Cross Validation in Human and Animal Model for Germinal Matrix Hemorrhage

There is an interesting paper published by Ballabh et al. on Nature Medicine regarding germinal matrix hemorrhage, one of major pathologies in premature infants that may lead to cerebral palsy, hydrocephalus, and mental retardation.

Starting with gross and microsopic observation of highly vascularization in germinal matrix by neuroanatomy approach, the authors hypothesize the role of VEGF (vascular endothelial growth factor) in the development of germinal matrix.

By autopsy of human infants suffered from premature death or spontaneous abortion, the authors revealed that VEGF, angiopoietin-2, and endothelial proliferation index, are highly increased in germinal matrix, compared to those in the white matter analagen, or cortical mantle. These histological, biological and genetic findings are then validated in rabbit pups, who were delivered pretermly by cesarean section.

Then the authors further extended the experiments for pharmacology with this rabbit model, whose gestational period is around 31 days. Prenatal treatment with COX-2 inhibitor celecoxib decreased VEGF level, decreased angiopoietin-2 level, decreased germinal matrix enthelial proliferation, and substantially decreased the incidence of germinal matrix hemorrhage. On the other hand, prenatal VEGFR2 inhibitor ZD6474 (vandetanib) treatment also reduced the incidence of germinal matrix hemorrhage.

This is a very interesting paper. First, the experiment design successfully cross validated a disease between human and an animal model. Second, employing the validated animal model, the authors soon bridged the pathogenesis and the treatment solutions together. Third, for selection of angiogenic inhibitors, they not only test ZD6474 as most people would do so intuitively, but also celecoxib, a popular, commonly-seen, and well-developed FDA-labelled drug that clinical trial may be at hand.



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Tags: Medicine, Medicine-Medical Science, Medicine-Biological Science, Medicine-Translational study, Medicine-Translational Biology, Medicine-Biomedical Science, Medicine-Clinical Study, Medicine-Clinical Trial, GMH, Germinal Matrix Hemorrhage, Preterm, Prematurity, Cerebral palsy, Hydrocephalus, Mental retardation, Gross pathology, Microscopic pathology, Medicine-Neurology, Medicine-Obstetrics, Medicine-OBGYN, Medicine-Pediatrics, Medicine-Neuroanatomy, Medicine-Anatomy, Medicine-Pathology, Medicine-Developmental Biology, VEGF, Vascular endothelial growth factor, Autopsy, Spontaneous abortion, angiopoietin, angiopoietin-2, endothelial proliferation index, white matter analagen, cortical mantle, Medicine-Histology, Medicine-Biochemistry, Medicine-Genetics, Rabbit, animal model, Cesarean section, Medicine-Pharmacology, COX-2 inhibitor, Cyclooxygenase-2 inhibitor, celecoxib, Celebrex, ZD6474, vandetanib, VEGFR2 inhibitor, Zactima, Pathogenesis, FDA, Food and Drug Administration