Endogenous neuropeptide Y prevents recurrence of experimental febrile seizures by increasing seizure threshold
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Febrile seizures (FSs) typically occur at the onset of fever and do not recur within the same febrile episode despite enduring or increased hyperthermia. Recurrent seizures during the same febrile episode are considered “complex,” with potentially altered prognosis. A characterized immature rat model of FS was used to test the hypotheses that (1) a first FS influences the threshold temperature for subsequent ones, and (2) the underlying mechanisms involve the release and actions of the endogenous inhibitory hippocampal neuropeptide Y (NPY). Experimental FSs were induced two or three times, at 3- to 4-h intervals, and threshold temperatures measured. To determine the potential effects of seizure-induced endogenous NPY on thresholds for subsequent seizures, an antagonist of the major hippocampal NPY receptor (type 2) was infused prior to induction of the second seizure. As an indicator of NPY release, NPY expression was determined 4 and 24 h later. Threshold core and brain temperatures for hyperthermic seizures were consistent with those observed during human fever. Threshold temperatures for a second and third seizure were significantly and progressively higher than those required for the first. This “protective” effect involved induction of endogenous NPY because it was abolished by the NPY antagonist. In addition, NPY mRNA expression was increased in dentate gyrus, CA3 and CA1, after an experimental FS, consistent with peptide release. Collectively these data indicate that the absence of repetitive seizures during a febrile episode involves the inhibitory actions of endogenous NPY, suggesting that the signaling cascade triggered by this peptide might provide targets for therapeutic intervention.
Index EntriesSeizures fever febrile neuropeptide NPY hippocampus animal model rat immature
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- Baram T. Z. (2002) Animal models for febrile seizures, in Febrile Seizures, Baram, T. Z., and Shinnar, S., eds., Academic Press, San Diego, CA, pp. 189–203.Google Scholar
- Berg A. T. (2002) Recurrent febrile seizures, in Febrile Seizures, Baram, T. Z., and Shinnar, S., eds., Academic Press, San Diego, CA, pp. 37–52.Google Scholar
- Brunson K. L., Eghbal-Ahmadi M., Bender R., Chen Y., and Baram T. Z. (2001) Long-term, progressive hippocampal cell loss and dysfunction induced by early-life administration of corticotropin-releasing hormone reproduce the effects of early-life stress. Proc. Natl. Acad. Sci. U. S. A. 98, 8856–8861.PubMedCrossRefGoogle Scholar
- Eghbal-Ahmadi M., Avishai-Eliner S., Hatalski C. G., and Baram T. Z. (1999) Differential regulation of the expression of corticotropin-releasing factor receptor type 2 (CRF2) in hypothalamus and amygdala of the immature rat by sensory input and food intake. J. Neurosci. 19, 3982–3991.PubMedGoogle Scholar
- International League Against Epilepsy: Commission on Classification and Terminology. (1981) Proposal for revised clinical and electroencephalographic classification of epileptic seizures. Epilepsia 33, 661–666.Google Scholar
- Nelson K. B. and Ellenberg J. H. (1981) Febrile seizures, Raven Press, New York.Google Scholar
- Sherwood N. M. and Timiras P.S. (1970) A Stereotaxic Atlas of the Developing Rat Brain, University of California Press Berkeley, CA.Google Scholar
- Stafstrom C. E. (2002) The incidence and prevalence of febrile seizures, in Febrile Seizures, Baram, T.Z., and Shinnar, S., eds., Academic Press, San Diego, CA, pp. 1–21.Google Scholar