The effects of bilirubin on brain energy metabolism during hyperosmolar opening of the blood-brain barrier: an in vivo study using 31P nuclear magnetic resonance spectroscopy.
Despite intensive investigation it remains uncertain how bilirubin enters the brain and how it exerts a toxic effect on neurones. Studies of induced hyperbilirubinemia in animal models in vivo have failed to reproduce bilirubin encephalopathy without additional factors such as hypoxia, asphyxia, hypercapnia, and disruption of the blood-brain barrier. The aim of this study was to investigate, using 31P NMRS, whether hyperbilirubinemia alone or in association with hyperosmolar opening of the blood-brain barrier caused any disturbance of cerebral energy metabolism in vivo. Spectra were acquired using a surface coil positioned over the right cerebral hemisphere of anaesthetized adult rats placed in the bore of a 1.9 Tesla magnet. Hyperbilirubinemia alone at a maximum mean serum concentration of 1063 +/- 175 mumol/L (mean +/- SD, n = 7) caused no apparent disruption in brain energy metabolism. However, in combination with hyperosmolar blood-brain barrier opening a serum bilirubin concentration of 483 +/- 52 mumol/L (mean +/- SD, n = 9) was associated with a reduction in PCr/(PCr + Pi) ratio from 0.68 +/- 0.06 to 0.44 +/- 0.14 (mean +/- SD, p less than 0.001). A significant correlation was demonstrated between cerebral hemisphere bilirubin content and the reduction in PCr/(PCr + Pi) (r = 0.84, n = 9, p less than 0.01). These results demonstrate in vivo a disruptive effect of bilirubin on cerebral energy metabolism in the presence of an open BBB. This mode of entry and mechanism of toxicity may be factors in the pathophysiology of bilirubin encephalopathy in the newborn infant.
Ives
N K
NK
Department of Paediatrics, John Radcliffe Hospital, Headington, Oxford, United Kingdom.
Bolas
N M
NM
Gardiner
R M
RM
D000818:Animals; D001663:Bilirubin / Q000494:pharmacology*; D001812:Blood-Brain Barrier / Q000502:physiology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004734:Energy Metabolism / Q000187:drug effects*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009994:Osmolar Concentration; D010710:Phosphates / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D010710:Phosphates; D010725:Phosphocreatine; D001663:Bilirubin