Abstracts

While status epilepticus (SE) results in less brain damage in immature animals than mature animals, SE does predispose the immature brain to greater injury following a second seizure, the so-called [quot]second-hit[quot] phenomenon. Whether this increased vulnerability occurs immediately following the SE is not yet known. In this study we addressed the question of whether repeated seizures following status epilepticus in young rats has any effect on subsequent learning or memory. Male Long Evans rats were divided into 4 groups at postnatal (P) day 10: SE induced by lithium-pilocarpine followed by 5 flurothyl-induced seizure for 5 days (P11-P15)(n=11); SE followed by saline injections (n=11); Sham SE followed by flurothyl-induced seizures (n=6) ; and Sham SE followed by saline injections (controls)(n=10). Flurothyl was administered by inhalation and animals were exposed until they had tonic seizures. At P30 animals were evaluated for visual-spatial learning and memory in the Morris water maze. Histological evaluations were performed following completion of the water maze testing. Lithium-pilocarpine resulted in SE in all animals with bilateral forelimb clonus, head nodding, and chewing. All animals learned the position of the hidden platform over four days of testing. Animals subjected to SE followed by 25 flurothyl-induced seizures performed significantly worse than animals with SE only or flurothyl-induced seizures only (p[lt]0.05). No significant differences in motivation or swimming speed were found. SE followed by recurrent flurothyl seizures results in greater impairment in visual-spatial memory than SE alone or flurothyl seizures alone. These findings demonstrate that despite the lack of SE-induced pathological lesions in immature animals, SE immediately predisposes the brain to subsequent seizure-induced cognitive impairment. These finding suggest that the time window for intervention following SE in the immature brain is limited. (Supported by The Western Massachusetts Epilepsy Awareness Committee and National Institutes of Health, NINDS (NS41495 and NS044296).)