Journal
NEUROCHEMICAL RESEARCH
Volume 47, Issue 12, Pages 3682-3696Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11064-022-03718-6
Keywords
Cerebral ischemia; Mitochondria; Glia; Cytoskeleton; microRNA; Oxidative stress
Categories
Funding
- American Heart Association [14FTF19970029]
- NIH [NS119462]
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Ischemic stroke is a devastating cerebrovascular disease, and research suggests that miR-182 plays a crucial role in stroke injury and recovery. Inhibition of miR-182 has been found to protect mitochondrial structure, mitigate neuroinflammation, and reduce cell death.
Ischemic stroke remains a devastating cerebrovascular disease that accounts for a high proportion of mortality and disability worldwide. MicroRNAs (miRNAs) are a class of small non-coding RNAs that are responsible for regulation of post-transcriptional gene expression, and growing evidence supports a role for miRNAs in stroke injury and recovery. The current study examined the role of miR-182 in experimental stroke using both in vitro and in vivo models of ischemic injury. Brain levels of miR-182 significantly increased after transient middle cerebral artery occlusion (MCAO) in mice and in primary astrocyte cultures subjected to combined oxygen-glucose deprivation/reperfusion (OGD/R) injury. In vivo, stroke volume and neurological score were significantly improved by pre-treatment with miR-182 antagomir. Astrocyte cultures stressed with OGD/R resulted in mitochondrial fragmentation and downregulation of cortactin, an actin-binding protein. Inhibition of miR-182 significantly preserved cortactin expression, reduced mitochondrial fragmentation and improved astrocyte survival after OGD/R. In parallel, lipopolysaccharide (LPS)-induced nitric-oxide release in astrocyte cultures was significantly reduced by miR-182 inhibition, translating to reduced injury in primary neuronal cultures subjected to conditioned medium from LPS-treated astrocytes. These findings identify miR-182 and/or cortactin as potential clinical targets to preserve mitochondrial structure and mitigate neuroinflammation and cell death after ischemic stroke.
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