Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 308-314 |
| Number of pages | 7 |
| Journal | Brain Research |
| Volume | 1382 |
| DOIs | |
| Publication status | Published - Mar 25 2011 |
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Keywords
- Amlodipine
- AT2R
- Atorvastatin
- Cerebral infarction
- Collagen IV
- MMP-9
- Zucker rat
ASJC Scopus subject areas
- Neuroscience(all)
- Clinical Neurology
- Developmental Biology
- Molecular Biology
Cite this
Protection against ischemic stroke damage by synergistic treatment with amlodipine plus atorvastatin in Zucker metabolic rat. / Kawai, Hiromi; Deguchi, Shoko; Deguchi, Kentaro; Yamashita, Toru; Ohta, Yasuyuki; Omote, Yoshio; Kurata, Tomoko; Ikeda, Yoshio; Matsuura, Tohru; Abe, Koji.
In: Brain Research, Vol. 1382, 25.03.2011, p. 308-314.Research output: Contribution to journal › Article
}
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, Yoshio
AU - Kurata, Tomoko
AU - Ikeda, Yoshio
AU - Matsuura, Tohru
AU - Abe, Koji
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 - Amlodipine
KW - AT2R
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
VL - 1382
SP - 308
EP - 314
JO - Brain Research
JF - Brain Research
SN - 0006-8993
ER -