With the overall objective of elucidating the cellular mechanism(s) producing epileptic seizures, the potential role of microglial cells will be assessed in this project. Epilepsy in its many forms is a major health problem causing distress, personpower loss and death, and understanding the underlying mechanism can lead directly to more effective treatment. Both anatomical and functional properties of brain microglia will be investigated in the cerebral cortex and hippocampus of seven (7) different animal models of epilepsy; these models include tottering, stargazer, DBA/2J and BXD-15 mice, and GEPR-9 and pentylenetetrazol-treated rats. The microglia will be revealed in brain tissue from these animals (as well as controls) through selective staining with horseradish peroxidase-conjugated B4 isolectin of Griffonia simplicifolia, and the highly ordered specific properties of cellular morphology, distribution and density will be determined with light microscopy. These features will be examined before and after developmental onset of seizures and during seizure activity. Also, the functional properties of pinocytosis and motility, which have been previously demonstrated for these cells in vitro, will be investigated in microglia from the GEPR-9 rat in tissue culture. Primary cultures of dissociated cerebral cortical cells from GEPR-9 fetuses will be prepared; pinocytosis will be evaluated by incubation with lucifer yellow dye and epiflourescence microscopy, and motility will be determined through time- lapse video recording. These studies may also reveal cellular defects which could produce seizures. These experiments constitute a novel study as, to this investigator's knowledge, there have been no previous studies of microglia in relation to epilepsy.
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