Infantile Spasms and Down Syndrome: A New Animal Model
Infantile spasms is a catastrophic childhood seizure disorder for which few animal models exist. Children with Down syndrome are highly susceptible to infantile spasms. The Ts65Dn mouse is a valid model for Down syndrome; therefore, we tested the hypothesis that the Ts65Dn mouse represents a substra...
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Published in: | Pediatric research Vol. 65; no. 5; pp. 499 - 503 |
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Main Authors: | , , , , , , , , , , |
Format: | Journal Article |
Language: | English |
Published: |
New York
Nature Publishing Group US
01-05-2009
Lippincott Williams & Wilkins |
Subjects: | |
Online Access: | Get full text |
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Summary: | Infantile spasms is a catastrophic childhood seizure disorder for which few animal models exist. Children with Down syndrome are highly susceptible to infantile spasms. The Ts65Dn mouse is a valid model for Down syndrome; therefore, we tested the hypothesis that the Ts65Dn mouse represents a substrate for an animal model of infantile spasms. The baseline of naïve Ts65Dn mice showed spontaneous spike-and-wave discharges, a pattern that worsened with baclofen and γ-butyrolactone, which induced acute epileptic extensor spasms (AEES) associated with epileptiform polyspike bursts and an electrodecremental response on the EEG. GABA
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R-agonist-induced AEES were significantly reduced with vigabatrin, rodent ACTH fragment, valproic acid, ethosuximide, and CGP 35348. Porcine ACTH had no effect. GABA
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R protein expression was significantly increased in the thalamus and medulla oblongata of Ts65D mice in comparison with wild-type controls. The GABA
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R agonist-treated Ts65Dn mouse shows the unique clinical, electrographic, and pharmacologic signature of infantile spasms and represents a valid, acute model of this disorder. GABA
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R-mediated mechanisms may contribute to the increased susceptibility of children with Down syndrome to infantile spasms. |
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ISSN: | 0031-3998 1530-0447 |
DOI: | 10.1203/PDR.0b013e31819d9076 |