ArticlePloS one2014
Astrocytic Toll-like receptor 3 is associated with ischemic preconditioning-induced protection against brain ischemia in rodents.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.
- A systematic review of the causes and consequences of spreading depolarization in neuroinflammation; implications for neurovascular disorders.Journal of neuroinflammation · 2025Pooled it
- Innate immune signaling and functions in astrocytes.Nature immunology · 2026Review
- The Role of Toll-like Receptors and Viral Infections in the Pathogenesis and Progression of Pulmonary Arterial Hypertension-A Narrative Review.International journal of molecular sciences · 2025Review
- Poly-IC Alleviates Nitroglycerin-Induced Migraine by Inhibiting Neuroinflammation via TLR3/TRIF Signaling Pathway.CNS neuroscience & therapeutics · 2025Article
- Hypoxic preconditioning increases mitochondrial respiration and HFrontiers in molecular neuroscience · 2025Article
- Toll-Like Receptor mRNA Levels in Schizophrenia: Association With Complement Factors and Cingulate Gyrus Cortical Thinning.Schizophrenia bulletin · 2024Article
- Research hotspots and frontiers of preconditioning in cerebral ischemia: A bibliometric analysis.Heliyon · 2024Review
- Toll-like receptor 4 (TLR4): new insight immune and aging.Immunity & ageing : I & A · 2023Review
- Early activation of Toll-like receptor-3 reduces the pathological progression of Alzheimer's disease in APP/PS1 mouse.Alzheimer's research & therapy · 2023Article
- Neuroprotective effects and mechanisms of ischemic/hypoxic preconditioning on neurological diseases.CNS neuroscience & therapeutics · 2021Review
- Resolvin D1 Attenuates Innate Immune Reactions in Experimental Subarachnoid Hemorrhage Rat Model.Molecular neurobiology · 2021Article
- Review
- Molecular Basis of Sex Difference in Neuroprotection induced by Hypoxia Preconditioning in Zebrafish.Molecular neurobiology · 2020Article
- Aneurysmal Subarachnoid Hemorrhage: an Overview of Inflammation-Induced Cellular Changes.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2020Review
- Review Cerebral Ischemic Tolerance and Preconditioning: Methods, Mechanisms, Clinical Applications, and Challenges.Frontiers in neurology · 2020Review
- Berberine Ameliorates Subarachnoid Hemorrhage InjuryFrontiers in pharmacology · 2020Article
- Toll-like receptor 3 dynamics in female C57BL/6J mice: Regulation of alcohol intake.Brain, behavior, and immunity · 2019Article
- Toll-like receptor 3 activation increases voluntary alcohol intake in C57BL/6J male mice.Brain, behavior, and immunity · 2019Article
- Effects of hypoxic preconditioning on memory evaluated using the T-maze behavior test.Animal cells and systems · 2019Article
- Hippo/YAP signaling pathway mitigates blood-brain barrier disruption after cerebral ischemia/reperfusion injury.Behavioural brain research · 2019Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundCerebral ischemic preconditioning (IPC) protects brain against ischemic injury. Activation of Toll-like receptor 3 (TLR3) signaling can induce neuroprotective mediators, but whether astrocytic TLR3 signaling is involved in IPC-induced ischemic tolerance is not known.
methodsIPC was modeled in mice with three brief episodes of bilateral carotid occlusion. In vitro, IPC was modeled in astrocytes by 1-h oxygen-glucose deprivation (OGD). Injury and components of the TLR3 signaling pathway were measured after a subsequent protracted ischemic event. A neutralizing antibody against TLR3 was used to evaluate the role of TLR3 signaling in ischemic tolerance.
resultsIPC in vivo reduced brain damage from permanent middle cerebral artery occlusion in mice and increased expression of TLR3 in cortical astrocytes. IPC also reduced damage in isolated astrocytes after 12-h OGD. In astrocytes, IPC or 12-h OGD alone increased TLR3 expression, and 12-h OGD alone increased expression of phosphorylated NFκB (pNFκB). However, IPC or 12-h OGD alone did not alter the expression of Toll/interleukin receptor domain-containing adaptor-inducing IFNβ (TRIF) or phosphorylated interferon regulatory factor 3 (pIRF3). Exposure to IPC before OGD increased TRIF and pIRF3 expression but decreased pNFκB expression. Analysis of cytokines showed that 12-h OGD alone increased IFNβ and IL-6 secretion; 12-h OGD preceded by IPC further increased IFNβ secretion but decreased IL-6 secretion. Preconditioning with TLR3 ligand Poly I:C increased pIRF3 expression and protected astrocytes against ischemic injury; however, cells treated with a neutralizing antibody against TLR3 lacked the IPC- and Poly I:C-induced ischemic protection and augmentation of IFNβ.
conclusionsThe results suggest that IPC-induced ischemic tolerance is mediated by astrocytic TLR3 signaling. This reprogramming of TLR3 signaling by IPC in astrocytes may play an important role in suppression of the post-ischemic inflammatory response and thereby protect against ischemic damage. The mechanism may be via activation of the TLR3/TRIF/IRF3 signaling pathway.
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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.