Moderate seizures damage hippocampal neurons but do not affect function in an animal model of temporal lobe epilepsy
Greenwood, Shayri Jevonne
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Epilepsy is a chronic neurological disorder characterized by repetitive seizures. Seizures originating from the parahippocampal region reflect continuous neuronal overexcitation that can lead to subsequent cell loss in the hippocampus. In epilepsy, prolonged generalized seizures (i.e. your wordsstatus epilepticus, SE) are rare, yet remain the focus of studies in animal models. More often, seizures are focal and partial, as well as acute rather than prolonged. These moderate seizures can be studied in animal models allowing characterization of the damage and functional deficits. The studies conducted aimed to identify the impact moderate seizures have on brain integrity and cognitive function by a) testing the relationships between generalized seizures and subsequent function and damage, b) characterizing damage following moderate seizures through the analysis of cell morphology, and by c) studying behavioral deficits following moderate seizures. Seizures were coded after intraventricular infusion of kainic acid. Cell death was measured at three time points, 24 and 72 hour or 7-days after seizures. To test whether behavioral seizures were an indicator of cell death, seizure type and number were tested for a relationship with cell layer length, an indirect measure of cell loss. To test whether the type of seizures differentially affected the characteristics of cell death, morphological profiles of hippocampal neurons were categorized after seizures. To test for functional deficits, spatial working memory was tested in the Barnes Maze. The frequency of seizure types and the amount of cell loss were tested for a relationship with memory. Moderate seizures caused cell loss in the hippocampus that varied across animals, and was evident within 24 hours. The number of generalized seizures predicted the magnitude of cell loss, suggesting that behavioral manifestations of seizures are valid predictors of damage. Normal neuronal profiles decreased after moderate seizures whereas the proportion of glial cell profiles and neurons with darkened condensed cytoplasm increased. Even in areas that appear intact, there are more neurons with shrunken condensed cytoplasm. Whereas spatial memory task performance was impaired after SE, it was intact after moderate seizures. Although moderate seizures do not always produce cell loss, nor functional deficits, when cell loss occurs it is related to the number of generalized seizures.