ABSTRACT
Dyslexia and seizures are just part of the neurological sequelae that result from early damage to the developing cortical plate. To understand mechanisms underlying such neurological deficits associated with cortical malformations, the timing of both the precipitating incident and onset of symptoms are critical issues. The structure of the cortical malformation varies in form and severity with the timing and type of the insult (Ruddick & Khera, 1975; Ferrer, 1993; Cohen & Roessmann, 1994). In addition, there is often a delay between the insult and seizure onset (Raymond et al., 1995; Bartolomei et al., 1999). Although epilepsy is commonly associated with developmental cortical malformations, not every malformation results in seizures, suggesting that in some cases, an additional abnormality or reinforcing activation is necessary to induce epileptogenesis. The rat freeze lesion model of microgyria mimics these clinical characteristics, including association with hyperexcitability in most but not all cases, a structural pathology that varies with insult timing and delayed onset of epileptiform activity (Luhmann & Raabe, 1996; Jacobs, Gutnick, & Prince, 1996; Jacobs, Hwang, & Prince 1999). In this model, a transcranial freeze lesion given within the first 48 hours of birth produces a focal abnormal four-layered cortical region that is histopathologically similar to human four-layered polymicrogyria. Lesions given on postnatal day (P) 6 in the rat do not produce microgyria (Dvorak & Feit, 1977). After P0 or P1 lesions, the onset of hyperexcitability is dramatically sudden. It is entirely absent when brain slices are examined from animals aged P9–10, but present in nearly every slice from nearly every animal by P12 (Jacobs, Hwang, & Prince, 1999).
