Prophylactic Edaravone Prevents Transient Hypoxic-Ischemic Brain Injury. Issue 7 (July 2015)

• Record Type: Journal Article
• Authors: Sun, Yu-Yo; Li, Yikun; Wali, Bushra; Li, Yuancheng; Lee, Jolly; Heinmiller, Andrew; Abe, Koji; Stein, Donald G.; Mao, Hui; Sayeed, Iqbal; Kuan, Chia-Yi
• Is Part Of: Stroke. Volume 46:Issue 7(2015)
• Publication Date: 2015-07
• Subjects: Cerebrovascular disease -- Periodicals; Cerebral circulation -- Periodicals; 616.81
• DOI: 10.1161/STROKEAHA.115.009162
• Languages: English
• ISSNs: 0039-2499

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title>Background and Purpose—</title> <p>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.</p> </sec> <sec> <title>Methods—</title> <p>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.</p> </sec> <sec> <title>Results—</title> <p>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.</p> </sec> <sec> <title>Conclusions—</title> <p>Acute application of Edaravone may be a useful strategy to prevent postsurgery stroke and cognitive impairment, especially in patients with severe carotid stenosis.</p> </sec> </abstract>