ArticleNeurotoxicity research2019
The Novel C5aR Antagonist DF3016A Protects Neurons Against Ischemic Neuroinflammatory Injury.
Article in Neurotoxicity research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 16 papers, 2 of them syntheses that pooled it.
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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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 2 syntheses or guidelines pooled it, 34 citations in OpenAlex.
- Clinicopathological features and prognostic significance of C5aR in human solid tumors: a Meta-analysis.BMC cancer · 2021Pooled it
- Pathophysiology and Therapeutic Perspectives of Oxidative Stress and Neurodegenerative Diseases: A Narrative Review.Advances in therapy · 2020Pooled it
- Biphasic modulation of large-fiber excitability accompanied by dynamic nerve-intrinsic immune activation following CFA-induced peripheral inflammation in mice.Scientific reports · 2026Article
- Identification of coagulation-related hub genes in ischemic stroke based on bioinformatics integration analysis and investigation of their immune regulatory mechanisms.European journal of medical research · 2025Article
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- Investigation and Evaluation of the Transdermal Delivery of Ibuprofen in Various Characterized Nano-Drug Delivery Systems.Pharmaceutics · 2023Article
- Comparative study on the topical and transdermal delivery of diclofenac incorporated in nano-emulsions, nano-emulgels, and a colloidal suspension.Drug delivery and translational research · 2023Article
- Emerging Approaches for the Management of Chemotherapy-Induced Peripheral Neuropathy (CIPN): Therapeutic Potential of the C5a/C5aR Axis.Pain and therapy · 2022Review
- Paclitaxel binds and activates C5aR1: A new potential therapeutic target for the prevention of chemotherapy-induced peripheral neuropathy and hypersensitivity reactions.Cell death & disease · 2022Article
- Expression and functions of adenylyl cyclases in the CNS.Fluids and barriers of the CNS · 2022Review
- Article
- Guhong Injection Prevents Ischemic Stroke-Induced Neuro-Inflammation and Neuron Loss Through Regulation of C5ar1.Frontiers in pharmacology · 2022Article
- Emerging Role of C5 Complement Pathway in Peripheral Neuropathies: Current Treatments and Future Perspectives.Biomedicines · 2021Review
- Hepatitis B Virus Core Protein Mediates the Upregulation of C5α Receptor 1 via NF-κB Pathway to Facilitate the Growth and Migration of Hepatoma Cells.Cancer research and treatment · 2021Article
- Therapeutic Hypothermia Inhibits the Classical Complement Pathway in a Rat Model of Neonatal Hypoxic-Ischemic Encephalopathy.Frontiers in neuroscience · 2021Article
- Towards an Effective and Safe Treatment of Inflammatory Pain: A Delphi-Guided Expert Consensus.Advances in therapy · 2019Article
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
The central nervous system (CNS) constitutively expresses complement (C) membrane receptors and complement proteins, including the component C5a. This is a crucial terminal effector of the C cascade, mostly involved in pain and neuroinflammatory conditions. Aberrant activation of C5a protein and its receptor C5aR has been reported to play a critical role in neurodegenerative diseases, with important clinical consequences. Here we have investigated the effects of DF3016A, a novel selective C5aR antagonist, able to penetrate the blood-brain barrier (BBB), on cortical neurons exposed to oxygen-glucose deprivation-reoxygenation (OGD/R), a neuroinflammation-related process. We demonstrated that a mild ischemic insult induces an early upregulation of C5aR associated with the over-production of pro-inflammatory cytokines and the over-expression of the transcriptional regulatory factor miR-181. Furthermore, we report the first experimental evidence of the effect of DF3016A, modulating complement component C5a, on neurons in a model of injury. Interestingly, DF3016A protects neuronal viability by restoring intracellular calcium levels, thus opposing the increase in pro-inflammatory cytokine levels and miR-181 expression. Based on our results, we suggest that DF3016A is a novel C5aR antagonist promoting protective effects against OGD/R-induced damage that could be a new therapeutic approach to controlling CNS neuroinflammatory conditions.
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Registered trials
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.