Kernicterus in asphyxiated newborn rhesus monkeys

Abstract

Newborn rhesus monkeys have “physiological jaundice,” reticulocytosis, lower level of glucuronyl transferase in the liver and slower bilirubin clearnace time than adults. We deliverd monkey infants by cesarian section near term and made them hyperbilirubinemic by injecting a solution of indirect-reacting bilirubin every 6 hours from 1 to 3 hours after birth for as long as 4 days. Marked jaundice developed in 6 hours; slight lethargy but no other clinical neurological signs and no kernicterus were seen. Other monkey infants were asphyxiated for 10 or 12 min during cesarian-section birth, resuscitated and then made hyperbilirubinemic. These exhibited neurological deficits clinically, with abnormal EEG, and had kernicterus. The most severely affected ones were lethargic for 12 hours and the developed tremors, seizures and prolonged opisthotonos. Brain slices showed selective canary-yellow staining of certain nuclei of the diencephalon, midbrain, brain stem, spinal cord, cerebellum and some regions in the cerebrum. Microscopical examination of frozen sections revealed bilirubin-pigmented neurons and neuroglia cells. Electron micrographs showed nerve cells in early stages of lysis. Probably asphyxia is only one of several agents causing cellular injury to bring about the picture of kernicterus in the presence of excess bilirubin in the blood.