Pathophysiological dual action of adiponectin after transient focal ischemia in mouse brain.
BACKGROUND
Adiponectin, an adipocyte-derived bioactive protein, provides vascular protection. Recent clinical studies have suggested that plasma adiponectin plays a role in cerebrovascular disease (CVD). The present study was designed to determine the serial changes in adiponectin expression in the brain and plasma after transient focal cerebral ischemia in mice.


METHODS
C57BL/6 mice (n=100) were subjected to 60 min of middle cerebral artery occlusion followed by 1, 3, 6, 12, 24, 48, 72 h and 7-day reperfusion. Plasma adiponectin levels were determined by ELISA kit, and expression of adiponectin was assessed by immunohistochemistry, western blot analysis, and reverse transcription-polymerase chain reaction.


RESULTS
Cerebral ischemia-reperfusion injury resulted in a transient rise in the acute phase and decrease in the late phase, in plasma adiponectin levels (P<0.05). The same insult resulted in upregulation of adiponectin expression, with two peaks at 3 and 24 h after reperfusion (P<0.05). Adiponectin protein was negligible in nonischemic contralateral hemispheres, but relatively high levels of the protein were detected in the ischemic hemisphere. Adiponectin mRNA was detected in neither nonischemic nor ischemic hemisphere. Adiponectin accumulated only in endothelial cells of ischemic brain in response to cerebral ischemia.


CONCLUSIONS
Our results indicate that ischemic insult results in a transient rise in plasma adiponectin level during the acute phase, and that circulating adiponectin then accumulates in damaged vessels in the ischemic brain during the late phase. These findings suggest that time-targeting administration of adiponectin could be potentially useful in the treatment of stroke.
Yatomi
Kenji
K
Department of Neurosurgery, Juntendo University School of Medicine, Tokyo, Japan.
Miyamoto
Nobukazu
N
Komine-Kobayashi
Miki
M
Liu
Meizi
M
Oishi
Hidenori
H
Arai
Hajime
H
Hattori
Nobutaka
N
Urabe
Takao
T
D052242:Adiponectin / Q000097:blood / Q000235:genetics; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D001923:Brain Chemistry / Q000502:physiology*; D002545:Brain Ischemia / Q000378:metabolism* / Q000503:physiopathology; D002536:Cerebral Arteries / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000503:physiopathology; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology; D015854:Up-Regulation / Q000502:physiology
D052242:Adiponectin; C499919:Adipoq protein, mouse; D012333:RNA, Messenger