Major remodeling of brain microvessels during neonatal period in the mouse: A proteomic and transcriptomic study.

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In mice, neonate brain endothelial cells are more prone than adult cells to secrete proteases under glutamate challenge, and invalidation of the Serpine 1 gene is accompanied by high brain hemorrhage risk up to five days after birth. We hypothesized that the structural and functional states of microvessels might account for age-dependent vulnerability in mice up to five days after birth and might represent a pertinent paradigm to approach the hemorrhage risk window observed in extreme preterms. Mass spectrometry proteome analyses of forebrain microvessels at days 5, 10 and in adult mice revealed 899 proteins and 36 enriched pathways. Microarray transcriptomic study identified 5873 genes undergoing at least two-fold change between ages and 93 enriched pathways. Both approaches pointed towards extracellular matrix, cell adhesion and junction pathways, indicating delayed microvascular strengthening after P5. Furthermore, glutamate receptors, proteases and their inhibitors exhibited convergent evolutions towards excitatory aminoacid sensitivity and low proteolytic control likely accounting for vascular vulnerability in P5 mice. Thus, age vascular specificities must be considered in future therapeutic interventions in preterms. Data are available on ProteomeXchange (identifier PXD001718) and NCBI Gene-Expression-Omnibus repository (identification GSE67870).", "claims": [{"id": "claim-target-result", "statement": "The paper does not explicitly name a statistical method; it reports mass spectrometry proteome analyses and a microarray transcriptomic study, with the source data available through ProteomeXchange (PXD001718) and the NCBI Gene-Expression-Omnibus repository (GSE67870).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:26873886", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Mass spectrometry proteome analyses of forebrain microvessels at days 5, 10 and in adult mice revealed 899 proteins and 36 enriched pathways."}, {"asset": "source:pmid:26873886", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Microarray transcriptomic study identified 5873 genes undergoing at least two-fold change between ages and 93 enriched pathways."}, {"asset": "source:pmid:26873886", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Data are available on ProteomeXchange (identifier PXD001718) and NCBI Gene-Expression-Omnibus repository (identification GSE67870)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The paper does not explicitly name a statistical method; it reports mass spectrometry proteome analyses and a microarray transcriptomic study, with the source data available through ProteomeXchange (PXD001718) and the NCBI Gene-Expression-Omnibus repository (GSE67870).", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:26873886"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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