Albumin administration prevents neurological damage and death in a mouse model of severe neonatal hyperbilirubinemia

Simone Vodret, Giulia Bortolussi, Andrea B. Schreuder, Jana Jasprova, Libor Vitek, Henkjan J. Verkade, Andres F. Muro*

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    22 Citations (Scopus)
    391 Downloads (Pure)

    Abstract

    Therapies to prevent severe neonatal unconjugated hyperbilirubinemia and kernicterus are phototherapy and, in unresponsive cases, exchange transfusion, which has significant morbidity and mortality risks. Neurotoxicity is caused by the fraction of unconjugated bilirubin not bound to albumin (free bilirubin, Bf). Human serum albumin (HSA) administration was suggested to increase plasma bilirubin-binding capacity. However, its clinical use is infrequent due to difficulties to address its potential preventive and curative benefits, and to the absence of reliable markers to monitor bilirubin neurotoxicity risk. We used a genetic mouse model of unconjugated hyperbilirubinemia showing severe neurological impairment and neonatal lethality. We treated mutant pups with repeated HSA administration since birth, without phototherapy application. Daily intraperitoneal HSA administration completely rescued neurological damage and lethality, depending on dosage and administration frequency. Albumin infusion increased plasma bilirubin-binding capacity, mobilizing bilirubin from tissues to plasma. This resulted in reduced plasma Bf, forebrain and cerebellum bilirubin levels. We showed that, in our experimental model, Bf is the best marker to determine the risk of developing neurological damage. These results support the potential use of albumin administration in severe acute hyperbilirubinemia conditions to prevent or treat bilirubin neurotoxicity in situations in which exchange transfusion may be required.

    Original languageEnglish
    Article number16203
    Number of pages13
    JournalScientific Reports
    Volume5
    DOIs
    Publication statusPublished - 6-Nov-2015

    Keywords

    • HUMAN-SERUM-ALBUMIN
    • LOW-BIRTH-WEIGHT
    • CRIGLER-NAJJAR SYNDROME
    • BRAIN-STEM RESPONSE
    • EXCHANGE-TRANSFUSION
    • UNBOUND BILIRUBIN
    • CLINICAL KERNICTERUS
    • JAUNDICED NEWBORNS
    • GENE-TRANSFER
    • FC-RECEPTOR

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