ArticleCNS neuroscience & therapeutics2020
Aging alters Hv1-mediated microglial polarization and enhances neuroinflammation after peripheral surgery.
Article in CNS neuroscience & therapeutics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 50 citations in OpenAlex.
- Central microglia-adenosine-related signaling impairs bone-tendon interface repair via sympathetic ADRB2 activation.Journal of neuroinflammation · 2026Article
- Article
- Postoperative neurocognitive disorder: migration and crosstalk of inflammation in the peripheral and central nervous system.Perioperative medicine (London, England) · 2026Review
- Risk Assessment of Serum Biomarkers with Perioperative Neurocognitive Dysfunction in Elderly Patients Undergoing Thoracic Surgery: A Prospective Cohort Study.Cellular and molecular neurobiology · 2025Article
- Adiponectin pathway regulates cerebral metabolic dysfunction and neuroinflammation via the AdipoR1/PI3K/Akt axis in Perioperative Neurocognitive Disorder.BMC geriatrics · 2025Article
- Hv1 channel in immune cells and pharmacology.Pharmacological research · 2025Review
- Decoding brain aging trajectory: predictive discrepancies, genetic susceptibilities, and emerging therapeutic strategies.Frontiers in aging neuroscience · 2025Review
- Glia dysfunction in schizophrenia: evidence of possible therapeutic effects of nervonic acid in a preclinical model.Psychopharmacology · 2024Article
- The Effects of Appropriate Perioperative Exercise on Perioperative Neurocognitive Disorders: a Narrative Review.Molecular neurobiology · 2024Review
- The Emerging Role of Microglial Hv1 as a Target for Immunomodulation in Myelin Repair.Aging and disease · 2024Review
- Oral administration of ellagic acid mitigates perioperative neurocognitive disorders, hippocampal oxidative stress, and neuroinflammation in aged mice by restoring IGF-1 signaling.Scientific reports · 2024Article
- Transforming Growth Factor β1 Ameliorates Microglial Activation in Perioperative Neurocognitive Disorders.Neurochemical research · 2023Article
- Role of the Voltage-Gated Proton Channel Hv1 in Nervous Systems.Neuroscience bulletin · 2023Review
- Voltage-Gated Proton Channels in the Tree of Life.Biomolecules · 2023Review
- Microglial reprogramming by Hv1 antagonism protects neurons from inflammatory and glutamate toxicity.Journal of neurochemistry · 2023Article
- Neuron-targeted Knockout of APE1 Forces Premature Cognitive Impairment and Synaptic Dysfunction in Adult Mice.Aging and disease · 2022Article
- Modulation of the Microglial Nogo-A/NgR Signaling Pathway as a Therapeutic Target for Multiple Sclerosis.Cells · 2022Review
- mTOR-mediated autophagy in the hippocampus is involved in perioperative neurocognitive disorders in diabetic rats.CNS neuroscience & therapeutics · 2022Article
- Microglia autophagy in ischemic stroke: A double-edged sword.Frontiers in immunology · 2022Review
- Metabolic reprogramming mediates hippocampal microglial M1 polarization in response to surgical trauma causing perioperative neurocognitive disorders.Journal of neuroinflammation · 2021Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Perioperative neurocognitive disorders have been widely recognized as common adverse events after surgical intervention. Aging is one of the most important independent risk factors for worsened cognitive outcome, and this deterioration is linked to exacerbated microglia-mediated neuroinflammation in the aged brain. Under pathological stimulation, microglia are capable of polarizing toward proinflammatory M1 and anti-inflammatory M2 phenotypes. In the present study, we examined how aging affects microglial responses and neuroinflammation following peripheral surgery. Adult (2-3 months) and aged (18 months old) male C57/BL6 mice were subjected to tibial fracture or sham surgery. Aged mice exhibited higher level of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the hippocampus. The expression of synaptic protein synaptophysin (SYP) was also markedly reduced in the aged brain after the surgery. Both adult and aged mice showed significant increases in M1 microglial polarization (CD16/32). In contrast, tibial fracture surgery induced a decreased M2 microglial polarization (CD206, Ym1/2, Arg1) in aged brain but enhanced M2 microglial polarization in adult brain. Aged mice have upregulated voltage-gated proton channel (Hv1) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit expression compared with adult mice. The percentage of CD16/32-positive M1 microglia colabeling with Hv1 was higher in aged mice after tibial fracture surgery. Thus, Hv1/NADPH oxidase upregulation in the aged brain may shift the dynamic equilibrium of microglial activation toward M1 polarization and exaggerate postoperative neuroinflammatory responses after peripheral surgical intervention.
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