title: Maturational changes in laminin, fibronectin, collagen IV, and perlecan in germinal matrix, cortex, and white matter and effect of betamethasone.
abstract: Germinal matrix is selectively vulnerable to hemorrhage in premature infants, and use of prenatal betamethasone is associated with a lower occurrence of germinal matrix hemorrhage. Because the major components of extracellular matrix of the cerebral vasculature-laminin, fibronectin, collagen IV, and perlecan-provide structural stability to blood vessels, we examined whether the expression of these molecules was decreased in the germinal matrix and affected by betamethasone. In both human fetuses and premature infants, fibronectin was significantly lower in the germinal matrix than in the cortical mantle or white matter anlagen. Conversely, laminin alpha1 gene expression was greater in the human germinal matrix compared with the cortical mantle or white matter. Expression of alpha1- and alpha2(IV) collagen chains increased with advancing gestational age. Low-dose prenatal betamethasone treatment enhanced fibronectin level by 1.5-2-fold whereas a high dose reduced fibronectin expression by 2-fold in rabbit pups. Because fibronectin provides structural stability to the blood vessels, its reduced expression in the germinal matrix may contribute to the fragility of germinal matrix vasculature and the propensity to hemorrhage in premature neonates.
authors.affiliation: Department of Pediatrics, New York Medical College-Westchester Medical Center, Valhalla, New York 10595, USA.
authors.forename: Hongmin
authors.initials: H
authors.lastname: Xu
authors.forename: Furong
authors.initials: F
authors.lastname: Hu
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Sado
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Ninomiya
authors.forename: Dorin-Bogdan
authors.initials: DB
authors.lastname: Borza
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Ungvari
authors.forename: Edmund F
authors.initials: EF
authors.lastname: Lagamma
authors.forename: Anna
authors.initials: A
authors.lastname: Csiszar
authors.forename: Maiken
authors.initials: M
authors.lastname: Nedergaard
authors.forename: Praveen
authors.initials: P
authors.lastname: Ballabh
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001623:Betamethasone / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D002552:Cerebral Ventricles / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D024141:Collagen Type IV / Q000378:metabolism; D005260:Female; D005333:Fetus; D005353:Fibronectins / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D005865:Gestational Age; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D007797:Laminin / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D009457:Neuroglia / Q000378:metabolism*; D020286:Pericytes / Q000166:cytology / Q000378:metabolism; D011247:Pregnancy; D011817:Rabbits
chemical_list: D000893:Anti-Inflammatory Agents; D024141:Collagen Type IV; D005353:Fibronectins; D019812:Heparan Sulfate Proteoglycans; D007797:Laminin; D008562:Membrane Glycoproteins; C071927:perlecan; D001623:Betamethasone