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Updated: Sep 19, 2025
A Model for Encephalomyosynangiosis Treatment after Middle Cerebral Artery Occlusion-Induced Stroke in Mice
Published on: June 22, 2022
MicroRNA-29a-5p attenuates hemorrhagic transformation and improves outcomes after mechanical reperfusion for acute
Chang-Luo Li1,2,3, Jin-Kun Zhuang1,2,3, Zhong Liu2,4
1Department of Neurosurgery (C-LL, J-KZ, Z-RH, CX, Z-SS), Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
Background:
Hemorrhage transformation (HT) following endovascular reperfusion treatment is associated with worse clinical outcomes in acute ischemic stroke patients. MicroRNA (miR) modulates several aspects of cerebral ischemia-reperfusion injury, including blood-brain barrier (BBB) integrity, inflammation, oxidative stress, and apoptosis, significantly impacting cerebral recovery and function. This study investigated the role of astrocytic miR-29a-5p in HT in the transient middle cerebral artery occlusion (MCAO) model and oxygen-glucose deprivation reoxygenation (OGD/R) model of astrocytes.
Methods:
MiR-29a-5p expression in the OGD/R astrocyte model was assessed. The astrocyte injury, the expression of A1 and A2 phenotypes of reactive astrocytes, and the regulation of miR-29a-5p target genes were evaluated after the miR-29a-5p intervention. A mechanical reperfusion-induced HT model was established in hyperglycemic rats using 5-h MCAO following reperfusion at 6 h. MiR-29a-5p agomir was administered intravenously before reperfusion. Infarct volume, HT, BBB damage, neurological score, the expression of miR-29a-5p, and its target genes were evaluated.
Results:
MiR-29a-5p expression decreased in OGD/R-treated astrocytes and the peri-infarction tissue and blood of the MCAO model. Elevating miR-29a-5p levels reduced astrocyte injury, suppressed neurotoxic A1 astrocyte markers (C3, Fkbp5, and Serping1), while enhanced neuroprotective A2 astrocyte markers (S100a10 and Emp1) in the OGD/R and MCAO models. Intravenous administration of miR-29a-5p agomir increased the expression of miR-29a-5p and reduced infarct volume, reperfusion-induced HT, and BBB breakdown after ischemia, improving neurological outcomes in the MCAO model. Overexpression of miR-29a-5p effectively suppressed the expression of its direct target genes, glycogen synthase kinase 3 beta and aquaporin 4 in the OGD/R and MCAO models.
Conclusions:
MiR-29a-5p alleviates astrocyte injury and regulates A1 and A2 astrocyte markers, glycogen synthase kinase 3 beta, and aquaporin 4 in astrocytes subjected to ischemia-reperfusion injury. Astrocytic miR-29a-5p may be a protective target for reducing HT and improving outcomes following mechanical reperfusion in acute ischemic stroke.
Insights
MicroRNA-29a-5p protects against hemorrhage transformation in acute ischemic stroke by reducing astrocyte injury and blood-brain barrier damage. Increasing miR-29a-5p levels improves neurological outcomes after reperfusion therapy.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- Hemorrhage transformation (HT) after endovascular reperfusion worsens outcomes in acute ischemic stroke.
- MicroRNAs (miRs) influence cerebral ischemia-reperfusion injury, affecting blood-brain barrier (BBB) integrity, inflammation, oxidative stress, and apoptosis.
- Astrocytic miR-29a-5p's role in HT following ischemic stroke was investigated.
Purpose of the Study:
- To investigate the role of astrocytic miR-29a-5p in hemorrhage transformation (HT) after ischemic stroke.
- To evaluate the impact of miR-29a-5p on astrocyte injury and phenotypes in an in vitro and in vivo stroke model.
- To determine if modulating miR-29a-5p can mitigate HT and improve outcomes.
Main Methods:
- Assessed miR-29a-5p expression in oxygen-glucose deprivation/reoxygenation (OGD/R) astrocyte and transient middle cerebral artery occlusion (MCAO) rat models.
- Evaluated astrocyte injury, A1/A2 reactive astrocyte phenotypes, and miR-29a-5p target gene regulation post-intervention.
- Administered miR-29a-5p agomir intravenously before reperfusion in a hyperglycemic rat MCAO model to assess infarct volume, HT, BBB damage, and neurological scores.
Main Results:
- miR-29a-5p expression was decreased in OGD/R astrocytes and MCAO models.
- Elevated miR-29a-5p reduced astrocyte injury, suppressed neurotoxic A1 markers, and enhanced neuroprotective A2 markers.
- miR-29a-5p agomir administration reduced infarct volume, HT, BBB breakdown, and improved neurological function in MCAO rats.
- Overexpression of miR-29a-5p suppressed its direct targets, glycogen synthase kinase 3 beta and aquaporin 4.
Conclusions:
- Astrocytic miR-29a-5p alleviates astrocyte injury and modulates astrocyte phenotypes and key target genes in ischemia-reperfusion injury.
- Astrocytic miR-29a-5p represents a potential therapeutic target for reducing hemorrhage transformation and improving outcomes in acute ischemic stroke patients undergoing mechanical reperfusion.
