title: New autopsy findings in different brain regions of a preterm neonate with kernicterus: neurovascular alterations and up-regulation of efflux transporters.
abstract: BACKGROUND
  Kernicterus is an irreversible brain damage caused by bilirubin deposition in selective brain regions. Sick and preterm infants with hyperbilirubinemia are particularly susceptible to the condition.
  
  
  METHODS
  We studied autopsied brain tissue from a premature female infant with kernicterus with a bilirubin:albumin molar ratio of 1.0, hypoxia, acidosis, and seizures. The patient, previously described as having cerebellar axon/myelin loss and angiogenic sprouting, was assessed for histopathological features in brain regions less investigated, such as hippocampus and corpus striatum. Results were compared with age-matched controls.
  
  
  RESULTS
  Increased blood vessel density with poorly defined lumen structures was observed in the mesencephalon, pons, and medulla oblongata, and, more predominantly, in the corpus striatum and hippocampus. These two regions exhibited increased expression of vascular endothelial growth factor, paralleled by vascular endothelial growth factor receptor-2, and albumin extravasation into the brain parenchyma. No similar findings were observed in the nonjaundiced babies with hypoxia that served as controls (one preterm with sepsis and a term infant with pneumonia). We found increased cellular expression of multidrug resistance-associated protein 1 and P-glycoprotein in the hippocampus, known as defensive mechanisms against bilirubin-induced cytotoxicity. Increased density of blood vessels and microvascular permeability, together with parenchymal albumin, may have contributed to increasing the brain content and retention of bilirubin, a condition implicated in kernicterus disease.
  
  
  CONCLUSIONS
  This novel finding in a premature baby with kernicterus and associated risk factors deserves to be investigated in similar patients to better understand the less-well described effects of bilirubin-induced neurological sequelae in preterm infants.
authors.affiliation: Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Faculdade de Farmácia, Universidade de Lisboa, Lisbon, Portugal; Department of Biochemistry and Human Biology, Faculdade de Farmácia, Universidade de Lisboa, Lisbon, Portugal. Electronic address: abrito@ff.ul.pt.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Brito
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: D000418:Albumins / Q000378:metabolism; D018952:Antigens, CD34 / Q000378:metabolism; D001344:Autopsy; D001808:Blood Vessels / Q000473:pathology; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D062507:Claudin-5 / Q000378:metabolism; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D007223:Infant; D007647:Kernicterus / Q000175:diagnosis*; D008297:Male; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D047928:Premature Birth; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D000418:Albumins; D018952:Antigens, CD34; D062507:Claudin-5; D005904:Glial Fibrillary Acidic Protein; 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
keywords: albumin; blood-brain barrier; corpus striatum; efflux transporters; hippocampus; kernicterus; microvascularization; vascular endothelial growth factor