Abstract | BACKGROUND: METHODS: The 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-/-) mice. At the onset of reperfusion, tPA (10 mg/kg) was intravenously administered within 30 min, followed by an intravenous injection of CD21 (13.79 mg/kg/day). Neuropathological changes were detected in mice 3 days after surgery. The effect of CD21 on phagocytosis of the DAMP peroxiredoxin 1 (Prx1) in lysosomes was observed in cultured primary microglial cells from brain tissues of WT and MSR1-/- mice. RESULTS: Seventy-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-/- mice, respectively. CONCLUSION:
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Authors | Dong-Ling Liu, Zhi Hong, Jing-Ying Li, Yu-Xin Yang, Chu Chen, Jun-Rong Du |
Journal | Journal of neuroinflammation
(J Neuroinflammation)
Vol. 18
Issue 1
Pg. 143
(Jun 24 2021)
ISSN: 1742-2094 [Electronic] England |
PMID | 34162400
(Publication Type: Journal Article)
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Chemical References |
- Benzofurans
- NF-kappa B
- Receptors, Scavenger
- Toll-Like Receptor 4
- phthalide derivative CD21
- Peroxiredoxins
- Tissue Plasminogen Activator
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Topics |
- Animals
- Benzofurans
(pharmacology, therapeutic use)
- Brain
(metabolism, pathology)
- Cell Line
- Cerebral Hemorrhage
(drug therapy, metabolism, pathology)
- Disease Models, Animal
- Infarction, Middle Cerebral Artery
- Ischemic Stroke
(drug therapy, pathology)
- Male
- Mice
- Mice, Inbred C57BL
- NF-kappa B
(metabolism)
- Peroxiredoxins
(metabolism)
- Receptors, Scavenger
(metabolism)
- Reperfusion
- Tissue Plasminogen Activator
(adverse effects)
- Toll-Like Receptor 4
(metabolism)
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