ArticleJournal of molecular medicine (Berlin, Germany)2012
Early steps of microglial activation are directly affected by neuroprotectant FK506 in both in vitro inflammation and in rat model of stroke.
Article in Journal of molecular medicine (Berlin, Germany), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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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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Who cites it
18 citing papers in PubMed, 36 citations in OpenAlex.
- Evaluating the Neuroprotective and Acetylcholinesterase Inhibitory Properties of Four Calcineurin Inhibitor Drugs: Tacrolimus, Pimecrolimus, Cyclosporin A, and Voclosporin.Molecular neurobiology · 2025Article
- Engineered Extracellular Vesicles Loaded with MiR-100-5p Antagonist Selectively Target the Lesioned Region to Promote Recovery from Brain Damage.Neuroscience bulletin · 2025Article
- Sustained Release of Tacrolimus Embedded in a Mixed Thermosensitive Hydrogel for Improving Functional Recovery of Injured Peripheral Nerves in Extremities.Pharmaceutics · 2023Article
- Recent development of polymer nanomicelles in the treatment of eye diseases.Frontiers in bioengineering and biotechnology · 2023Review
- Article
- Purinoreceptors and ectonucleotidases control ATP-induced calcium waveforms and calcium-dependent responses in microglia: Roles of P2 receptors and CD39 in ATP-stimulated microglia.Frontiers in physiology · 2022Article
- Cannabinoids as Glial Cell Modulators in Ischemic Stroke: Implications for Neuroprotection.Frontiers in pharmacology · 2022Review
- Localized co-delivery of CNTF and FK506 using a thermosensitive hydrogel for retina ganglion cells protection after traumatic optic nerve injury.Drug delivery · 2020Article
- Combined Cyclosporin A and Hypothermia Treatment Inhibits Activation of BV-2 Microglia but Induces an Inflammatory Response in an Ischemia/Reperfusion Hippocampal Slice Culture Model.Frontiers in cellular neuroscience · 2019Article
- An Elastomeric Polymer Matrix, PEUU-Tac, Delivers Bioactive Tacrolimus Transdurally to the CNS in Rat.EBioMedicine · 2017Article
- Inhibition of Calcineurin A by FK506 Suppresses Seizures and Reduces the Expression of GluN2B in Membrane Fraction.Neurochemical research · 2017Article
- FcRγ-dependent immune activation initiates astrogliosis during the asymptomatic phase of Sandhoff disease model mice.Scientific reports · 2017Article
- Immediate Remote Ischemic Postconditioning Reduces Brain Nitrotyrosine Formation in a Piglet Asphyxia Model.Oxidative medicine and cellular longevity · 2016Article
- Tim-3 cell signaling and iNOS are involved in the protective effects of ischemic postconditioning against focal ischemia in rats.Metabolic brain disease · 2015Article
- Anandamide, Acting via CB2 Receptors, Alleviates LPS-Induced Neuroinflammation in Rat Primary Microglial Cultures.Neural plasticity · 2015Article
- Trans-caryophyllene suppresses hypoxia-induced neuroinflammatory responses by inhibiting NF-κB activation in microglia.Journal of molecular neuroscience : MN · 2014Article
- The signal transducers Stat1 and Stat3 and their novel target Jmjd3 drive the expression of inflammatory genes in microglia.Journal of molecular medicine (Berlin, Germany) · 2014Article
- Brazilian green propolis suppresses the hypoxia-induced neuroinflammatory responses by inhibiting NF-κB activation in microglia.Oxidative medicine and cellular longevity · 2013Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuroprotective and/or neuroregenerative activity of FK506, its derivatives, and to a lesser extent cyclosporin A (CsA) in animal models of neurodegenerative diseases of different etiology have been reported. Here, we verified a hypothesis that the most likely mechanism of their neuroprotective action is inhibition of the early steps of inflammatory activation of microglia by interference with mitogen-activated protein kinase (MAPK) signaling. The effect of immunosuppressants on lipopolysaccharide (LPS)-induced changes in morphology, proliferation, and motility of rat primary microglial cultures was evaluated. FK506 and CsA directly inhibited LPS-induced microglia activation and inflammatory responses. While both drugs efficiently reduced the expression of iNOS and the release of nitric oxide, only FK506 strongly inhibited the expression of Cox-2 and secretion of the mature form of IL-1β. FK506 strongly reduced LPS-induced activation of MAPK, and its downstream signaling crucial for inflammatory responses. Comparative analysis of global gene expression in rat ischemic brains and in LPS-stimulated microglial cultures revealed many genes and signaling pathways regulated in the same way in both systems. FK506 treatment blocked a majority of genes induced by an ischemic insult in the cortex, in particular inflammatory/innate immunity and apoptosis-related genes. Microglia-mediated inflammation is considered as one of the most important components of brain injury after trauma or stroke; thus, effective and multifaceted blockade of microglial activation by FK506 has clinical relevance and potential therapeutic implications.
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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.