Abstracts

Febrile seizures typically occur at the onset of a fever episode and do not recur within the same episode despite persistent or increased hyperthermia. Indeed, seizure recurrence within hours in a febrile episode are considered an atypical, complex feature that alters prognosis. Here we used an appropriate-age, characterized immature rat model to test the hypothesis that a first febrile seizure influences the threshold temperature for subsequent ones, and to determine the underlying mechanisms.
Experimental febrile seizures were induced two or three times at 4h intervals. To determine whether NPY was involved in increased thresholds for subsequent seizures, the NPY Y2 receptor antagonist (BIIE0246, 100nm/kg), was infused icv prior to induction of the second seizure, and release-provoked upregulation of hippocampal NPY mRNA expression was determined 4 and 24h after seizures.
Experimental febrile seizures (involving the hippocampal formation) emerged at temperatures similar to those of febrile infants. Threshold temperatures for the onset of a second and third seizure were significantly and progressively higher than those required for the first. NPY Y2 receptor antagonist abolished the increased threshold for a second compared with a first seizure. NPY mRNA expression was increased 4h (in dentate gyrus [DG]) and 24 h (DG and CA1) after febrile seizures.
The basis for the single-seizure-per-febrile-episode phenomenon occurring in most children involves inhibitory actions of endogenous NPY, suggesting that the signaling cascade of this peptide may provide therapeutic targets.
[Supported by: NIH NS28912, NS35439 (TZB); Epilepsy Foundation of America Post-doctoral Research Training Fellowship (CD).]