title: Systemic glycerol decreases neonatal rabbit brain and cerebellar growth independent of intraventricular hemorrhage.
abstract: BACKGROUND
  Cerebellar hypoplasia is a common problem in preterm infants and infants suffering from intraventricular hemorrhage (IVH). To evaluate the effects of IVH on cerebellar growth and development, we used a neonatal rabbit model of systemic glycerol to produce IVH.
  
  
  METHODS
  New Zealand White rabbit kits were surgically delivered 2 d preterm and treated with intraperitoneal glycerol (3.25-6.5 g/kg). Controls were born at term. IVH was documented by ultrasonography. Brain volumes determined by magnetic resonance imaging, cerebellar foliation, proliferation (Ki-67), and Purkinje cell density were assessed at 2 wk of life. Tissue glycerol and glutathione concentrations were measured.
  
  
  RESULTS
  Glycerol increased IVH, subarachnoid hemorrhages, and mortality in a dose-dependent manner. Total cerebellar volumes, cerebellar foliation, and cerebellar proliferation were decreased in a dose-dependent manner. Glycerol accumulated rapidly in blood, brain, and liver and was associated with increased glutathione concentration. All of these results were independent of IVH status.
  
  
  CONCLUSIONS
  Cerebellar hypoplasia was induced after glycerol administration in a dose-dependent manner. Given the rapid tissue accumulation of glycerol, dose-dependent decrease in brain growth, and lack of IVH effect on measured outcomes, we question the validity of this model because glycerol toxicity cannot be ruled out. A better physiological model of IVH is needed.
authors.affiliation: Department of Pediatrics, University of Washington, Seattle, Washington.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Traudt
authors.affiliation: Department of Pediatrics, University of Washington, Seattle, Washington.
authors.forename: Ron J
authors.initials: RJ
authors.lastname: McPherson
authors.affiliation: Department of Pediatrics, University of Washington, Seattle, Washington.
authors.forename: Colin
authors.initials: C
authors.lastname: Studholme
authors.affiliation: Department of Pediatrics, University of Washington, Seattle, Washington.
authors.forename: Kathleen J
authors.initials: KJ
authors.lastname: Millen
authors.affiliation: Department of Pediatrics, University of Washington, Seattle, Washington.
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Juul
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000097:blood / Q000254:growth & development*; D016022:Case-Control Studies; D002531:Cerebellum / Q000002:abnormalities* / Q000473:pathology; D002658:Developmental Disabilities / Q000209:etiology / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005990:Glycerol / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D006352:Heart Ventricles / Q000473:pathology*; D006470:Hemorrhage / Q000139:chemically induced / Q000150:complications* / Q000000981:diagnostic imaging / Q000473:pathology; D007274:Injections, Intraperitoneal; D008279:Magnetic Resonance Imaging; D009421:Nervous System Malformations / Q000209:etiology* / Q000473:pathology; D011817:Rabbits / Q000097:blood / Q000254:growth & development*; D013997:Time Factors; D014463:Ultrasonography
chemical_list: D005990:Glycerol