Abstract
Our previous study revealed that miR-184 expression is significantly altered in the brain following ischemic stroke in rats. However, it is unknown whether this alteration in miR-184 expression contributes to brain injury after ischemic stroke. Here, we aim to address the potential of miR-184 to impact nerve injury following ischemia and reperfusion. Rats received ICV injection of miR-184 adenovirus or empty vector and were subjected to right middle cerebral artery occlusion (MCAO) to establish an ischemic stroke model. We cultured SH-SY5Y cells under oxygen-glucose deprivation/reoxygenation (OGD/R) and transfected them with miR-184 lentivirus to explore the primary mechanisms. To evaluate miR-184 expression, neurological function deficits, the cerebral infarct volume, cell viability, and apoptosis, qRT-PCR analysis of miR-184 expression, the modified neurological severity score (mNSS) system, TTC staining, the CCK-8 assay, flow cytometry, and dual-luciferase reporter assays were utilized. We found that miR-184 expression was downregulated and that the cerebral infarct volume and mNSSs were increased following ischemic stroke; however, increasing the level of miR-184 alleviated brain damage. Overexpression of miR-184 resulted in increased viability and reduced apoptosis of SH-SY5Y cells following OGD/R in vitro. We identified the phosphatidic acid phosphatase type 2B (PPAP2B) gene as a direct target gene of miR-184. In summary, our results reveal that attenuation of miR-184 levels in ischemic stroke contributes to ischemic injury through targeting PPAP2B mRNA-mediated apoptosis, which may be a promising therapeutic target for ischemic stroke.
Highlights
As the most common type of stroke, ischemic stroke results from cerebral blood flow thrombosis or embolism, leading to oxygen and glucose deprivation, subsequent brain damage, and neurologic deficits (Han et al, 2014)
We found that ischemic stroke rats had higher modified neurological severity score (mNSS) scores than sham operation rats, but ischemic stroke rats injected with miR-184 adenovirus had lower mNSS scores than ischemic stroke rats injected with empty vector (Figure 1A)
We measured the relative expression levels of miR-184 in brain tissue from various groups. Quantitative Real-Time PCR (qRT-PCR) analysis showed that ischemic stroke rats exhibited significantly lower expression of miR-184 than sham rats (p < 0.05) and that rats injected with miR-184 adenovirus had higher expression of miR184 than rats injected with empty vector (p < 0.05) (Figure 1D). These results reveal that the expression levels of miR-184 affect nerve injury following ischemic stroke and that downregulation of miR-184 expression after ischemia-reperfusion contributes to brain damage in rats
Summary
As the most common type of stroke, ischemic stroke results from cerebral blood flow thrombosis or embolism, leading to oxygen and glucose deprivation, subsequent brain damage, and neurologic deficits (Han et al, 2014). The process involves various elements, such as energy failure, oxidative stress, excitotoxicity, and ion imbalance, all of which can lead to a complex series of cellular reactions, changes in the expression patterns of genes, and subsequent brain damage and dysfunction in the ischemic brain (Cheon et al, 2018). MicroRNAs that are expressed after stroke are involved in excitotoxicity, oxidative stress, inflammatory reactions, blood-brain barrier disruption, edema after stroke, and neuronal apoptosis (Li et al, 2018). It contributes to cardiomyocyte injury during myocardial infarction (Zou et al, 2020) and cellular apoptosis in retinoblastoma (He et al, 2019) It is unknown whether the alteration of miR-184 expression contributes to brain injury after ischemic stroke. The results may shed new light on the underlying mechanism of poststroke brain injury and provide clues for new gene therapies for stroke recovery
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
