Studies on the Pathogenesis of Kernicterus

Abstract

Kernicteric pigment was extracted by means of chloroform from the brains of 3 infants. Solutions of it gave a positive diazo reaction, and, as determined electrophotometrically, gave maximum absorption of light having a wavelength of 425 mµ, being identical in these properties with chloroform solutions of crystalline mesobilirubin. Experimental kernicterus was regularly induced by injecting crystalline mesobilirubin intracerebrally in newborn kittens, the pigment staining the cerebral tissues a bright canary-yellow and being deposited abundantly in the nerve cells, as microscopic examinations showed, although these latter were otherwise intact. Bilirubin, likewise injected intracerebrally in newborn kittens, had no such effects. The possibility is discussed that the blood-brain barrier is altered in some infants with hyperbilirubinemia in such a way that bilirubin crosses it and is then reduced within the brain to mesobilirubin thus giving rise to the cerebral pigmentation of kernicterus. The fact that the pigment itself does not seem to damage the neurons, as the present studies show, makes it necessary to seek some other cause for the neuronal damage that is sometimes seen, in association with the pigmentation, in the naturally occurring disease.

Experimental bilirubin encephalopathy. The mode of entry of bilirubin-14C into the central nervous system.

“…Although the exact process by which bilirubin damages the nervous system is not understood, the results of the survival studies (Table III) combined with the observation that virtually all radioactivity in the brain was present in the form of bilirubin-14C leave little doubt that bilirubin rather than related compounds (9,70,71) is responsible for the neurotoxicity. In the newborn guinea pigs analysis of the pigment level in different anatomical regions of the brain failed to reveal significant differences.…”