There is some evidence of unconjugated bilirubin's direct neurotoxicity in animal models of provoked intracranial hemorrhage around the hematoma and in the hippocampi of asphyxiated rats. Why is it toxic? Is there a dose response? Can it be toxic without predisposing factors? I know the special case of kernicterus, of course, but can anybody explain why and how bilirubin causes it?
Please read my paper in Visnik CDTU, 2008, N 1-2, pages 145-162.
Quantum chemical calculation of bilirubin and its ozonolysis.
Minaev B.F., Eyvtuhov Yu., Stolyarenko G.S., Gromyko K.N.
Boris, I'm sorry, but I cannot find your paper. Can you give me a hint?
Unconjugated bilirubin (UCB) triggers the release of cytochrome c from the mitochondria. This activates the apoptotic caspase cascade ultimately leading to neuronal cell death, Check out Rodrigues CMP, Sola S, Brites D. Bilirubin induces apoptosis via the mitochondrial pathway in developing rat brain neurons.
HEPATOLOGY 2002;35:1186-1195 for more information on the pathophysiology of UCB.
Are there really no newer hypotheses than the caspase pathway? Anybody?
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