Brain infection with Staphylococcus aureus leads to high extracellular levels of glutamate, aspartate, γ-aminobutyric acid, and zinc

J Neurosci Res. 2014 Dec;92(12):1792-800. doi: 10.1002/jnr.23444. Epub 2014 Jul 4.


Staphylococcal brain infections may cause mental deterioration and epileptic seizures, suggesting interference with normal neurotransmission in the brain. We injected Staphylococcus aureus into rat striatum and found an initial 76% reduction in the extracellular level of glutamate as detected by microdialysis at 2 hr after staphylococcal infection. At 8 hr after staphylococcal infection, however, the extracellular level of glutamate had increased 12-fold, and at 20 hr it had increased >30-fold. The extracellular level of aspartate and γ-aminobutyric acid (GABA) also increased greatly. Extracellular Zn(2+) , which was estimated at ∼2.6 µmol/liter in the control situation, was increased by 330% 1-2.5 hr after staphylococcal infection and by 100% at 8 and 20 hr. The increase in extracellular glutamate, aspartate, and GABA appeared to reflect the degree of tissue damage. The area of tissue damage greatly exceeded the area of staphylococcal infiltration, pointing to soluble factors being responsible for cell death. However, the N-methyl-D-aspartate receptor antagonist MK-801 ameliorated neither tissue damage nor the increase in extracellular neuroactive amino acids, suggesting the presence of neurotoxic factors other than glutamate and aspartate. In vitro staphylococci incubated with glutamine and glucose formed glutamate, so bacteria could be an additional source of infection-related glutamate. We conclude that the dramatic increase in the extracellular concentration of neuroactive amino acids and zinc could interfere with neurotransmission in the surrounding brain tissue, contributing to mental deterioration and a predisposition to epileptic seizures, which are often seen in brain abscess patients.

Keywords: MK-801; Zn2+; brain abscess; glutamine; staphylococci.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Aspartic Acid / metabolism*
  • Brain Abscess / complications
  • Brain Abscess / metabolism*
  • Caspase 3 / metabolism
  • Disease Models, Animal
  • Excitatory Amino Acid Transporter 2 / metabolism
  • Extracellular Fluid / metabolism
  • Glial Fibrillary Acidic Protein / metabolism
  • Glutamic Acid / metabolism*
  • Male
  • Microdialysis
  • Phosphopyruvate Hydratase / metabolism
  • Rats
  • Rats, Wistar
  • Staphylococcal Infections / complications
  • Staphylococcus aureus / pathogenicity*
  • Synaptophysin / metabolism
  • Zinc / metabolism*
  • gamma-Aminobutyric Acid / metabolism*


  • Excitatory Amino Acid Transporter 2
  • Glial Fibrillary Acidic Protein
  • Synaptophysin
  • Aspartic Acid
  • Glutamic Acid
  • gamma-Aminobutyric Acid
  • Caspase 3
  • Phosphopyruvate Hydratase
  • Zinc