MicroRNA dysregulation in spinal cord injury: causes, consequences and therapeutics

Abstract

Trauma to the spinal cord causes permanent disability to more than 180,000 people every year worldwide. The initial mechanical damage triggers a complex set of secondary events involving the neural, vascular, and immune systems that largely determine the functional outcome of the spinal cord injury (SCI). Cellular and biochemical mechanisms responsible for this secondary injury largely depend on activation and inactivation of specific gene programs. Recent studies indicate that microRNAs function as gene expression switches in key processes of the SCI. Microarray data from rodent contusion models reveal that SCI induces changes in the global microRNA expression patterns. Variations in microRNA abundance largely result from alterations in the expression of the cells at the damaged spinal cord. However, microRNA expression levels after SCI are also influenced by the infiltration of immune cells to the injury site and the death and migration of specific neural cells after injury. Evidences on the role of microRNAs in the SCI pathophysiology have come from different sources. Bioinformatic analysis of microarray data has been used to identify specific variations in microRNA expression underlying transcriptional changes in target genes, which are involved in key processes in the SCI. Direct evidences on the role of microRNAs in SCI are scarcer, although recent studies have identified several microRNAs (miR-21, miR-486, miR-20) involved in key mechanisms of the SCI such as cell death or astrogliosis, among others. From a clinical perspective, different evidences make clear that microRNAs can be potent therapeutic tools to manipulate cell state and molecular processes in order to enhance functional recovery. The present article reviews the actual knowledge on how injury affects microRNA expression and the meaning of these changes in the SCI pathophysiology, to finally explore the clinical potential of microRNAs in the SCI.

Update on critical care for acute spinal cord injury in the setting of polytrauma

“…54 In the laboratory it has been shown to have antiapoptotic and antiinflammatory properties, although its expression decreases 14 days postinsult. 54,59 As a novel therapeutic agent, miR-21 antagomir administered by intrathecal injection decreased recovery of hindlimb motor function, 59 and overexpression of miR-21 has been shown to protect against transient ischemia.…”

Practical Considerations of Convection Enhanced Delivery for Novel Therapies Treating Spinal Cord Injury Related Neuropathic Pain

“…Following injury, the differential expression of miRNAs in the nervous system may play a role in predicting the development of chronic pain [29]. CED has not been explored extensively as a delivery method for miRNAs in the treatment of NP, recent studies have identified several microRNAs including miR-21, miR-486, miR-20 involved in key mechanisms of SCI such as cell death or astrogliosis, direct evidence on the role of miRNAs in SCI is scarce [30]. Furthermore, from clinical perspective, evidence makes it clear that miRNAs may be potent therapeutic tools that can manipulate cell state and molecular processes in order to enhance functional recovery.…”

“…Could the injured spinal cord also have limited diffusion via CED similar to nerves, needs to confirm. Small silica cannula inserted in peripheral nerve; (10,20,30,40, and 80 ml) of 14C-labeled or gadolinium-labeled albumin were infused unilaterally or bilaterally into the tibial nerves of primates @ 0.5ml/min; and one primate infused bilaterally with gadoliniumbound albumin (40 ml/nerve) underwent MR imaging 16 weeks after infusion.…”

“…MiRNAs cause gene expressions to switch in key processes of the spinal cord (Nieto-Diaz et al, 2014) [30]. In a rat model, global miRNA expression patterns change as SCI progresses due to the alteration of the expression of cells involved in molecular processes such as apoptosis or astrogliosis.…”

Protective role of microRNA‑219‑5p inhibitor against spinal cord injury via liver receptor homolog‑1/Wnt/β‑catenin signaling pathway regulation

“…Due to their key roles in the regulation of gene expression, cell differentiation, proliferation and apoptosis, miRNAs have been observed to participate in various neurological diseases (10,11). Furthermore, an increasing number of studies have suggested that miRNA serve an important role in the development of SCI (12)(13)(14).…”