Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 118, Issue 26, Pages -Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2100866118
Keywords
capillary; brain; angiogenesis; venule; pericyte
Categories
Funding
- NIH/National Institute of Neurological Disorders and Stroke [NS096997, NS106138, NS097775]
- NIH/National Institute on Aging [AG063031, AG062738]
- NIH/National Institute of Mental Health [MH083680]
- American Heart Association [20POST35160001]
- LusoAmerican Development Foundation [2017/165]
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The study reveals that brain capillary networks originate exclusively from cortical ascending venules, with early, long-range sprouts connecting venules to upstream arteriolar input, establishing the backbone of the capillary bed, and short-range sprouts contributing to expansion of anastomotic connectivity within the capillary bed.
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.
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