AUTHOR=Lee Minyoung , Yum Mi-Sun , Woo Dong-Cheol , Shim Woo-Hyun , Ko Tae-Sung , Velíšek Libor 

TITLE=In Vivo Multimodal Magnetic Resonance Imaging Changes After N-Methyl-d-Aspartate-Triggered Spasms in Infant Rats

JOURNAL=Frontiers in Neurology

VOLUME=Volume 9 - 2018

YEAR=2018

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2018.00248

DOI=10.3389/fneur.2018.00248

ISSN=1664-2295

ABSTRACT=Objective: Despite the serious neurodevelopmental sequaelae of epileptic encephalopathy during infancy, the pathomechanisms involved remain unclear. To find potential biomarkers that can reflect the pathogenesis of epileptic encephalopathy, we explored the neurometabolic and microstructural sequalae after infantile spasms using a rat model of infantile spasms and in vivo magnetic resonance imaging techniques.
Methods: Rats prenatally exposed to betamethasone were subjected to three rounds of intraperitoneal NMDA triggering of spasms or received saline injections (controls) on postnatal days (P) 12, 13, and 15. Chemical exchange saturation transfer imaging of glutamate (GluCEST) were performed at P15, 22 and diffusion tensor imaging and additional spectroscopy (1H-MRI/MRS) of the cingulate cortex were serially done at P16, 23, 30 and analyzed. Pathological analysis and western blotting were performed with rats sacrificed on P35.
Results: Within 24 h of the three rounds of NMDA-induced spasms, there was an acute increase in the GluCEST (%) in the cortex, hippocampus, and striatum. When focused on the cingulate cortex, mean diffusivity was significantly decreased during the acute period after multiple spasms with an increase in ɣ-aminobutyric acid (GABA), glutamate, and glutamine N-acetylaspartate-plus-N-acetylaspartylglutamate (tNAA), total choline, and total creatine. The juvenile rats also showed decreased mean diffusivity on diffusion tensor imaging and significant decreases in taurine, tNAA, and macromolecules-plus-lipids in the cingulate cortex. Pathologically, there was a significant reduction in glial fibrillary acidic protein, myelin basic protein, and NeuN expression in the cingulate cortex of rats with NMDA-induced spasms.
Significance: These neurometabolic and microstructural alterations after NMDA-triggered spasms might be potential imaging biomarkers of epileptic encephalopathy.