PC1095: Magnetic Resonance Imaging Findings in Gunn Rat Model of Preterm Hyperbilirubinemia

Background: Bilirubin is produced by the breakdown of hemoglobin and is normally catabolized and excreted. Accumulation of bilirubin can become neurotoxic, as is often the case in premature infants. The homozygous Gunn rat (jj) lacks uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1), the enzyme needed to biotransform bilirubin and can be made acutely hyperbilirubinemic by injection of sulfadimethoxine. This drug displaces bilirubin from albumin and thus increases free bilirubin. The objective of this study was to determine if changes in the cerebellum could be seen on Magnetic Resonance Imaging of adult animals made hyperbilirubinemic on a postnatal day 5.

Methods: Gunn rat pups were further randomly assigned to be injected intraperitoneally with either sulfadimethoxine (sulfa) (200 mg/kg) or an equivalent volume of saline on a postnatal day 5 (P5). A 7T Bruker Biospec scanner with a 30cm bore and 400 mT/m magnetic field gradients and a 35mm ID mouse volume coil for signal detection were used to acquire T2-weighted images in vivo P37. Region of Interest analysis was performed in the cerebellum, and cerebellar volumes were measured via Paravision 5.1 software.

Results: Cerebellar volume analysis showed significant decreases in jj-sulfa animals compared to jj-saline. jj-sulfa rats exhibit significant white matter changes as increased intensity in the middle cerebellar peduncle (MCP). Hyperintensity areas are predominantly localized peripherally in MCP.

Conclusion: An acute change in bilirubin toxicity affects the cerebellum volume in the later period of life. Additionally, acute bilirubin encephalopathy in preterms results in white matter changes in the cerebellum, which is reported in patients with Crigler Najjar syndrome.