Treatment with recombinant tissue plasminogen activator alters the microRNA expression profiles in mouse brain after acute ischemic stroke.

Thrombolysis with recombinant tissue plasminogen activator (rtPA) is the only FDA approved treatment for the brain ischemic stroke. MicroRNAs, non-coding RNA sequences that regulate gene expression, might play important roles in regulating the rtPA thrombolysis process. The present study investigated changes in the microRNA profiles in a middle cerebral artery occlusion (MCAo) mouse model after rtPA treatment. Using microarrays containing 1179 microRNAs, we compared microRNAs expression profiles of brain tissues from C57 BL/6J mice subjected to focal cerebral ischemia with and without rtPA thrombolysis. We found that rtPA treatment upregulated 31 microRNAs and downregulated 11 microRNAs. Expression alterations of selected microRNAs mmu-miR-125a-3p, -208a-5p, -709, -721 were confirmed by real-time PCR. Differentially expressed microRNAs were analyzed using Targetscan v6.2 and David v6.7. 2200 predicted genes were subjected to GO analysis and pathway analysis, which identified mediators involved in multiple signaling pathways during proliferation. These data demonstrated that rtPA treatment alters microRNAs expression after stroke, and provided new insight into understanding the biological process of rtPA thrombolysis.