Basic mechanisms of catastrophic epilepsy - Overview from animal models

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Infantile spasms are age-specific seizures of infantile epileptic encephalopathies that are usually associated with poor epilepsy and neurodevelopmental outcomes. The current treatments are not always effective and may be associated with significant side effects. Various mechanisms have been proposed as pathogenic for infantile spasms, including cortical or brainstem dysfunction, disruption of normal cortical-subcortical communications, genetic defects, inflammation, stress, developmental abnormalities. Many of these have been recently tested experimentally, resulting into the emergence of several animal models of infantile spasms. The stress theory of spasms yielded the corticotropin releasing hormone (CRH)-induced model, which showed the higher proconvulsant potency of CRH in developing rats, although only limbic seizures were observed. Models of acute induction of infantile spasms in rodents include the N-methyl-. d-aspartate (NMDA) model of emprosthotonic seizures, the prenatal betamethasone and prenatal stress variants of the NMDA model, and the γ-butyrolactone induced spasms in a Down's syndrome mouse model. Chronic rodent models of infantile spasms include the tetrodotoxin model and the multiple-hit models in rats, as well as two genetic mouse models of interneuronopathies with infantile spasms due to loss of function of the aristaless X-linked homeobox-related gene (ARX). This review discusses the emerging mechanisms for generation of infantile spasms and their associated chronic epileptic and dyscognitive phenotype as well as the recent progress in identifying pathways to better treat this epileptic encephalopathy.

Original languageEnglish (US)
Pages (from-to)748-756
Number of pages9
JournalBrain and Development
Volume35
Issue number8
DOIs
StatePublished - Sep 2013

Fingerprint

Infantile Spasms
Epilepsy
Animal Models
Corticotropin-Releasing Hormone
Spasm
Brain Diseases
N-Methylaspartate
Rodentia
Seizures
Betamethasone
X-Linked Genes
Homeobox Genes
Genetic Models
Tetrodotoxin
Down Syndrome
Aspartic Acid
Brain Stem
Communication
Inflammation
Phenotype

Keywords

  • ACTH
  • ARX
  • Carisbamate
  • Cognitive
  • Infantile spasms
  • MTOR
  • NMDA
  • Rapamycin
  • Vigabatrin

ASJC Scopus subject areas

  • Clinical Neurology
  • Developmental Neuroscience
  • Pediatrics, Perinatology, and Child Health

Cite this

Basic mechanisms of catastrophic epilepsy - Overview from animal models. / Galanopoulou, Aristea S.

In: Brain and Development, Vol. 35, No. 8, 09.2013, p. 748-756.

Research output: Contribution to journalArticle

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