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PMID: 15737406 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, P.H.S. Review

Cellular mechanisms underlying acquired epilepsy: the calcium hypothesis of the induction and maintainance of epilepsy.

Pharmacology & therapeutics ·Vol. 105 ·No. 3 ·2005-03-00 ·Pages 229-66

Delorenzo RJ, Sun DA, Deshpande LS

Abstract

Epilepsy is one of the most common neurological disorders. Although epilepsy can be idiopathic, it is estimated that up to 50% of all epilepsy cases are initiated by neurological insults and are called acquired epilepsy (AE). AE develops in 3 phases: (1) the injury (central nervous system [CNS] insult), (2) epileptogenesis (latency), and (3) the chronic epileptic (spontaneous recurrent seizure) phases. Status epilepticus (SE), stroke, and traumatic brain injury (TBI) are 3 major examples of common brain injuries that can lead to the development of AE. It is especially important to understand the molecular mechanisms that cause AE because it may lead to innovative strategies to prevent or cure this common condition. Recent studies have offered new insights into the cause of AE and indicate that injury-induced alterations in intracellular calcium concentration levels [Ca(2+)](i) and calcium homeostatic mechanisms play a role in the development and maintenance of AE. The injuries that cause AE are different, but they share a common molecular mechanism for producing brain damage-an increase in extracellular glutamate concentration that causes increased intracellular neuronal calcium, leading to neuronal injury and/or death. Neurons that survive the injury induced by glutamate and are exposed to increased [Ca(2+)](i) are the cellular substrates to develop epilepsy because dead cells do not seize. The neurons that survive injury sustain permanent long-term plasticity changes in [Ca(2+)](i) and calcium homeostatic mechanisms that are permanent and are a prominent feature of the epileptic phenotype. In the last several years, evidence has accumulated indicating that the prolonged alteration in neuronal calcium dynamics plays an important role in the induction and maintenance of the prolonged neuroplasticity changes underlying the epileptic phenotype. Understanding the role of calcium as a second messenger in the induction and maintenance of epilepsy may provide novel insights into therapeutic advances that will prevent and even cure AE.

MeSH Terms
Animals Brain Injuries/classification,complications Calcium/metabolism,physiology Electroencephalography Epilepsy/drug therapy,etiology,metabolism Homeostasis/physiology Humans
Chemicals
Calcium
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Delorenzo Robert J
Department of Neurology, Virginia Commonwealth University, School of Medicine, Richmond, VA 23298-0599, USA. [email protected]
Sun David A
Deshpande Laxmikant S
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Article Info
Journal
Pharmacology & therapeutics
Abbr.
Pharmacol Ther
ISSN
0163-7258
DOI
10.1016/j.pharmthera.2004.10.004
Email
[email protected]
Published
2005-03-00
Epub
2004-00-09
Pages
229-66
Language
English
Region
England
NLM ID
7905840
PMCID
PMC2819430
Subset
IM
Grants
NINDS NIH HHS · R01 NS023350-20 · United States
NINDS NIH HHS · P50 NS025630-150001 · United States
NIDA NIH HHS · P50 DA005274 · United States
NINDS NIH HHS · R01-NS · United States
NINDS NIH HHS · P50 NS025630 · United States
NINDS NIH HHS · P50-NS · United States
NIDA NIH HHS · P50 DA005274-180016 · United States
NINDS NIH HHS · R01 NS023350 · United States
NINDS NIH HHS · R01 NS051505-03 · United States
NINDS NIH HHS · R01 NS051505 · United States
Corrections
ErratumIn
-
RepublishedIn
PMID: 16832874
External Links
PubMed source DOI: 10.1016/j.pharmthera.2004.10.004 PMC Full Text View journal details
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