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Ann Neurol. 2007 Feb;61(2):109-19.

Model of infantile spasms induced by N-methyl-D-aspartic acid in prenatally impaired brain.

Author information

1
Saul R. Korey Department of Neurology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. velisek@aecom.yu.edu

Abstract

OBJECTIVE:

Infantile spasms (a catastrophic epileptic syndrome of childhood) are insensitive to classic antiepileptic drugs. New therapies are limited by lack of animal models. Here we develop a new model of flexion spasms based on prenatal exposure to betamethasone combined with postnatal administration of N-methyl-D-aspartic acid (NMDA) and determine brain structures involved in the induction of flexion spasms.

METHODS:

Pregnant rats received two doses of betamethasone on day 15 of gestation. Offspring was injected with NMDA on postnatal day 15. Effects of adrenocorticotropin therapy on the development of age-specific flexion spasms were determined and electroencephalographic correlates recorded. C-fos immunohistochemistry and [14C]2-deoxyglucose imaging identified brain structures involved in the development of flexion spasms.

RESULTS:

Prenatal betamethasone exposure sensitizes rats to development of NMDA-induced spasms and, most importantly, renders the spasms sensitive to adrenocorticotropin therapy. Ictal electroencephalogram results correspond to human infantile spasms: electrodecrement or afterdischarges were observed. Imaging studies defined three principal regions involved in NMDA spasms: limbic areas (except the dorsal hippocampus), hypothalamus, and the brainstem.

INTERPRETATION:

Despite certain limitations, our new model correlates well with current infantile spasm hypotheses and opens an opportunity for development and testing of new effective drugs.

PMID:
17315208
DOI:
10.1002/ana.21082
[Indexed for MEDLINE]

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