Long Noncoding RNAs in the Pathophysiology of Ischemic Stroke.

Abstract

Ischemic stroke is an acute brain injury with high mortality and disability rates worldwide. The pathophysiological effects of ischemic stroke are driven by a multitude of complex molecular and cellular interactions that ultimately result in brain damage and neurological dysfunction. The Human Genome Project revealed that the vast majority of the human genome (and mammalian genome in general) is transcribed into noncoding RNAs. These RNAs have several important roles in the molecular biology of the cell. Of these, the long noncoding RNAs are gaining particular importance in stroke biology. High-throughput analysis of gene expression using methodologies such as RNA-seq and microarrays have identified a number of aberrantly expressed lncRNAs in the post-stroke brain and blood in experimental models as well as in clinical samples. These expression changes exhibited distinct temporal and cell-type-dependent patterns. Many of these lncRNAs were shown to modulate molecular pathways that resulted in deleterious as well as neuroprotective outcomes in the post-stroke brain. In this review, we consolidate the latest data from the literature that elucidate the roles and functions of lncRNAs in ischemic stroke. We also summarize clinical studies identifying differential lncRNA expression changes between stroke patients and healthy individuals, and genetic variations in lncRNA loci that are correlated with an increased risk of stroke development.