Abstract
Ischemic stroke is the leading cause of disability and deaths worldwide. MiRNAs have been shown to play an important role in development and pathogenesis of the nervous system. However, the precise function and mechanism of miRNAs are not fully understood in the brain injury induced by ischemia/reperfusion (I/R). Herein, our study showed that miR-375 expression was significantly down-regulated in the rat I/R brain. With the in vivo and in vitro I/R stroke models, we found that miR-375 mimic provides significant protection from injury to cerebral I/R, which is reflected by reduced infarct volumes and cell apoptosis, and increased proliferation and migration of PC12 cells. Mechanistically, our findings showed that miR-375 binds to 3′-UTR region of Ctgf mRNA, subsequently leading to the decreased expression of Ctgf in the I/R brain. Furthermore, we showed that miR-375/Ctgf-mediated protective effects are associated with p21/PI3K/Akt signaling pathways. Our findings thus provide a new insight into the mechanism of cerebral I/R injury and pave a potential new way for the therapy of cerebral I/R injury.
Highlights
Ischemic stroke is the main cause of permanent injury, disability, and deaths in the world
With middle cerebral artery occlusion (MCAO) rat model and in vitro hypoxia/reoxygenation (H/R) PC12 model, we provided direct evidence that miR-375 shows a protection from injury of cerebral I/R through targetting connective tissue growth factor (Ctgf) mRNA and decreasing Ctgf protein expression
Our results showed that expression of Ctgf mRNA and protein were significantly decreased in the I/R group treated with miR-375 mimic and fastigial nucleus electrostimulation (FNS) compared with the I/R group with negative control (NC) treatment or without treatment (Figure 2D and 2E)
Summary
Ischemic stroke is the main cause of permanent injury, disability, and deaths in the world. Ischemic stroke is usually treated by intravenous thrombolytic with alteplase or intra-arterial mechanical thrombectomy with stent retriever devices. This therapy, known as cerebral ischemia/reperfusion (I/R), can lead to increased brain injury. Accumulating evidence shows that apoptosis and death of neural cells after I/R are the leading causes of aggravated brain injury [1,2]. It should be an important strategy to perform anti-apoptotic treatment as early as possible following cerebral I/R. The exact mechanisms underlying cerebral I/R-induced neuronal death and dysfunction are not fully understood
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.
