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Strategic Endothelial Cell Tube Formation Assay: Comparing Extracellular Matrix and Growth Factor Reduced Extracellular Matrix
Published on: August 14, 2016
Angiogenic inhibition reduces germinal matrix hemorrhage
Praveen Ballabh1, Hongmin Xu, Furong Hu
1Department of Pediatrics, New York Medical College-Westchester Medical Center, Valhalla, New York 10595, USA. pballabh@msn.com
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.
Insights
Prenatal treatment with angiogenic inhibitors like celecoxib or ZD6474 can reduce germinal matrix hemorrhage (GMH) in premature infants by suppressing blood vessel growth in the brain.
Area of Science:
- Neonatal neurology
- Developmental biology
- Vascular biology
Background:
- Germinal matrix hemorrhage (GMH) is a significant risk for premature infants.
- Vascular immaturity in the germinal matrix contributes to GMH.
- Active vessel remodeling occurs in the germinal matrix.
Purpose of the Study:
- To investigate the role of vascular immaturity in GMH.
- To evaluate the effect of prenatal angiogenic inhibitors on GMH incidence.
Main Methods:
- Assessed germinal matrix angiogenesis in human fetuses and premature infants, and premature rabbit pups.
- Measured levels of vascular endothelial growth factor (VEGF) and angiopoietin-2.
- Evaluated endothelial cell proliferation.
- Administered prenatal celecoxib or ZD6474 to premature rabbit pups.
Main Results:
- Higher levels of VEGF, angiopoietin-2, and endothelial proliferation were observed in the germinal matrix.
- Celecoxib treatment reduced angiopoietin-2, VEGF, and germinal matrix endothelial proliferation.
- Prenatal treatment with celecoxib or ZD6474 significantly decreased GMH incidence.
Conclusions:
- Suppression of germinal matrix angiogenesis may reduce GMH incidence and severity.
- Prenatal administration of celecoxib or ZD6474 shows potential for preventing GMH in susceptible infants.
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