Article abstract
Nature Medicine 13, 477 - 485 (2007)
Published online: 1 April 2007 | doi:10.1038/nm1558
Angiogenic inhibition reduces germinal matrix hemorrhage
Praveen Ballabh1,2,8, Hongmin Xu1, Furong Hu1, Alex Braun3, Kira Smith4, Aracelie Rivera4, Nanhong Lou5, Zoltan Ungvari4, Steven A Goldman5,6, Anna Csiszar4 & Maiken Nedergaard7
Abstract
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.
- Department of Pediatrics, New York Medical College-Westchester Medical Center, Valhalla, New York 10595, USA.
- Department of Anatomy & Cell Biology, New York Medical College-Westchester Medical Center, Valhalla, New York 10595, USA.
- Department of Pathology, New York Medical College-Westchester Medical Center, Valhalla, New York 10595, USA.
- Department of Physiology, New York Medical College-Westchester Medical Center, Valhalla, New York 10595, USA.
- Department of Neurosurgery, University of Rochester, Rochester, New York 15642, USA.
- Department of Neurology, University of Rochester, Rochester, New York 15642, USA.
- Center for Aging and Developmental Biology, University of Rochester, Rochester, New York 15642, USA.
- Present address: Regional Neonatal Center, Maria Fareri Children's Hospital, Westchester Medical Center, Valhalla, New York 10595, USA.
Correspondence to: Praveen Ballabh1,2,8 e-mail: pballabh@msn.com
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