In vivo imaging of cerebral microvascular plasticity from birth to death. J Cereb Blood Flow Metab

Department of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism (Impact Factor: 5.41). 10/2012; 33(1). DOI: 10.1038/jcbfm.2012.152
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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 advance online publication, 24 October 2012; doi:10.1038/jcbfm.2012.152.

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Available from: Jaime Grutzendler, Feb 21, 2015
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    • "Of all the organs, the brain has the most intensive metabolic activity. The young adult brain retains the ability to form vessels under hypoxic conditions, but this capacity is lost in mature and aged brains (Shao et al., 2010; Sonnotag et al., 1997; Harb et al., 2013). "
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    • "Both these results were reported (see Fig. 4, Keller et al. 2011). Much of the brain's vascular system forms during fetal life, but considerable elaboration and remodeling of vessels occur during postnatal life (Harb et al. 2013). In the macaque, CO Figure 8. Differences between layer 2 and layer 3 can affect measurement of blood vessel density and size. "
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    • "The latter concept is supported by the following findings: (1) VEGFR2 gene expression decreases with development (Greene et al., 2011). Also, vessel branching in the brain increases until 10 days postpartum and stabilizes to adult levels between days 10 and 25 in mice (Harb et al., 2013); (2) mature (4–5 month old) mouse brains lose their ability to undergo angiogenesis in response to hypoxia (Harb et al., 2013), suggesting that the process of angiogenesis , even in stressful conditions, is limited after birth; (3) VEGF production and activity are both impaired in the feto-placental circulation during preeclampsia (Lyall et al., 1997; Andraweera et al., 2012; Kim et al., 2012); (4) Inhibition of angiogenesis with humanized antibodies targeting VEGF or orally active small tyrosine kinase inhibitors targeting VEGF receptors is commonly associated with severe hypertension (Lankhorst et al., 2013); (5) Loss of microvessel growth has been reported to precede elevations in blood pressure (Murfee and Schmid-Schonbein, 2008); (6) Programming of elevated blood pressure in the offspring has been associated with a reduced angiogenic capacity of vessels cultured in vitro (Pladys et al., 2005). Taking all these data into account, we believe that abnormal angiogenic processes present after birth in offspring born from preeclamptic pregnancies may contribute to elevation in blood pressure later in life. "
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