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

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

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1947-1955
Number of pages9
JournalStroke
Volume46
Issue number7
DOIs
Publication statusPublished - Jul 4 2015

    Fingerprint

Keywords

  • MCI-186
  • antioxidants
  • stroke
  • thrombosis

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialised Nursing

Cite this

Sun, Y. Y., Li, Y., Wali, B., Li, Y., Lee, J., Heinmiller, A., Abe, K., Stein, D. G., Mao, H., Sayeed, I., & Kuan, C. Y. (2015). Prophylactic Edaravone Prevents Transient Hypoxic-Ischemic Brain Injury: Implications for Perioperative Neuroprotection. Stroke, 46(7), 1947-1955. https://doi.org/10.1161/STROKEAHA.115.009162