BACKGROUND AND PURPOSE: Prenatal glucocorticoids prevent germinal matrix hemorrhage in premature infants. The underlying mechanism, however, is elusive. Germinal matrix is enriched with angiogenic vessels exhibiting paucity of pericytes and glial fibrillary acidic protein-positive astrocyte end feet. Therefore, we asked whether glucocorticoid treatment would suppress angiogenesis and enhance periendothelial coverage by pericytes and glial fibrillary acidic protein-positive end feet in the germinal matrix microvasculature. METHODS: We treated pregnant rabbits with intramuscular betamethasone and delivered pups prematurely by cesarean section at E29 (term=32 days). Endothelial turnover, vascular density, pericyte coverage, glial fibrillary acidic protein-positive end feet, cell death, and growth factors orchestrating angiogenesis, including vascular endothelial growth factor, angiopoietins, transforming growth factor-beta, and platelet-derived growth factor-B, were compared between betamethasone-treated and untreated pups. Similar comparisons were done between autopsy materials from premature infants exposed and unexposed to prenatal glucocorticoids. RESULTS: Antenatal glucocorticoid treatment reduced endothelial proliferation, vascular density, and vascular endothelial growth factor expression in the germinal matrix of both rabbits and humans. The pericyte coverage was greater in glucocorticoid-treated rabbit pups and human infants than in controls, but not the glial fibrillary acidic protein-positive end feet coverage. Transforming growth factor-beta, but not angiopoietins and platelet-derived growth factor-B, were elevated in glucocorticoid-treated rabbit pups compared with controls. Betamethasone treatment induced apoptosis, neuronal degeneration, and gliosis in rabbit pups. However, there was no evidence of increased cell death in glucocorticoid-exposed human infants. CONCLUSIONS: Prenatal glucocorticoid suppresses vascular endothelial growth factor and elevates transforming growth factor-beta levels, which results in angiogenic inhibition, trimming of neovasculature, and enhanced pericyte coverage. These changes contribute to stabilizing the germinal matrix vasculature, thereby reducing its propensity to hemorrhage. Prenatal glucocorticoid exposure does not induce neural cell death in humans, unlike rabbits.
BACKGROUND AND PURPOSE: Prenatal glucocorticoids prevent germinal matrix hemorrhage in premature infants. The underlying mechanism, however, is elusive. Germinal matrix is enriched with angiogenic vessels exhibiting paucity of pericytes and glial fibrillary acidic protein-positive astrocyte end feet. Therefore, we asked whether glucocorticoid treatment would suppress angiogenesis and enhance periendothelial coverage by pericytes and glial fibrillary acidic protein-positive end feet in the germinal matrix microvasculature. METHODS: We treated pregnant rabbits with intramuscular betamethasone and delivered pups prematurely by cesarean section at E29 (term=32 days). Endothelial turnover, vascular density, pericyte coverage, glial fibrillary acidic protein-positive end feet, cell death, and growth factors orchestrating angiogenesis, including vascular endothelial growth factor, angiopoietins, transforming growth factor-beta, and platelet-derived growth factor-B, were compared between betamethasone-treated and untreated pups. Similar comparisons were done between autopsy materials from premature infants exposed and unexposed to prenatal glucocorticoids. RESULTS: Antenatal glucocorticoid treatment reduced endothelial proliferation, vascular density, and vascular endothelial growth factor expression in the germinal matrix of both rabbits and humans. The pericyte coverage was greater in glucocorticoid-treated rabbit pups and humaninfants than in controls, but not the glial fibrillary acidic protein-positive end feet coverage. Transforming growth factor-beta, but not angiopoietins and platelet-derived growth factor-B, were elevated in glucocorticoid-treated rabbit pups compared with controls. Betamethasone treatment induced apoptosis, neuronal degeneration, and gliosis in rabbit pups. However, there was no evidence of increased cell death in glucocorticoid-exposed humaninfants. CONCLUSIONS: Prenatal glucocorticoid suppresses vascular endothelial growth factor and elevates transforming growth factor-beta levels, which results in angiogenic inhibition, trimming of neovasculature, and enhanced pericyte coverage. These changes contribute to stabilizing the germinal matrix vasculature, thereby reducing its propensity to hemorrhage. Prenatal glucocorticoid exposure does not induce neural cell death in humans, unlike rabbits.
Authors: Damon Klebe; Jerry J Flores; Devin W McBride; Paul R Krafft; William B Rolland; Tim Lekic; John H Zhang Journal: J Cereb Blood Flow Metab Date: 2016-12-20 Impact factor: 6.200
Authors: Gabryella S P Santos; Luiz A V Magno; Marco A Romano-Silva; Akiva Mintz; Alexander Birbrair Journal: Neurosci Bull Date: 2018-10-26 Impact factor: 5.203
Authors: Muhammad T K Zia; Govindaiah Vinukonda; Linnea R Vose; Bala B R Bhimavarapu; Sanda Iacobas; Nishi K Pandey; Ann Marie Beall; Preeti Dohare; Edmund F LaGamma; Dumitru A Iacobas; Praveen Ballabh Journal: Exp Neurol Date: 2014-09-28 Impact factor: 5.330
Authors: P Naomi Franco; Lara M Durrant; Desirelys Carreon; Elizabeth Haddad; Adam Vergara; Catherine Cascavita; Andre Obenaus; William J Pearce Journal: Am J Physiol Regul Integr Comp Physiol Date: 2019-10-02 Impact factor: 3.619