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(Stroke. 2008;39:463.)
© 2008 American Heart Association, Inc.

Original Contributions

Edaravone Attenuates Brain Edema and Neurologic Deficits in a Rat Model of Acute Intracerebral Hemorrhage

Takehiro Nakamura, MD, PhD; Yasuhiro Kuroda, MD, PhD; Susumu Yamashita, MD; Xia Zhang, MD, PhD; Osamu Miyamoto, MD, PhD; Takashi Tamiya, MD, PhD; Seigo Nagao, MD, PhD; Guohua Xi, MD; Richard F. Keep, PhD Toshifumi Itano, PhD

From the Departments of Neurobiology (T.N., X.Z., O.M., T.I.), Neurological Surgery (T.N., T.T., S.N.), and Emergency and Critical Care Medicine (Y.K., S.Y.), Kagawa University Faculty of Medicine, Miki, Kagawa, Japan, and the Department of Neurosurgery (G.X., R.F.K.), University of Michigan, Ann Arbor, Mich.

Correspondence to Takehiro Nakamura, MD, PhD, Department of Neurobiology, Kagawa University Faculty of Medicine, 1750-1 Ikenobe, Miki, Kagawa 761-0793, Japan. E-mail tanakamu{at}kms.ac.jp

Background and Purpose— Our previous studies have demonstrated that oxidative DNA injury occurs in the brain after intracerebral hemorrhage (ICH). We therefore examined whether edaravone, a free-radical scavenger, could reduce ICH-induced brain injury.

Methods— These experiments used pentobarbital-anesthetized, male Sprague-Dawley rats that received an infusion of either 100 µL autologous whole blood (ICH), FeCl₂, or thrombin into the right basal ganglia. The rats were humanely killed 24 hours later. There were 4 sets of experiments. In the first, the dose-dependent effects of edaravone on ICH-induced brain injury were examined by measuring brain edema and neurologic deficits. In the second set, apurinic/apyrimidinic abasic sites and 8-hydroxyl-2'-deoxyguanosine, which are hallmarks of DNA oxidation, were investigated after treatment for ICH. In the third, the effect of delayed treatment with edaravone on ICH-induced injury was determined, whereas the fourth examined the effects of edaravone on iron- and thrombin-induced brain injury.

Results— Systemic administration of edaravone immediately or 2 hours after ICH reduced brain water content 24 hours after ICH compared with vehicle (P<0.05). Edaravone treatment immediately or 2 hours after ICH also ameliorated neurologic deficits (P<0.05). Edaravone also attenuated ICH-induced changes in apurinic/apyrimidinic abasic sites and 8-hydroxyl-2'-deoxyguanosine and reduced iron- and thrombin-induced brain injury.

Conclusions— Edaravone attenuates ICH-induced brain edema, neurologic deficits, and oxidative injury. It also reduces iron- and thrombin-induced brain injury. These results suggest that edaravone is a potential therapeutic agent for ICH.

Key Words: behavior • cerebral hemorrhage • edema • oxidative stress • rat

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