Stereological methods reveal the robust size and stability of ectopic hilar granule cells after pilocarpine-induced status epilepticus in the adult rat

Authors

  • Daniel P. McCloskey,

    1. Center for Neural Recovery and Rehabilitation Research, Helen Hayes Hospital, Route 9W, West Haverstraw, NY 10993, USA
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  • Tana M. Hintz,

    1. Center for Neural Recovery and Rehabilitation Research, Helen Hayes Hospital, Route 9W, West Haverstraw, NY 10993, USA
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  • Joseph P. Pierce,

    1. Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, NY 10021, USA
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  • Helen E. Scharfman

    1. Center for Neural Recovery and Rehabilitation Research, Helen Hayes Hospital, Route 9W, West Haverstraw, NY 10993, USA
    2. Departments of Pharmacology and Neurology, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA
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Dr D. P. McCloskey, as above.
E-mail: mccloskeyd@helenhayeshosp.org

Abstract

Following status epilepticus in the rat, dentate granule cell neurogenesis increases greatly, and many of the new neurons appear to develop ectopically, in the hilar region of the hippocampal formation. It has been suggested that the ectopic hilar granule cells could contribute to the spontaneous seizures that ultimately develop after status epilepticus. However, the population has never been quantified, so it is unclear whether it is substantial enough to have a strong influence on epileptogenesis. To quantify this population, the total number of ectopic hilar granule cells was estimated using unbiased stereology at different times after pilocarpine-induced status epilepticus. The number of hilar neurons immunoreactive for Prox-1, a granule-cell-specific marker, was estimated using the optical fractionator method. The results indicate that the size of the hilar ectopic granule cell population after status epilepticus is substantial, and stable over time. Interestingly, the size of the population appears to be correlated with the frequency of behavioral seizures, because animals with more ectopic granule cells in the hilus have more frequent behavioral seizures. The hilar ectopic granule cell population does not appear to vary systematically across the septotemporal axis, although it is associated with an increase in volume of the hilus. The results provide new insight into the potential role of ectopic hilar granule cells in the pilocarpine model of temporal lobe epilepsy.

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