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Sci Rep. 2015 Sep 18;5:14143. doi: 10.1038/srep14143.

MicroRNA profiles in hippocampal granule cells and plasma of rats with pilocarpine-induced epilepsy--comparison with human epileptic samples.

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Department of Medical Sciences, Section of Pharmacology and Neuroscience Center, University of Ferrara, Italy.
National Institute of Neuroscience, Italy.
Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Italy.
Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, University of Ferrara, Italy.
Division of Brain Sciences, Imperial College London, Charing Cross Hospital,UK.
Medical Research Council (MRC) Clinical Sciences Centre, Imperial College London, Hammersmith Hospital, UK.
Department of Biomedical and NeuroMotor Sciences (DiBiNeM), Section of Pathology, Bellaria Hospital, Bologna, Italy.
IRCCS Institute of Neurological Sciences, Section of Neurology, Bellaria Hospital, Bologna, Italy.
Danish Epilepsy Center, Filadelfia/University of Copenhagen, Dianalund, Denmark.


The identification of biomarkers of the transformation of normal to epileptic tissue would help to stratify patients at risk of epilepsy following brain injury, and inform new treatment strategies. MicroRNAs (miRNAs) are an attractive option in this direction. In this study, miRNA microarrays were performed on laser-microdissected hippocampal granule cell layer (GCL) and on plasma, at different time points in the development of pilocarpine-induced epilepsy in the rat: latency, first spontaneous seizure and chronic epileptic phase. Sixty-three miRNAs were differentially expressed in the GCL when considering all time points. Three main clusters were identified that separated the control and chronic phase groups from the latency group and from the first spontaneous seizure group. MiRNAs from rats in the chronic phase were compared to those obtained from the laser-microdissected GCL of epileptic patients, identifying several miRNAs (miR-21-5p, miR-23a-5p, miR-146a-5p and miR-181c-5p) that were up-regulated in both human and rat epileptic tissue. Analysis of plasma samples revealed different levels between control and pilocarpine-treated animals for 27 miRNAs. Two main clusters were identified that segregated controls from all other groups. Those miRNAs that are altered in plasma before the first spontaneous seizure, like miR-9a-3p, may be proposed as putative biomarkers of epileptogenesis.

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