The in vivo effect of bilirubin on the N-methyl-D-aspartate receptor/ion channel complex in the brains of newborn piglets

Pediatric Research
D J HoffmanM Delivoria-Papadopoulos

Abstract

Bilirubin neurotoxicity can be mediated by numerous mechanisms due to its increased permeability in neuronal membranes. The present study tests the hypothesis that a prolonged bilirubin infusion modifies the N-methyl-D-aspartate (NMDA) receptor/ ion channel complex in the cerebral cortex of newborn piglets. Studies were performed in seven control and six bilirubin-exposed piglets, 2-4 d of age. Piglets in the bilirubin group received a 35 mg/kg bolus of bilirubin followed by a 4-h infusion (25 mg/kg/h) of a buffer solution containing 0.1 N NaOH, 5% human albumin, and 0.055 Na2HPO4 with 3 mg/mL bilirubin. The final mean bilirubin concentration in the bilirubin group was 495.9 +/- 85.5 mumol/L (29.0 +/- 5.0 mg/dL). The control group received a bilirubin-free buffer solution. Sulfisoxazole was administered to animals in both groups. P2 membrane fractions were prepared from the cerebral cortex. [3H]MK-801 binding assays were performed to study NMDA receptor modification. The Bmax in the control and bilirubin groups were 1.20 +/- 0.10 (mean +/- SD) and 1.32 +/- 0.14 pmol/mg protein, respectively. The value for Kd in the control brains was 6.97 +/- 0.80 nM compared with 4.80 +/- 0.28 nM in the bilirubin-exposed brains (p < 0.001). [3...Continue Reading

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Citations

May 23, 2001·Progress in Neurobiology·N C Danbolt
Sep 5, 2002·Hearing Research·Rosamaria Santarelli, Edoardo Arslan
May 1, 2002·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Cecília M P RodriguesDora Brites
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Jan 8, 2009·Pediatric Research·Monika BernsMichael Obladen
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