AUTHOR=Lv Bo , Cheng Xiyuan , Sharp Frank R. , Ander Bradley P. , Liu Da Zhi 

TITLE=MicroRNA-122 Mimic Improves Stroke Outcomes and Indirectly Inhibits NOS2 After Middle Cerebral Artery Occlusion in Rats

JOURNAL=Frontiers in Neuroscience

VOLUME=12

YEAR=2018

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2018.00767

DOI=10.3389/fnins.2018.00767

ISSN=1662-453X

ABSTRACT=<p><bold>Aim:</bold> Our previous study demonstrated miR-122 mimic decreased NOS2 expression in blood leucocytes and improved stroke outcomes when given immediately after middle cerebral artery occlusion (MCAO) in rats. Since NOS2 is associated with neuro-inflammation in stroke and decreasing NOS2 expression alone in leucocytes is insufficient to improve stroke outcomes, we hypothesized that miR-122 mimic may also decrease NOS2 expression in brain microvascular endothelial cells (BMVECs) even at extended time windows.</p><p><bold>Methods:</bold> We administered PEG-liposome wrapped miR-122 mimic (2.4 mg/kg, i.v.) 0 or 6 h after MCAO, and assessed stroke volume and NOS2 expression in BMVECs 24 h following MCAO in rats. Luciferase reporter assays were used to determine if miR-122 binds to 3′ untranslated regions (3′UTR) of NOS2.</p><p><bold>Results:</bold> The data showed that miR-122 mimic decreased infarct volumes and decreased MCAO-induced NOS2 over-expression in BMVECs. However, miR-122 did not bind to 3′UTR of NOS2 in the luciferase assays.</p><p><bold>Conclusion:</bold> The data show the 6-h period of therapeutic efficacy of miR-122 mimic which could relate to indirect knockdown of NOS2 in both BMVECs and leucocytes.</p>