Astrocyte metabolism is disturbed in the early development of experimental hydrocephalus

J Neurochem. 2003 Apr;85(1):274-81. doi: 10.1046/j.1471-4159.2003.01656.x.

Abstract

The proper diagnosis of the arrested or the progressive form of hydrocephalus has a critical impact on treatment, but remains difficult. The assessment of early changes in cerebral metabolism might help in the development of adequate non-invasive diagnostic tools. This study examined the alterations in label incorporation in neurotransmitter amino acids and other compounds in kaolin-induced progressive hydrocephalus in rats by means of magnetic resonance spectroscopy (MRS) combined with the administration of [1-13C]glucose and [1,2-13C]acetate. Some 2, 4 and 6 weeks after kaolin injection into the cisterna magna, cerebrum, brainstem and cerebellum were dissected. Interestingly, labelling of most amino acids derived from [1-13C]glucose showed no alterations, whereas labelling from [1,2-13C]acetate was affected. Two weeks after induction of hydrocephalus the taurine concentration was decreased, whereas the concentration of [1,2-13C]lactate was increased in the cerebrum and that of [1,2-13C]GABA in the brainstem. Furthermore, labelling from [1,2-13C]acetate was significantly decreased in [4,5-13C]glutamate, [1,2-13C]glutamate and [1,2-13C]GABA in cerebrum from 4 weeks after hydrocephalus induction. The concentration of N-acetylaspartate, a neuronal marker, was unchanged. However, labelling of the acetyl group from [1-13C]glucose was decreased in cerebellum and brainstem at 6 weeks after the induction of hydrocephalus. As glucose is metabolized predominately by neurones, whereas acetate is exclusively taken up by astrocytes, these results indicate that mostly astrocytic, and only later neuronal, metabolism is disturbed in the kaolin model of hydrocephalus. If verified in patients using in vivo MRS, impaired astrocyte metabolism might serve as an early indication for operative treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates / metabolism
  • Acetates / pharmacokinetics
  • Animals
  • Astrocytes / metabolism*
  • Biomarkers / analysis
  • Brain Stem / metabolism
  • Carbon Isotopes
  • Disease Models, Animal
  • Disease Progression
  • Glucose / metabolism
  • Glucose / pharmacokinetics
  • Glutamic Acid / metabolism
  • Glutamine / metabolism
  • Hydrocephalus / chemically induced
  • Hydrocephalus / diagnosis
  • Hydrocephalus / metabolism*
  • Kaolin
  • Lactic Acid / metabolism
  • Magnetic Resonance Spectroscopy
  • Male
  • Neurotransmitter Agents / metabolism
  • Neurotransmitter Agents / pharmacokinetics
  • Predictive Value of Tests
  • Rats
  • Rats, Sprague-Dawley
  • Taurine / metabolism
  • Telencephalon / metabolism
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Acetates
  • Biomarkers
  • Carbon Isotopes
  • Neurotransmitter Agents
  • Glutamine
  • Taurine
  • Kaolin
  • Lactic Acid
  • Glutamic Acid
  • gamma-Aminobutyric Acid
  • Glucose