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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

Samuelsson, Carolina LU ; Kumlien, Eva ; Elfving, Ase ; Lindholm, Dan and Ronne-Engström, Elisabeth (2003) In Epilepsy Research 56(2-3). p.73-165
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... (More)

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.

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author
; ; ; and
publishing date
type
Contribution to journal
publication status
published
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
in
Epilepsy Research
volume
56
issue
2-3
pages
73 - 165
publisher
Elsevier
external identifiers
  • pmid:14643001
  • scopus:0345258453
ISSN
0920-1211
DOI
10.1016/j.eplepsyres.2003.09.004
language
English
LU publication?
no
id
2c1da7a8-53fd-4fc7-babb-254c30880f1b
date added to LUP
2019-06-05 16:08:38
date last changed
2021-01-06 07:02:59
@article{2c1da7a8-53fd-4fc7-babb-254c30880f1b,
  abstract     = {<p>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.</p>},
  author       = {Samuelsson, Carolina and Kumlien, Eva and Elfving, Ase and Lindholm, Dan and Ronne-Engström, Elisabeth},
  issn         = {0920-1211},
  language     = {eng},
  number       = {2-3},
  pages        = {73--165},
  publisher    = {Elsevier},
  series       = {Epilepsy Research},
  title        = {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},
  url          = {http://dx.doi.org/10.1016/j.eplepsyres.2003.09.004},
  doi          = {10.1016/j.eplepsyres.2003.09.004},
  volume       = {56},
  year         = {2003},
}