Effects of Focal Cerebral Ischemia on Exosomal Versus Serum miR126

Abstract

Emerging data suggest that exosomal microRNA (miRNA) may provide potential biomarkers in acute ischemic stroke. However, the effects of ischemia-reperfusion on total versus exosomal miRNA responses in circulating blood remain to be fully defined. Here, we quantified levels of miR-126 in whole serum versus exosomes extracted from serum and compared these temporal profiles against reperfusion and outcomes in a rat model of acute focal cerebral ischemia. First, in vitro experiments confirmed the vascular origin and changes in miR-126 in brain endothelial cultures subjected to oxygen-glucose deprivation. Then in vivo experiments were performed by inducing permanent or transient focal cerebral ischemia in rats, and total serum and exosomal miR-126 levels were quantified, along with measurements of infarction and neurological outcomes. Exosomal levels of miR-126 showed a transient reduction at 3 h post-ischemia that appeared to normalize back close to pre-ischemic baselines after 24 h. There were no detectable differences in exosomal miR-126 responses in permanent or transient ischemia. Serum miR-126 levels appeared to differ in permanent versus transient ischemia. Significant reductions in serum miR-126 were detected at 3 h after permanent ischemia but not transient ischemia. By 24 h, serum miR-126 levels were back close to baseline in both permanent and transient ischemia. Overall, there were no correlations between serum miR-126 and exosomal miR-126. This proof-of-concept study suggests that changes in serum miR-126 may be able to distinguish severe permanent ischemia from milder injury after transient ischemia.

MiR-126 Affects Brain-Heart Interaction after Cerebral Ischemic Stroke

“…Previous studies have reported that knockout of miR-126 induces cardiac dysfunction [38, 39]. MiR-126 expression level in circulation is an indicator of systemic inflammatory and angiogenic status [40, 41]. MiR-126 concentration in the circulation is significantly decreased in ischemic stroke [17] and acute myocardial infarction patients [16].…”

Non-coding RNAs and neuroprotection after acute CNS injuries

“…In some studies, expression profiling of blood was conducted in parallel with brain (Liu et al, 2010; Jeyaseelan et al, 2008) and CSF (Sørensen et al, 2014) that showed overlapping patterns of miRNA levels between blood/brain and blood/CSF. The miRNAs that showed altered levels in blood after stroke include miR-107 (Yang et al, 2016b), miR-128b (Yang et al, 2016b), miR-153 (Yang et al, 2016b), miR-124 (Weng et al, 2011; Laterza et al, 2009), miR-210 (Zeng et al, 2011), miR-145 (Gan et al, 2012), miR-21 (Zhou and Zhang, 2014; Tsai et al, 2013), miR-221 (Tsai et al, 2013), miR-30a (Long et al, 2013), miR-126 (Chen et al, 2015a; Long et al, 2013), let-7b (Long et al, 2013), miR-223 (Wang et al, 2014d) and miR-24 (Zhou and Zhang., 2014). Importantly, Yang et al (2014) showed that miR-107 was elevated in the plasma of both rats and humans after stroke.…”

NADPH oxidase inhibitor regulates microRNAs with improved outcome after mechanical reperfusion

“…Studies have suggested a neuroprotective role of miR-29c 20 21. Serum miR-126 has been associated with the severity of cerebral ischemia and correlated with the extent of edema surrounding intracerebral hemorrhage 22 23. The overexpression of miR-126 may promote vascular integrity and protect the kidney from ischemic reperfusion injury 24.…”