Role of Plasma miRNA223 and High Mobility Group Box 1(HMGB1) as Predictors of Drug Resistant Epilepsy

Epilepsy is the most prevalent neurological disorders (1). Drug-resistant epilepsy (DRE) represent approximately 30% of epilepsy..DRE is defined as failure to achieve sustained seizure freedom after adequate and well tolerated trials of two antiseizure medications( ASMs).The identification of circulating biomarkers for DRE could give an early idea about the prognosis and improve the choice of correct treatment.

MiRNAs are small noncoding RNAs that span between 19 and 24 nucleotide bases((2).They gain biological activity through base pairing in the 30-untranslated regions of target messenger RNA (mRNA) , thereby guiding a protein complex termed the RNA-induced silencing complex (RISC) that bind to the mRNA sequence and results in either the inhibition of translational processes or the degradation of the mRNA (3). Dysregulated miRNA expression has been associated with inflammatory pathways, cell death, neuronal excitability, and synaptic reorganization, which underlie epileptogenesis (4).

High- mobility group box 1(HMGB1) is a chromatin component that is physiologically attached to nuclei. However, following CNS insult, it can promptly be migrated towards cytoplasm and is discharged extracellularly. HMGB1mediates sterile neuro-inflammation evoked by epileptogenic injury and recurrent seizures(5) .HMGB1 increases in neurons, glia, and endothelial cells of the blood brain barrier (BBB) in DRE.

The HMGB1 contributes to the overexpression of P-glycoprotein, a BBB protein, which is induced in DRE foci and extrudes various ASMs from the brain(6) .