries. However, the mechanism by which microglia respond to LPS stimulation and participate in subsequent neuroprotection has not been documented. In this study, we first established a novel LPS treatment paradigm where mice were injected intraperitoneally with 1.0 mg/kg LPS for four consecutive days to globally activate CNS microglia. By using a reciprocal bone marrow transplantation procedure between wild-type and Toll-like receptor 4 (TLR4) mutant mice, we demonstrated that the presence of LPS receptor (TLR4) is not required on hematogenous immune cells but is required on cells that are not replaced by bone marrow transplantation, such as vascular endothelia and microglia, to transduce microglial activation and neuroprotection. Furthermore, we showed that activated microglia physically ensheathe cortical projection neurons, which have reduced axosomatic inhibitory synapses from the neuronal perikarya. In line with previous reports that inhibitory synapse reduction protects neurons from degeneration and injury, we show here that neuronal cell death and lesion volumes are significantly reduced in LPS-treated animals following experimental brain injury. Together, our results suggest that activated microglia participate in neuroprotection and that this neuroprotection is likely achieved through reduction of inhibitory axosomatic synapses. The therapeutic significance of these findings rests not only in identifying neuroprotective functions of microglia, but also in establishing the CNS location of TLR4 activation.
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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.