Pretreatment with eplerenone reduces stroke volume in mouse middle cerebral artery occlusion model.
Eplerenone, a mineralocorticoid receptor antagonist, is reported to be effective to prevent end-stage cardiovascular damage induced by aldosterone. However, the effect of eplerenone on brain damage is not fully understood. Here, we investigated whether pretreatment with eplerenone attenuates stroke size in mice subjected to middle cerebral artery occlusion. Middle cerebral artery occlusion with a microfilament technique induced focal ischemia, to approximately 25% of the total area in a coronal section of the brain. Treatment with eplerenone at a dose of 1.67 mg/g chow significantly reduced the ischemic area, ischemic volume, and neurological deficit, without a blood pressure-lowering effect. Laser-Doppler flowmetry analysis showed a decrease in surface cerebral blood flow in the peripheral region after 1 h of middle cerebral artery occlusion. This decrease was smaller in mice treated with eplerenone. Superoxide production evaluated by staining with dihydroethidium was attenuated in the ischemic area of the brain in eplerenone-treated mice. Taken together, our findings suggest that eplerenone has a protective effect on ischemic brain damage, at least partly due to improvement of cerebral blood flow in the penumbra and reduction of oxidative stress.
Iwanami
Jun
J
Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University, Graduate School of Medicine, Tohon, Ehime 791-0295, Japan.
Mogi
Masaki
M
Okamoto
Shoko
S
Gao
Xin-Yu
XY
Li
Jian-Mei
JM
Min
Li-Juan
LJ
Ide
Ayumi
A
Tsukuda
Kana
K
Iwai
Masaru
M
Horiuchi
Masatsugu
M
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D000077545:Eplerenone; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology*; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D013318:Stroke Volume / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism
D000451:Mineralocorticoid Receptor Antagonists; D013481:Superoxides; D013148:Spironolactone; D000077545:Eplerenone