Edaravone attenuates cerebral ischemic injury by suppressing aquaporin-4.
Aquaporin-4 (AQP4) plays a role in the generation of post-ischemic edema. Pharmacological modulation of AQP4 function may thus provide a novel therapeutic strategy for the treatment of stroke, tumor-associated edema, epilepsy, traumatic brain injury, and other disorders of the central nervous system (CNS) associated with altered brain water balance. Edaravone, a free radical scavenger, is used for the treatment of acute ischemic stroke (AIS) in Japan. In this study, edaravone significantly reduced the infarct area and improved the neurological deficit scores at 24h after reperfusion in a rat transient focal ischemia model. Furthermore, edaravone markedly reduced AQP4 immunoreactivity and protein levels in the cerebral infarct area. In light of observations that edaravone specifically inhibited AQP4 in a rat transient focal ischemia model, we propose that edaravone might reduce cerebral edema through the inhibition of AQP4 expression following cerebral infarction.
Kikuchi
Kiyoshi
K
Division of Laboratory and Vascular Medicine, Field of Cardiovascular and Respiratory Disorders, Department of Advanced Therapeutics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.
Tancharoen
Salunya
S
Matsuda
Fumiyo
F
Biswas
Kamal Krishna
KK
Ito
Takashi
T
Morimoto
Yoko
Y
Oyama
Yoko
Y
Takenouchi
Kazunori
K
Miura
Naoki
N
Arimura
Noboru
N
Nawa
Yuko
Y
Meng
Xiaojie
X
Shrestha
Binita
B
Arimura
Shinichiro
S
Iwata
Masahiro
M
Mera
Kentaro
K
Sameshima
Hisayo
H
Ohno
Yoshiko
Y
Maenosono
Ryuichi
R
Tajima
Yutaka
Y
Uchikado
Hisaaki
H
Kuramoto
Terukazu
T
Nakayama
Kenji
K
Shigemori
Minoru
M
Yoshida
Yoshihiro
Y
Hashiguchi
Teruto
T
Maruyama
Ikuro
I
Kawahara
Ko-Ichi
K
D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D051401:Aquaporin 4 / Q000037:antagonists & inhibitors*; D001929:Brain Edema / Q000188:drug therapy* / Q000209:etiology; D002545:Brain Ischemia / Q000150:complications*; D004195:Disease Models, Animal; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D008297:Male; D051381:Rats
D051401:Aquaporin 4; D016166:Free Radical Scavengers; D000077553:Edaravone; D000983:Antipyrine