Abstract
Insults to the brain that are sub-threshold for damage activate endogenous protective pathways, which can temporarily protect the brain against a subsequent harmful episode. This mechanism has been named as tolerance and its protective effects have been shown in experimental models of ischemia and epilepsy. The preconditioning-stimulus can be a short period of ischemia or mild seizures induced by low doses of convulsant drugs. Gene-array profiling has shown that both ischemic and epileptic tolerance feature large-scale gene down-regulation but the mechanism are unknown. MicroRNAs are a class of small non-coding RNAs of ~20–22 nucleotides length which regulate gene expression at a post-transcriptional level via mRNA degradation or inhibition of protein translation. MicroRNAs have been shown to be regulated after non-harmful and harmful stimuli in the brain and to contribute to neuroprotective mechanisms. This review focuses on the role of microRNAs in the development of tolerance following ischemic or epileptic preconditioning.
Highlights
Specialty section: This article was submitted to Neurodegeneration, a section of the journal Frontiers in Neuroscience
The preconditioning-stimulus can be a short period of ischemia or mild seizures induced by low doses of convulsant drugs
This review focuses on the role of microRNAs in the development of tolerance following ischemic or epileptic preconditioning
Summary
A model of hibernation, a natural model of tolerance to ischemia, was used to study the role of microRNAs during neuroprotection in the brain (Lee et al, 2012). Inhibition of miR-184 in vivo resulted in neuronal death after a normally non-damaging preconditional stimulus (McKiernan et al, 2012) and an increase in neurodegeneration during the tolerant state after status epilepticus (damaging injury stimulation). Together, these results show a neuroprotective role of miR-184 during preconditioning (McKiernan et al, 2012). This study shows the specific response of microRNAs after brain stimulation, and its possible role in the different tolerant-stages
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