Prolonged febrile seizures in the immature rat model enhance hippocampal excitability long term

Authors

  • Celine Dube MSc,

    1. Department of Anatomy and Neurobiology, University of California at Irvine, Irvine, CA
    2. Department of Pediatrics, University of California at Irvine, Irvine, CA
    3. INSERM 398, University of Strasbourg, Strasbourg, France
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  • Kang Chen PhD,

    1. Department of Anatomy and Neurobiology, University of California at Irvine, Irvine, CA
    2. Department of Pediatrics, University of California at Irvine, Irvine, CA
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  • Mariam Eghbal-Ahmadi BSc,

    1. Department of Anatomy and Neurobiology, University of California at Irvine, Irvine, CA
    2. Department of Pediatrics, University of California at Irvine, Irvine, CA
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  • Kristen Brunson MSc,

    1. Department of Anatomy and Neurobiology, University of California at Irvine, Irvine, CA
    2. Department of Pediatrics, University of California at Irvine, Irvine, CA
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  • Ivan Soltesz PhD,

    1. Department of Anatomy and Neurobiology, University of California at Irvine, Irvine, CA
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  • Tallie Z. Baram MD, PhD

    Corresponding author
    1. Department of Anatomy and Neurobiology, University of California at Irvine, Irvine, CA
    2. Department of Pediatrics, University of California at Irvine, Irvine, CA
    • Departments of Anatomy and Neurobiology, and Pediatrics, ZOT 4475, University of California at Irvine, Irvine, CA 92697-4475
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Abstract

Febrile seizures (FSs) constitute the most prevalent seizure type during childhood. Whether prolonged FSs alter limbic excitability, leading to spontaneous seizures (temporal lobe epilepsy) during adulthood, has been controversial. Recent data indicate that, in the immature rat model, prolonged FSs induce transient structural changes of some hippocampal pyramidal neurons and long-term functional changes of hippocampal circuitry. However, whether these neuroanatomical and electrophysiological changes promote hippocampal excitability and lead to epilepsy has remained unknown. By using in vivo and in vitro approaches, we determined that prolonged hyperthermia-induced seizures in immature rats caused long-term enhanced susceptibility to limbic convulsants that lasted to adulthood. Thus, extensive hippocampal electroencephalographic and behavioral monitoring failed to demonstrate spontaneous seizures in adult rats that had experienced hyperthermic seizures during infancy. However, 100% of animals developed hippocampal seizures after systemic administration of a low dose of kainate, and most progressed to status epilepticus. Conversely, a minority of normothermic and hyperthermic controls had (brief) seizures, none developing status epilepticus. In vitro, spontaneous epileptiform discharges were not observed in hippocampal-entorhinal cortex slices derived from either control or experimental groups. However, Schaeffer collateral stimulation induced prolonged, self-sustaining, status epilepticus-like discharges exclusively in slices from experimental rats. These data indicate that hyperthermic seizures in the immature rat model of FSs do not cause spontaneous limbic seizures during adulthood. However, they reduce thresholds to chemical convulsants in vivo and electrical stimulation in vitro, indicating persistent enhancement of limbic excitability that may facilitate the development of epilepsy. Ann Neurol 2000;47:336–344

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