Project name: Expression data from the mouse brain after 90'-MCAO and sham-control surgery

Description: Stroke remains a major leading cause of death and disability worldwide. Despite continuous advances, the identification of key molecular signatures of ischemic stroke within the hyper-acute phase of the disease is still of primary interest for a real translational research on stroke diagnosis, prognosis and treatment. High-throughput -omics technologies are enabling large-scale studies on stroke pathology at different molecular levels. Data integration resulting from these -omics approaches is becoming crucial to unravel the interactions among all different molecular elements and highly contribute to interpret all findings in a complex biological context. Here, we have used advanced data integration methods for multi-level joint analysis of transcriptomics and proteomics datasets depicted from the mouse brain 2h after cerebral ischemia. By modeling net-like correlation structures, we identified a set of differentially expressed genes and proteins with a relevant association in stroke pathology. The ischemia-induced deregulation of 10 of these inter-correlated elements was successfully verified in a new cohort of ischemic mice and changes in their expression pattern were also evaluated at a later time-point after cerebral ischemia. Of those, CLDN20, GADD45G, RGS2, BAG5 and CTNND2 were highlighted as potential candidates as blood biomarkers of cerebral ischemia and hence they were evaluated in blood samples from ischemic and sham-control mice and in ischemic strokes and patients presenting stroke-mimicking conditions. Our findings indicated that CTNND2 and GADD45G levels in blood within the first hours after ischemic stroke might be potentially useful to discriminate ischemic strokes from mimics and to predict patients’ poor outcome after stroke, respectively. In summary, we have here used for the first time an integrative approach that enabled us to elucidate by means of biostatistical tools key elements of the initial stages of the stroke pathophysiology and highlight new outstanding proteins that might be further considered as blood biomarkers of ischemic stroke.Overall design: Mice were submitted to 90'-middle cerebral artery occlusion (intraluminal model) or sham-control surgery. Thirty minutes later (2h from the induction of ischemia) animals were euthanized and transcardially perfused with cold-saline. Brains were collected and ipsilateral (IP) and contralateral (CL) brain hemispheres were separated. mRNA fraction was obtained from each sample with the mirVana Paris kit and kept frozen (-80ºC) until the transcriptomic array was conducted.

Data type: Transcriptome or Gene expression

Sample scope: Multiisolate

Relevance: ModelOrganism

Last updated: 2019-09-17