title: A new rat model of neonatal bilirubin encephalopathy (kernicterus).
abstract: BACKGROUND
  Hemolytic kernicterus, an indirect bilirubin-induced brain dysfunction, is associated with hyper-bilirubinemia in mammalian neonates. In this study, a new model of kernicterus has been developed using intra-peritoneal injections of phenyl hydrazine and subcutaneous injections of sulfisoxazole. These drugs can potentially induce kernicterus in neonatal through changes in hemolysis and hypo-albumin.
  
  
  METHODS
  For this purpose, 7-day-old male Wistar rats (n=72; mean weight 11±1g) were used. The animals have been divided into six different groups which received the drugs alone and their combination, and the drugs' solvents and their combination. Biochemical parameters, brain iron and bilirubin, behavioural performance, auditory function and apoptosis were measured using auto-analyser instruments; atomic absorption spectroscopy, Sawasaki, footprint, auditory brainstem response (ABR) and TUNEL test, respectively.
  
  
  RESULTS
  The drug-injected groups showed a significant reduction in serum haematocrit and an increase in the concentration of brain bilirubin, total and indirect bilirubin as well as TUNEL positive cells in basal ganglia. In addition, the obtained results showed that there was a significant increase in behavioural disturbance and auditory dysfunction in the group injected with the combination of two drugs.
  
  
  CONCLUSIONS
  This kernicterus-induced rat model could perfectly mimic the common conditions of the hyperbilirubinemia in human neonates. This study offers an easy technique to develop more stable models for follow-up studies.
authors.affiliation: Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran; Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Naser
authors.initials: N
authors.lastname: Amini
authors.affiliation: Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; Iranian National Center for Addiction Studies, Tehran University of Medical Science, Tehran, Iran. Electronic address: n-vousooghi@tums.ac.ir.
authors.forename: Nasim
authors.initials: N
authors.lastname: Vousooghi
authors.affiliation: Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran; Department of Anatomy, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Mansoureh
authors.initials: M
authors.lastname: Soleimani
authors.affiliation: Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran; Department of Tissue Engineering & Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Samadikuchaksaraei
authors.affiliation: Audiology Department, Rehabilitation Faculty, Iran university of Medical Sciences, Tehran, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Akbari
authors.affiliation: Neuroscience Department, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Hosein
authors.initials: H
authors.lastname: Safakheil
authors.affiliation: Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran; Department of Tissue Engineering & Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Pezhman
authors.initials: P
authors.lastname: Atafimanesh
authors.affiliation: Neuroscience Department, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Shahbazi
authors.affiliation: Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran; Department of Tissue Engineering & Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran; Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Peiman
authors.initials: P
authors.lastname: Brouki Milan
authors.affiliation: Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; Neuroscience Research Center, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran.
authors.forename: Sara
authors.initials: S
authors.lastname: Ramezani
authors.affiliation: Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran; Department of Tissue Engineering & Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Masoud
authors.initials: M
authors.lastname: Mozafari
authors.affiliation: Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran; Department of Tissue Engineering & Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran; Neuroscience Department, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran. Electronic address: mt.joghataei@yahoo.com.
authors.forename: Mohammad Taghi
authors.initials: MT
authors.lastname: Joghataei
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001663:Bilirubin / Q000378:metabolism*; D004195:Disease Models, Animal; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects / Q000502:physiology; D007647:Kernicterus / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D010659:Phenylhydrazines / Q000633:toxicity; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013444:Sulfisoxazole / Q000633:toxicity
chemical_list: D010659:Phenylhydrazines; C030299:phenylhydrazine; D013444:Sulfisoxazole; D001663:Bilirubin
keywords: Chloroform (PubChem CID: 6212); Hydrogen peroxide (PubChem CID: 784); Hyperbilirubinemia; Kernicterus; Methanol (PubChem CID: 887); Nitric acid (PubChem CID: 944); Paraformaldehyde (PubChem CID: 712); Phenyl hydrazine; Phenyl hydrazine hydrochloride (PubChem CID: 75331); Sucrose (PubChem CID: 5988); Sulfisoxazole; Sulfisoxazole (PubChem CID: 5344); Tris (PubChem CID: 6503); Xylitol (PubChem CID: 6912)