GENETIC DETERMINANTS OF BILIRUBIN ENCEPHALOPATHY

The damage induced by unconjugated bilirubin on neruronal cells (formerly known as kernicterus) is rather frequent in the newborns due to the physiological elevation of bilirubin levels immediately after birth. In spite of the first description more that 150 years ago, the molecular events at the basis of the bilirubin encephalopathy are still undefined. In the recent past, however, data have been provided indicating that bilirubin homeostasis inside the cells is regulated by a balance between entry and extrusion of the pigment, the latter accounted mainly by MRP1. The extrusion keeps the intracellular concentration of bilirubin low and prevents the damage. Bilirubin is a potent antioxidant al low concentration (<70 nM) while acts as pro-oxidant, toxic substance at higher concentration. The definition of the molecular mechanisms, and the relevant genes involved in governing bilirubin accumulation and redox state alteration within astrocytes and neurons will provide important information on the cellular pathways involved in the damage by the pigment. Also important will be the understanding of the role of the transporters at the level of the different barriers separating the brain from both the blood and the cerebrospinal fluid. Collectively, the data may be useful for an early recognition and successful prevention of the bilirubin-induced neurological damage.