Beyond plasma bilirubin: the effects of herapy and albumin on brain bilirubin levels in Gunn rats.

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Bilirubin accumulation and Cyp mRNA expression in selected brain regions of jaundiced Gunn rat pups.

Background:Few data exist on regional brain bilirubin content in the neonatal period when acute bilirubin-induced neurologic damage may occur, and no information is available on regional brain expression of cytochrome P450 monooxygenases (Cyps) that oxidize bilirubin.Methods:Bilirubin content was analyzed by HPLC and Cyp1a1, 1a2 and 2a3 mRNA expression by quantitative polymerase chain reaction, in cortex (Cx); cerebellum (Cll); superior and inferior colliculi (SC and IC) of 17 day old hyperbilirubinemic (jj) Gunn rat pups before and after administration of sulphadimethoxine to acutely displace bilirubin from plasma albumin.Results:There was no difference in bilirubin content among brain regions in untreated rats. After i.p. sulphadimethoxine, bilirubin content peaked 4 fold in Cx and SC at 1 h; but 11-13 times in Cll and IC at 24 h; returning to control levels at 72 h. The Cyp mRNA peaked at 30-70X control at 1 h in Cx and SC, but at 3-9X times control at 24 h in Cll and IC.Conclusions:The close relationship in distinct brain regions between the extent of bilirubin accumulation and induction of mRNA of Cyps suggests they may have a role in protecting selected brain areas from bilirubin neurotoxicity