When an otherwise harmful insult to the brain is preceded by a brief, 
noninjurious stimulus, the brain becomes tolerant, and the resulting damage is 
reduced. Epileptic tolerance develops when brief seizures precede an episode of 
prolonged seizures (status epilepticus). MicroRNAs (miRNAs) are small, noncoding 
RNAs that function as post-transcriptional regulators of gene expression. We 
investigated how prior seizure preconditioning affects the miRNA response to 
status epilepticus evoked by intra-amygdalar kainic acid in mice. The miRNA was 
extracted from the ipsilateral CA3 subfield 24 hours after focal-onset status 
epilepticus in animals that had previously received either seizure 
preconditioning (tolerance) or no preconditioning (injury), and mature miRNA 
levels were measured using TaqMan low-density arrays. Expression of 21 miRNAs 
was increased, relative to control, after status epilepticus alone, and 
expression of 12 miRNAs was decreased. Increased miR-132 levels were matched 
with increased binding to Argonaute-2, a constituent of the RNA-induced 
silencing complex. In tolerant animals, expression responses of >40% of the 
injury-group-detected miRNAs differed, being either unchanged relative to 
control or down-regulated, and this included miR-132. In vivo microinjection of 
locked nucleic acid-modified oligonucleotides (antagomirs) against miR-132 
depleted hippocampal miR-132 levels and reduced seizure-induced neuronal death. 
Thus, our data strongly suggest that miRNAs are important regulators of 
seizure-induced neuronal death.