Angiogenic inhibition reduces germinal matrix hemorrhage

Praveen Ballabh, Hongmin Xu, Furong Hu, Alex Braun, Kira Smith, Aracelie Rivera, Nanhong Lou, Zoltan Ungvari, Steven A. Goldman, Anna Csiszar, Maiken Nedergaard

Research output: Contribution to journalArticlepeer-review

122 Scopus citations


The germinal matrix of premature infants is selectively vulnerable to hemorrhage within the first 48 h of life. To assess the role of vascular immaturity in germinal matrix hemorrhage (GMH), we evaluated germinal matrix angiogenesis in human fetuses and premature infants, as well as in premature rabbit pups, and noted active vessel remodeling in all three. Vascular endothelial growth factor (VEGF), angiopoietin-2 and endothelial cell proliferation were present at consistently higher levels in the germinal matrix relative to the white matter anlagen and cortical mantle. On that basis, we asked whether prenatal treatment with either of two angiogenic inhibitors, the COX-2 inhibitor celecoxib, or the VEGFR2 inhibitor ZD6474, could suppress the incidence of GMH in premature rabbit pups. Celecoxib treatment decreased angiopoietin-2 and VEGF levels as well as germinal matrix endothelial proliferation. Furthermore, treatment with celecoxib or ZD6474 substantially decreased the incidence of GMH. Thus, by suppressing germinal matrix angiogenesis, prenatal celecoxib or ZD6474 treatment may be able to reduce both the incidence and severity of GMH in susceptible premature infants.

Original languageEnglish (US)
Pages (from-to)477-485
Number of pages9
JournalNature Medicine
Issue number4
StatePublished - Apr 2007
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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