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Go "West," young man...The quest for animal models of infantile spasms (West syndrome).

  • Author(s): Baram, Tallie Z
  • et al.
Abstract

Model of Infantile Spasms Induced by N-methyl-D-aspartic Acid in Prenatally Impaired Brain. Velisek L, Jehle K, Asche S, Veliskova J. Ann Neurol 2007;61(2):109–119. 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.

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