期刊
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
卷 33, 期 1, 页码 146-156出版社
SAGE PUBLICATIONS INC
DOI: 10.1038/jcbfm.2012.152
关键词
aging; angiogenesis; hypoxia; in vivo imaging; microvascular; plasticity; two-photon
资金
- AHA [10POST2570007]
- [R01AG027855]
- [R01HL106815]
- [F31NS068041]
- NATIONAL CANCER INSTITUTE [R21CA158726] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR RESEARCH RESOURCES [S10RR024746] Funding Source: NIH RePORTER
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [T32HL007974, R01HL106815] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [F31NS068041] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [R01AG027855] Funding Source: NIH RePORTER
Cerebral function and viability are critically dependent on efficient delivery of oxygen and glucose through the microvasculature. Here, we studied individual microvessels in the intact brain using high-resolution confocal imaging and long-term time-lapse two-photon microscopy across the lifetime of a mouse. In the first postnatal month, we found large-scale sprouting but to our surprise the majority of sprouts underwent pruning and only a small fraction became perfused capillaries. After the first month, microvessel formation and elimination decreased and the net number of vessels stabilized. Although vascular stability was the hallmark of the adult brain, some vessel formation and elimination continued throughout life. In young adult mice, vessel formation was markedly increased after exposure to hypoxia; however, upon return to normoxia, no vessel elimination was observed, suggesting that new vessels constitute a long-term adaptive response to metabolic challenges. This plasticity was markedly reduced in older adults and aging where hypoxia-induced angiogenesis was absent. Our study describes, for the first time in vivo patterns of cerebral microvascular remodeling throughout life. Disruption of the observed balance between baseline turnover and vascular stability may underlie a variety of developmental and age-related degenerative neurological disorders. Journal of Cerebral Blood Flow & Metabolism (2013) 33, 146-156; doi:10.1038/jcbfm.2012.152; published online 24 October 2012
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