ArticleGlia2021
Proton extrusion during oxidative burst in microglia exacerbates pathological acidosis following traumatic brain injury.
Article in Glia, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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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.
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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
47 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Inorganic, Synthetic, Natural, and Innovative Hybrid Hydrogen Sulfide Donors and Inhibitors of Its Biosynthesis in the Treatment of Central and Peripheral Nervous System Injuries: A Systematic Analytical Review.International journal of molecular sciences · 2025Pooled it
- A Question of Origins: Non-neuronal Sources of Amyloid-β.Neuroscience bulletin · 2026Review
- Mirror Effect of Parvalbumin and Connexin 43 Expression in the Acute and Subacute Phases After Penetrating Traumatic Brain Injury Reveals a Non-Canonical Interaction.Molecules (Basel, Switzerland) · 2026Article
- Persistent dysmorphology and dysfunction of the brain microvasculature following repeated trauma.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Article
- Phagocytosis and neuroinflammation: orchestrating central nervous system homeostasis, repair, and the resolution of inflammation.Trends in neurosciences · 2026Review
- Association Between Serum Anion Gap and Risk of Postoperative Delirium in Patients Undergoing Gastric Surgery in ICU: A Retrospective Study From the MIMIC-IV Database.Anesthesiology research and practice · 2026Article
- Neuroprotection and Axonal Regeneration via ECM-Mimetic Nanofibers Incorporating Metal-Phenolic Network Nanoparticles Toward Spinal Cord Injury Repair.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Amyloid precursor protein and C99 are subunits in human microglial Hv1 channels that enhance current and inflammatory mediator release.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Investigation of the Expression, Localization, and Acidosis-Associated Conformational Changes in Connexin 43 in Traumatic Brain Injury with the Development of a Neural Network Model for Assessing Systemic Inflammation.International journal of molecular sciences · 2025Article
- Validation of HvFrontiers in cellular neuroscience · 2025Article
- Article
- NHE1 Protein in Repetitive Mild TBI-Mediated Neuroinflammation and Neurological Function Impairment.Antioxidants (Basel, Switzerland) · 2024Article
- The Emerging Role of Microglial Hv1 as a Target for Immunomodulation in Myelin Repair.Aging and disease · 2024Review
- Bi-directional neuro-immune dysfunction after chronic experimental brain injury.Journal of neuroinflammation · 2024Article
- Ablation of the integrin CD11b mac-1 limits deleterious responses to traumatic spinal cord injury and improves functional recovery in mice.Research square · 2024Article
- Human Glial Cells as Innovative Targets for the Therapy of Central Nervous System Pathologies.Cells · 2024Review
- Deletion of Slc9a1 in Cx3cr1Journal of neuroinflammation · 2024Article
- Inhibition of the HFrontiers in immunology · 2024Article
- The FGFR inhibitor Rogaratinib reduces microglia reactivity and synaptic loss in TBI.Frontiers in immunology · 2024Article
- Traumatic brain injury-induced inflammatory changes in the olfactory bulb disrupt neuronal networks leading to olfactory dysfunction.Brain, behavior, and immunity · 2023Article
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
Acidosis is among the least studied secondary injury mechanisms associated with neurotrauma. Acute decreases in brain pH correlate with poor long-term outcome in patients with traumatic brain injury (TBI), however, the temporal dynamics and underlying mechanisms are unclear. As key drivers of neuroinflammation, we hypothesized that microglia directly regulate acidosis after TBI, and thereby, worsen neurological outcomes. Using a controlled cortical impact model in adult male mice we demonstrate that intracellular pH in microglia and extracellular pH surrounding the lesion site are significantly reduced for weeks after injury. Microglia proliferation and production of reactive oxygen species (ROS) were also increased during the first week, mirroring the increase in extracellular ROS levels seen around the lesion site. Microglia depletion by a colony stimulating factor 1 receptor (CSF1R) inhibitor, PLX5622, markedly decreased extracellular acidosis, ROS production, and inflammation in the brain after injury. Mechanistically, we identified that the voltage-gated proton channel Hv1 promotes oxidative burst activity and acid extrusion in microglia. Compared to wildtype controls, microglia lacking Hv1 showed reduced ability to generate ROS and extrude protons. Importantly, Hv1-deficient mice exhibited reduced pathological acidosis and inflammation after TBI, leading to long-term neuroprotection and functional recovery. Our data therefore establish the microglial Hv1 proton channel as an important link that integrates inflammation and acidosis within the injury microenvironment during head injury.
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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.