MRS of brain metabolite levels demonstrates the ability of scavenging of excess brain glutamate to protect against nerve agent induced seizures

Int J Mol Sci. 2015 Feb 2;16(2):3226-36. doi: 10.3390/ijms16023226.

Abstract

This study describes the use of in vivo magnetic resonance spectrocopy (MRS) to monitor brain glutamate and lactate levels in a paraoxon (PO) intoxication model. Our results show that the administration of recombinant glutamate-oxaloacetate transaminase (rGOT) in combination with oxaloacetate (OxAc) significantly reduces the brain-accumulated levels of glutamate. Previously we have shown that the treatment causes a rapid decrease of blood glutamate levels and creates a gradient between the brain and blood glutamate levels which leads to the efflux of excess brain glutamate into the blood stream thereby reducing its potential to cause neurological damage. The fact that this treatment significantly decreased the brain glutamate and lactate levels following PO intoxication suggests that it could become a new effective neuroprotective agent.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Aspartate Aminotransferases / administration & dosage
  • Aspartate Aminotransferases / genetics
  • Aspartate Aminotransferases / metabolism
  • Brain / metabolism*
  • Brain / pathology
  • Glutamic Acid / metabolism*
  • Humans
  • Lactic Acid / metabolism
  • Magnetic Resonance Imaging
  • Magnetic Resonance Spectroscopy
  • Male
  • Metabolome*
  • Metabolomics / methods
  • Oxaloacetic Acid / administration & dosage
  • Paraoxon / adverse effects
  • Rats
  • Seizures / chemically induced
  • Seizures / diagnosis
  • Seizures / drug therapy
  • Seizures / genetics
  • Seizures / metabolism*

Substances

  • Oxaloacetic Acid
  • Lactic Acid
  • Glutamic Acid
  • Aspartate Aminotransferases
  • Paraoxon