HYPEREXCITABILITY IN A MODEL OF CORTICAL MALDEVELOPMENT

The presence of developmental cortical malformations has been associat ed with the occurrence of epilepsy, and correlative anatomic-clinical electrophysiological studies suggest that microdysgenic lesions may ac tually initiate epileptiform activity. We have investigated the electr ophysiological properties of an animal model of polymicrogyria created by making cortical freeze lesions in rat pups at P0 or P1. Such lesio ns create microgyri with histological features similar to those of hum an polymicrogyria, We have determined that there is a focal region of hyperexcitability around the lesion in this rat microgyrus. Field pote ntials evoked by stimulation within a few millimeters of the microgyru s have characteristics typical of epileptiform activity, This aberrant activity is seen as early as 12 d after the lesion, as well as in ani mals as old as 118 d, Immunochemical staining for the calcium binding protein, parvalbumin, shows a decrease in neuronal and neuropil staini ng within the microgyrus. These findings suggest that inhibition might he decreased within the lesion, which may contribute to generation of the adjacent hyperexcitable region. These results demonstrate that th is animal model is appropriate for examining the mechanisms contributi ng to epileptogenesis associated with a cortical malformation.