Hippocampal slices: glutamate overflow and cellular damage from ischemia are reduced by sodium-channel blockade

J Neurosci Methods. 1995 Jun;59(1):121-8. doi: 10.1016/0165-0270(94)00202-r.


We evaluated concentrations of excitatory amino acids released from slices into the superfusing solution and also evaluated extracellular field potential recordings and histological appearance of slice tissues to evaluate several sodium-channel modulating drugs as potential treatments for ischemia. The selective sodium-channel blocker tetrodotoxin (TTX, 1 microM) reduced glutamate release from deprivation of oxygen and D-glucose, while calcium-channel blockade was ineffective. Thus, during ischemia, we propose that glutamate may be released from the free cytosolic pool ('metabolic' glutamate) rather than by exocytosis. TTX (100-500 nM) and voltage-dependent sodium-channel blockers (phenytoin, 20-100 microM; lidocaine, 2-200 microM) each prevented damage to slices without blocking action potentials. The reduction of cellular depolarization and sodium loading during ischemia may explain the neuroprotective action of several sodium-channel modulating drugs in our in vitro studies and also in animal models.

MeSH terms

  • Animals
  • Brain Ischemia / drug therapy*
  • Electrophysiology
  • Glutamic Acid / pharmacology*
  • Hippocampus / physiology*
  • In Vitro Techniques
  • Phenytoin / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Sodium Channel Blockers*
  • Tetrodotoxin / pharmacology*
  • Time Factors


  • Sodium Channel Blockers
  • Glutamic Acid
  • Tetrodotoxin
  • Phenytoin