Maturational changes in laminin, fibronectin, collagen IV, and perlecan in germinal matrix, cortex, and white matter and effect of betamethasone.
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.
Xu
Hongmin
H
Department of Pediatrics, New York Medical College-Westchester Medical Center, Valhalla, New York 10595, USA.
Hu
Furong
F
Sado
Yoshikazu
Y
Ninomiya
Yoshifumi
Y
Borza
Dorin-Bogdan
DB
Ungvari
Zoltan
Z
Lagamma
Edmund F
EF
Csiszar
Anna
A
Nedergaard
Maiken
M
Ballabh
Praveen
P
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
D000893:Anti-Inflammatory Agents; D024141:Collagen Type IV; D005353:Fibronectins; D019812:Heparan Sulfate Proteoglycans; D007797:Laminin; D008562:Membrane Glycoproteins; C071927:perlecan; D001623:Betamethasone