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Regeneration Of Neurotransmission Transcriptome In A Model Of Epileptic Encephalopathy After Antiinflammatory Treatment, Dumitru Iacobas, Libor Velisek Oct 2018

Regeneration Of Neurotransmission Transcriptome In A Model Of Epileptic Encephalopathy After Antiinflammatory Treatment, Dumitru Iacobas, Libor Velisek

NYMC Faculty Publications

Inflammation is an established etiopathogenesis factor of infantile spasms (IS), a therapy-resistant epileptic syndrome of infancy. We investigated the IS-associated transcriptomic alterations of neurotransmission in rat hypothalamic arcuate nucleus, how they are corrected by antiinflamatory treatments and whether there are sex differences. IS was triggered by repeated intraperitoneal administration of N-methyl-D-aspartic acid following anti-inflammatory treatment (adreno-cortico-tropic-hormone (ACTH) or PMX53) or normal saline vehicle to prenatally exposed to betamethasone young rats. We found that treatments with both ACTH and PMX53 resulted in substantial recovery of the genomic fabrics of all types of synaptic transmission altered by IS. While ACTH represents the …


Acth And Pmx53 Recover Synaptic Transcriptome Alterations In A Rat Model Of Infantile Spasms, Dumitru Iacobas, Tamar Chachua, Sanda Iacobas, Melissa Benson, Karin Borges, Jana Veliskova, Libor Velisek Apr 2018

Acth And Pmx53 Recover Synaptic Transcriptome Alterations In A Rat Model Of Infantile Spasms, Dumitru Iacobas, Tamar Chachua, Sanda Iacobas, Melissa Benson, Karin Borges, Jana Veliskova, Libor Velisek

NYMC Faculty Publications

We profiled the gene expression in the hypothalamic arcuate nuclei (ARC) of 20 male and 20 female rats to determine the infantile spasms (IS) related transcriptomic alteration of neurotransmission and recovery following two treatments. Rats were prenatally exposed to betamethasone or saline followed by repeated postnatal subjection to NMDA-triggered IS. Rats with spasms were treated with ACTH, PMX53 or saline. Since ACTH, the first line treatment for IS, has inconsistent efficacy and potential harsh side effects, PMX53, a potent complement C5ar1 antagonist, was suggested as a therapeutic alternative given its effects in other epilepsy models. Novel measures that consider all …


In Vivo Multimodal Magnetic Resonance Imaging Changes After N-Methyl-D-Aspartate-Triggered Spasms In Infant Rats, Minyoung Lee, Mi-Sun Yum, Dong-Cheol Woo, Woo-Hyun Shim, Tae-Sung Ko, Libor Velisek Apr 2018

In Vivo Multimodal Magnetic Resonance Imaging Changes After N-Methyl-D-Aspartate-Triggered Spasms In Infant Rats, Minyoung Lee, Mi-Sun Yum, Dong-Cheol Woo, Woo-Hyun Shim, Tae-Sung Ko, Libor Velisek

NYMC Faculty Publications

Objective: Despite the serious neurodevelopmental sequelae 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 sequelae 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 N-methyl-d-aspartate (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 and 22 and diffusion tensor …