Paucity of pericytes in germinal matrix vasculature of premature infants

Alex Braun, Hongmin Xu, Furong Hu, Praneeth Kocherlakota, Donald Siegel, Praveen Chander, Zoltan Ungvari, Anna Csiszar, Maiken Nedergaard, Praveen Ballabh

Research output: Contribution to journalArticle

87 Scopus citations

Abstract

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-β1 (TGF-β1) protein expression was lower, whereas sphingosine-1-phosphate1 (S1P1) and N-cadherin levels were higher in the GM than in the cortex or white matter. Low TGF-β1 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-β1 could be a basis of reduced pericyte density in its vasculature.

Original languageEnglish (US)
Pages (from-to)12012-12024
Number of pages13
JournalJournal of Neuroscience
Volume27
Issue number44
DOIs
StatePublished - Oct 31 2007
Externally publishedYes

Keywords

  • ALK-1
  • ALK-5
  • Cortex
  • GM
  • GM hemorrhage
  • Intraventricular hemorrhage
  • N-cadherin
  • PDGF-B
  • PDGFR-β
  • Pericytes
  • Sphingosine 1 phosphate
  • TGF-β
  • White matter

ASJC Scopus subject areas

  • Neuroscience(all)

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  • Cite this

    Braun, A., Xu, H., Hu, F., Kocherlakota, P., Siegel, D., Chander, P., Ungvari, Z., Csiszar, A., Nedergaard, M., & Ballabh, P. (2007). Paucity of pericytes in germinal matrix vasculature of premature infants. Journal of Neuroscience, 27(44), 12012-12024. https://doi.org/10.1523/JNEUROSCI.3281-07.2007