Linked Life Data

15519132

Source:http://linkedlifedata.com/resource/pubmed/id/15519132

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2004-11-2
pubmed:abstractText
Medically refractory seizure disorders in children usually have malignant neurodevelopmental outcomes and often are associated with the presence of congenital cortical dysplasias in the brain. To date, there are no animal models of these disorders by which to test hypotheses of pathogenesis or to screen novel drugs for antiepileptic activity. In rats, treatment with the antimitotic agent methylazoxymethanol acetate (MAM) on gestational day (G) 15 produces a neuronal migration disorder similar to the cortical dysplasias seen in human brain. We sought to produce chronic, recurrent, medically refractory seizures by administration of the cholesterol biosynthesis inhibitor AY-9944 (AY) during postnatal development in rats exposed prenatally to MAM. Prenatal MAM and postnatal AY treatments resulted in spontaneous, recurrent atypical absence seizures that were characterized by bilaterally synchronous slow spike-and-wave discharges (SWD) with a frequency of 6 Hz. The MAM-AY-induced seizures were refractory to ethosuximide, sodium valproate, and the GABABR antagonist CGP 35348, and were exacerbated by carbamazepine. Histological examination of brains from MAM-treated rats showed hippocampal heterotopias, in addition to atrophy and abnormalities of cortical lamination. The MAM-AY-treated rat represents a reproducible model of refractory atypical absence seizures in children with brain dysgenesis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0920-1211
pubmed:author
pubmed:issnType
Print
pubmed:volume
62
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
53-63
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Refractory atypical absence seizures in rat: a two hit model.
pubmed:affiliation
Division of Neurology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ont., Canada M5G 1X8.
pubmed:publicationType
Journal Article