How can methylprednisolone work on epileptic spasms with malformation of cortical development?
Adrenocorticotropic Hormone
/ pharmacology
Animals
Animals, Newborn
Brain
/ drug effects
Disease Models, Animal
Epilepsy
/ drug therapy
Female
Methylprednisolone
/ administration & dosage
N-Methylaspartate
/ administration & dosage
Neurogenesis
/ drug effects
Pregnancy
Prenatal Exposure Delayed Effects
/ chemically induced
Rats
GluCEST
epileptic spasms
fast oscillations
malformation of cortical development
methylprednisolone
Journal
The European journal of neuroscience
ISSN: 1460-9568
Titre abrégé: Eur J Neurosci
Pays: France
ID NLM: 8918110
Informations de publication
Date de publication:
12 2019
12 2019
Historique:
received:
19
04
2019
revised:
04
07
2019
accepted:
25
07
2019
pubmed:
10
8
2019
medline:
24
9
2020
entrez:
10
8
2019
Statut:
ppublish
Résumé
Although steroids are suggested as the treatment of choice for infantile spasms, the mechanism of action is still unclear. Using a rat model of malformation of cortical development with refractory infantile spasms, we evaluated the efficacy of methylprednisolone on spasms susceptibility and behaviors. Additionally, we investigated the in vivo electrophysiological and neurochemical changes of the brain after methylprednisolone treatment. Infant rats with prenatal exposure of methylazoxymethanol at gestational day 15 were used. After a single dose of methylprednisolone or three different doses of methylprednisolone for 3 days, spasms were triggered by intraperitoneal injection of N-methyl-d-aspartic acid. In rats with 3 days of methylprednisolone pretreatment and their controls, behavioral testing was performed at postnatal day 15. In vivo magnetic resonance imaging was conducted at postnatal day 15 after 3 days of methylprednisolone treatment. The rats with single methylprednisolone pretreatment showed significantly delayed onset of spasms and multiple doses of methylprednisolone significantly suppressed the development of spasms in a dose-dependent manner. After multiple methylprednisolone pretreatment and a cluster of N-methyl-d-aspartic acid-induced spasms, the rats showed significantly increased freezing behaviors to conditioned stimuli. Glutamate-weighted chemical exchange saturation transfer revealed significant elevation of glutamate concentration in the cortices of the rats with multiple methylprednisolone pretreatments. Methylprednisolone pretreatment could attenuate N-methyl-d-aspartic acid-induced spasms with in vivo neurochemical and electrophysiological changes, which indicates this steroid's action on the brain and in epilepsy.
Substances chimiques
N-Methylaspartate
6384-92-5
Adrenocorticotropic Hormone
9002-60-2
Methylprednisolone
X4W7ZR7023
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4018-4027Informations de copyright
© 2019 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
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