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Extremely preterm infants are more vulnerable to bilirubin neurotoxicity, but the mechanism and extent of injury is not well understood. A preterm version of the Gunn rat model was utilized to investigate severe preterm NHB. Homozygous\/jaundiced Gunn rat pups were injected (i.p.) on postnatal day (P) 5 with sulfadimethoxine, which increases serum free bilirubin capable of crossing the blood\u2013brain barrier and causing brain injury. The neurochemical profiles of the cerebellum and hippocampus were determined using in vivo <jats:sup>1<\/jats:sup>H MRS at 9.4\u2009T on P30 and compared with those of heterozygous\/non\u2010jaundiced control rats. Transcript expression of related genes was determined by real\u2010time quantitative PCR. MRI revealed significant morphological changes in the cerebellum of jaundiced rats. The concentrations of <jats:italic>myo<\/jats:italic>\u2010inositol (+54%), glucose (+51%), <jats:italic>N<\/jats:italic>\u2010acetylaspartylglutamate (+21%), and the sum of glycerophosphocholine and phosphocholine (+17%) were significantly higher in the cerebellum of the jaundiced group compared with the control group. Despite the lack of morphologic changes in the hippocampus, the concentration of <jats:italic>myo<\/jats:italic>\u2010inositol (+9%) was higher and the concentrations of creatine (\u22128%) and of total creatine (\u22123%) were lower in the jaundiced group. In the hippocampus, expression of calcium\/calmodulin dependent protein kinase II alpha (<jats:italic>Camk2a<\/jats:italic>), glucose transporter 1 (<jats:italic>Glut1<\/jats:italic>), and <jats:italic>Glut3<\/jats:italic> transcripts were downregulated in the jaundiced group. In the cerebellum, glial fibrillary acidic protein (<jats:italic>Gfap<\/jats:italic>), myelin basic protein (<jats:italic>Mbp<\/jats:italic>), and <jats:italic>Glut1<\/jats:italic> transcript expression was upregulated in the jaundiced group. These results indicate osmotic imbalance, gliosis, and changes in energy utilization and myelination, and demonstrate that preterm NHB critically affects brain development in a region\u2010specific manner, with the cerebellum more severely impacted than the hippocampus.<\/jats:p>","DOI":"10.1002\/nbm.4946","type":"journal-article","created":{"date-parts":[[2023,4,3]],"date-time":"2023-04-03T05:53:51Z","timestamp":1680501231000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Neonatal hyperbilirubinemia differentially alters the neurochemical profiles of the developing cerebellum and hippocampus in a preterm Gunn rat model"],"prefix":"10.1002","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0893-3641","authenticated-orcid":false,"given":"Katherine M.","family":"Satrom","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Division of Neonatology University of Minnesota  Minneapolis MN 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