Prophylactic Edaravone Prevents Transient Hypoxic-Ischemic Brain Injury

• DOI: 10.1161/strokeaha.115.009162
• Publication Date: 2015-06-10T18:05:14Z
• Authors: Yu-Yo Sun; Yikun Li; Bushra Wali; Yuancheng Li; Jolly Lee; Andrew Heinmiller; Koji Abe; Donald G. Stein; Hui Mao; Iqbal Sayeed; Chia-Yi Kuan
• Keywords: Male; Free Radical Scavengers; Perioperative Care; 3. Good health; Mice, Inbred C57BL; Mice; Random Allocation; 03 medical and health sciences; Neuroprotective Agents; 0302 clinical medicine; Edaravone; Hypoxia-Ischemia, Brain; Animals; Antipyrine

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.