Hyperexcitability in a model of cortical maldevelopment.
The presence of developmental cortical malformations has been associated with the occurrence of epilepsy, and correlative anatomic-clinical electrophysiological studies suggest that microdysgenic lesions may actually initiate epileptiform activity. We have investigated the electrophysiological properties of an animal model of polymicrogyria created by making cortical freeze lesions in rat pups at P0 or P1. Such lesions create microgyri with histological features similar to those of human polymicrogyria. We have determined that there is a focal region of hyperexcitability around the lesion in this rat microgyrus. Field potentials evoked by stimulation within a few millimeters of the microgyrus have characteristics typical of epileptiform activity. This aberrant activity is seen as early as 12 d after the lesion, as well as in animals as old as 118 d. Immunochemical staining for the calcium binding protein, parvalbumin, shows a decrease in neuronal and neuropil staining within the microgyrus. These findings suggest that inhibition might be decreased within the lesion, which may contribute to generation of the adjacent hyperexcitable region. These results demonstrate that this animal model is appropriate for examining the mechanisms contributing to epileptogenesis associated with a cortical malformation.
Jacobs
K M
KM
Department of Neurology and Neurological Sciences, Stanford University Medical Center, Stanford, CA 94305, USA.
Gutnick
M J
MJ
Prince
D A
DA
D000818:Animals; D000831:Animals, Newborn; D002540:Cerebral Cortex / Q000002:abnormalities* / Q000293:injuries / Q000503:physiopathology; D004594:Electrophysiology; D004827:Epilepsy / Q000503:physiopathology*; D005615:Freezing; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000502:physiology; D008959:Models, Neurological; D051381:Rats