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Transcriptomic data from a non-human primate model of stroke reproducing endovascular thrombectomy

ABSTRACT: Background and purpose: Rodent models have demonstrated the key pathogenic role of the lectin pathway (LP) of complement activation in brain ischemic injury. Here we assessed the LP activation and its association with stroke severity and outcome in a well-characterized model of stroke mimicking mechanical thrombectomy in non-human primates. Methods: Transient middle cerebral artery occlusion was performed in Macaca fascicularis randomly allocated in cyclosporine A or placebo group. Neurological status was serially assessed. The occlusion lesion, the ischemic penumbra, the final lesion, the lesion growth between occlusion and day 7 as well as the blood-brain barrier permeability using quantitative transfer constant Ktrans ratio and inflammation by quantitative [11C]PK11195 imaging were assessed using positron emission tomography–magnetic resonance (PET-MRI) imaging. Functional residual LP-specific C3b deposition assay was performed in plasma. C3b/iC3b, mannose binding lectin (MBL), MBL associated serine proteases-2 (MASP-2) and interleukin-6 were measured in plasma, cerebrospinal fluid and brain homogenates. Brain tissue was used to perform immunofluorescence and confocal analyses (C3b/iC3b, MBL and MASP-2 and glycocalyx) as well as transcriptomic analysis. Results: Twenty-three subjects were included with a mean age of 6.7 +/- 0.5 years. LP residual activation in plasma collected late after recanalization was significantly decreased compared to baseline conditions. C3b/iC3b peaked at day 7 and this increase correlated with a more severe neurological deficit at day 1 and day 7, a larger final lesion and lesion growth volumes as well as a greater Ktrans ratio. C3b/iC3b, MBL and MASP-2 were found in microvascular thrombi at day 30. At this time point, 760 genes were differentially expressed within the lesion, including 13 LP-related genes. Conclusions: Our results support that the LP of complement activation is involved in thromboinflammation in a non-human primate model of stroke mimicking mechanical thrombectomy in humans.

ORGANISM(S): Macaca fascicularis

PROVIDER: GSE283970 | GEO | 2025/07/01

REPOSITORIES: GEO

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Project description:Genes upregulated in stroke infiltrating stem cells were compared against the parent non-infiltrated mouse stem cell line derived from immortomouseTM. Abstract Background and Purpose- Although the therapeutic potential of bone marrow-derived stem cells (SC) has been addressed in different experimental models of ischemic stroke, it is still unclear how SC induce neuroprotection following stroke. In this study, we describe a novel method for recovering SC infiltrating post-stroke brain tissue allowing the determination of genes which become persistently activated / or depressed (compared to their naïve counterparts) during SC-mediated neuroprotection. Methods- Ischemic stroke was induced in C57BL/6 mice by middle cerebral artery occlusion for 1 h, followed by reperfusion. SC were isolated from H-2Kb-tsA58 (immortomouseTM) mice, and were administered (i.v.) 24 h after reperfusion. At the onset of therapeutic improvement (14 days after ischemia), infarcted brain tissue was isolated and infarct-infiltratng SC cultured at 33°C. Microarray analysis and RT-PCR were performed to compare persistent differential gene expression between naïve and infiltrating SC populations. Results- Z-scoring revealed dramatic changes in extracellular genes of analyzed cells. Pair-wise analysis detected 80 extracellular factor genes that were up-regulated ( 2 fold, P<0.05, Benjamini-Hochberg correction) between naïve and infiltrated SC. Although several conventional neuroregenerative, nerve guidance and angiogenic factors (bFGF, bone morphogenetic protein, angiopoietins, neural growth factors were among the expressed genes detected we identified Cytokine receptor-like factor 1 (Crlf1), Fgf7, family with sequence similarity 19, member A5 (Fam19a5), Glypican 1 (Gpc1), Dickkopf homolog 2 (Dkk2), Endothelial cell-specific molecule 1, Osteopontin (OPN)35, Tissue factor pathway inhibitor 2, Masp3 mRNA for MBL-associated serine protease-3, Glial cell line derived neurotrophic factor (Gdnf), Bone morphogenetic protein 2 (Bmp2), Olfactomedin 1, Sushi-repeat-containing protein, X-linked 2 (Srpx2). Conclusions- SC infiltrating the post-i schemic brain assume a persistently altered pattern of expressed extracellular genes compared to naïve SC that contributes to neuroprotection, regeneration and angiogenesis in infarcts. Keywords: Gene activation / suppression study Comparison of persistent stem cell gene expression induced by stroke-infarct infiltration

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Transcriptomic data from a non-human primate model of stroke reproducing endovascular thrombectomy

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