Abstracts

Rationale: Developmental delay and cognitive impairment are common co-morbidities in people with epilepsy associated with malformations of cortical development. We studied cognition and behavior in an animal model of diffuse cortical dysplasia (CD), in utero irradiation, using a battery of behavioral tests for neuromuscular and cognitive function.Methods: Fetal rats were exposed to 2.25 Gy external radiation on E17 (N = 14) and compared to controls (N = 8). At one month of age they were tested using an open field task, a grip strength task, a grid walk task, inhibitory avoidance, an object recognition task and the Morris water maze task. For all comparisons, significance was set at P < 0.05.Results: Rats with CD showed reduced non-locomotor activity in the open field task and impaired motor coordination for grid walking but normal grip strength. They showed a reduced tendency to recognize novel objects and reduced retention in an inhibitory avoidance task. Water maze testing showed that learning and memory were impaired in irradiated rats for both cue discrimination and spatially oriented tasks. These results demonstrate significant deficits in cortex- and hippocampus-dependent cognitive functions associated with the diffuse abnormalities of cortical and hippocampal development that have been documented in this model.Conclusions: This study documents multi-modal cognitive deficits associated with CD and can serve as the foundation for future investigations into the mechanisms of and possible therapeutic interventions for this problem. Acknowledgments This work was supported by the Citizens United for Epilepsy Research (CURE), the McKnight Foundation and the Densch Foundation.