title: Cerebellar axon/myelin loss, angiogenic sprouting, and neuronal increase of vascular endothelial growth factor in a preterm infant with kernicterus.
abstract: We performed histologic and immunohistochemical analysis of cerebellar sections from a preterm infant (32 weeks 5 days) dead on the 4th day of life with the diagnosis of kernicterus and compared the results with 1 age-matched nonicteric patient. Poorer Luxol fast blue-periodic acid Schiff and Bodian-Luxol fast blue stainings as well as neurofilament expression were observed in the kernicterus case, indicating loss of axon neurites and myelin fibers. Elevated claudin-5 and cluster of differentiation 34 expression associated with increased blood vessel density suggests bilirubin-induced angiogenic sprouting. Upregulation of vascular endothelial growth factor and its receptor 2 was observed in nucleus dentatus and Purkinje neurons. Although upregulation of multidrug resistance-associated protein 1 was increased in cerebellar neurons, it was not able to prevent bilirubin-induced neurotoxicity. These data add new insights into the pathophysiology of kernicterus, revealing vascular endothelial growth factor and its receptor 2, as well as angiogenic sprouting, as new players in neurologic damage by unconjugated bilirubin.
authors.affiliation: Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL) and Department of Biochemistry and Human Biology, Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal. abrito@ff.ul.pt
authors.forename: Maria A
authors.initials: MA
authors.lastname: Brito
authors.forename: Emanuele
authors.initials: E
authors.lastname: Zurolo
authors.forename: Pedro
authors.initials: P
authors.lastname: Pereira
authors.forename: Cândida
authors.initials: C
authors.lastname: Barroso
authors.forename: Eleonora
authors.initials: E
authors.lastname: Aronica
authors.forename: Dora
authors.initials: D
authors.lastname: Brites
mesh_terms: D001369:Axons / Q000473:pathology; D002531:Cerebellum / Q000473:pathology*; D062507:Claudin-5; D057167:Claudins / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D007647:Kernicterus / Q000150:complications / Q000473:pathology*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000209:etiology*; D047928:Premature Birth / Q000473:pathology*; D011689:Purkinje Cells / Q000378:metabolism* / Q000473:pathology*; D015854:Up-Regulation / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D062507:Claudin-5; D057167:Claudins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2; C107466:CLDN5 protein, human; C421109:multidrug resistance-associated protein 1