Resistance of immature hippocampus to morphologic and physiologic alterations following status epilepticus or kindling

Authors

  • Kurt Z. Haas,

    Corresponding author
    1. Department of Neuroscience, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York
    • Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY11724
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  • Ellen F. Sperber,

    1. Department of Neuroscience, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York
    2. Department of Neurology, Montefiore/Einstein Epilepsy Management Center, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York
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  • Lisa A. Opanashuk,

    1. Department of Environmental Medicine, University of Rochester, Rochester, New York
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  • Patric K. Stanton,

    1. Department of Neuroscience, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York
    2. Department of Neurology, Montefiore/Einstein Epilepsy Management Center, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York
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  • Solomon L. Moshé

    1. Department of Neuroscience, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York
    2. Department of Neurology, Montefiore/Einstein Epilepsy Management Center, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York
    3. Department of Pediatrics, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, New York
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Abstract

Seizures in adult rats result in long-term deficits in learning and memory, as well as an enhanced susceptibility to further seizures. In contrast, fewer lasting changes have been found following seizures in rats younger than 20 days old. This age-dependency could be due to differing amounts of hippocampal neuronal damage produced by seizures at different ages. To determine if there is an early developmental resistance to seizure-induced hippocampal damage, we compared the effects of kainic acid (KA)-induced status epilepticus and amygdala kindling on hippocampal dentate gyrus anatomy and electrophysiology, in immature (16 day old) and adult rats. In adult rats, KA status epilepticus resulted in numerous silver-stained degenerating dentate hilar neurons, pyramidal cells in fields CA1 and CA3, and marked numerical reductions in CA3c pyramidal neuron counts (−57%) in separate rats. Two weeks following the last kindled seizure, some, but significantly less, CA3c pyramidal cell loss was observed (−26%). Both KA status epilepticus and kindling induced mossy-fiber sprouting, as evidenced by ectopic Timm staining in supragranular layers of the dentate gyrus. In hippocampal slices from adult rats, paired-pulse stimulation of perforant path axons revealed a persistent enhancement of dentate granule-cell inhibition following KA status epilepticus or kindling. While seizures induced by KA or kindling in 16-day-old rats were typically more severe than in adults, the immature hippocampus exhibited markedly less KA-induced cell loss (−22%), no kindling-induced loss, no detectable synaptic rearrangement, and no change in dentate inhibition. These results demonstrate that, in immature rats, neither severe KA-induced seizures nor repeated kindled seizures produce the kind of hippocampal damage and changes associated with even less severe seizures in adults. The lesser magnitude of seizure-induced hippocampal alterations in immature rats may explain their greater resistance to long-term effects of seizures on neuronal function, as well as future seizure susceptibility. Conversely, hippocampal neuron loss and altered synaptic physiology in adults may contribute to increased sensitivity to epileptogenic stimuli, spontaneous seizures, and behavioral deficits. Hippocampus 2001;11:615–625. © 2001 Wiley-Liss, Inc.

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