New Autopsy Findings in Different Brain Regions of a Preterm Neonate With Kernicterus: Neurovascular Alterations and Up-regulation of Efflux Transporters

• Published in: Pediatric neurology Vol. 49; no. 6; pp. 431 - 438
• Main Authors: Brito, Maria A., PhD, Pereira, Pedro, MSc, Barroso, Cândida, MD, Aronica, Eleonora, MD, PhD, Brites, Dora, PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2013
• Subjects: albumin; Albumins - metabolism; Antigens, CD34 - metabolism; Autopsy; Blood Vessels - pathology; blood-brain barrier; Brain - metabolism; Brain - pathology; Claudin-5 - metabolism; corpus striatum; efflux transporters; Female; Glial Fibrillary Acidic Protein - metabolism; hippocampus; Humans; Infant; kernicterus; Kernicterus - diagnosis; Male; microvascularization; Multidrug Resistance-Associated Proteins - metabolism; Neurology; Pediatrics; Premature Birth; vascular endothelial growth factor; Vascular Endothelial Growth Factor A - metabolism; Vascular Endothelial Growth Factor Receptor-2 - metabolism; blood-brain barrier; corpus striatum; hippocampus; kernicterus; vascular endothelial growth factor; albumin; microvascularization; efflux transporters
• ISSN: 0887-8994; 1873-5150
• DOI: 10.1016/j.pediatrneurol.2013.08.020

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.