Cerebral white matter oxidation and nitrosylation in young rodents with kaolin-induced hydrocephalus

Marc R. Del Bigio*, Osaama H. Khan, Luiza Da Silva Lopes, Packiasamy A R Juliet

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Hydrocephalus is associated with reduced blood flow in periventricular white matter. To investigate hypoxic and oxidative damage in the brains of rats with hydrocephalus, kaolin was injected into the cisterna magna of newborn 7- and 21-day-old Sprague-Dawley rats, and ventricle size was assessed by magnetic resonance imaging at 7, 21, and 42 days of age. In-situ evidence of hypoxia in periventricular capillaries and glial cells was shown by pimonidazole hydrochloride binding. Biochemical assay of thiobarbituric acid reaction and immunohistochemical detection of malondialdehyde and 4-hydroxy-2-nonenal indicated the presence of lipid peroxidation in white matter. Biochemical assay of nitrite indicated increased nitric oxide production. Nitrotyrosine immunohistochemistry showed nitrosylated proteins in white matter reactive microglia and astrocytes. Activities ofthe antioxidant enzymes catalase and glutathione peroxidase were notincreased, and altered hypoxia-inducible factor 1α was not detectedby quantitative reverse transcription-polymerase chain reaction. Cerebral vascular endothelial growth factor expression determined byquantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay was not changed, but vascular endothelial growth factor immunoreactivity was increased in reactive astrocytes of hydrocephalic white matter. To determine if nitric oxide synthase is involved in the pathogenesis, we induced hydrocephalus in 7-day-old wild-type and neuronal nitric oxide synthase-deficient mice. At 7 days, the wild-type and mutant mice exhibited equally severe ventriculomegaly and no behavioral differences, although increased glial fibrillary acidic protein was less in the mutant mice. We conclude that hypoxia, via peroxidation and nitrosylation, contributes to brain changes in young rodents with hydrocephalus and that compensatory mechanisms are negligible.

Original languageEnglish (US)
Pages (from-to)274-288
Number of pages15
JournalJournal of neuropathology and experimental neurology
Volume71
Issue number4
DOIs
StatePublished - Apr 2012

Keywords

  • Hydrocephalus
  • Hypoxia
  • Mouse
  • Nitric oxide
  • Rat

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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