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- Title
A New Rat Model of Epileptic Spasms Based on Methylazoxymethanol-lnduced Malformations of Cortical Development.
- Authors
Eun-Hee Kim; Mi-Sun Yum; Minyoung Lee; Eun-Jin Kim; Woo-Hyun Shim; Tae-Sung Ko
- 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.
- Subjects
ANIMAL models in epilepsy research; ADRENOCORTICOTROPIC hormone; METHYL aspartate
- Publication
Frontiers in Neurology, 2017, p1
- ISSN
1664-2295
- Publication type
Article
- DOI
10.3389/fneur.2017.00271