Systemic glycerol decreases neonatal rabbit brain and cerebellar growth independent of intraventricular hemorrhage

Pediatr Res. 2014 Mar;75(3):389-94. doi: 10.1038/pr.2013.236. Epub 2013 Dec 17.

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.

Conclusion: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn / blood
  • Animals, Newborn / growth & development*
  • Case-Control Studies
  • Cerebellum / abnormalities*
  • Cerebellum / pathology
  • Developmental Disabilities / etiology
  • Developmental Disabilities / pathology
  • Dose-Response Relationship, Drug
  • Glycerol / administration & dosage
  • Glycerol / blood
  • Glycerol / pharmacology*
  • Heart Ventricles / pathology*
  • Hemorrhage / chemically induced
  • Hemorrhage / complications*
  • Hemorrhage / diagnostic imaging
  • Hemorrhage / pathology
  • Injections, Intraperitoneal
  • Magnetic Resonance Imaging
  • Nervous System Malformations / etiology*
  • Nervous System Malformations / pathology
  • Rabbits / blood
  • Rabbits / growth & development*
  • Time Factors
  • Ultrasonography

Substances

  • Glycerol

Supplementary concepts

  • Cerebellar Hypoplasia