Yu-Yo Sun1, Yikun Li1, Bushra Wali1, Yuancheng Li1, Jolly Lee1, Andrew Heinmiller1, Koji Abe1, Donald G Stein1, Hui Mao1, Iqbal Sayeed1, Chia-Yi Kuan2. 1. From the Department of Pediatrics and Center for Neurodegenerative Diseases, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA (Y.-Y.S., Y.L., J.L., C.-Y.K.); Department of Emergency Medicine, Brain Research Laboratory, Emory University School of Medicine, Atlanta, GA (B.W., D.G.S., I.S.); Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA (Y.L., H.M.); VisualSonics Inc. Toronto, ON, Canada (A.H.); and Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan (K.A.). 2. From the Department of Pediatrics and Center for Neurodegenerative Diseases, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA (Y.-Y.S., Y.L., J.L., C.-Y.K.); Department of Emergency Medicine, Brain Research Laboratory, Emory University School of Medicine, Atlanta, GA (B.W., D.G.S., I.S.); Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, GA (Y.L., H.M.); VisualSonics Inc. Toronto, ON, Canada (A.H.); and Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan (K.A.). alex.kuan@emory.edu.
Abstract
BACKGROUND AND PURPOSE: Hypoperfusion-induced thrombosis is an important mechanism for postsurgery stroke and cognitive decline, but there are no perioperative neuroprotectants to date. This study investigated whether prophylactic application of Edaravone, a free radical scavenger already used in treating ischemic stroke in Japan, can prevent infarct and cognitive deficits in a murine model of transient cerebral hypoxia-ischemia. METHODS: Adult male C57BL/6 mice were subjected to transient hypoxic-ischemic (tHI) insult that consists of 30-minute occlusion of the unilateral common carotid artery and exposure to 7.5% oxygen. Edaravone or saline was prophylactically applied to compare their effects on cortical oxygen saturation, blood flow, coagulation, oxidative stress, metabolites, and learning-memory using methods that include photoacoustic imaging, laser speckle contrast imaging, solid-state NMR, and Morris water maze. The effects on infarct size by Edaravone application at different time points after tHI were also compared. RESULTS: Prophylactic administration of Edaravone (4.5 mg/kg×2, IP, 1 hour before and 1 hour after tHI) improved vascular reperfusion, oxygen saturation, and the maintenance of brain metabolites, reducing oxidative stress, thrombosis, white-matter injury, and learning impairment after tHI insult. Delayed Edaravone treatment after 3 h post-tHI became unable to reduce infarct size. CONCLUSIONS: Acute application of Edaravone may be a useful strategy to prevent postsurgery stroke and cognitive impairment, especially in patients with severe carotid stenosis.
BACKGROUND AND PURPOSE: Hypoperfusion-induced thrombosis is an important mechanism for postsurgery stroke and cognitive decline, but there are no perioperative neuroprotectants to date. This study investigated whether prophylactic application of Edaravone, a free radical scavenger already used in treating ischemic stroke in Japan, can prevent infarct and cognitive deficits in a murine model of transient cerebral hypoxia-ischemia. METHODS: Adult male C57BL/6 mice were subjected to transient hypoxic-ischemic (tHI) insult that consists of 30-minute occlusion of the unilateral common carotid artery and exposure to 7.5% oxygen. Edaravone or saline was prophylactically applied to compare their effects on cortical oxygen saturation, blood flow, coagulation, oxidative stress, metabolites, and learning-memory using methods that include photoacoustic imaging, laser speckle contrast imaging, solid-state NMR, and Morris water maze. The effects on infarct size by Edaravone application at different time points after tHI were also compared. RESULTS: Prophylactic administration of Edaravone (4.5 mg/kg×2, IP, 1 hour before and 1 hour after tHI) improved vascular reperfusion, oxygen saturation, and the maintenance of brain metabolites, reducing oxidative stress, thrombosis, white-matter injury, and learning impairment after tHI insult. Delayed Edaravone treatment after 3 h post-tHI became unable to reduce infarct size. CONCLUSIONS: Acute application of Edaravone may be a useful strategy to prevent postsurgery stroke and cognitive impairment, especially in patients with severe carotid stenosis.
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