ArticleJournal of neuroinflammation2021
Phthalide derivative CD21 attenuates tissue plasminogen activator-induced hemorrhagic transformation in ischemic stroke by enhancing macrophage scavenger receptor 1-mediated DAMP (peroxiredoxin 1) clearance.
Article in Journal of neuroinflammation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis 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.
The trial behind it
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
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- Targeting NETosis in Acute Brain Injury: A Systematic Review of Preclinical and Clinical Evidence.Cells · 2024Pooled it
- Peroxiredoxins in Stroke: Friends and Foes.Cells · 2026Review
- The spatiotemporal dynamic evolution of post-stroke neuroinflammation: energy metabolism mechanisms of acute response and chronic progression.Frontiers in pharmacology · 2026Review
- Z-Ligustilide: A Potential Therapeutic Agent for Atherosclerosis Complicating Cerebrovascular Disease.Biomolecules · 2024Review
- Multi-targeted olink proteomics analyses of cerebrospinal fluid from patients with aneurysmal subarachnoid hemorrhage.Proteome science · 2024Article
- Article
- COVID-19-induced neurological symptoms: focus on the role of metal ions.Inflammopharmacology · 2023Review
- Predictive Value of CT Perfusion in Hemorrhagic Transformation after Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.Brain sciences · 2023Review
- Efferocytosis in the Central Nervous System.Frontiers in cell and developmental biology · 2021Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundHemorrhagic transformation (HT) is a critical issue in thrombolytic therapy in acute ischemic stroke. Damage-associated molecular pattern (DAMP)-stimulated sterile neuroinflammation plays a crucial role in the development of thrombolysis-associated HT. Our previous study showed that the phthalide derivative CD21 attenuated neuroinflammation and brain injury in rodent models of ischemic stroke. The present study explored the effects and underlying mechanism of action of CD21 on tissue plasminogen activator (tPA)-induced HT in a mouse model of transient middle cerebral artery occlusion (tMCAO) and cultured primary microglial cells.
methodsThe tMCAO model was induced by 2 h occlusion of the left middle cerebral artery with polylysine-coated sutures in wildtype (WT) mice and macrophage scavenger receptor 1 knockout (MSR1
resultsSeventy-two hours after brain ischemia, CD21 significantly attenuated neurobehavioral dysfunction and infarct volume. The tPA-infused group exhibited more severe brain dysfunction and hemorrhage. Compared with tPA alone, combined treatment with tPA and CD21 significantly attenuated ischemic brain injury and hemorrhage. Combined treatment significantly decreased Evans blue extravasation, matrix metalloproteinase 9 expression and activity, extracellular Prx1 content, proinflammatory cytokine mRNA levels, glial cells, and Toll-like receptor 4 (TLR4)/nuclear factor κB (NF-κB) pathway activation and increased the expression of tight junction proteins (zonula occludens-1 and claudin-5), V-maf musculoaponeurotic fibrosarcoma oncogene homolog B, and MSR1. MSR1 knockout significantly abolished the protective effect of CD21 against tPA-induced HT in tMCAO mice. Moreover, the CD21-induced phagocytosis of Prx1 was MSR1-dependent in cultured primary microglial cells from WT and MSR1
conclusionThe phthalide derivative CD21 attenuated tPA-induced HT in acute ischemic stroke by promoting MSR1-induced DAMP (Prx1) clearance and inhibition of the TLR4/NF-κB pathway and neuroinflammation.
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