To investigate seizure susceptibility in polymicrogyria, the seizure threshold and growth-associated protein GAP43 expression were analyzed in a rat experimental model of polymicrogyria induced by intracerebral injection of ibotenate. A total of 72 neonates from 9 pregnant rats were used. Intraperitoneal pentylenetetrazole injection did not induce any seizure activity in the control rats, although it elicited seizures of variable severity in the polymicrogyria rats. Fluoro-Jade B–positive degenerating interneurons were found in the polymicrogyria brains; however, no such neurons were detected in the control brains. In the polymicrogyria rats, the GAP43 expression was significantly and widely distributed in the brain, and the percentage of parvalbumin-positive interneurons in the GAP43-positive cells was significantly higher than that observed in the nonphosphorylated neurofilament-positive pyramidal cells. We conclude that the relatively selective vulnerability of inhibitory interneurons constitutes the basis for the decreased seizure threshold observed in this model of polymicrogyria.
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