Vascular development of fetal and postnatal neocortex of the pig, the European wild boarSus scrofa

Abstract

AbstractThe development of the brain’s vascular system is a predominantly prenatal process in mammalian species and required for neurogenesis and further brain development. Our recent work on fetal pig has revealed that many neurodevelopmental processes start well before birth and proceed rapidly reaching near-mature status already around birth. Here, we analyzed the development of neocortical vasculature from embryonic day (E) 45 onwards (gestation in pig lasts 114 days) using qualitative and quantitative image analyses and protein blots. In all cortical layers, vessel volume from total brain volume at E100 resembled that of a postnatal day (P) 30 piglet. Endothelial cells expressed the tight junction protein claudin-5 from E45 onwards. GFAP+ and AQP4+ astrocytes, PDGFRβ+ pericytes and α-SMA+ smooth muscle cells are detectable near vessels at E60 suggesting an early assembly of blood-brain barrier components. The vascular system in the visual cortex is advanced before birth with an almost mature pattern at E100. Findings were confirmed by blots which showed a steady increase of expression of tight junction and angiogenesis-related proteins (claudin-5, occludin, VE-cadherin, PECAM-1/CD31) from E65 onwards until P90. The expression profile was similar in visual and somatosensory cortex. Together, we report a rapid maturation of the vascular system in pig cortex. Regarding activity-dependent aspects, the data suggest that angiogenesis might be influenced by spontaneous rather than sensory-evoked activity.Author contributionConceptualization and methodology: ES and PW; investigation and analysis: ES, KC; provided resources: CB, CB, MM, DU; visualization: ES, MM, DU; writing—original draft: ES, PW; writing—review and editing: ES, GM, PW; supervision and project administration: PW. All authors approved the manuscript.Summary statementVascular impairment is associated with neurodegenerative disorders. As a groundwork for future studies, we quantitatively analyzed development of cortical vasculature in the emerging translational model, the pig.ETHICAL APPROVALAll applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures were in accordance with the ethical standards or practice of the institution at which the studies were conducted.