title: Paucity of pericytes in germinal matrix vasculature of premature infants.
abstract: Germinal matrix (GM) is a richly vascularized collection of neuronal-glial precursor cells in the developing brain, which is selectively vulnerable to hemorrhage in premature infants. It has rapid angiogenesis associated with high levels of vascular endothelial growth factor (VEGF). Because pericytes provide structural stability to blood vessels, we asked whether pericytes were fewer in the GM than in the subjacent white matter and neocortex and, if so, whether angiogenic inhibition could increase the pericyte density in the GM. We found pericyte coverage and density less in the GM vasculature than in the cortex or white matter in human fetuses, premature infants, and premature rabbit pups. Notably, although VEGF suppression significantly enhanced pericyte coverage in the GM, it remained less than in other brain regions. Therefore, to further elucidate the basis of fewer pericytes in the GM vasculature, we examined expression of ligand-receptor systems responsible for pericyte recruitment. Transforming growth factor-beta1 (TGF-beta1) protein expression was lower, whereas sphingosine-1-phosphate1 (S1P1) and N-cadherin levels were higher in the GM than in the cortex or white matter. Low TGF-beta1 may be involved in promoting endothelial proliferation, whereas elevated S1P1 with N-cadherin may assist vascular maturation. Hence, a paucity of pericytes in the GM vasculature may contribute to its propensity to hemorrhage, and a lower expression of TGF-beta1 could be a basis of reduced pericyte density in its vasculature.
authors.affiliation: Department of Pathology, New York Medical College, Westchester Medical Center, Valhalla, New York 10595, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Braun
authors.forename: Hongmin
authors.initials: H
authors.lastname: Xu
authors.forename: Furong
authors.initials: F
authors.lastname: Hu
authors.forename: Praneeth
authors.initials: P
authors.lastname: Kocherlakota
authors.forename: Donald
authors.initials: D
authors.lastname: Siegel
authors.forename: Praveen
authors.initials: P
authors.lastname: Chander
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Ungvari
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: D000818:Animals; D000941:Antigens / Q000378:metabolism; D018952:Antigens, CD34 / Q000378:metabolism; D001344:Autopsy / Q000379:methods; D001812:Blood-Brain Barrier; D015820:Cadherins / Q000378:metabolism; D002540:Cerebral Cortex / Q000196:embryology / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D005333:Fetus; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D008246:Lysophospholipids / Q000378:metabolism; D020286:Pericytes / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D010880:Piperidines / Q000494:pharmacology; D011247:Pregnancy / Q000187:drug effects; D047928:Premature Birth / Q000473:pathology*; D011509:Proteoglycans / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology; D011817:Rabbits; D013110:Sphingosine / Q000031:analogs & derivatives / Q000378:metabolism; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000941:Antigens; D018952:Antigens, CD34; D015820:Cadherins; D008246:Lysophospholipids; D010880:Piperidines; D011509:Proteoglycans; D011799:Quinazolines; D013110:Sphingosine; D053773:Transforming Growth Factor beta1; D000099216:Chondroitin Sulfate Proteoglycan 4; C060506:sphingosine 1-phosphate; C452423:vandetanib