title: Effect of prenatal glucocorticoids on cerebral vasculature of the developing brain.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Pediatrics, New York Medical College-Westchester Medical Center, Valhalla, NY 10595, USA.
authors.forename: Govindaiah
authors.initials: G
authors.lastname: Vinukonda
authors.forename: Krishna
authors.initials: K
authors.lastname: Dummula
authors.forename: Sabrina
authors.initials: S
authors.lastname: Malik
authors.forename: Furong
authors.initials: F
authors.lastname: Hu
authors.forename: Carl I
authors.initials: CI
authors.lastname: Thompson
authors.forename: Anna
authors.initials: A
authors.lastname: Csiszar
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Ungvari
authors.forename: Praveen
authors.initials: P
authors.lastname: Ballabh
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001623:Betamethasone / Q000494:pharmacology*; D015153:Blotting, Western; D001921:Brain / Q000098:blood supply / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005911:Gliosis / Q000378:metabolism; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D007231:Infant, Newborn; D042282:Microdissection; D009410:Nerve Degeneration / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D005938:Glucocorticoids; D042461:Vascular Endothelial Growth Factor A; D001623:Betamethasone