IJPPP Copyright © 2009-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Int J Physiol Pathophysiol Pharmacol 2009;1(2):97-115.

Review Article
Apoptosis, Bcl-2 family proteins and Caspases: the ABCs of seizure-damage and
epileptogenesis?

Tobias Engel, David C. Henshall

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

Received March 15, 2009; accepted March 20, 2009; available online March 30, 2009

Abstract: Epilepsy is a common, chronic neurological disorder. It is characterized by recurring seizures which are the result of
abnormal electrical activity in the brain. Molecular pathways underlying neuronal death are of importance because prolonged seizure
episodes (status epilepticus) cause significant damage to the brain, particularly within vulnerable structures such as the hippocampus.
Additionally, repeated seizures over time in patients with poorly controlled epilepsy may cause further cell loss. Biochemical hallmarks
associated with apoptosis have been identified in hippocampal and neocortical material removed from patients with
pharmacoresistant epilepsy: altered expression of pro-apoptotic Bcl-2 family genes and increased expression of caspases and the
presence of their cleaved forms. However, apoptotic cells are rarely detected in such patient material and there is evidence of anti-
apoptotic signaling changes in the same tissue, including upregulation of Bcl-2 and Bcl-w. From animal studies there is evidence that
both brief and prolonged seizures can cause neuronal apoptosis within the hippocampus. Such cell death can be associated with
caspase and pro-apoptotic Bcl-2 family protein activation. Pharmacological or genetic modulations of these pathways can significantly
influence DNA fragmentation and neuronal cell death after seizures. Thus, the signaling pathways associated with apoptosis are
potentially important for the pathogenesis of epilepsy and may represent targets for neuroprotective and perhaps anti-epileptogenic
therapies. (IJPPP903003).

Key words: Apoptosis, Epilepsy, Epileptogenesis, Hippocampal sclerosis, Necrosis, Programmed cell death

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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
Email:
dhenshall@rcsi.ie