ArticleBritish journal of pharmacology2021
TLR4 pathway impairs synaptic number and cerebrovascular functions through astrocyte activation following traumatic brain injury.
Article in British journal of pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 72 citations in OpenAlex.
- Toll like receptor 4 (TLR4) in neuroinflammation: From acute hemorrhagic stroke to chronic neurodegeneration.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Review
- Glial Cells in Behavioral and Psychological Symptoms of Alzheimer's Disease.International journal of molecular sciences · 2026Review
- Pathological Roles of Astrocytes in Traumatic Brain Injury.CNS neuroscience & therapeutics · 2026Review
- Lipid nanoparticle-mediated Cd14 siRNA delivery ameliorates the acute inflammatory response to intracortical microelectrode implantation.Acta biomaterialia · 2026Article
- Uncovering the Role of Thrombospodin-1 and Occludin as Potential Prognostic and Diagnostic Biomarkers in Traumatic Brain Injury.International journal of molecular sciences · 2026Article
- Plant-Derived Nanovesicles for Ischemic Stroke Therapy via the Gut Microbiota-Gut-Brain Axis: A New Paradigm of Systemic Regulation.International journal of nanomedicine · 2026Review
- Flavonoids fromFoods (Basel, Switzerland) · 2025Article
- Contralateral Structure and Molecular Response to Severe Unilateral Brain Injury.Brain sciences · 2025Article
- Review
- Revisiting the critical roles of reactive microglia in traumatic brain injury.International journal of surgery (London, England) · 2025Review
- Calcium signaling at the interface between astrocytes and brain inflammation.Current opinion in neurobiology · 2025Review
- TLR4 Targeting: A Promising Therapeutic Approach Across Multiple Human Diseases.Current protein & peptide science · 2025Review
- Astrocytic and microglial cell functions in neuroinflammatory diseases and their animal models.Frontiers in cellular neuroscience · 2025Review
- High-temperature requirement serine protease A2 inhibitor UCF-101 ameliorates damaged neurons in traumatic brain-injured rats by the AMPK/NF-κB pathway.Open life sciences · 2025Article
- Immune Response in Traumatic Brain Injury.Current neurology and neuroscience reports · 2024Review
- Progress of Astrocyte-Neuron Crosstalk in Central Nervous System Diseases.Neurochemical research · 2024Review
- TLR-4: a promising target for chemotherapy-induced peripheral neuropathy.Molecular biology reports · 2024Review
- Curcumin attenuated neuroinflammation via the TLR4/MyD88/NF-κB signaling way in the juvenile rat hippocampus following kainic acid-induced epileptic seizures.Metabolic brain disease · 2024Article
- Inflammation, brain connectivity, and neuromodulation in post-traumatic headache.Brain, behavior, & immunity - health · 2024Review
- Article
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeActivation of astrocytes contributes to synaptic remodelling, tissue repair and neuronal survival following traumatic brain injury (TBI). The mechanisms by which these cells interact to resident/infiltrated inflammatory cells to rewire neuronal networks and repair brain functions remain poorly understood. Here, we explored how TLR4-induced astrocyte activation modified synapses and cerebrovascular integrity following TBI. EXPERIMENTAL APPROACH: To determine how functional astrocyte alterations induced by activation of TLR4 pathway in inflammatory cells regulate synapses and neurovascular integrity after TBI, we used pharmacology, genetic approaches, live calcium imaging, immunofluorescence, flow cytometry, blood-brain barrier (BBB) integrity assessment and molecular and behavioural methods. KEY
resultsShortly after a TBI, there is a recruitment of excitable and reactive astrocytes mediated by TLR4 pathway activation with detrimental effects on post-synaptic density-95 (PSD-95)/vesicular glutamate transporter 1 (VGLUT1) synaptic puncta, BBB integrity and neurological outcome. Pharmacological blockage of the TLR4 pathway with resatorvid (TAK-242) partially reversed many of the observed effects. Synapses and BBB recovery after resatorvid administration were not observed in IP CONCLUSIONS AND IMPLICATIONS: Our data demonstrate that TLR4-mediated signalling, most probably through microglia and/or infiltrated monocyte-astrocyte communication, plays a crucial role in the TBI pathophysiology and that its inhibition prevents synaptic loss and BBB damage accelerating tissue recovery/repair, which might represent a therapeutic potential in CNS injuries and disorders.
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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.