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
(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.
(Less)
- author
- Samuelsson, Carolina LU ; Kumlien, Eva ; Elfving, Ase ; Lindholm, Dan and Ronne-Engström, Elisabeth
- publishing date
- 2003-10
- 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
- 2024-06-26 20:03:45
@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}},
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}},
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}},
}