| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 340815 | Seizure | 2008 | 7 Pages |
SummaryPurposeIntracortical 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.MethodsTwenty-seven male Sprague Dawley rats (250–400 g) were studied with chronically implanted electrodes and cannulae in the occipital cortices. A week after surgery, awake behaving rats were injected with 0.2 μl 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) 48 h after the injections.ResultsSeizures developed within an hour of injection in all the rats that received ≥0.8 nmol fluorocitrate and 2 of 4 rats that received 0.4 nmol fluorocitrate. Five of 12 animals that received ≥1.2 nmol fluorocitrate experienced status epilepticus. There was a significant increase in GFAP staining at the injection site in doses ≥0.8 nmol fluorocitrate. There was only mild neuronal loss revealed by NeuN staining at the injection site in the animals that had received 1.6 nmol flourocitrate.ConclusionThis 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.
