title: Pretreatment with eplerenone reduces stroke volume in mouse middle cerebral artery occlusion model.
abstract: 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.
authors.affiliation: Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University, Graduate School of Medicine, Tohon, Ehime 791-0295, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Iwanami
authors.forename: Masaki
authors.initials: M
authors.lastname: Mogi
authors.forename: Shoko
authors.initials: S
authors.lastname: Okamoto
authors.forename: Xin-Yu
authors.initials: XY
authors.lastname: Gao
authors.forename: Jian-Mei
authors.initials: JM
authors.lastname: Li
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Min
authors.forename: Ayumi
authors.initials: A
authors.lastname: Ide
authors.forename: Kana
authors.initials: K
authors.lastname: Tsukuda
authors.forename: Masaru
authors.initials: M
authors.lastname: Iwai
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Horiuchi
mesh_terms: 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
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D013481:Superoxides; D013148:Spironolactone; D000077545:Eplerenone