Administration of excitatory amino acid antagonists via microdialysis attenuates the increase in glucose utilization seen following concussive brain injury

J Cereb Blood Flow Metab. 1992 Jan;12(1):12-24. doi: 10.1038/jcbfm.1992.3.

Abstract

Immediately following concussive brain injury, cells exhibit an increase of energy demand represented by the activation of glucose utilization. We have proposed that this trauma-induced hypermetabolism reflects the effort of cells to restore normal ionic balance disrupted by massive ionic fluxes through transmitter-gated ion channels. In the present study, changes in local CMRglc following fluid-percussion concussive injury were determined using [14C]2-deoxy-D-glucose autoradiography, and the effects of in situ administration (via microdialysis) of excitatory amino acid (EAA) antagonists [kynurenic acid (KYN), 2-amino-5-phosphonovaleric acid (APV; 100 microM, 1 mM, and 10 mM), and 6-cyano-7-nitroquinoxaline-2,3-dine (CNQX; 300 microM, 1 mM, and 10 mM] on glucose utilization were investigated. Animals that did not receive dialysis showed a remarkable increase (up to 181% of normal control) in cortical glucose utilization following injury. In contrast, this high demand for glucose was reduced in areas infiltrated with KYN, APV, and CNQX. These results indicate that EAA-activated ion channels are involved in the posttraumatic increase in glucose utilization, reflecting the energy demand of cells required to drive pumping mechanisms against an ionic perturbation seen immediately following the concussive injury. The effects of KYN, APV, and CNQX suggest that although all subtypes of the glutamate receptor appear to be involved in this phenomenon, N-methyl-D-aspartate-activated channels may play a major role.

Publication types

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

MeSH terms

  • 2-Amino-5-phosphonovalerate / pharmacology*
  • 6-Cyano-7-nitroquinoxaline-2,3-dione
  • Animals
  • Brain / metabolism*
  • Brain Concussion / metabolism*
  • Brain Concussion / physiopathology
  • Dialysis
  • Energy Metabolism / drug effects*
  • Excitatory Amino Acid Antagonists*
  • Glucose / metabolism*
  • Glutamic Acid
  • Ions
  • Kynurenic Acid / pharmacology*
  • Male
  • N-Methylaspartate / antagonists & inhibitors
  • Quinoxalines / pharmacology*
  • Rats
  • Rats, Inbred Strains

Substances

  • Excitatory Amino Acid Antagonists
  • Ions
  • Quinoxalines
  • Glutamic Acid
  • N-Methylaspartate
  • 6-Cyano-7-nitroquinoxaline-2,3-dione
  • 2-Amino-5-phosphonovalerate
  • Kynurenic Acid
  • Glucose