Circulating microRNAs from plasma as preclinical biomarkers of epileptogenesis and epilepsy

Background: Epilepsy frequently develops as a result of brain insult, e.g., brain injury or stroke; however, currently, there are no tools allowing us to predict which patients suffering from trauma will eventually develop epilepsy. microRNAs are interesting candidates for biomarkers, as several of them have been described to change their levels in the brains of epileptic subjects. There is evidence suggesting that microRNA levels are also altered in the plasma during epilepsy. This study was conducted to evaluate the usefulness of plasma miRNAs as epileptogenesis/epilepsy biomarkers. Methods In our studies, we used a rat model of temporal lobe epilepsy. An epileptogenic insult was status epilepticus evoked by stimulation of the left lateral nucleus of the amygdala. Next, animals were continuously video and EEG monitored for 3 months. Blood was collected at 14, 30, 60, and 90 days after stimulation from the tail vein. Blood plasma was separated and processed using Affymetrix miRNA 4.1 array strip microarrays. Results We compared miRNA levels between sham-operated (n = 12) and stimulated animals (n = 15). We detected 14 miRNAs differentiating between sham-operated and stimulated animals at 14 days, 6 at 30 days, 16 at 60 days, and 11 at 90 days. We also compared the miRNA levels between animals with high and low numbers of seizures. We found differences in the levels of 11 miRNAs at 14 d, 7 at 30 d, 11 at 60 d and 8 at 90 d (p < 0.01). Conclusions We propose three miRNAs that could be potential biomarkers of different stages of epileptogenesis: miR-671, miR-9a-3p and miR-7a-5p. According to us, miR-206-5p is a potential biomarker of epileptogenesis, and miR-221-3p is a potential biomarker of epilepsy severity, characterized by the number of seizures. We also think that these five miRNAs can be considered in the future as potential treatment targets.