Biology subjects

Shi, Z.-S.

Publications and source records attributed to Shi, Z.-S..

4 recordsLinked to original sources

bioRxiv2025

MicroRNA-383-5p alleviates hemorrhagic transformation and improves outcomes after endovascular recanalization for acute ischemic stroke

BackgroundHemorrhage transformation (HT) after reperfusion therapy is linked with poor outcomes in acute ischemic stroke patients. This study aimed to determine the role of neuronal microRNA-383 in alleviating HT-associated injury using middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation reoxygenation (OGD/R) models. MethodsIn neurons following OGD/R, the family of miR-383 and NADPH oxidase (NOX) expression was evaluated. After miR-383-5p intervention and small interfering RNA, reactive oxygen species (ROS) and neuronal injury were assessed. Two hundred and five hyperglycemic rats were used to establish the HT model induced by mechanical reperfusion after 5-hour MCAO, followed by 3 and 6 hours of reperfusion, and treated with intravenous administration of miR-383-5p agomir before reperfusion. Brain water content, hemorrhage severity, infarct volume, blood-brain barrier (BBB) disruption, neuronal apoptosis, ROS production, miR-383-5p and NOX4 expression, and BBB-associated proteins were assessed. ResultsMiR-383-5p expression significantly decreased in OGD/R-treated neurons, while miR-383-3p expression did not differ. Elevating miR-383-5p levels reduced neuronal injury, ROS overproduction, and NOX4 overexpression as a target of miR-383-5p, shown in OGD/R-treated neurons. In the MCAO model, increased miR-383-5p suppressed NOX4 upregulation, alleviated brain edema, infarct volume, and hemorrhage severity, reduced neuronal apoptosis and ROS overproduction, and preserved BBB integrity after mechanical reperfusion for ischemia, thereby improving short-term neurological outcomes. ConclusionsMiR-383-5p alleviates oxidative stress injury and neuronal apoptosis, and preserves BBB integrity by regulating NOX4. Neuronal miR-383-5p could become a potential target for intervention to decrease HT and ameliorate outcomes in endovascular reperfusion treatment for acute ischemic stroke.

neuroscience↗

bioRxiv2025

MicroRNA-21-3p regulation of NOX4 and VEGFA contributes to hemorrhage in cerebral cavernous malformations

ObjectiveMicroRNAs regulate the brain vascular integrity and are involved in the lesion development of cerebral cavernous malformations (CCM). This study examines the role of microRNA-21-3p in CCM-related cerebral hemorrhage and its underlying mechanisms. MethodsThe expression of miRNA-21-3p and its target genes of NADPH oxidase 4 (NOX4) and vascular endothelial growth factor A (VEGFA) in brain microvascular endothelial cells (BMECs) and pericytes were assessed in cavernous malformation lesions of 20 sporadic CCM patients by fluorescence in situ hybridization. The association of their expression with hemorrhage manifestation was evaluated. Cell proliferation, permeability, reactive oxygen species (ROS), migration, tubule formation, and the expression of NOX4 and VEGFA were assessed in CCM2 gene-depleted human BMECs and pericytes after miRNA-21-3p intervention. Cerebral hemorrhage, vascular permeability, vascular dilation, and angiogenesis after miRNA-21-3p intervention were evaluated in the ccm2 gene-knockdown zebrafish. ResultsDecreased miRNA-21-3p and increased NOX4 and VEGFA were shown in BMECs and pericytes of the CCM lesions compared to peri-lesion normal vessels from epilepsy patients, which were also correlated with the presence of cerebral hemorrhage in CCM patients. Increasing miRNA-21-3p attenuated cell proliferation, permeability, ROS expression, cell migration, and tubule formation by targeting NOX4 and VEGFA in CCM2 gene-depleted BMECs and pericytes. In vivo studies revealed that increasing miRNA-21-3p reduced cerebral hemorrhage, vascular permeability, vascular dilation, angiogenesis, and the overexpression of nox4 and vegfa in ccm2 gene-knockdown zebrafish. ConclusionMiRNA-21-3p can be a novel therapeutic target by regulating NOX4 and VEGFA, thereby stabilizing vascular integrity and reducing cerebral hemorrhage in CCM lesions.

neuroscience↗

bioRxiv2024

MicroRNA-29a-5p Attenuates Oxygen-glucose Deprivation and Reoxygenation Injury in Astrocytes by Targeting Glycogen Synthase Kinase beta

BackgroundHemorrhage 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. MethodsMiR-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-hour MCAO following reperfusion at 6 hours. 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. ResultsMiR-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. ConclusionsMiR-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.

neuroscience↗

bioRxiv2024

MicroRNAs and mRNA Regulatory Network of Parenchymal Hematoma after Endovascular Mechanical Reperfusion for Acute Ischemic Stroke in Rat

Hemorrhagic transformation after endovascular thrombectomy predicts poor outcomes in acute ischemic stroke with large vessel occlusion. The roles of microRNAs in the pathogenesis of parenchymal hematoma (PH) are still unclear. This study aims to investigate the microRNA and mRNA regulatory network associated with PH after mechanical reperfusion in the animal stroke model and oxygen-glucose deprivation/reoxygenation (OGD/R) model. Twenty-five microRNAs were assessed in the reperfusion-induced hemorrhage model in rats with hyperglycemic conditions receiving 5-hour middle cerebral artery occlusion. Thirteen down-regulated microRNAs (miRNA-29a-5p, miRNA-29c-3p, miRNA-126a-5p, miRNA-132-3p, miRNA-136-3p, miRNA-142-3p, miRNA-153-5p, miRNA-218a-5p, miRNA-219a-2-3p, miRNA-369-5p, miRNA-376a-5p, miRNA-376b-5p, miRNA-383-5p) and one up-regulated microRNA (miRNA-195-3p) were found in rat peri-infarct with PH. Ten of these 14 PH-related microRNAs were significantly differentially expressed in at least two of five models of neuron, astrocyte, microglia, BMEC, and pericyte after OGD/R, consistent with the animal model results. Thirty-one predicted hub target genes were significantly differentially expressed in rat peri-infarct with PH. Forty-nine microRNA-mRNA regulatory axes of PH were revealed, which were related to the mechanisms of oxidative stress, apoptosis, immune, and inflammation. Simultaneously differentially expressed microRNAs and related genes in several cells of the neurovascular unit may serve as valuable targets for PH after endovascular thrombectomy in acute ischemic stroke.

neuroscience↗