title: Major remodeling of brain microvessels during neonatal period in the mouse: A proteomic and transcriptomic study.
abstract: Preterm infants born before 29 gestation weeks incur major risk of subependymal/intracerebral/intraventricular hemorrhage. 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).
authors.affiliation: 1 INSERM-ERI28, NeoVasc Laboratory, Microvascular Endothelium and Neonate Brain Lesions, Normandie Université, Institute for Research and Innovation in Biomedicine (IRIB), Rouen, France.
authors.forename: Baptiste
authors.initials: B
authors.lastname: Porte
authors.affiliation: 2 UMR-6270, CNRS, Polymers, Biopolymers, Surfaces, Biofilm Resistance, Cell Surfaces Interactions Group (PBS), CNRS, IRIB, Normandie Université, Mont-Saint-Aignan, France.|3 Proteomic Facility PISSARO, IRIB, Normandie Université, Mont-Saint-Aignan, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Hardouin
authors.affiliation: 4 UMR-S1079, INSERM, Genetic of Cancer and Neurogenetics (GCM), IRIB, Normandie Université, Rouen, France.
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Zerdoumi
authors.affiliation: 5 UMR-S905, INSERM, Pathophysiology and Biotherapy of Inflammatory and Autoimmune Diseases, IRIB, Normandie Université, Rouen, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Derambure
authors.affiliation: 1 INSERM-ERI28, NeoVasc Laboratory, Microvascular Endothelium and Neonate Brain Lesions, Normandie Université, Institute for Research and Innovation in Biomedicine (IRIB), Rouen, France.
authors.forename: Michèle
authors.initials: M
authors.lastname: Hauchecorne
authors.affiliation: 1 INSERM-ERI28, NeoVasc Laboratory, Microvascular Endothelium and Neonate Brain Lesions, Normandie Université, Institute for Research and Innovation in Biomedicine (IRIB), Rouen, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Dupre
authors.affiliation: 3 Proteomic Facility PISSARO, IRIB, Normandie Université, Mont-Saint-Aignan, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Obry
authors.affiliation: 5 UMR-S905, INSERM, Pathophysiology and Biotherapy of Inflammatory and Autoimmune Diseases, IRIB, Normandie Université, Rouen, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Lequerre
authors.affiliation: 1 INSERM-ERI28, NeoVasc Laboratory, Microvascular Endothelium and Neonate Brain Lesions, Normandie Université, Institute for Research and Innovation in Biomedicine (IRIB), Rouen, France.|6 Metabolic Biochemistry, Rouen University Hospital, Rouen, France.
authors.forename: Soumeya
authors.initials: S
authors.lastname: Bekri
authors.affiliation: 1 INSERM-ERI28, NeoVasc Laboratory, Microvascular Endothelium and Neonate Brain Lesions, Normandie Université, Institute for Research and Innovation in Biomedicine (IRIB), Rouen, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Gonzalez
authors.affiliation: 4 UMR-S1079, INSERM, Genetic of Cancer and Neurogenetics (GCM), IRIB, Normandie Université, Rouen, France.
authors.forename: Jean M
authors.initials: JM
authors.lastname: Flaman
authors.affiliation: 1 INSERM-ERI28, NeoVasc Laboratory, Microvascular Endothelium and Neonate Brain Lesions, Normandie Université, Institute for Research and Innovation in Biomedicine (IRIB), Rouen, France.|7 Neonatal Pediatrics and Intensive Care, Rouen University Hospital, Rouen, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Marret
authors.affiliation: 2 UMR-6270, CNRS, Polymers, Biopolymers, Surfaces, Biofilm Resistance, Cell Surfaces Interactions Group (PBS), CNRS, IRIB, Normandie Université, Mont-Saint-Aignan, France.|3 Proteomic Facility PISSARO, IRIB, Normandie Université, Mont-Saint-Aignan, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Cosette
authors.affiliation: 1 INSERM-ERI28, NeoVasc Laboratory, Microvascular Endothelium and Neonate Brain Lesions, Normandie Université, Institute for Research and Innovation in Biomedicine (IRIB), Rouen, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Leroux
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply* / Q000196:embryology* / Q000502:physiology; D002543:Cerebral Hemorrhage / Q000209:etiology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008297:Male; D051379:Mice / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D008810:Mice, Inbred C57BL; D055806:Microvessels / Q000196:embryology* / Q000502:physiology; D020543:Proteome / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D040901:Proteomics; D059467:Transcriptome; D066253:Vascular Remodeling
chemical_list: D020543:Proteome
keywords: Brain development; capillaries; mouse; pediatric stroke; proteomics; subependymal/intraparenchymal/intraventricular hemorrhage; transcriptomics