Abstract
Anesthetized young adult Wistar rats were given either human serum albumin (HSA), 1.5 gm/kg, or saline, intravenously. Ten minutes later the blood brain barrier (BBB) in one hemisphere was opened by carotid artery infusion of hypertonic arabinose. Bilirubin was then infused intravenously over 8 minutes. Serial blood samples were obtained for total bilirubin (TB) and free bilirubin (FB) determinations (peroxidase method) until sacrifice 30 minutes later. Cortical EEGs were recorded continuously.
Osmotic opening of the BBB resulted in yellow coloration of the affected hemisphere in both control and HSA primed animals. EEG changes, ranging from a transient decrease in amplitude to permanent cessation of electrical activity, occurred at a mean TB of 54.8±12.6 mg/dl in HSA primed rats (n=8) compared with a threshold of 30.4±6.4 mg/dl in control rats (n=11) (p<.001). At comparable TB levels, FB levels were lower in HSA primed animals. Neither EEG changes nor staining developed in animals with an intact BBB.
These data suggest that yellow "staining" of brains may sometimes represent non-toxic interstitial bilirubin-albumin since neurotoxicity, as measured by EEG changes, was related to the level of FB available for binding to tissue rather than the TB level. Given a critical level of FB variations in BBB permeability to bilirubin or albumin-bilirubin may contribute to the risk for encephalopathy.
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Wennberg, R., Hance, A. ROLE OF FREE BILIRUBIN AND BLOOD BRAIN BARRIER IN BILIRUBIN NEUROTOXICITY. Pediatr Res 18 (Suppl 4), 355 (1984). https://doi.org/10.1203/00006450-198404001-01570
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DOI: https://doi.org/10.1203/00006450-198404001-01570