ArticleThe Journal of clinical investigation2023
Complement C3a treatment accelerates recovery after stroke via modulation of astrocyte reactivity and cortical connectivity.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 49 citations in OpenAlex.
- Targeting C3aR/STAT3 signaling attenuates neuroinflammation and reverses neurological impairment in Neuromyelitis optica.Fundamental research · 2026Article
- Microglial Immunometabolic Remodeling After Ischemic Stroke: The Interplay Between Mitochondrial Stress and the Ischemic Microenvironment.Translational stroke research · 2026Review
- C3aR inhibition alleviates cerebral ischemia-reperfusion injury via STING-mediated ferroptosis through SLC7A11/GPX4.iScience · 2026Article
- The ubiquitin E3 ligase TRIM59 in myeloid cell regulates complement C3 through degrading CCAAT/enhancer binding protein β to promote neuron survival after ischemic stroke.Cell & bioscience · 2026Article
- Lack of cortistatin drives neuroimmune and vascular dysfunction in brain ischemia.Journal of biomedical science · 2026Article
- Physical exercise promotes white matter repair after ischemic stroke.Neural regeneration research · 2026Article
- Electroacupuncture Promotes Synaptic Recovery After Cerebral Ischemia-Reperfusion by Activating SIRT1 to Inhibit the NF-κB Pathway and Regulate Astrocyte Phenotypic Transformation.Neurochemical research · 2026Article
- Emerging Roles of Adenosine Metabolism in Astrocytes During Brain Injury.CNS neuroscience & therapeutics · 2026Review
- Structural-functional connectivity coupling in motor-brain networks following acute ischemic stroke.Journal of neuroengineering and rehabilitation · 2026Article
- Curing the brain: in search for new astrocyte-specific therapies.Experimental & molecular medicine · 2026Review
- The Interaction of Neutrophil Extracellular Traps and Complement in Intracerebral Hemorrhage.Cellular and molecular neurobiology · 2026Review
- Phagocytosis and neuroinflammation: orchestrating central nervous system homeostasis, repair, and the resolution of inflammation.Trends in neurosciences · 2026Review
- Targeting Reactive Astrocytes with Flavonoids to Alleviate Neuroinflammation and Promote Synaptic Function.Molecular neurobiology · 2026Review
- Associations of Serum Complement Biomarkers With Adverse Clinical Outcomes Among Patients With Ischemic Stroke.Journal of the American Heart Association · 2026Article
- Inflammation-centered neurovascular-immune-metabolic remodeling in ischemic stroke: stage-dependent mechanisms, regulated cell death, and therapeutic translation.Frontiers in immunology · 2026Review
- The immunothrombosis pathway linking pulmonary disease to stroke and neurodegeneration: mechanisms and therapeutic implications.Frontiers in pharmacology · 2026Review
- The Role of the C3a-C3aR Pathway in Diseases: Latest Research Advances.Mediators of inflammation · 2026Review
- "Stand by me": astrocyte-microglia crosstalk in central nervous system development, homeostasis, injury, and disease.Frontiers in network physiology · 2026Review
- Article
- Proteomic Analysis of Mouse Cerebral Cortex Following Experimental Ischemic Stroke: Identifying Novel Biomarkers of Damage and Repair.Cellular and molecular neurobiology · 2025Article
Corrections and comments
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Authors and funding
19 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite advances in acute care, ischemic stroke remains a major cause of long-term disability. Approaches targeting both neuronal and glial responses are needed to enhance recovery and improve long-term outcome. The complement C3a receptor (C3aR) is a regulator of inflammation with roles in neurodevelopment, neural plasticity, and neurodegeneration. Using mice lacking C3aR (C3aR-/-) and mice overexpressing C3a in the brain, we uncovered 2 opposing effects of C3aR signaling on functional recovery after ischemic stroke: inhibition in the acute phase and facilitation in the later phase. Peri-infarct astrocyte reactivity was increased and density of microglia reduced in C3aR-/- mice; C3a overexpression led to the opposite effects. Pharmacological treatment of wild-type mice with intranasal C3a starting 7 days after stroke accelerated recovery of motor function and attenuated astrocyte reactivity without enhancing microgliosis. C3a treatment stimulated global white matter reorganization, increased peri-infarct structural connectivity, and upregulated Igf1 and Thbs4 in the peri-infarct cortex. Thus, C3a treatment from day 7 after stroke exerts positive effects on astrocytes and neuronal connectivity while avoiding the deleterious consequences of C3aR signaling during the acute phase. Intranasal administration of C3aR agonists within a convenient time window holds translational promise to improve outcome after ischemic stroke.
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