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 NfB, 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).
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: firstname.lastname@example.org