Anti-apoptotic and neuroprotective effects of edaravone following transient focal ischemia in rats.
To investigate the effect of an antioxidant edaravone on the apoptotic process, we examined Bax and Bcl-2 immunohistochemical expression and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) reactivity. Rat focal ischemia models were prepared by 2 h transient middle cerebral artery occlusion. Edaravone or physiological saline was intravenously administered after reperfusion. After 24 h of reperfusion, infarction volume assessments, Bax and Bcl-2 immunohistochemistry and TUNEL staining were performed as well as neurological evaluation. Cortical cerebral blood flow was not statistically different between the treatment-groups. Edaravone-treated animals showed significantly improved neurological outcome. Total and cortical infarct volumes in the edaravone group significantly decreased. In addition, edaravone-treatment provided a significant reduction in the number of TUNEL-positive apoptotic cells, a decrease in Bax immunoreactivity and an increase in Bcl-2 expression within the peri-infarct area. Edaravone shows an excellent neuroprotective effect against ischemia/reperfusion brain injury through a Bax/Bcl-2 dependent anti-apoptotic mechanism.
Amemiya
Shimon
S
Division of Neurology, Second Department of Internal Medicine, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan. amemiya@nms.ac.jp
Kamiya
Tatsushi
T
Nito
Chikako
C
Inaba
Toshiki
T
Kato
Kengo
K
Ueda
Masayuki
M
Shimazaki
Kuniko
K
Katayama
Yasuo
Y
D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001929:Brain Edema / Q000473:pathology / Q000517:prevention & control; D002545:Brain Ischemia / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D002540:Cerebral Cortex / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D002544:Cerebral Infarction / Q000473:pathology / Q000517:prevention & control; D002560:Cerebrovascular Circulation / Q000187:drug effects; D000077553:Edaravone; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D051028:bcl-2-Associated X Protein
C494828:Bax protein, rat; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D000077553:Edaravone; D000983:Antipyrine