Systemic antimiR-337-3p delivery inhibits cerebral ischemia-mediated injury.

Neurobiology of Disease(2017)

Cited 20|Views22
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Abstract
Modulation of miRNA expression has been shown to be beneficial in the context of multiple diseases. The purpose of this study was to determine if an inhibitor of miR-337-3p is neuroprotective for hypoxic injury after tail vein injection. We evaluated miR-337-3p expression levels and in brain tissue in vivo before and after permanent middle cerebral artery occlusion (pMCAO) in mice. Subsequently, a custom locked nucleic acid (LNA) antimir-337-3p oligonucleotide was developed and tested in vitro after induction of oxygen glucose-deprivation (OGD) and in vivo by injection into the mouse tail vein for 3 consecutive days before pMCAO. Ischemic lesion volume was measured by TTC staining. We show that systemically administered LNA antimir-337-3p crosses the blood brain-brain-barrier (BBB), penetrates into neurosn, downregulates endogenous miR-337-3p expression and reduces ischemic brain injury. The findings support the use of similar antimir-LNA constructs as novel therapies in neurological disease.
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Key words
Neuroprotection,Stroke,microRNA,LNA,Anti-mRNA,Systemic delivery
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