In vivo effect of chronic hypoxia on the neurochemical profile of the developing rat hippocampus

Brain Res Dev Brain Res. 2005 May 12;156(2):202-9. doi: 10.1016/j.devbrainres.2005.02.013.

Abstract

The cognitive deficits observed in children with cyanotic congenital heart disease suggest involvement of the developing hippocampus. Chronic postnatal hypoxia present during infancy in these children may play a role in these impairments. To understand the biochemical mechanisms of hippocampal injury in chronic hypoxia, a neurochemical profile consisting of 15 metabolite concentrations and 2 metabolite ratios in the hippocampus was evaluated in a rat model of chronic postnatal hypoxia using in vivo 1H NMR spectroscopy at 9.4 T. Chronic hypoxia was induced by continuously exposing rats (n = 23) to 10% O2 from postnatal day (P) 3 to P28. Fifteen metabolites were quantified from a volume of 9-11 microl centered on the left hippocampus on P14, P21, and P28 and were compared with normoxic controls (n = 14). The developmental trajectory of neurochemicals in chronic hypoxia was similar to that seen in normoxia. However, chronic hypoxia had an effect on the concentrations of the following neurochemicals: aspartate, creatine, phosphocreatine, GABA, glutamate, glutamine, glutathione, myoinositol, N-acetylaspartate (NAA), phosphorylethanolamine, and phosphocreatine/creatine (PCr/Cr) and glutamate/glutamine (Glu/Gln) ratios (P < 0.001 each, except glutamate, P = 0.04). The increased PCr/Cr ratio is consistent with decreased brain energy consumption. Given the well-established link between excitatory neurotransmission and brain energy metabolism, we postulate that elevated glutamate, Glu/Gln ratio, and GABA indicate suppressed excitatory neurotransmission in an energy-limited environment. Decreased NAA and phosphorylethanolamine suggest reduced neuronal integrity and phospholipid metabolism. The altered hippocampal neurochemistry during its development may underlie some of the cognitive deficits present in human infants at risk of chronic hypoxia.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Age Factors
  • Analysis of Variance
  • Animals
  • Animals, Newborn
  • Aspartic Acid / analogs & derivatives
  • Aspartic Acid / analysis
  • Body Weight / physiology
  • Brain Chemistry / physiology*
  • Creatine / analysis
  • Energy Metabolism
  • Female
  • Hippocampus / growth & development
  • Hippocampus / metabolism*
  • Hypoxia / metabolism*
  • Iron / metabolism
  • Magnetic Resonance Imaging / methods
  • Magnetic Resonance Spectroscopy / methods
  • Male
  • Organ Size / physiology
  • Phosphocreatine / metabolism
  • Pregnancy
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors
  • Tritium / metabolism
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Phosphocreatine
  • Tritium
  • Aspartic Acid
  • gamma-Aminobutyric Acid
  • N-acetylaspartate
  • Iron
  • Creatine