title: A gliotoxin model of occipital seizures in rats.
abstract: OBJECTIVE
  Intracortical microinjection of fluorocitrate, a reversible inhibitor of glial tricarboxylic acid (TCA), results in impaired glial metabolism and epileptic seizures. To determine the potential contribution of epileptic activities to the metabolic properties of fluorocitrate, we investigated the seizure-inducing property of fluorocitrate at different doses.
  
  
  METHODS
  Twenty-seven male Sprague Dawley rats (250-400g) were studied with chronically implanted electrodes and cannulae in the occipital cortices. A week after surgery, awake behaving rats were injected with 0.2microl solution containing various concentrations of fluorocitrate or saline in the right occipital cortex; two sham-treated animals did not receive an injection. EEG was recorded with implanted electrodes. Thionin staining was used to verify injection sites. Twenty rats underwent immunohistochemistry for glial fibrilary acidic protein (GFAP) and neuronal nuclear-specific antigen (NeuN) 48h after the injections.
  
  
  RESULTS
  Seizures developed within an hour of injection in all the rats that received > or =0.8nmol fluorocitrate and 2 of 4 rats that received 0.4nmol fluorocitrate. Five of 12 animals that received > or =1.2nmol fluorocitrate experienced status epilepticus. There was a significant increase in GFAP staining at the injection site in doses > or =0.8nmol fluorocitrate. There was only mild neuronal loss revealed by NeuN staining at the injection site in the animals that had received 1.6nmol flourocitrate.
  
  
  CONCLUSIONS
  This study shows that fluorocitrate results in focal epileptic seizures with secondary generalization in a dose-dependent manner, including low doses of this agent previously used for studies of brain metabolism.
authors.affiliation: Department of Graduate Studies, University of Western Ontario, London, Ontario, Canada. smirsat2@uwo.ca
authors.forename: Seyed M
authors.initials: SM
authors.lastname: Mirsattari
authors.forename: Bixia
authors.initials: B
authors.lastname: Shen
authors.forename: L Stan
authors.initials: LS
authors.lastname: Leung
authors.forename: Nagalingam
authors.initials: N
authors.lastname: Rajakumar
mesh_terms: D000818:Animals; D002951:Citrates / Q000633:toxicity*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D004828:Epilepsies, Partial / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000378:metabolism; D009778:Occipital Lobe / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D002951:Citrates; D005904:Glial Fibrillary Acidic Protein; C007744:fluorocitrate; D010751:Phosphopyruvate Hydratase