Effect of age on cognitive sequelae following early life seizures in rats

Abstract

Clinical studies have suggested that seizures in newborns are more damaging than seizures occurring in older children. However, these studies are difficult to interpret for a variety of factors including differing etiologies of seizures across ages. Animal studies can provide insights into the question of whether age of seizure onset in children is a factor in cognitive outcome. To evaluate the effect of age on seizure-induced cognitive impairment we subjected rats to 50 seizures from postnatal days P0-P10 or P15-P25. As adults the rats were studied in the Morris water maze, radial-arm water maze, open field, and active avoidance. To assess synaptic strength and network excitatory and inhibitory function animals were evaluated with long-term potentiation (LTP) and paired-pulse facilitation/inhibition. Compared to controls, both groups of rats with recurrent seizures were impaired in spatial memory in both water maze tests, had altered activity in the open field, and did not differ from controls in active avoidance. Rats with recurrent seizures had impaired LTP but showed no deficits in paired-pulse facilitation or inhibition. While rats with later onset showed a trend to worse performance than rats with earlier seizures, the differences were not substantial. Recurrent seizures during development are associated with long-term behavioral deficits in learning, memory and activity level as well as impaired synaptic efficiency. Age of seizure onset was not a strong predictor of outcome.