MicroRNA (miRNA) is a class of small non-coding RNA which regulates 
post-transcriptional gene expression by repressing and thereby fine-tuning 
protein production, mainly via sequence-specific binding within the 
3'untranslated region of mRNA transcripts. Although in humans there are only 
∼1600 miRNAs, bioinformatics, systems studies and advanced quantitative 
proteomics reveal miRNA regulation of over half of all protein-coding genes and 
that each miRNA can regulate multiple proteins. Epilepsy is a common, serious 
neurologic disorder characterized by recurring unprovoked seizures that result 
from abnormal firing of populations of neurons in the brain. The brain expresses 
several unique miRNAs which control dendritic morphology as well as ion channel 
levels, neuronal migration and glial function. There is an emerging view that 
the patho-mechanisms underlying the process of epileptogenesis, as well as 
maintenance and progression of the epileptic state, involve miRNAs that control 
multiple genes and proteins on a systems level. Expression profiling studies 
reveal select changes to brain miRNA levels following prolonged seizures (status 
epilepticus) in animal models. Inflammation, stress signaling and neuronal 
excitation are among the pathways most impacted. Analysis of miRNA expression in 
human epilepsy has also been performed, where again neuroinflammatory processes 
were prominent. These studies suggest that miRNAs may regulate certain key 
processes but are not necessarily broadly altering all patho-mechanisms in 
epilepsy. Functional studies employing antagomirs have identified contributions 
from miR-34a and miR-132 to seizure-induced neuronal death whereas silencing 
miR-134 potently reduced status epilepticus, seizure-damage and the later 
occurrence of spontaneous seizures. Efforts to identify the in vivo target(s) of 
epilepsy-regulated miRNAs, is now a priority. Last, miRNAs are stable, 
information-carrying (paracrine) signals. Profiling miRNA in biofluids may 
represent a novel source of disease biomarkers in epilepsy. In summary, miRNA is 
emerging as a critical new layer of gene expression control with implications 
for the cause and treatment of epilepsy.