Effect of topiramate on cognitive function and activity level following neonatal seizures.
Topiramate, an antiepileptic drug with a number of mechanisms of action including blockade of AMPA/KA receptor subtypes, was assessed as a neuroprotective agent following seizures. We administered topiramate or saline chronically during and following a series of 25 neonatal seizures. After completion of the topiramate treatment, animals were tested in the water maze for spatial learning and the open field for activity level. Brains were then examined for cell loss and sprouting of mossy fibers. Rats treated with topiramate performed significantly better in the water maze than rats treated with saline. Topiramate treatment also reduced the amount of seizure-induced sprouting in the supragranular region. There were no differences between topiramate- and saline-treated rats in activity level in the open field, swimming speed, or weight gain. These findings show that long-term treatment with topiramate after neonatal seizures changes the long-term consequences of seizures and improves cognitive function.