Transcriptomic data from a non-human primate model of stroke reproducing endovascular thrombectomy
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1196436 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description: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.
2025-07-01 | GSE283970 | GEO
Project description:Stroke is a devastating disease. Endovascular mechanical thrombectomy is dramatically changing the management of acute ischemic stroke, raising new challenges regarding brain outcome and opening up new avenues for brain protection. In this context, relevant experiment models are required for testing new therapies and addressing important questions about infarct progression despite successful recanalization, reversibility of ischemic lesions, blood-brain barrier disruption and reperfusion damage. Here, we developed a minimally invasive non-human primate model of cerebral ischemia (Macaca fascicularis) based on an endovascular transient occlusion and recanalization of the middle cerebral artery (MCA). We evaluated per-occlusion and post-recanalization impairment on PET-MRI, in addition to acute and chronic neuro-functional assessment. Voxel-based analyses between per-occlusion PET-MRI and day-7 MRI showed two different patterns of lesion evolution: "symptomatic salvaged tissue" (SST) and "asymptomatic infarcted tissue" (AIT). Extended SST was present in all cases. AIT, remote from the area at risk, represented 45% of the final lesion. This model also expresses both worsening of fine motor skills and dysexecutive behavior over the chronic post-stroke period, a result in agreement with cortical-subcortical lesions. We thus fully characterized an original translational model of ischemia-reperfusion damage after stroke, with consistent ischemia time, and thrombus retrieval for effective recanalization.
| S-EPMC7983495 | biostudies-literature
Project description:In the past decade, noble gases have emerged as highly promising neuroprotective agents. Previous studies have demonstrated the efficacy of argon neuroprotection in rodent models of cerebral ischemia. The objective of the present pre-clinical study was to confirm the neuroprotective effect of argon in a non-human primate model of endovascular ischemic stroke. Thirteen adult Macaca mulatta were subjected to a focal cerebral ischemia induced by a transient (90 min) middle cerebral artery occlusion (tMCAO). The monkeys were randomly allocated to a control group (n = 8) and an argon group (n = 5). Pre-mixed gas (40-60 oxygen-argon) was applied 30 min after the onset of tMCAO to 30 min after reperfusion. Infarct volumes were measured from the MRI scans conducted 1 hour and 1 month after the reperfusion. A clinical neurological assessment was performed 24 hours and 1 month after tMCAO. Our results show that Argon dramatically reduced ischemic core volume after ischemia compared to the control group with a long-lasting improvement of post-stroke infarct volume at 1 month. In addition, the neurological scale suggests a better prognosis in argon-treated animals without reaching the significance threshold. These pre-clinical results in gyrencephalic non-human primates support the potential use of this therapeutic approach for future clinical studies.
| S-EPMC11615904 | biostudies-literature
Project description:Reperfusion therapies in acute ischemic stroke have demonstrated their efficacy in promoting clinical recovery. However, ischemia/reperfusion injury and related inflammation remain a major challenge in patient clinical management. We evaluated the spatio-temporal evolution of inflammation using sequential clinical [11C]PK11195 PET-MRI in a non-human primate (NHP) stroke model mimicking endovascular thrombectomy (EVT) with a neuroprotective cyclosporine A (CsA) treatment. The NHP underwent a 110-min transient endovascular middle cerebral artery occlusion. We acquired [11C]PK11195 dynamic PET-MR imaging at baseline, 7 and 30 days after intervention. Individual voxel-wise analysis was performed thanks to a baseline scan database. We quantified [11C]PK11195 in anatomical regions and in lesioned areas defined on per-occlusion MR diffusion-weighted imaging and perfusion [15O2]H2OPET imaging. [11C]PK11195 parametric maps showed a clear uptake overlapping the lesion core at D7, which further increased at D30. Voxel-wise analysis identified individuals with significant inflammation at D30, with voxels located within the most severe diffusion reduction area during occlusion, mainly in the putamen. The quantitative analysis revealed that thalamic inflammation lasted until D30 and was significantly reduced in the CsA-treated group compared to the placebo. In conclusion, we showed that chronic inflammation matched ADC decrease at occlusion time, a region exposed to an initial burst of damage-associated molecular patterns, in an NHP stroke model mimicking EVT. We described secondary thalamic inflammation and the protective effect of CsA in this region. We propose that major ADC drop in the putamen during occlusion may identify individuals who could benefit from early personalized treatment targeting inflammation.
| S-EPMC10275847 | biostudies-literature
Project description:Endovascular Device for Endothelial Cell Sampling
| PRJNA812000 | ENA
Project description:We have developed an endovascular catheter-based device for sampling of the endothelium, intended for RNA-seq analysis. With an outer diameter of 0.23 mm it is capable of reaching peripheral vessels for endothelial sampling, and favourably compares to other approaches with stent retrievers or similar tools. Here, we have collected samples from liver and kidney vessels from swine and performed RNA-sequencing to validate the sample quality.
2022-08-21 | GSE197756 | GEO
Project description:Budd-Chiari syndrome (BCS) results in sinusoidal congestion and hepatocyte apoptosis, which can further progress to liver fibrosis, cirrhosis, and hepatocellular carcinoma. Endovascular (EV) treatment has been the primary therapeutic method and achieved excellent outcomes. However, whether EV treatment could reverse liver cirrhosis in patients with BCS is still unclear. To investigate the effect of endovascular treatment on liver cirrhosis in patients with Budd-Chiari syndrome, we performed gene expression profiling analysis of the liver from patients with or without EV treatment.
2023-03-26 | GSE228205 | GEO
Project description:Stroke is a prevalent disorder representing the third leading cause of death and major cause of disability. Post-stroke epilepsy (PSE) has been recognized as a common clinical issue after stroke, accounting for 30-40% of the causes of epilepsy among older adults. In this study, we determined GABAA receptor-mediated seizure susceptibility after PT cerebral stroke in aged mice. Young adult mice around 10 weeks of age are widely used in stroke experiments. However, as most strokes are diagnosed in the elderly and PSE has been recognized as a common clinical incidence after stroke, we utilized photothrombosis (PT) model of cerebral ischemia and examined seizure susceptibility and brain injury using combined behavioral (video) and EEG monitoring and histological (MRI) assessments. To investigate GABAA receptor-mediated convulsive/non-convulsive seizures, lower-doses of pentylenetetrazol (PTZ) was injected. PTZ susceptibility in aging mice increased compared to young adults. One month after PT stroke, aged PT stroke mice exhibited severe convulsive seizures (late-onset). These findings exhibited the increase of GABAA receptor-mediated seizures susceptibility in PT stroke aging mice, but not in young adults.
2023-11-27 | GSE241528 | GEO
Project description:This program addresses the gene signature associated with brain (cortex) in the tMCAO rat model for stroke. The tMCAO stroke model profiling data was analyzed by identifying genes that were up- and down-regulated at selected p value and fold change in brain cortex of the Sprague Dawley rats following middle cerebral artery occlusion compared to the sham-operated controls.
2013-03-22 | E-GEOD-38037 | biostudies-arrayexpress
Project description:In this study, we examined a Macaca fascicularis transient middle cerebral artery occlusion surgery-induced stroke model, consisting of two sample groups, determined by MRI-quantified infarct volumes as a measure of the stroke severity 28 days after the ischemic episode.
2017-01-21 | PXD003173 | Pride