Format

Send to

Choose Destination
Neurobiol Dis. 2017 Sep;105:156-163. doi: 10.1016/j.nbd.2017.04.018. Epub 2017 Apr 28.

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

Author information

1
Department of Neurological Surgery, Neuroapoptosis Laboratory, University of Pittsburgh School of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, United States.
2
Department of Neurological Surgery, Neuroapoptosis Laboratory, University of Pittsburgh School of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, United States. Electronic address: yuzhang@pitt.edu.
3
Department of Neurological Surgery, Neuroapoptosis Laboratory, University of Pittsburgh School of Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, United States. Electronic address: friedlanderr@upmc.edu.

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.

KEYWORDS:

Anti-mRNA; LNA; Neuroprotection; Stroke; Systemic delivery; microRNA

PMID:
28461247
DOI:
10.1016/j.nbd.2017.04.018
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center