a new rat model of epileptic spasms based on methylazoxymethanol-induced malformations of cortical development

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ID: 230949
2017
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Abstract
Malformations of cortical development (MCDs) can cause medically intractable epilepsies and cognitive disabilities in children. We developed a new model of MCD-associated epileptic spasms by treating rats prenatally with methylazoxymethanol acetate (MAM) to induce cortical malformations and postnatally with N-methyl-d-aspartate (NMDA) to induce spasms. To produce cortical malformations to infant rats, two dosages of MAM (15 mg/kg, intraperitoneally) were injected to pregnant rats at gestational day 15. In prenatally MAM-exposed rats and the controls, spasms were triggered by single (6 mg/kg on postnatal day 12 (P12) or 10 mg/kg on P13 or 15 mg/kg on P15) or multiple doses (P12, P13, and P15) of NMDA. In prenatally MAM-exposed rats with single NMDA-provoked spasms at P15, we obtain the intracranial electroencephalography and examine the pretreatment response to adrenocorticotropic hormone (ACTH) or vigabatrin. Rat pups prenatally exposed to MAM exhibited a significantly greater number of spasms in response to single and multiple postnatal NMDA doses than vehicle-exposed controls. Vigabatrin treatment prior to a single NMDA dose on P15 significantly suppressed spasms in MAM group rats (p < 0.05), while ACTH did not. The MAM group also showed significantly higher fast oscillation (25–100 Hz) power during NMDA-induced spasms than controls (p = 0.047). This new model of MCD-based epileptic spasms with corresponding features of human spasms will be valuable for future research of the developmental epilepsy.
Reference Key
kim2017frontiersa Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors ;Eun-Hee Kim;Mi-Sun Yum;Minyoung Lee;Eun-Jin Kim;Woo-Hyun Shim;Tae-Sung Ko
Journal journal of photochemistry and photobiology a: chemistry
Year 2017
DOI
10.3389/fneur.2017.00271
URL
http://journal.frontiersin.org/article/10.3389/fneur.2017.00271/full
Keywords
gaba diseases of the nervous system

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