ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2010
Activation of microglia depends on Na+/H+ exchange-mediated H+ homeostasis.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.
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Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 88 citations in OpenAlex.
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- SGLT2 Inhibitor Canagliflozin Alleviates High Glucose-Induced Inflammatory Toxicity in BV-2 Microglia.Biomedicines · 2023Article
- Pharmacological Inhibition of NHE1 Protein Increases White Matter Resilience and Neurofunctional Recovery after Ischemic Stroke.International journal of molecular sciences · 2023Article
- Microglial reprogramming by Hv1 antagonism protects neurons from inflammatory and glutamate toxicity.Journal of neurochemistry · 2023Article
- Guanidine Derivatives of Quinazoline-2,4(1Life (Basel, Switzerland) · 2022Article
- Microglial-oligodendrocyte interactions in myelination and neurological function recovery after traumatic brain injury.Journal of neuroinflammation · 2022Article
- Anti-Inflammatory Properties of the SGLT2 Inhibitor Empagliflozin in Activated Primary Microglia.Cells · 2022Article
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- Elevated microglial oxidative phosphorylation and phagocytosis stimulate post-stroke brain remodeling and cognitive function recovery in mice.Communications biology · 2022Article
- Synthesis and multifaceted pharmacological activity of novel quinazoline NHE-1 inhibitors.Scientific reports · 2021Article
- Attenuating vascular stenosis-induced astrogliosis preserves white matter integrity and cognitive function.Journal of neuroinflammation · 2021Article
- Phagocytic activity of splenic macrophages is enhanced and accompanied by cytosolic alkalinization in TRPM7 kinase-dead mice.The FEBS journal · 2021Article
- Inhibition of NaJournal of neural engineering · 2021Article
- Cerebral Edema Formation After Stroke: Emphasis on Blood-Brain Barrier and the Lymphatic Drainage System of the Brain.Frontiers in cellular neuroscience · 2021Review
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
H(+) extrusion is important for sustained NADPH oxidase activation after "respiratory" burst in macrophage/microglia activation. In this study, we investigated the role of Na(+)/H(+) exchanger isoform 1 (NHE-1) in activation of microglia after lipopolysaccharide (LPS) or oxygen and glucose deprivation and reoxygenation (OGD/REOX) exposure. NHE-1 functioned in maintaining basal pH(i) of immortalized M4T.4 microglia or mouse primary microglia. Pharmacological inhibition of NHE-1 activity with the potent inhibitor cariporide [HOE 642 (4-isopropyl-3-methylsulfonyl-benzoyl-guanidine-methanesulfonate)] abolished pH(i) regulation in microglia under basal conditions. Activation of microglia either by LPS, phorbol myristate acetate, or OGD/REOX accelerated pH(i) regulation and caused pH(i) elevation, which was accompanied with an increase in [Na(+)](i) and [Ca(2+)](i) as well as production of superoxide anion and cytokines. Interestingly, inhibition of NHE-1 not only abolished pH(i) regulation but also reduced production of superoxide anion as well as expression of cytokines and inducible nitric oxide synthase. Together, these results reveal that there was a concurrent activation of NHE-1 in microglia in response to proinflammatory stimuli. The study suggests that NHE-1 functions to maintain microglial pH(i) homeostasis allowing for sustained NADPH oxidase function and "respiratory" burst.
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