Bilirubin entry into and clearance from rat brain during hypercarbia and hyperosmolality

Abstract

Brain bilirubin concentrations are increased by hyperosmolality and hypercarbia, but the mechanism is not known. The same applies to the mechanism for preferential localization of bilirubin to basal ganglia. Young Sprague-Dawley rats were used. Groups were: control (n = 15), hypercarbia (n = 16, pH ≃ 6.95), and hyperosmolality (n = 13, serum osmolality ≃390 mosm/L). Hyperbilirubinemia was induced by a 5-min infusion of 50 mg/kg bilirubin, containing ≃20 μCi [3H]bilirubin. Rats were killed at 15-min intervals up to 60 min, and the brains were flushed in situ, dissected into seven regions, weighed, and dissolved. Brain bilirubin was determined by scintillation counting. The half-life of bilirubin in brain was calculated by exponential fitting, which also allowed an estimation of brain bilirubin at the end of the bilirubin bolus. The kinetics of bilirubin clearance from brain were first order. The half-life of bilirubin in brain was significantly prolonged in hyperosmolality (38.2 ± 28.8 min [mean ± SD]) compared with control (16.1 ± 7.7 min) and hypercarbia (12.6 ± 8.6 min) (F = 12.6, p < 0.0001 after log transformation) results. The estimated acute entry of bilirubin into brain was significantly increased in hypercarbia (13.9 ± 7.4 nmol/g) compared with control (5.6 ± 2.1 nmol/g) and hyperosmolality (6.5 ± 2.1 nmol/g) (F = 19.2, p < 0.0001 after log transformation) results. There were no significant differences between brain regions in acute entry or clearance of bilirubin. The kinetics of increased brain bilirubin differ between hypercarbia (increased acute entry) and hyperosmolality (delayed clearance). Preferential localization of bilirubin to basal ganglia is not produced under, and may not be explained by, the conditions investigated.