Amlodipine treatment reduces stroke size in apolipoprotein E-deficient mice.
BACKGROUND
This study investigated the effects of amlodipine, an L-type calcium channel blocker, on stroke size after focal brain ischemia in apolipoprotein E-deficient (ApoE KO) mice.


METHODS
Mice were subjected to middle cerebral artery (MCA) occlusion after being given a high-cholesterol (HCD) or normal diet for 10 weeks with or without amlodipine at a nonhypotensive dose of 3 mg/kg/day. Ischemic brain area was measured by 2,3,5-triphenyltetrazolium chloride staining. Cerebral blood flow was analyzed by laser-Doppler flowmetry. Superoxide anion production in the brain was detected by dihydroethidium staining.


RESULTS
The ApoE KO mice given HCD for 10 weeks showed a larger ischemic lesion size than mice with a normal diet. Amlodipine treatment in parallel with HCD feeding reduced the ischemic lesion size in ApoE KO mice. Interestingly, amlodipine treatment for only the last 2 weeks was also effective in reducing the ischemic lesion size in HCD-fed ApoE KO mice. The neurologic deficit after MCA occlusion was also improved by amlodipine treatment for either 10 weeks or 2 weeks. The decrease in surface cerebral blood flow after MCA occlusion was significantly attenuated in the peripheral region of the MCA territory in amlodipine-treated mice. Amlodipine treatment in HCD-fed ApoE KO mice also reduced superoxide production in the ischemic area of the brain.


CONCLUSIONS
These results suggest that amlodipine treatment reduces stroke size and neurologic deficit after focal brain ischemia, possibly through an increase in cerebral blood flow and inhibition of superoxide production.
Mogi
Masaki
M
Department of Molecular and Cellular Biology, Division of Medical Biochemistry and Cardiovascular Biology, Ehime University School of Medicine, Ehime, Japan.
Iwai
Masaru
M
Chen
Rui
R
Iwanami
Jun
J
Ide
Ayumi
A
Tsukuda
Kana
K
Yoshii
Toyofumi
T
Horiuchi
Masatsugu
M
D017311:Amlodipine / Q000627:therapeutic use*; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D002784:Cholesterol; D004032:Diet; D020244:Infarction, Middle Cerebral Artery; D017078:Laser-Doppler Flowmetry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000187:drug effects; D020521:Stroke / Q000188:drug therapy* / Q000378:metabolism; D013481:Superoxides / Q000037:antagonists & inhibitors / Q000378:metabolism
D001057:Apolipoproteins E; D002121:Calcium Channel Blockers; D013481:Superoxides; D017311:Amlodipine; D002784:Cholesterol