Abstracts

RATIONALE: Recently we demonstrated that large photothrombotic infarcts of the neocortex in adult rats were associated with the development of epileptic seizures. However, the number of animals that underwent photothrombosis was small and continuous video-EEG recording was limited. We sought to more fully evaluate the latent period of epileptogenesis and the epileptic state by expanding our previous video-EEG recordings while eliminating or minimizing potentially influential variables such as toxicity of the photosensitive dye rose bengal and cortical irritation due to blood or indwelling intracranial electrodes. At the end of this activity the participants should be able to discuss the photothrombotic model of poststroke epilepsy and the electroencephalographic and behavioral properties of animals during epileptogenesis and the epileptic state.
METHODS: Twenty 2 mo old male Sprague-Dawley rats were used in this study. Ten animals underwent photothrombotic brain infarction of the left sensorimotor cortex with the photosensitive dye rose bengal (30 mg/kg; femoral vein injection; 20 min photoactivation; lesioned animal). Three rats were injected with rose bengal but not photostimulated (sham-operated control). Seven animals were aged-matched and received no treatment (naive control). All animals had 6 skull screws placed for EEG recordings. Digital video-EEG monitoring was performed intermittently for each animal for 6 months. All video-EEG files were reviewed manually. Animals were anesthetized, sacrificed by cardiac perfusion, and brains were sectioned and Nissl-stained to evaluate infarct volumes and cortical cytoarchitecture.
RESULTS: All lesioned animals demonstrated intermittent rhythmic 4-6 Hz spike wave discharges lasting 1-3 sec over the lesioned hemisphere variably maximal over frontal, frontocentral, or parietal areas. No clear behavioral changes occurred during these discharges. More prolonged ipsilateral spike wave or polyspike discharges were associated with motor arrest, prominent facial clonus, or mild multifocal body jerking. One lesioned animal demonstrated frequent prolonged tonic clonic seizures. All lesioned, sham-operated, and control animals demonstrated periods of solitary generalized spike discharges occurring every 1-1.5 sec variably associated with no movement, brief body jerks, or multifocal body clonus that could occur during locomotion. One naive control animal demonstrated frequent prolonged 7 Hz spike wave absence seizures and multiple tonic clonic seizures. Nissl-stained tissue sections from lesioned animals showed that the infarct was transformed into a vacant space with maximum extent to the cortical-subcortical interface. There were no observable abnormalities in cortical cytoarchitecture in sham-operated and naive control animals.
CONCLUSIONS: These video-EEG results validate and expand our previous findings of the development of epileptic seizures following cortical photothrombosis and brain infarction. We propose that this model can be a useful tool for studying the molecular, cellular, and network properties associated with neocortical injury and mechanisms of secondary epileptogenesis.
[Supported by: American Heart Association Grant-in-Aid to KMK.]