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.
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.
Samuelsson
Carolina
C
Department of Neuroscience, Section of Neurosurgery, Uppsala University Hospital, Uppsala 75185, Sweden. carolina.samuelsson@neurokir.uu.se
Kumlien
Eva
E
Elfving
Ase
A
Lindholm
Dan
D
Ronne-Engström
Elisabeth
E
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003497:Cyclic N-Oxides; D004734:Energy Metabolism / Q000187:drug effects*; D004834:Epilepsy, Post-Traumatic / Q000139:chemically induced / Q000378:metabolism*; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism*; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D015151:Immunoblotting; D007267:Injections; D007501:Iron / Q000008:administration & dosage; D008297:Male; D017551:Microdialysis; D009589:Nitrogen Oxides / Q000097:blood / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000596:Amino Acids; D003497:Cyclic N-Oxides; D027342:Excitatory Amino Acid Transporter 2; D009589:Nitrogen Oxides; C029217:phenyl-N-tert-butylnitrone; D007501:Iron