TY - JOUR
T1 - Protection against ischemic stroke damage by synergistic treatment with amlodipine plus atorvastatin in Zucker metabolic rat
AU - Kawai, Hiromi
AU - Deguchi, Shoko
AU - Deguchi, Kentaro
AU - Yamashita, Toru
AU - Ohta, Yasuyuki
AU - Omote, Yosio
AU - Kurata, Tomoko
AU - Ikeda, Yoshio
AU - Matsuura, Tohru
AU - Abe, Koji
N1 - Funding Information:
This work was partly supported by Grant-in-Aid for Scientific Research (B) 21390267 and the Ministry of Education, Science, Culture and Sports of Japan , and by Grants-in-Aid from the Research Committee of CNS Degenerative Diseases (Nakano I.), and grants (Itoyama Y., Imai T., Sobue G.) from the Ministry of Health, Labour and Welfare of Japan .
PY - 2011/3/25
Y1 - 2011/3/25
N2 - Ischemic stroke is a major neurologic disorder and a leading cause of disability and death in the world. We compared neuroprotective effects of single or combination therapy of amlodipine (AM) and atorvastatin (AT) in such a metabolic syndrome model Zucker rat. The animals were pretreated with vehicle, AM, AT, or the combination of AM plus AT for 28 days, and physical and serum parameters were analyzed, then 90 min of transient middle cerebral artery occlusion (tMCAO), was performed followed by immunohistochemical analyses at 24 h. Without affecting serum levels of lipids, adiponectin, and leptin, the combination therapy of AM plus AT ameliorated the post-ischemic brain weight increase. The single treatment with AM or AT itself exerted neuroprotective effects with reducing inductions of MMP-9 and AT2R, as well as with preserving collagen IV, and the combination therapy of AM plus AT showed a further synergistic benefit against acute ischemic neural damages. Single AT was more protective on these 3 molecules than single AM at this time point of 24 h after tMCAO. Thus, the combination therapy with AM plus AT extended the neuroprotectives effect of single treatment with AM or AT on a part of neurovascular unit and a hypertension-related receptor.
AB - Ischemic stroke is a major neurologic disorder and a leading cause of disability and death in the world. We compared neuroprotective effects of single or combination therapy of amlodipine (AM) and atorvastatin (AT) in such a metabolic syndrome model Zucker rat. The animals were pretreated with vehicle, AM, AT, or the combination of AM plus AT for 28 days, and physical and serum parameters were analyzed, then 90 min of transient middle cerebral artery occlusion (tMCAO), was performed followed by immunohistochemical analyses at 24 h. Without affecting serum levels of lipids, adiponectin, and leptin, the combination therapy of AM plus AT ameliorated the post-ischemic brain weight increase. The single treatment with AM or AT itself exerted neuroprotective effects with reducing inductions of MMP-9 and AT2R, as well as with preserving collagen IV, and the combination therapy of AM plus AT showed a further synergistic benefit against acute ischemic neural damages. Single AT was more protective on these 3 molecules than single AM at this time point of 24 h after tMCAO. Thus, the combination therapy with AM plus AT extended the neuroprotectives effect of single treatment with AM or AT on a part of neurovascular unit and a hypertension-related receptor.
KW - AT2R
KW - Amlodipine
KW - Atorvastatin
KW - Cerebral infarction
KW - Collagen IV
KW - MMP-9
KW - Zucker rat
UR - http://www.scopus.com/inward/record.url?scp=79952535409&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79952535409&partnerID=8YFLogxK
U2 - 10.1016/j.brainres.2011.01.062
DO - 10.1016/j.brainres.2011.01.062
M3 - Article
C2 - 21276424
AN - SCOPUS:79952535409
SN - 0006-8993
VL - 1382
SP - 308
EP - 314
JO - Molecular Brain Research
JF - Molecular Brain Research
ER -