Agnieszka A Ardelt1, Randall S Carpenter2, Ifeanyi Iwuchukwu3, An Zhang4, William Lin5, Ewa Kosciuczuk6, Cyrus Hinkson7, Tania Rebeiz8, Sydney Reitz9, Peter H King10. 1. Department of Neurology, University of Chicago, 5841 S. Maryland Ave, MC2030, Chicago, IL 60637, United States. Electronic address: aaardelt@yahoo.com. 2. Department of Neurology, University of Chicago, 5841 S. Maryland Ave, MC2030, Chicago, IL 60637, United States. Electronic address: carpenter.794@buckeyemail.osu.edu. 3. Department of Neurocritical Care, Ochsner Medical Center, 1514 Jefferson Hwy., New Orleans, LA 70121, United States. Electronic address: iiwuchukwu@gmail.com. 4. Department of Neurology, University of Chicago, 5841 S. Maryland Ave, MC2030, Chicago, IL 60637, United States. Electronic address: anzhang518@gmail.com. 5. Department of Neurology, University of Chicago, 5841 S. Maryland Ave, MC2030, Chicago, IL 60637, United States. Electronic address: william.lin.phd@gmail.com. 6. Division of Hematology-Oncology, Northwestern University, 675 North St. Clair, Chicago, IL 60611, United States. Electronic address: ewa.kosciuczuk@northwestern.edu. 7. Department of Neurology, University of Chicago, 5841 S. Maryland Ave, MC2030, Chicago, IL 60637, United States. Electronic address: clhinkson223@gmail.com. 8. Department of Neurology, University of Chicago, 5841 S. Maryland Ave, MC2030, Chicago, IL 60637, United States. Electronic address: Tania.Rebeiz@uchospitals.edu. 9. Department of Neurology, University of Chicago, 5841 S. Maryland Ave, MC2030, Chicago, IL 60637, United States. Electronic address: sydneyreitz@gmail.com. 10. Birmingham Veterans Affairs Medical Center, Birmingham, AL, United States. Electronic address: phking@uabmc.edu.
Abstract
BACKGROUND AND PURPOSE: Ischemic stroke produces significant morbidity and mortality, and acute interventions are limited by short therapeutic windows. Novel approaches to neuroprotection and neurorepair are necessary. HuR is an RNA-binding protein (RBP) which modulates RNA stability and translational efficiency of genes linked to ischemic stroke injury. METHODS: Using a transgenic (Tg) mouse model, we examined the impact of ectopic HuR expression in astrocytes on acute injury evolution after transient middle cerebral artery occlusion (tMCAO). RESULTS: HuR transgene expression was detected in astrocytes in perilesional regions and contralaterally. HuR Tg mice did not improve neurologically 72h after injury, whereas littermate controls did. In Tg mice, increased cerebral vascular permeability and edema were observed. Infarct volume was not affected by the presence of the transgene. CONCLUSIONS: Ectopic expression of HuR in astrocytes worsens outcome after transient ischemic stroke in mice in part by increasing vasogenic cerebral edema. These findings suggest that HuR could be a therapeutic target in cerebral ischemia/reperfusion.
BACKGROUND AND PURPOSE:Ischemic stroke produces significant morbidity and mortality, and acute interventions are limited by short therapeutic windows. Novel approaches to neuroprotection and neurorepair are necessary. HuR is an RNA-binding protein (RBP) which modulates RNA stability and translational efficiency of genes linked to ischemic stroke injury. METHODS: Using a transgenic (Tg) mouse model, we examined the impact of ectopic HuR expression in astrocytes on acute injury evolution after transient middle cerebral artery occlusion (tMCAO). RESULTS:HuR transgene expression was detected in astrocytes in perilesional regions and contralaterally. HuR Tg mice did not improve neurologically 72h after injury, whereas littermate controls did. In Tg mice, increased cerebral vascular permeability and edema were observed. Infarct volume was not affected by the presence of the transgene. CONCLUSIONS: Ectopic expression of HuR in astrocytes worsens outcome after transient ischemic stroke in mice in part by increasing vasogenic cerebral edema. These findings suggest that HuR could be a therapeutic target in cerebral ischemia/reperfusion.
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