Effect of levetiracetam on visual-spatial memory following status epilepticus

Abstract

Status epilepticus (SE) is often followed by severe cognitive impairment, including memory impairment. Previous studies have shown that SE is associated with impairment of single cells in the hippocampus that fire action potentials when the animal is in a specific location in space, the so-called place cells, and that place cell function correlates well with performance in tasks of visual-spatial memory. Place cell patterns therefore appear to be an excellent measure of spatial memory and may serve as a tool to assess seizure-induced impairment in memory. In this study we determined the relationship between visual-spatial memory and place cell function following SE. In addition, we determined if levetiracetam (LEV), an antiepileptic drug with a novel mechanism of action, can improve cognitive function and place cell firing patterns when administered following SE. SE was induced in adult male rats which were then randomized to post-SE treatment with LEV or normal saline (NS) treatment for 14 days. Non-SE control rats also were randomized to LEV or NS. Following discontinuation of LEV rats were tested for visual-spatial memory in the Morris water-maze and then underwent unit recording in the CA1 region of the hippocampus. Brains were then evaluated for cell loss and mossy fiber sprouting. SE was associated with severely impaired performance in the water-maze with SE rats demonstrating no learning over four days of testing. Paralleling this memory deficit was a marked disturbance in firing patterns of pyramidal neurons in CA1. Non-SE rats learned quickly over four days of water-maze testing and had normal pyramidal cell firing patterns. LEV had no major effects on water-maze performance or place cell function. Histopathological examination of the brains showed severe cell loss in CA1 in all of the SE rats with lesser degrees of injury in CA3 and the hilus. LEV treatment resulted in less histological damage in the hippocampus but had no effect on visual-spatial function or place cell physiology in either control or SE rats.