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Updated: Apr 15, 2026
Author Spotlight: Establishing a Reliable Distal MCA Occlusion Model in Mice for Stroke Research
Published on: December 15, 2023
Treatment with recombinant tissue plasminogen activator alters the microRNA expression profiles in mouse brain after
Yan Yan Zhao1, Wen An Wang, Hua Hu
1Department of Neurology, Xin Hua Hospital (Chongming), Shanghai Jiao Tong University, 25 Nanmen Road, Shanghai, China.
Abstract:
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.
Insights
Recombinant tissue plasminogen activator (rtPA) treatment for ischemic stroke alters microRNA expression in the brain. This study identified specific microRNAs affected by rtPA, offering new insights into stroke thrombolysis.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Recombinant tissue plasminogen activator (rtPA) is the sole FDA-approved treatment for acute ischemic stroke.
- MicroRNAs, key regulators of gene expression, are implicated in the rtPA thrombolysis process.
- Understanding microRNA dynamics post-rtPA is crucial for optimizing stroke treatment.
Purpose of the Study:
- To investigate microRNA expression profile changes in a mouse model of ischemic stroke following rtPA administration.
- To identify specific microRNAs upregulated or downregulated by rtPA treatment.
- To explore the functional implications of altered microRNAs in stroke pathophysiology.
Main Methods:
- Utilized a middle cerebral artery occlusion (MCAo) mouse model to induce focal cerebral ischemia.
- Employed microarray analysis to compare microRNA expression profiles in brain tissues with and without rtPA treatment.
- Validated expression changes of selected microRNAs using real-time PCR.
- Performed bioinformatic analyses (Targetscan, David) for gene prediction, Gene Ontology (GO), and pathway analysis.
Main Results:
- rtPA treatment resulted in the upregulation of 31 microRNAs and downregulation of 11 microRNAs in ischemic brain tissue.
- Expression alterations of specific microRNAs (mmu-miR-125a-3p, -208a-5p, -709, -721) were confirmed.
- Bioinformatic analysis predicted 2200 genes and identified involvement in multiple signaling pathways related to proliferation.
Conclusions:
- rtPA treatment significantly alters the brain's microRNA expression profile after ischemic stroke.
- These findings provide novel insights into the molecular mechanisms underlying rtPA-mediated thrombolysis.
- The identified microRNAs and pathways may represent potential therapeutic targets for stroke management.
