Resveratrol preconditioning induces cerebral ischemic tolerance but has minimal effect on cerebral microRNA profiles

Abstract

The health benefits of the plant-derived polyphenol resveratrol were established in multiple disease systems. Notably, pre-treatment with resveratrol was shown to be neuroprotective in several models of cerebral ischemia. Mechanisms of resveratrol-mediated neuroprotection have been explored in the context of canonical resveratrol targets, but epigenetic and non-coding RNA processes have not yet been evaluated. Resveratrol was shown to alter microRNAs in cancer and cardiac ischemia. Previous studies also showed that ischemic preconditioning that induces ischemic tolerance significantly alters cerebral microRNA levels, particularly those that target neuroprotective pathways. Therefore, we tested if resveratrol-mediated ischemic tolerance also alters microRNA expression with a goal to identify microRNAs that are amenable to manipulation to induce neuroprotection after cerebral ischemia. Hence, we tested the microRNA profiles in mouse brain following intraperitoneal administration of resveratrol that induced significant tolerance against transient focal ischemia. We analyzed microRNA profiles using microarrays from both Affymetrix and LC Sciences that contain probes for all known mouse microRNAs. The results show that there is no consistent change in any of the microRNAs tested between resveratrol and vehicle groups indicating that microRNAs play a minimal role in resveratrol-mediated cerebral ischemic tolerance.

Keywords: Acute stroke; basic science; focal ischemia; genetics; neuroprotection.

Figure 1.

Resveratrol preconditioning induces ischemic tolerance. Three days following resveratrol (10 mg/kg; i.p.) or vehicle administration, mice were subjected to a 1-h transient MCAO and were euthanized at three days of reperfusion. Panel A shows serial brain sections stained with TTC from representative mice of the two groups. The percentage of infarcted hemisphere was used to quantify infarct volumes. Panel B shows infarct volume quantitated from the TTC-stained serial brain sections. Panel C shows BDNF mRNA expression in vehicle and resveratrol-treated groups. Panels D (mmu-miR-124-5p) and E (mmu-miR-21a-5p) show expression levels of murine miRNAs in vehicle and resveratrol-treated groups. Bars are mean ± SD of n = 7 for vehicle and 6 for resveratrol groups in B and n = 3/group in C, D, and E. *p < 0.05 by unpaired Student’s t-test.