CpG Preconditioning Regulates Mirna Expression That Modulates Genomic Reprogramming Associated with Neuroprotection against Ischemic Injury

Abstract

Cytosine-phosphate-guanine (CpG) preconditioning reprograms the genomic response to stroke to protect the brain against ischemic injury. The mechanisms underlying genomic reprogramming are incompletely understood. MicroRNAs (miRNAs) regulate gene expression; however, their role in modulating gene responses produced by CpG preconditioning is unknown. We evaluated brain miRNA expression in response to CpG preconditioning before and after stroke using microarray. Importantly, we have data from previous gene microarrays under the same conditions, which allowed integration of miRNA and gene expression data to specifically identify regulated miRNA gene targets. CpG preconditioning did not significantly alter miRNA expression before stroke, indicating that miRNA regulation is not critical for the initiation of preconditioning-induced neuroprotection. However, after stroke, differentially regulated miRNAs between CpG-and saline-treated animals associated with the upregulation of several neuroprotective genes, implicating these miRNAs in genomic reprogramming that increases neuroprotection. Statistical analysis revealed that the miRNA targets were enriched in the gene population regulated in the setting of stroke, implying that miRNAs likely orchestrate this gene expression. These data suggest that miRNAs regulate endogenous responses to stroke and that manipulation of these miRNAs may have the potential to acutely activate novel neuroprotective processes that reduce damage.

Loss of consciousness at ictus and/or poor World Federation of Neurosurgical Societies grade on admission reflects the impact of EBI and predicts poor outcome in patients with SAH

“…[8] We believe that finding microRNA that is altered by the rupture of aneurysms could more simply explain the complex mechanism of EBI because each miRNA has many potential mRNA targets; thus, a broad spectrum of gene expression could be affected by the presence or absence of an individual miRNA. [20] e current study also has certain limitations. e number of patients included in the current study was relatively small.…”

Non-Coding RNA in Acute Ischemic Stroke: Mechanisms, Biomarkers and Therapeutic Targets

“…Previous studies have indicated that electroacupuncture, fastigial nucleus stimulation, and vagus nerve stimulation promote neuroprotection through induction of the microRNA in cerebral ischemic animal models, respectively [79][80][81] . Some molecules, such as cytosine-phosphate-guanine, insulin-like growth factor-1, natural vitamin E a-tocotrienol, and lithium induce neuroprotection in cerebral ischemia by regulating some specific miRNAs [82][83][84][85] .…”

Noncoding RNAs in ischemic stroke: time to translate

“…CpG preconditioning after stroke showed that large numbers of miRNAs are regulated within 24 hours. However, a unique set of miRNAs was suppressed that are associated with upregulation of several neuroprotective genes in CpG‐preconditioned mice, compared to saline‐treated mice, after stroke, implying that upregulation of miRNAs can play a role in neuroprotection by genomic reprogramming …”