ArticleJournal of neurotrauma2018
Elucidating Pro-Inflammatory Cytokine Responses after Traumatic Brain Injury in a Human Stem Cell Model.
Article in Journal of neurotrauma, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed.
- Neuroprotective Role of Oral Vitamin D Supplementation on Consciousness and Inflammatory Biomarkers in Determining Severity Outcome in Acute Traumatic Brain Injury Patients: A Double-Blind Randomized Clinical Trial.Clinical drug investigation · 2020Trial
- A Dynamic and Complex Early Inflammatory Response in Blood and Cerebrospinal Fluid of Severe Traumatic Brain Injury Patients: A Dual Platform Analysis.Inflammation · 2026Observational
- Mechanisms of inflammatory response in secondary brain injury: a review of computational approaches, challenges, and future directions.Biomechanics and modeling in mechanobiology · 2026Review
- Research progress on biomarkers of traumatic brain injury.Animal models and experimental medicine · 2026Review
- Concurrent Toxoplasma gondii infection and neuroinflammation in traumatic brain injury patients in a referral hospital in Douala Cameroon.Scientific reports · 2026Article
- The Dynamics of Neuroinflammation in Traumatic Brain Injury: Molecular Markers Useful for Establishing the Post-Traumatic Interval in Forensic Practice.International journal of molecular sciences · 2026Review
- Stem cell and stem cell-derived extracellular vesicle therapy for traumatic brain injury: mechanisms, engineering and translation.Frontiers in neuroscience · 2026Review
- Synaptic Pathology in Traumatic Brain Injury and Therapeutic Insights.International journal of molecular sciences · 2025Review
- Urapidil as a neuroprotective agent: targeting hypoxia, inflammation, and oxidative stress in traumatic brain injury.European journal of trauma and emergency surgery : official publication of the European Trauma Society · 2025Article
- The immunological landscape of traumatic brain injury: insights from pathophysiology to experimental models.Frontiers in neurology · 2025Review
- Neuroprotective effects of naltrexone in a mouse model of post-traumatic seizures.Scientific reports · 2024Article
- Pathophysiology-Based Management of Secondary Injuries and Insults in TBI.Biomedicines · 2024Review
- Validation and characterization of a novel blood-brain barrier platform for investigating traumatic brain injury.Scientific reports · 2023Article
- Stem cell-derived brainstem mouse astrocytes obtain a neurotoxic phenotype in vitro upon neuroinflammation.Journal of inflammation (London, England) · 2023Article
- Partial Depletion of Microglia Attenuates Long-Term Potentiation Deficits following Repeated Blast Traumatic Brain Injury in Organotypic Hippocampal Slice Cultures.Journal of neurotrauma · 2023Article
- Models of traumatic brain injury-highlights and drawbacks.Frontiers in neurology · 2023Review
- Inflammasomes: a rising star on the horizon of COVID-19 pathophysiology.Frontiers in immunology · 2023Review
- Biofluid Biomarkers in Traumatic Brain Injury: A Systematic Scoping Review.Neurocritical care · 2021Article
- SARS-CoV-2 may trigger inflammasome and pyroptosis in the central nervous system: a mechanistic view of neurotropism.Inflammopharmacology · 2021Review
- Design and Evaluation of an In Vitro Mild Traumatic Brain Injury Modeling System Using 3D Printed Mini Impact Device on the 3D Cultured Human iPSC Derived Neural Progenitor Cells.Advanced healthcare materials · 2021Article
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
Cytokine mediated inflammation likely plays an important role in secondary pathology after traumatic brain injury (TBI). The aim of this study was to elucidate secondary cytokine responses in an in vitro enriched (>80%) human stem cell-derived neuronal model. We exposed neuronal cultures to pre-determined and clinically relevant pathophysiological levels of tumor necrosis factor-α (TNF), interleukin-6 (IL-6) and interleukin-1β (IL-1β), shown to be present in the inflammatory aftermath of TBI. Data from this reductionist human model were then compared with our in vivo data. Human embryonic stem cell (hESC)-derived neurons were exposed to recombinant TNF (1-10,000 pg/mL), IL-1β (1-10,000 pg/mL), and IL-6 (0.1-1000 ng/mL). After 1, 24, and 72 h, culture supernatant was sampled and analyzed using a human cytokine/chemokine 42-plex Milliplex kit on the Luminex platform. The culture secretome revealed both a dose- and/or time-dependent release of cytokines. The IL-6 and TNF exposure each resulted in significantly increased levels of >10 cytokines over time, while IL-1β increased the level of C-X-C motif chemokine 10 (CXCL10/IP10) alone. Importantly, these patterns are consistent with our in vivo (human) TBI data, thus validating our human stem cell-derived neuronal platform as a clinically useful reductionist model. Our data cumulatively suggest that IL-6 and TNF have direct actions, while the action of IL-1β on human neurons likely occurs indirectly through inflammatory cells. The hESC-derived neurons provide a valuable platform to model cytokine mediated inflammation and can provide important insights into the mechanisms of neuroinflammation after TBI.
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Registered trials
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