Abstracts

In humans, the highest incidence of status epilepticus (SE) is in childhood, while ischemic stroke affects mainly adulthood. In a previous study we found that, in rats, an early bout of SE with seizures of limbic origin and secondary generalization increases the susceptibility to ischemic stroke in adulthood. In the present study we evaluated the effect of SE at PN15 with flurothyl ether (FE), a model of SE with primarily generalized clonic-tonic seizures. Male Sprague Dawley rats at PN15 were submitted to 1-hour SE by continuous exposure to FE in a sealed chamber. One month after SE the same animals were subjected to middle cerebral artery occlusion (MCAo) by the intraluminal filament technique, for one or two hours. Twenty-four hours after MCAo the infarct volume for each rat was evaluated by computer scanning of 2 mm-brain sections stained with triphenyl-tetrazolium-chloride (TTC). Before sacrifice a graded neurological exam was determined using the following scale: 0=no deficit, 1= forelimb flexion; 2=decreased resistance to lateral push; 3= the same as 2 with circling. In adulthood, after 1 hour of ischemia rats submitted to FE-induced SE at PN15 had a significantly smaller volume of infarction as compared to littermates controls (36.82[plusmn]9.75 mm[sup3], and 101.24[plusmn]25 mm[sup3], respectively; p[lt]0.05 with t-student test), while the effect of two hours of ischemia was not modified (232[plusmn]72 mm[sup3] in the FE-SE group versus 208[plusmn]48 mm[sup3] in controls). Accordingly, a larger percentage of rats previously exposed to SE had no motor impairment after 1-hour ischemia as compared to controls (FE-SE: grade 0=86.7%; grade[gt]1=13.3%. Controls: grade 0=42.1%; grade[gt]1=57.9%). The protective effect of FE-induced SE on stroke volume was not due to FE by itself but rather to the SE; exposure at PN15 to the same amount of FE, but at such a low rate that did not induce seizures, did not alter the effect of one-hour ischemia in adulthood (volume of infarction 99.5[plusmn]31.13 mm[sup3]). A potential [quot]hypoxia-preconditioning[quot] effect toward ischemic damage was also ruled out, since arterial pO2 after one hour of FE-SE was not different from baseline (127.46[plusmn]7.2 and 138.5[plusmn]522.8 mmHg, respectively). These results suggest that the exposure of the immature brain to FE-SE attenuates the susceptibility to ischemic injury in adulthood. However, the net effect on stroke of a previous SE might be model-dependent, since we previously showed a worsening effect of an early Kainate-induced SE on 1-hour ischemia in adulthood. (Supported by NIH grant NS20253 and Heffer Family Medical Foundation (SLM), and by NIH EY11053 (DMR))