Imaging the construction of capillary networks in the neonatal mouse brain
| Autor: | Andrée-Anne Berthiaume, Heidi Stuhlmann, Vanessa Coelho-Santos, Andy Y. Shih, Sharon Ornelas |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Time Factors Capillary action Angiogenesis brain Green Fluorescent Proteins Neovascularization Physiologic Mice Transgenic Neuroimaging venule capillary angiogenesis 03 medical and health sciences 0302 clinical medicine pericyte medicine Animals Multidisciplinary Venule Chemistry Endothelial Cells Neonatal mouse Blood flow Biological Sciences Capillaries Arterioles 030104 developmental biology medicine.anatomical_structure Animals Newborn Regional Blood Flow Pericyte Pericytes Perfusion Neuroscience 030217 neurology & neurosurgery Lumen (unit) |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.2100866118 |
| Popis: | Significance The distribution of blood throughout the brain is facilitated by highly interconnected capillary networks. However, the steps involved in the construction of these networks has remained unclear. We used in vivo two-photon imaging through noninvasive cranial windows to study the engineering of capillary networks in the cerebral cortex of mouse neonates. We find that angiogenic activity originates at ascending venules, which undergo a burst of sprouting in the second postnatal week. This sprouting activity first establishes long paths to connect venules to blood input from neighboring arterioles, and then expands capillary interconnectivity with a multitude of short-range connections. Our study provides an experimental foundation to understand how capillary networks are shaped in the living mammalian brain during postnatal development. Capillary networks are essential for distribution of blood flow through the brain, and numerous other homeostatic functions, including neurovascular signal conduction and blood–brain barrier integrity. Accordingly, the impairment of capillary architecture and function lies at the root of many brain diseases. Visualizing how brain capillary networks develop in vivo can reveal innate programs for cerebrovascular growth and repair. Here, we use longitudinal two-photon imaging through noninvasive thinned skull windows to study a burst of angiogenic activity during cerebrovascular development in mouse neonates. We find that angiogenesis leading to the formation of capillary networks originated exclusively from cortical ascending venules. Two angiogenic sprouting activities were observed: 1) early, long-range sprouts that directly connected venules to upstream arteriolar input, establishing the backbone of the capillary bed, and 2) short-range sprouts that contributed to expansion of anastomotic connectivity within the capillary bed. All nascent sprouts were prefabricated with an intact endothelial lumen and pericyte coverage, ensuring their immediate perfusion and stability upon connection to their target vessels. The bulk of this capillary expansion spanned only 2 to 3 d and contributed to an increase of blood flow during a critical period in cortical development. |
| Databáze: | OpenAIRE |
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