Can we protect the brain via preconditioning? Role of microRNAs in neuroprotection

Preconditioning stimulus: Preconditioning is an adaptive response, whereby a small dose of a harmful substance protects the brain from a subsequent damaging insult (Dirnagl et al., 2009). The concept of preconditioning was first described in an ischemic heart model, it was observed that brief ischemic episodes protect against a subsequent ischemic insult (Murry et al., 1986). Consequently, several preconditioning treatment paradigms are used in the clinic to protect patients against an ischemic insult in heart pathologies (Jimenez-Mateos et al., 2015). 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 neuroprotection to the brain. The mechanisms of preconditioning-induced tolerance are not well known, but de novo protein synthesis is required and is correlated with repressed gene expression. Furthermore, the preconditioning stimulus produces a transient effect, having an effect only for few days after administration (Stenzel-Poore et al., 2007). 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 (Meller et al., 2008). 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 (Stenzel-Poore et al., 2007).