HomeCirculation ResearchVol. 127, No. 4In This Issue Free AccessIn BriefPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toFree AccessIn BriefPDF/EPUBIn This Issue Ruth Williams Ruth WilliamsRuth Williams Search for more papers by this author Originally published30 Jul 2020https://doi.org/10.1161/RES.0000000000000424Circulation Research. 2020;127:449is related toGut Microbiota–Derived Short-Chain Fatty Acids Promote Poststroke Recovery in Aged MiceThe Tumor-Suppressive Human Circular RNA CircITCH Sponges miR-330-5p to Ameliorate Doxorubicin-Induced Cardiotoxicity Through Upregulating SIRT6, Survivin, and SERCA2aRole of the GLUT1 Glucose Transporter in Postnatal CNS Angiogenesis and Blood-Brain Barrier IntegrityPost-Stroke Gut Microbiome Transplant and Recovery (p 453)Gut microbe manipulations after stroke can improve outcomes in mice, say Lee et al.Download figureDownload PowerPointPatients who suffer ischemic strokes often have significant imbalances of the microbes in their guts (dysbiosis). And, studies in mice suggest that while the stroke may be the initial trigger of dysbiosis, the imbalance can prompt inflammatory responses that further exacerbate the brain injury. Altering the gut microbiome prior to, or at the time of a stroke can influence stroke recovery, but Lee and colleagues wanted to know whether microbial manipulations after a stoke—a more likely scenario for treatment—would also work. To find out, they gave old mice strokes and then, on days 3 and 4 after the injury, treated the mice with fecal transplants from young healthy animals. Two weeks after treatment, the mice had less brain and gut inflammation, and improved cognition and locomoter activity compared with control animals that had received transplants from older mice. Because the young donor mice had significantly more short-chain-fatty acid (SCFA)-producing bacteria in their guts compared with older donor mice, the team also treated a group of stroke-injured mice with doses of SCFA-bacteria alone, and found these similarly improved the recipients outcomes. Together the results provide evidence for the benefits of bacteriotherapy after stroke and indicate the particular strains responsible.GLUT1 in Angiogenesis and BBB Integrity (p 466)Veys et al examine the role of a key glucose transporter in the blood-brain barrier.Download figureDownload PowerPointCompared with some other organs of the body, the brain requires large amounts of glucose as its primary energy source and, as such, the brain’s blood vessel endothelial cells, whose job it is to upload the sugar, produce large amounts of the glucose transporter protein GLUT1. Patients with genetic mutations in GLUT1 have neurological problems including seizures, movement disorders, and delayed neurological development. Unusually low GLUT1 levels in the blood-brain barrier have also been linked to Alzheimer’s disease in humans, and have been shown to exacerbate the disease in model mice. Veys and colleagues have now examined the role of GLUT1 in blood-brain barrier endothelial cells in more detail. They showed that inhibiting the activity of GLUT1 in newborn mice impaired aspects of normal blood vessel growth in the brain, while inhibiting the transporter in adult mice led to progressive neuron loss, behavioral abnormalities, reduced movement, seizures and signs of inflammation—including gliosis. The structural integrity of the blood-brain barrier remained in tact, however. The results provide further insights into GLUT1’s importance in the brain endothelial cells and into the pathology that develops in patients lacking the transporter.CircITCH Relieves DOXIC (p e108)Suppression of a circular RNA underpins the cardiotoxicity of doxorubicin, report Han et al.Download figureDownload PowerPointDoxorubicin (DOX) is a potent chemotherapeutic used for treating many types of cancer. Unfortunately, it has some nasty side effects, including damage to the heart that can be severe, sometimes even fatal. Han and colleagues have now discovered that in the hearts of cancer patients that suffered DOX-induced cardiomyopathy, as well as in cultured stem cell-derived cardiomyocytes exposed to the drug, levels of a particular circular RNA called CircITCH are lower than usual. Furthermore, boosting production of this RNA in such cells could prevent the contraction, calcium handling and electrical abnormalities caused by the drug as well as DOX-induced oxidative stress and DNA damage. CircITCH reportedly acts as a sponge for sequestering regulatory microRNA molecules in other cell types, and the team now shows that this activity is also responsible for its cardioprotective effects. In healthy cardiomyocytes, CircITCH sequestered miR-330-5p preventing this microRNA from silencing target genes involved in DNA repair, cell survival and calcium regulation. And, silencing miR-3320-5p directly similarly prevented the DOX-induced cell abnormalities. Together the results shed light on the mechanisms of DOX-induced toxicity and offer clues on how to pharmacologically prevent it. Previous Back to top Next FiguresReferencesRelatedDetailsRelated articlesGut Microbiota–Derived Short-Chain Fatty Acids Promote Poststroke Recovery in Aged MiceJuneyoung Lee, et al. Circulation Research. 2020;127:453-465The Tumor-Suppressive Human Circular RNA CircITCH Sponges miR-330-5p to Ameliorate Doxorubicin-Induced Cardiotoxicity Through Upregulating SIRT6, Survivin, and SERCA2aDong Han, et al. Circulation Research. 2020;127:e108-e125Role of the GLUT1 Glucose Transporter in Postnatal CNS Angiogenesis and Blood-Brain Barrier IntegrityKoen Veys, et al. Circulation Research. 2020;127:466-482 July 31, 2020Vol 127, Issue 4Article InformationMetrics Download: 296 © 2020 American Heart Association, Inc.https://doi.org/10.1161/RES.0000000000000424 Originally publishedJuly 30, 2020 PDF download