The effects of PBN (phenyl-butyl-nitrone) on GLT-1 levels and on the extracellular levels of amino acids and energy metabolites in a model of iron-induced posttraumatic epilepsy

Research output: Contribution to journalArticle

Abstract

This study investigates astrocytic glutamate uptake in the iron-induced animal model of posttraumatic epilepsy. Since formation of free radicals may be involved in epileptogenesis after brain trauma and hemorrhage the effects of the nitrone radical scavenger alpha-phenyl-tert-N-butyl nitrone (PBN) were also studied. Animals received an intracortical iron injection, or were sham-operated. They were given PBN intraperitoneally or saline as control. Twenty-four hours after lesion, brain tissue was collected and the level of glial glutamate transporter (GLT-1) was analyzed using immunoblotting. The extracellular concentrations of amino acids and energy metabolites were measured using microdialysis. The results showed significantly decreased levels of GLT-1 (70 kDa), higher basal levels of glutamate, and lower levels of glutamine as well as low arginine/citrulline ratios at the lesion compared to controls. PBN significantly attenuated the decrease of 70 kDa GLT-1 in the lesioned animals and attenuated the alterations in amino acid levels but not to a significant level. PBN also increased the arginine/citrulline ratios indicating reduced nitric oxide synthase activity. Our results suggest that astrocytic uptake of glutamate is oxidatively impaired in iron-induced epileptogenesis and that the administration of a radical scavenger can attenuate this process.

Details

Authors
External organisations
  • Uppsala University Hospital
Research areas and keywords

Keywords

  • Amino Acids/metabolism, Animals, Cerebral Cortex/drug effects, Cyclic N-Oxides, Energy Metabolism/drug effects, Epilepsy, Post-Traumatic/chemically induced, Excitatory Amino Acid Transporter 2/metabolism, Extracellular Space/drug effects, Immunoblotting, Injections, Iron/administration & dosage, Male, Microdialysis, Nitrogen Oxides/blood, Rats, Rats, Sprague-Dawley
Original languageEnglish
Pages (from-to)165-73
JournalEpilepsy Research
Volume56
Issue number2-3
Publication statusPublished - 2003 Oct
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes