Circulating microRNAs and isomiRs as biomarkers for the initial insult and epileptogenesis in four experimental epilepsy models: The EPITARGET study

Objective Structural epilepsies can manifest months or years after the occurrence of an initial epileptogenic insult, making them amenable for secondary prevention. However, development of preventive treatments has been challenged by a lack of biomarkers for identifying the subset of individuals wit...

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Published in:Epilepsia (Copenhagen) 2024-11, Vol.65 (11), p.3406-3420
Main Authors: Vliet, Erwin A., Scheper, Mirte, Mills, James D., Puhakka, Noora, Szydlowska, Kinga, Ferracin, Manuela, Lovisari, Francesca, Soukupova, Marie, Zucchini, Silvia, Srivastava, Prashant K., Johnson, Michael R., Lukasiuk, Katarzyna, Gorter, Jan A., Aronica, Eleonora, Pitkänen, Asla, Simonato, Michele
Format: Article
Language:English
Subjects:
amygdala stimulation
Animal models
Animals
Biomarkers
Biomarkers - blood
Circulating MicroRNA - blood
Circulating MicroRNA - genetics
Disease Models, Animal
EEG
Electroencephalography
Epilepsy
Epilepsy - blood
Epilepsy - genetics
Genomic analysis
Kainic Acid
Latency
Male
MicroRNAs
MicroRNAs - blood
MicroRNAs - genetics
miRNA
perforant pathway stimulation
pilocarpine
posttraumatic epilepsy
Rats
Rats, Sprague-Dawley
status epilepticus
traumatic brain injury
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Summary:Objective Structural epilepsies can manifest months or years after the occurrence of an initial epileptogenic insult, making them amenable for secondary prevention. However, development of preventive treatments has been challenged by a lack of biomarkers for identifying the subset of individuals with the highest risk of epilepsy after the epileptogenic insult. Methods Four different rat models of epileptogenesis were investigated to identify differentially expressed circulating microRNA (miRNA) and isomiR profiles as biomarkers for epileptogenesis. Plasma samples were collected on day 2 and day 9 during the latency period from animals that did or did not develop epilepsy during long‐term video‐electroencephalographic monitoring. miRNAs and isomiRs were identified and measured in an unsupervised manner, using a genome‐wide small RNA sequencing platform. Receiver operating characteristic analysis was performed to determine the performance of putative biomarkers. Results Two days after an epileptogenic insult, alterations in the levels of several plasma miRNAs and isomiRs predicted epileptogenesis in a model‐specific manner. One miRNA, miR‐3085, showed good sensitivity (but low specificity) as a prognostic biomarker for epileptogenesis in all four models (area under the curve = .729, sensitivity = 83%, specificity = 64%, p 
ISSN:0013-9580
1528-1167
1528-1167
DOI:10.1111/epi.18134