ArticleCNS neuroscience & therapeutics2026
Perivascular SPP1 Drives Microglial Synaptic Engulfment After Ischemic Stroke.
Article in CNS neuroscience & therapeutics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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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
2 citing papers in PubMed.
- SPP1 (osteopontin): a key regulator orchestrating cancer progression and non-cancerous pathologies - therapeutic opportunities and future directions.Frontiers in cell and developmental biology · 2026Review
- Inflammation-centered neurovascular-immune-metabolic remodeling in ischemic stroke: stage-dependent mechanisms, regulated cell death, and therapeutic translation.Frontiers in immunology · 2026Review
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
objectiveFollowing ischemic stroke (IS), activated microglia activity could contribute to neuronal injury and blood-brain barrier (BBB) disruption. The upstream vascular-derived signal initiating this transition remains unclear; therefore, we investigated whether perivascular SPP1 regulates microglia-mediated synapse engulfment during IS.
methodsMale C57BL/6 mice were assigned to sham, shSpp1, middle cerebral artery occlusion/reperfusion (MCAO/R), and MCAO/R + shSpp1 groups. Cerebral perfusion was assessed using laser speckle contrast imaging and super-resolution vascular imaging, while neuronal injury was evaluated using Nissl and TUNEL staining. Proteomic profiling of the ischemic penumbra identified regulators of microglia-mediated synaptic remodeling. Synaptic structure and glial-vascular unit (GVU) integrity were examined using transmission electron microscopy, immunofluorescence, and molecular analyses. Behavioral outcomes were assessed using the open-field, Barnes maze, rotarod, and wire-hanging tests.
resultsCompared with sham controls, MCAO/R mice displayed increased microglial synaptic engulfment and ultrastructural synaptic damage in the ischemic penumbra, accompanied by reduced synaptic protein expression. Proteomic analysis revealed upregulation of inflammatory and vascular-related pathways, with marked upregulation of SPP derived from perivascular macrophages. Spp1 silencing attenuated neuroinflammation, reduced infarct volume, improved cerebral perfusion, preserved GVU integrity, and alleviated behavioral deficits. Spp1 suppression also reduced microglial synaptic engulfment in vivo and restored synaptic protein and mRNA levels in vitro.
conclusionTargeting perivascular SPP1 suppresses excessive microglia-mediated synaptic engulfment, preserves BBB integrity and synaptic architecture, and offers a GVU-centered therapeutic strategy for IS.
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Registered trials
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