Abstract:

Preconditioning is an adaptive response, whereby a small dose of a harmful substance protects the brain from a subsequent damaging insult. Consequently, several preconditioning treatment paradigms are used in the clinic to protect patients against an ischemic insult in heart pathologies. This data shows the importance of understanding the underlying mechanism to preconditioning, and its translation in the clinic in brain disorders. In concordance, any injury to the brain applied below the threshold of cell damage, including seizures, will induce preconditioning and neuro-protection to the brain. Preconditioning can induce neuroprotection over two phases: Phase one, rapid tolerance, this occurs in a short period of time and is independent of protein production and associated with synapse remodelling. Phase two, delayed (classical) tolerance, this evolves over 1-3 days and requires de novo protein production with a peak at 3 days and diminishes over the course of 1 week. MicroRNAs are defined as small non-coding RNAs (~ 20-22 nucleotides) that regulate gene expression at a post-transcriptional level in a sequence-specific manner. MiRNAs are abundantly expressed in the central nervous system, being involved in diverse functions, including neuronal migration and differentiation, synaptic plasticity and maintenance of functions. The role of microRNAs in preconditioning in brain has been analysed in several experimental models, including ischemic and epileptic murine models. In these studies several microRNAs have been identified as mediators of the neuro-protected effect of the preconditioning stimulus. Both microRNAs regulated pathways are associated with de novo-protein synthesis regulation, supporting the original findings of the association of preconditioning with the de novo-protein synthesis and the efficiency of the preconditioning treatment in the brain. One major question is how faithful is the peripheral profile to the original biological situation in the CNS. However, the same microRNA will not be used as a biomarker and therapeutics target. But still, more deep studies should be necessary to evaluate the correlation between the circulating microRNAs and the neuro-physiological condition.