Prophylactic Edaravone Prevents Transient Hypoxic-Ischemic Brain Injury: Implications for Perioperative Neuroprotection.

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.

• 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
• Journal: Stroke (Stroke) Vol. 46 Issue 7 Pg. 1947-55 (Jul 2015) ISSN: 1524-4628 [Electronic] United States
• PMID: 26060244 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 American Heart Association, Inc.

Chemical References

• Free Radical Scavengers
• Neuroprotective Agents
• Edaravone
• Antipyrine

Topics

• Animals
• Antipyrine (administration & dosage, analogs & derivatives)
• Edaravone
• Free Radical Scavengers (administration & dosage)
• Hypoxia-Ischemia, Brain (metabolism, pathology, prevention & control)
• Male
• Mice
• Mice, Inbred C57BL
• Neuroprotective Agents (administration & dosage)
• Perioperative Care (methods)
• Random Allocation