Vascular endothelial growth factor and nitric oxide production in response to hypoxia in the choroid plexus in neonatal brain

Brain Pathol. 2008 Jan;18(1):71-85. doi: 10.1111/j.1750-3639.2007.00104.x. Epub 2007 Oct 9.

Abstract

Damage to the choroid plexus in 1-day-old Wistar rats subjected to hypoxia was investigated. The mRNA and protein expression of hypoxia-inducible factor-1alpha (HIF-1alpha), endothelial, neuronal, inducible nitric oxide synthase (eNOS, nNOS, iNOS), and vascular endothelial growth factor (VEGF) along with nitric oxide (NO) production and VEGF concentration was up-regulated significantly in hypoxic rats. Ultrastructurally, the choroid plexus epithelial cells showed massive accumulation of glycogen. A striking feature was the extrusion of cytoplasmic fragments from the apical cell surfaces into the ventricular lumen following the hypoxic insult. Intraventricular macrophages showed increased expression of complement type 3 receptors, major histocompatibility complex class I and II antigens, and ED1 antigens. Following an intravenous injection of horseradish peroxidase (HRP), a large number of intraventricular macrophages were labeled suggesting enhanced leakage of the tracer from the blood vessels in the choroid plexus connective tissue stroma into the ventricular lumen. We suggest that increased production of NO in hypoxia is linked to the structural alteration of the choroid plexus, and along with VEGF, may lead to increased vascular permeability. Melatonin treatment reduced VEGF and NO levels as well as leakage of HRP suggesting its potential value in ameliorating damage in choroid plexus pathologies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Animals, Newborn
  • Antigens, Surface / immunology
  • Capillary Permeability* / drug effects
  • Capillary Permeability* / physiology
  • Choroid Plexus / growth & development
  • Choroid Plexus / metabolism*
  • Choroid Plexus / pathology
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Glycogen / metabolism
  • Horseradish Peroxidase / pharmacokinetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Hypoxia-Ischemia, Brain / cerebrospinal fluid*
  • Hypoxia-Ischemia, Brain / pathology
  • Hypoxia-Ischemia, Brain / physiopathology
  • Isoenzymes / metabolism
  • Lateral Ventricles / growth & development
  • Lateral Ventricles / metabolism
  • Lateral Ventricles / pathology
  • Macrophages / immunology
  • Macrophages / ultrastructure
  • Melatonin / pharmacology
  • Melatonin / therapeutic use
  • Nitric Oxide / biosynthesis*
  • Nitric Oxide Synthase / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Treatment Outcome
  • Up-Regulation / physiology
  • Vascular Endothelial Growth Factor A / biosynthesis*

Substances

  • Antigens, Surface
  • Hif1a protein, rat
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Isoenzymes
  • RNA, Messenger
  • Vascular Endothelial Growth Factor A
  • Nitric Oxide
  • Glycogen
  • Horseradish Peroxidase
  • Nitric Oxide Synthase
  • Melatonin