Background:
Bilirubin is produced by the breakdown of hemoglobin, and is normally catabolized and excreted. Neurotoxic accumulation of serum bilirubin often occurs in premature infants. The homozygous Gunn rat lacks uridine diphosphate-glucuronosyltransferase-1A1 (UGT1A1), the enzyme needed to biotransform bilirubin. This rodent model of hyperbilirubinemia emulates many aspects of bilirubin toxicity observed in the human infant. We demonstrate that choline supplementation in early postnatal development is neuroprotective in the choline restricted Gunn rat, when hyperbilirubinemia is induced on postnatal day 5.
Methods:
We first compared behaviors and cerebellar weight of pups born to dams consuming regular rat chow to those of dams consuming choline-restricted diets. Secondly, we measured behaviors and cerebellar weights of pups born to choline-restricted dams, reared on a choline-restricted diet, supplemented with or without choline and treated with or without sulfadimethoxine (SDMX).
Results:
A choline-restricted diet did not change the behavioral outcomes, but cerebellar weight was reduced in the choline-restricted group regardless of genotype or SDMX administration. SDMX induced behavioral deficits in jj pups, and choline supplementation improved most behavioral effects and cerebellar weight in SDMX-treated jj rats.
Conclusion:
These results suggest that choline may be used as a safe and effective neuroprotective intervention against hyperbilirubinemia in the choline deficient premature infant.
Hypoxic-ischemic encephalopathy (HIE) is a devastating disease with lifelong disabilities. Hypothermia is currently the only treatment. At term, the neonatal cerebellum may be particularly vulnerable to the effects of HIE. At this time, many developmental processes depend on lipid raft function. These microdomains of the plasma membrane are critical for cellular signaling and axon extension. We hypothesized that HIE alters the protein content of lipid rafts in the cerebellum. Postnatal day (PN) 10 animals, considered human term equivalent, underwent hypoxic-ischemic (HI) injury by a right carotid artery ligation followed by hypoxia. For some animals, LPS was administered on PN7 and hypothermia (HT) was conducted for 4 hours post-hypoxia. Lipid rafts were isolated from right and left cerebella. The percent of total L1 cell adhesion molecule in lipid rafts was determined 4 and 72 h after hypoxia. No sex differences were found. HI alone caused significant increases in the percent of L1 in lipid rafts which persisted until 72 h in the right but not the left cerebellum. A small but significant effect of LPS was detected in the left cerebellum 72 h after HI. Hypothermia had no effect. Lipid rafts may be a new target for interventions of HIE.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.