Micrornas in ischemic brain: The fine-tuning specialists and novel therapeutic targets

Abstract

CNS injuries are associated with extensive spatio-temporal alterations in gene expression that dictate the extent of brain damage and subsequent plasticity. Studies in CNS injury models show that microRNAs (miRNAs) modulate gene expression, which contributes to development of the injury. The expression levels of brain miRNAs show diverse spatio-temporal profiles in the healthy brain and are altered significantly over a sustained period of time in injured states. Apart from the conventional mechanisms of translational inhibition of mRNAs, recent studies have revealed that miRNAs can also target gene promoters to induce or repress their expression, adding another layer to the already complex network of miRNA-gene interactions. The extent of the influence of miRNAs in the CNS is only beginning to be elucidated. miRNAs play a major role in the etiology of neurodegenerative diseases as well as in brain injuries such as traumatic brain injury, spinal cord injury, and ischemia. Studies have shown that they considerably influence the outcome of the ischemic pathophysiology. However, miRNAs have also been observed to play a role in endogenous (preconditioning) and exogenous neuroprotective treatments, indicating their role in inducing ischemic tolerance. Lately, miRNAs have shown promise for serving as clinical biomarkers of stroke and other CNS disorders.