ArticleJournal of molecular cell biology2022
NRF1-mediated microglial activation triggers high-altitude cerebral edema.
Article in Journal of molecular cell biology, 2022. 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, 46 citations in OpenAlex.
- Chronic high-altitude exposure and intracerebral hemorrhage: A novel perspective from the vascular-immune-neuronal network.Neuroprotection (Chichester, England) · 2026Review
- Cell-type-specific architecture of the hypothalamus in a socially plastic vertebrate.bioRxiv : the preprint server for biology · 2026Article
- Article
- Microglial cholesterol reprogramming drives cognitive impairment under hypobaric hypoxia.Journal of neuroinflammation · 2026Article
- From lactate to lactylation: novel pathological mechanisms and potential therapeutic targets for high-altitude cerebral oedema.Expert reviews in molecular medicine · 2026Review
- CAR Treg therapies for neurodegenerative diseases.iScience · 2026Review
- Evaluation of cerebral blood flow and glymphatic function in acute mountain sickness by MRI ASL and DTI ALPS.Scientific reports · 2026Article
- Elucidating Trigonelline's Therapeutic Mechanisms for Traumatic Brain Injury Through Integrated Network Pharmacology and In Vivo Validation.CNS neuroscience & therapeutics · 2026Article
- Intranasal Human NSC-Derived EVs Therapy Can Restrain Inflammatory Microglial Transcriptome, and NLRP3 and cGAS-STING Signalling, in Aged Hippocampus.Journal of extracellular vesicles · 2026Article
- Review
- Altitude hypoxia and hypoxemia: pathogenesis and management.Signal transduction and targeted therapy · 2026Review
- Selective antagonism of adenosine A2A receptor reduces hypobaric hypoxia-induced neuroinflammation by inhibiting cGAS-STING pathway.Scientific reports · 2026Article
- Transcriptomic profiling and targeted validation reveal molecular mechanisms of oxygen therapy in high-altitude cerebral injury.Frontiers in neuroscience · 2026Article
- The neurobiological regulatory mechanism of brain edema.Frontiers in cellular neuroscience · 2026Review
- Hydroxychloroquine Prevents High-altitude Cerebral Edema by Inhibiting Endothelial Claudin-5 Autophagic Degradation.Current neuropharmacology · 2026Article
- Carnosic acid alleviates high-altitude cerebral edema by suppressing oxidative stress and microglia activation-induced neuroinflammation.Frontiers in pharmacology · 2026Article
- A novel CT-based edema grading system combined with machine learning for precise prognostic prediction in traumatic brain injury.European journal of medical research · 2025Article
- Pro-Inflammatory Microglia Exacerbate High-Altitude-Induced Cognitive Impairment by Driving Lipid Droplet Accumulation in Astrocytes.Antioxidants (Basel, Switzerland) · 2025Article
- Single-Cell RNA Sequencing and Spatial Transcriptomics Reveal a Novel Mechanism of Oligodendrocyte-Neuron Interaction in Cognitive Decline After High-Altitude Cerebral Edema.CNS neuroscience & therapeutics · 2025Article
- NMN Supplementation Inhibits Endothelial Cell ROS-Mediated Src/Pi3k/Akt Signaling Pathway to Protect High-Altitude Blood-Retinal Barrier.Investigative ophthalmology & visual science · 2025Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
High-altitude cerebral edema (HACE) is a potentially fatal encephalopathy associated with a time-dependent exposure to the hypobaric hypoxia of altitude. The formation of HACE is affected by both vasogenic and cytotoxic edema. The over-activated microglia potentiate the damage of blood-brain barrier (BBB) and exacerbate cytotoxic edema. In light with the activation of microglia in HACE, we aimed to investigate whether the over-activated microglia were the key turning point of acute mountain sickness to HACE. In in vivo experiments, by exposing mice to hypobaric hypoxia (7000 m above sea level) to induce HACE model, we found that microglia were activated and migrated to blood vessels. Microglia depletion by PLX5622 obviously relieved brain edema. In in vitro experiments, we found that hypoxia induced cultured microglial activation, leading to the destruction of endothelial tight junction and astrocyte swelling. Up-regulated nuclear respiratory factor 1 (NRF1) accelerated pro-inflammatory factors through transcriptional regulation on nuclear factor kappa B p65 (NF-κB p65) and mitochondrial transcription factor A (TFAM) in activated microglia under hypoxia. NRF1 also up-regulated phagocytosis by transcriptional regulation on caveolin-1 (CAV-1) and adaptor-related protein complex 2 subunit beta (AP2B1). The present study reveals a new mechanism in HACE: hypoxia over-activates microglia through up-regulation of NRF1, which both induces inflammatory response through transcriptionally activating NF-κB p65 and TFAM, and enhances phagocytic function through up-regulation of CAV-1 and AP2B1; hypoxia-activated microglia destroy the integrity of BBB and release pro-inflammatory factors that eventually induce HACE.
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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.