Biliverdin-induced brainstem auditory evoked potential abnormalities in the jaundiced Gunn rat

Abstract

Brainstem auditory evoked potential (BAEP) abnormalities occur in jaundiced Gunn rats given sulfadimethoxine to displace bilirubin bound to serum albumin, releasing it into the tissues. One problem with the model is that after displacement, plasma bilirubin levels drop and do not correlate with neurological dysfunction. In this report, we administered biliverdin, the immediate precursor of bilirubin, in 15- to 17-day-old Gunn rat pups to create an improved model of bilirubin-induced neurological dysfunction. Total plasma bilirubin (TB) levels were measured with a Leica bilirubinometer. Biliverdin (40 mg/kg) or phosphate-buffered saline (PBS) was administered either once and BAEPs recorded 8 h later or twice, 12 h apart, and BAEPs recorded 24 h after the initial injection. A single biliverdin injection produced a significantly decreased amplitude of BAEP wave III, 1.21 ± 0.25 vs. 0.49 ± 0.27 μV (control vs. biliverdin). The two-injection paradigm resulted in a significantly elevated TB (9.9 ± 1.2 vs. 14.9 ± 3.1 mg/dl; control vs. biliverdin), significant increases in I–II (1.15 ± 0.08 vs. 1.42 ± 0.09 ms) and I–III (2.17 ± 0.08 vs. 2.5 ± 0.13 ms) interwave intervals and a decrease in the amplitude of wave III (1.36 ± 0.30 vs. 0.38 ± 0.26 μV). Additionally, there were significant correlations between TB and the amplitude of wave III ( r 2 = 0.74) and TB and the I–III interwave interval ( r 2 = 0.51). In summary, biliverdin administration in jaundiced Gunn rat pups produces BAEP abnormalities consistent with those observed in the sulfadimethoxine model and human newborn hyperbilirubinemia and resulted in increased plasma bilirubin levels that correlate with the degree of neurological dysfunction.