Abstract
Background: Analysis of circulating microRNA in young and middle aged male and female rats revealed distinct expression patterns of post-stroke microRNAs (Selvamani et al., 2014). Mir-363 expression was inversely related to infarct volume, such that adult females, who display the smallest infarct volumes, had the highest expression of miR363. Based on this association, we hypothesized that mir-363 may promote survival of ischemic neurons. As proof of concept, the present study utilized middle aged females to investigate the role of miR-363 in neuroprotection. Methods: Middle aged (12 mo) female rats were subject to middle cerebral artery occlusion (MCAo). At 4h post-stroke, animals received a tail-vein injection of miR-363 or scrambled control. Vibrissae-elicited forelimb placement (VIB) test was performed pre and post MCAo to assess motor deficits. Blood samples were drawn at 2d and 5d post stroke. All animals were terminated at 5d post MCAo and the brains processed for infarct analysis by standard histological procedures. Total RNA isolated from serum and brain was subject to QPCR amplification for miR-363 and U6 (normalization control) Results: IV injections of mir363 significantly elevated serum expression of this microRNA as compared to animals injected with scrambles control oligos, when measured 2d post stroke. Infarct volumes (cortex and striatum), at 5d post stroke, were significantly reduced in the miR-363 treated group as compared to controls (p ≤ 0.001). VIB-test indicated significant motor recovery post-stroke in the contralateral limb in miR-363 mimic treated group as compared to controls. RT-PCR analysis of brain tissue showed higher expression of miR-363 in the left (ischemic) hemisphere in the miR-363 mimic group while, no difference was observed in the non-ischemic, indicating that the mimetic is recruited to the ischemic site. Conclusion: The present study underscores the value of miRNA profiling in populations with different stroke outcomes as a strategy to identify new therapeutic targets for stroke.
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