ArticleGlia2014
High mobility group box protein-1 promotes cerebral edema after traumatic brain injury via activation of toll-like receptor 4.
Article in Glia, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 148 papers, 2 of them syntheses 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.
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Who cites it
148 citing papers in PubMed, 2 syntheses or guidelines pooled it, 255 citations in OpenAlex.
- An Interplay Between Post-Traumatic Epilepsy and Associated Cognitive Decline: A Systematic Review.Frontiers in neurology · 2022Pooled it
- The danger zone: Systematic review of the role of HMGB1 danger signalling in traumatic brain injury.Brain injury · 2017Pooled it
- Cottonseed Oil Attenuates Traumatic Brain Injury by Inhibiting AKT/GSK-3β-mediated Neuroinflammatory Responses.Molecular neurobiology · 2026Article
- Fenofibrate alleviates the brain edema after traumatic brain injury by enhancing endothelial OXPHOS.Redox biology · 2026Article
- RAGE Axis in the Pathogenesis and Treatment of CNS Neurodegeneration in Long-Term Hyperglycemia.International journal of molecular sciences · 2026Review
- Blood-Brain Barrier Disruption and Edema in Xenopus: Methods for Analysis.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Theragenerative Nanomaterials: Integrating Therapy, Regeneration, and Diagnosis-Navigating the Shared Pathways Between Tissue Repair and Malignancy.International journal of nanomedicine · 2026Review
- CX-01 mitigates trauma-induced acute kidney injury and improves survival in a combat-relevant polytrauma rat model.Frontiers in pharmacology · 2026Article
- Perceiving traumatic brain injury from glymphatic system.Molecular psychiatry · 2025Review
- Association between traumatic brain injury and risk of developing infections in the central nervous system and periphery.Metabolic brain disease · 2025Review
- Aquaporins in Acute Brain Injury: Insights from Clinical and Experimental Studies.Biomedicines · 2025Review
- Revisiting the critical roles of reactive microglia in traumatic brain injury.International journal of surgery (London, England) · 2025Review
- Cellular and molecular mechanisms of pathological tau phosphorylation in traumatic brain injury: implications for chronic traumatic encephalopathy.Molecular neurodegeneration · 2025Review
- Extracellular cold-inducible RNA-binding protein in CNS injury: molecular insights and therapeutic approaches.Journal of neuroinflammation · 2025Review
- Severity of Repetitive Mild Traumatic Brain Injury Depends on Microglial Heme Oxygenase-1 and Carbon Monoxide.The European journal of neuroscience · 2025Article
- Role of damage-associated molecular patterns in the pathogenesis and therapeutics of traumatic brain injury.Burns & trauma · 2025Review
- Astrocyte-microglia crosstalk in subarachnoid hemorrhage: mechanisms and treatments.Frontiers in immunology · 2025Review
- Exploring Aquaporins in Human Studies: Mechanisms and Therapeutic Potential in Critical Illness.Life (Basel, Switzerland) · 2024Review
- Single episode of moderate to severe traumatic brain injury leads to chronic neurological deficits and Alzheimer's-like pathological dementia.GeroScience · 2024Article
- Administration of monophosphoryl lipid A shortly after traumatic brain injury blocks the following spatial and avoidance memory loss and neuroinflammation.Scientific reports · 2024Article
88 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Traumatic brain injury (TBI) is a major cause of mortality and morbidity worldwide. Cerebral edema, a life-threatening medical complication, contributes to elevated intracranial pressure (ICP) and a poor clinical prognosis after TBI. Unfortunately, treatment options to reduce post-traumatic edema remain suboptimal, due in part, to a dearth of viable therapeutic targets. Herein, we tested the hypothesis that cerebral innate immune responses contribute to edema development after TBI. Our results demonstrate that high-mobility group box protein 1 (HMGB1) was released from necrotic neurons via a NR2B-mediated mechanism. HMGB1 was clinically associated with elevated ICP in patients and functionally promoted cerebral edema after TBI in mice. The detrimental effects of HMGB1 were mediated, at least in part, via activation of microglial toll-like receptor 4 (TLR4) and the subsequent expression of the astrocytic water channel, aquaporin-4 (AQP4). Genetic or pharmacological (VGX-1027) TLR4 inhibition attenuated the neuroinflammatory response and limited post-traumatic edema with a delayed, clinically implementable therapeutic window. Human and rodent tissue culture studies further defined the cellular mechanisms demonstrating neuronal HMGB1 initiates the microglial release of interleukin-6 (IL-6) in a TLR4 dependent mechanism. In turn, microglial IL-6 increased the astrocytic expression of AQP4. Taken together, these data implicate microglia as key mediators of post-traumatic brain edema and suggest HMGB1-TLR4 signaling promotes neurovascular dysfunction after TBI.
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What OpenQuestion holds
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.