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

BackgroundKernicterus 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.MethodsWe 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.ResultsIncreased 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.ConclusionsThis 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.