The emerging roles of microRNAs in CNS injuries

Abstract

The consequences of injuries to the CNS are profound and persistent, resulting in substantial burden to both the individual patient and society. Existing treatments for CNS injuries such as stroke, traumatic brain injury and spinal cord injury have proved inadequate, partly owing to an incomplete understanding of post-injury cellular and molecular changes. MicroRNAs (miRNAs) are RNA molecules composed of 20–24 nucleotides that function to inhibit mRNA translation and have key roles in normal CNS development and function, as well as in disease. However, a role for miRNAs as effectors of CNS injury has recently emerged. Use of bioinformatics to assess the mRNA targets of miRNAs enables high-order analysis of interconnected networks, and can reveal affected pathways that may not be identifiable with the use of traditional techniques such as gene knock-in or knockout approaches, or mRNA microarrays. In this Review, we discuss the findings of miRNA microarray studies of spinal cord injury, traumatic brain injury and stroke, as well as the use of gene ontological algorithms to discern global patterns of molecular and cellular changes following such injuries. Furthermore, we examine the current state of miRNA-based therapies and their potential to improve functional outcomes in patients with CNS injuries.

MiR-592 Regulates the Induction and Cell Death-Promoting Activity of p75NTRin Neuronal Ischemic Injury

“…n.s., Not significant. binding proteins and/or microRNAs (Barrett et al, 2012). A prior report has shown that serial truncation of the 3ЈUTR of p75 NTR leads to significantly higher levels of p75 NTR protein, thus implicating regulation of p75 NTR by its 3ЈUTR (Krygier and Djakiew, 2001).…”

“…All procedures were performed in accordance with institutional and federal guidelines for the treatment of animals. Focal cerebral ischemia was induced using the intraluminal filament model of middle cerebral artery occlusion (MCAO), as described previously (Abe et al, 2010;Jackman et al, 2011;Hochrainer et al, 2012). All experiments were performed in male C57BL/6 mice (6 -8 weeks) or p75 NTR Ϫ/Ϫ mice, which were purchased from the Jackson Laboratory.…”

Current State and Prospects of Development of Blood-based Biomarkers for Mild Traumatic Brain Injury

“…Even a single miRNA is known to regulate the entire mRNA network [78], and is expected to be used in therapeutics by blocking the pathophysiological cascade after brain injury. In particular, miRNAs are abundantly expressed in the brain tissue, and some are known to have brain-specific functions [79][80][81]. After brain injury, miRNA expression levels are known to vary significantly [82,83], with the downregulation of miR-23a and miR-27a being confirmed within 4 hours of the brain injury.…”

Spinal Cord Injury Induced Hyperalgesia is Associated with Increased Levels of Let-7 Family of MicroRNAs

“…Functional changes to the mu opioid receptor (MOR) have been observed following SCI, providing a potential explanation for why pain mitigation with opioids may be unsuccessful [12]. However, the mechanism behind these changes is not well understood MicroRNAs, small noncoding RNAs, are an emerging player in the field of pain research and have the potential to elucidate the chronic pain sequela associated with SCI at cellular level [13][14][15][16][17][18][19]. The Let-7 family of miRNAs has specifically been shown to target MOR, suggesting its link to opioid tolerance [20].…”