ArticleFrontiers in neuroscience2020
Activated Protein C Attenuates Experimental Autoimmune Encephalomyelitis Progression by Enhancing Vascular Integrity and Suppressing Microglial Activation.
Article in Frontiers in neuroscience, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 30 citations in OpenAlex.
- Targeting the Microglia-Astrocyte OSM-OSMR Axis Restores Blood-Brain Barrier Integrity After Experimental Cerebral Ischemia-Reperfusion in Mice.Molecular neurobiology · 2026Article
- Mild chronic hypoxia and the brain: an ambiguous relationship.Journal of neuroinflammation · 2026Review
- Microglia-vascular interactions after spinal cord injury: regulatory mechanisms and therapeutic advances.Frontiers in immunology · 2026Review
- Overexpression of endothelial β4 integrin has no impact on blood-brain barrier integrity or the pathogenesis of experimental autoimmune encephalomyelitis.Experimental neurology · 2025Article
- Research developments in the neurovascular unit and the blood‑brain barrier (Review).Biomedical reports · 2025Review
- The Mechanisms of Sepsis Induced Coagulation Dysfunction and Its Treatment.Journal of inflammation research · 2025Review
- Safety and tolerability of the protein C activator AB002 in end-stage renal disease patients on hemodialysis: a randomized phase 2 trial.Communications medicine · 2024Article
- Cellular and molecular mechanisms of the blood-brain barrier dysfunction in neurodegenerative diseases.Fluids and barriers of the CNS · 2024Review
- Biased agonism of protease-activated receptor-1 regulates thromboinflammation in murine sickle cell disease.Blood advances · 2024Article
- Communications between Neutrophil-Endothelial Interaction in Immune Defense against Bacterial Infection.Biology · 2024Review
- Cytoprotective E-WE thrombin reduces disease severity in a murine model of relapsing-remitting multiple sclerosis.American journal of physiology. Cell physiology · 2024Article
- Activated protein C modulates T-cell metabolism and epigenetic FOXP3 induction via α-ketoglutarate.Blood advances · 2023Article
- 3K3A-Activated Protein C Inhibits Choroidal Neovascularization Growth and Leakage and Reduces NLRP3 Inflammasome, IL-1β, and Inflammatory Cell Accumulation in the Retina.International journal of molecular sciences · 2023Article
- β-Actin: An Emerging Biomarker in Ischemic Stroke.Cellular and molecular neurobiology · 2023Review
- Neutrophil, neutrophil extracellular traps and endothelial cell dysfunction in sepsis.Clinical and translational medicine · 2023Review
- Activated protein C in epilepsy pathophysiology.Frontiers in neuroscience · 2023Review
- 3K3A-Activated Protein C Prevents Microglia Activation, Inhibits NLRP3 Inflammasome and Limits Ocular Inflammation.International journal of molecular sciences · 2022Article
- Factor VII, EPCR, aPC Modulators: novel treatment for neuroinflammation.Journal of neuroinflammation · 2022Article
- Expression and Clinical Correlation Analysis Between Repulsive Guidance Molecule a and Neuromyelitis Optica Spectrum Disorders.Frontiers in immunology · 2022Article
- Hemostasis components in cerebral amyloid angiopathy and Alzheimer's disease.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2021Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundActivated protein C (APC), a serine protease with antithrombotic effects, protects in animal models of ischemic stroke by suppressing inflammation and enhancing vascular integrity, angiogenesis, neurogenesis and neuroprotection. A small number of animal studies suggest it might also have therapeutic potential in multiple sclerosis (MS), though results have been mixed. Based on these conflicting data, the goals of this study were to clarify the therapeutic potential of APC in the experimental autoimmune encephalomyelitis (EAE) model of MS and to determine mechanistically how APC mediates this protective effect.
methodsThe protective potential of APC was examined in a chronic progressive model of EAE. Vascular breakdown, tight junction protein expression and vascular expression of fibronectin and α5β1 integrin as well as vascularity and glial activation were analyzed using immunofluorescence (IF) of spinal cord sections taken from mice with established EAE. The direct influence of APC on microglial activation was evaluated
resultsAPC attenuated the progression of EAE, and this was strongly associated at the histopathological level with reduced levels of leukocyte infiltration and concomitant demyelination. Further analysis revealed that APC reduced vascular breakdown which was associated with maintained endothelial expression of the tight junction protein zonula occludens-1 (ZO-1). In addition, APC suppressed microglial activation in this EAE model and
conclusionThese findings build on the work of others in demonstrating strong therapeutic potential for APC in the treatment of inflammatory demyelinating disease and suggest that enhancement of vascular integrity and suppression of microglial activation may be important mediators of this protection.
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