ArticleJournal of immunology (Baltimore, Md. : 1950)2012
The alternative complement pathway propagates inflammation and injury in murine ischemic stroke.
Article in Journal of immunology (Baltimore, Md. : 1950), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.
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Who cites it
58 citing papers in PubMed, 1 synthesis or guideline pooled it, 93 citations in OpenAlex.
- C1q as a target molecule to treat human disease: What do mouse studies teach us?Frontiers in immunology · 2022Pooled it
- Terazosin Attenuates Neuronal Pyroptosis by Regulating the Mitochondrial ROS/NLRP3 Inflammasome Axis Through Mitophagy in Cerebral Ischemia-Reperfusion Injury.The Kaohsiung journal of medical sciences · 2026Article
- Serum Amyloid A-Dependent Inflammasome Activation and Acute Injury in a Mouse Model of Experimental Stroke.International journal of molecular sciences · 2026Article
- Impact of Oxidized Phospholipids on Outcomes from Cerebral Ischemia and Reperfusion Injury.Pharmaceutics · 2026Article
- Integrated Transcriptomic and Proteomic Analysis Elucidates the Mechanisms of Huperzine A Injection Against Cerebral Ischemia/Reperfusion Injury.Drug design, development and therapy · 2026Article
- Review
- Comprehensive Transcriptomic Analysis of Brain Tissues From the Infarcted Area of MCAO Rats Revealed That Acupuncture Attenuates Brain Injury via the Complement System.Brain and behavior · 2025Article
- Complement inhibition targets a rich-club within the neuroinflammatory network after stroke to improve radiographic and functional outcomes.Journal of neuroinflammation · 2025Article
- Immune-mediated blood-brain barrier disruption after ischemic stroke: mechanisms and therapeutic targets.Frontiers in immunology · 2025Review
- Neuroinflammation in Acute Ischemic and Hemorrhagic Stroke.Current neurology and neuroscience reports · 2023Review
- ER stress induced immunopathology involving complement in CADASIL: implications for therapeutics.Acta neuropathologica communications · 2023Article
- Contribution of animal models to the mechanistic understanding of Alternative Pathway and Amplification Loop (AP/AL)-driven Complement-mediated Diseases.Immunological reviews · 2023Review
- Properdin inhibition ameliorates hepatic ischemia/reperfusion injury without interfering with liver regeneration in mice.Frontiers in immunology · 2023Article
- Complement factor B is essential for the proper function of the peripheral auditory system.Frontiers in neurology · 2023Article
- Brain injury environment critically influences the connectivity of transplanted neurons.Science advances · 2022Article
- Hemorrhagic Transformation After Tissue Plasminogen Activator Treatment in Acute Ischemic Stroke.Cellular and molecular neurobiology · 2022Review
- Aberrant Complement System Activation in Neurological Disorders.International journal of molecular sciences · 2021Review
- Neuroimmune crosstalk and evolving pharmacotherapies in neurodegenerative diseases.Immunology · 2021Review
- Complement Initiation Varies by Sex in Intestinal Ischemia Reperfusion Injury.Frontiers in immunology · 2021Article
- Effects of GrandFusion Diet on Cognitive Impairment in Transgenic Mouse Model of Alzheimer's Disease.Nutrients · 2020Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
There is mounting evidence indicating an important role for complement in the pathogenesis of cerebral ischemia-reperfusion injury, or ischemic stroke. The role of the alternative complement pathway in ischemic stroke has not been investigated, and there is conflicting data on the role of the terminal pathway. In this study, we show that compared with wild-type mice, mice deficient in the alternative pathway protein factor B or mice treated with the alternative pathway inhibitor CR2-fH have improved outcomes after 60-min middle cerebral artery occlusion and 24-h reperfusion. Factor B-deficient or CR2-fH-treated mice were protected in terms of improved neurologic function and reduced cerebral infarct, demyelination, P-selectin expression, neutrophil infiltration, and microthrombi formation. Mice deficient in both the classical and lectin pathways (C1q/MBL deficient) were also protected from cerebral ischemia-reperfusion injury, and there was no detectable C3d deposition in the ipsilateral brain of these mice. These data demonstrate that the alternative pathway is not alone sufficient to initiate complement activation and indicate that the alternative pathway propagates cerebral injury via amplification of the cascade. Deficiency of C6, a component of the terminal cytolytic membrane attack complex, had no effect on outcome after ischemic stroke, indicating that the membrane attack complex is not involved in mediating injury in this model. We additionally show that the protective effect of factor B deficiency and CR2-fH treatment is sustained in the subacute stage of infarct development, adding to the clinical relevance of these findings.
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