Paucity of Pericytes in germinal matrix vasculature of premature infants

被引:97
作者
Braun, Alex
Xu, Hongmin
Hu, Furong
Kocherlakota, Praneeth
Siegel, Donald
Chander, Praveen
Ungvari, Zoltan
Csiszar, Anna
Nedergaard, Maiken
Ballabh, Praveen [1 ]
机构
[1] Maria Fareri Childrens Hosp, Westchester Med Ctr, New York Med Coll, Reg Neonatal Ctr,Dept Pathol, Valhalla, NY 10595 USA
[2] New York Med Coll, Westchester Cty Med Ctr, Dept Pediat, Valhalla, NY 10595 USA
[3] New York Med Coll, Westchester Cty Med Ctr, Dept Anat & Cell Biol, Valhalla, NY 10595 USA
[4] New York Med Coll, Westchester Cty Med Ctr, Dept Physiol, Valhalla, NY 10595 USA
[5] Univ Rochester, Ctr Aging & Dev Biol, Rochester, NY 14642 USA
关键词
GM; intraventricular hemorrhage; GM hemorrhage; pericytes; cortex; white matter; PDGF-B; PDGFR-beta; TGF-beta; ALK-1; ALK-5; N-cadherin; sphingosine; 1; phosphate;
D O I
10.1523/JNEUROSCI.3281-07.2007
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Germinal matrix ( GM) is a richly vascularized collection of neuronal - glial precursor cells in the developing brain, which is selectively vulnerable to hemorrhage in premature infants. It has rapid angiogenesis associated with high levels of vascular endothelial growth factor ( VEGF). Because pericytes provide structural stability to blood vessels, we asked whether pericytes were fewer in the GM than in the subjacent white matter and neocortex and, if so, whether angiogenic inhibition could increase the pericyte density in the GM. We found pericyte coverage and density less in the GM vasculature than in the cortex or white matter in human fetuses, premature infants, and premature rabbit pups. Notably, although VEGF suppression significantly enhanced pericyte coverage in the GM, it remained less than in other brain regions. Therefore, to further elucidate the basis of fewer pericytes in the GM vasculature, we examined expression of ligand - receptor systems responsible for pericyte recruitment. Transforming growth factor-beta 1 (TGF-beta 1) protein expression was lower, whereas sphingosine-1-phosphatel (S1P1) and N-cadherin levels were higher in the GM than in the cortex or white matter. Low TGF-beta 1 whereas sphingosine-1-phosphatel (S1P1) and N-cadherin levels were higher in the GM than in the cortex or white matter. Low TGF- whereas sphingosine-1-phosphatel (S1P1) and N-cadherin levels were higher in the GM than in the cortex or white matter. Low TGF-beta 1 may be involved in promoting endothelial proliferation, whereas elevated S1P1 with N-cadherin may assist vascular maturation. Hence, a paucity of pericytes in the GM vasculature may contribute to its propensity to hemorrhage, and a lower expression of TGF-beta 1 could be a basis of reduced pericyte density in its vasculature.
引用
收藏
页码:12012 / 12024
页数:13
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