IJPPP Copyright © 2009-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Int J Physiol Pathophysiol Pharmacol 2009;1(2):180-191.

Review Article
Seizure preconditioning and epileptic tolerance: models and mechanisms

Eva M. Jimenez-Mateos, David C. Henshall

Department of Physiology & Medical Physics, Royal College of Surgeons in Ireland, Dublin, Ireland

Received October 15, 2009; accepted; October 28, 2009; available online November 2, 2009

Abstract: One or more brief seizures can serve to activate endogenous protective programmes which render brain regions temporarily
less susceptible to damage following an otherwise harmful episode of status epilepticus (a prolonged seizure). Epileptic tolerance has
been demonstrated using a variety of seizure preconditioning paradigms, including electroconvulsive shocks and low doses of
excitotoxins such as kainic acid. The cell and molecular mechanisms underlying the protection are not fully understood but proposed
mediators include the transcription factor NfB, altered ion channel expression, upregulation of growth factors and other protective
genes, and suppression of pro-apoptotic Bcl-2 family proteins. Application of microarrays to profile the transcriptome of seizure-
preconditioning and tolerance has provided further insights, including roles for chromatin remodeling and evidence that
preconditioning generates an anti-excitotoxicity phenotype by reprogramming the transcriptional response to status epilepticus. This
review summarizes the various animal models of epileptic tolerance, reviews the key effector(s) and the utility of this experimental
paradigm for identifying novel targets for neuroprotection and anti-epileptogenesis. (IJPPP910001).

Key words: Apoptosis; epileptogenesis; hippocampal sclerosis; ischemic tolerance; neuroprotection

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Address all correspondence to:
David C. Henshall, PhD
Department of Physiology & Medical Physics
Royal College of Surgeons in Ireland
123 St. Stephen’s Green
Dublin 2, Ireland.
Tel: +353 1 402 8629; Fax: +353 1 402 2447
E-mail:
dhenshall@rcsi.ie