TY - JOUR
T1 - Telmisartan reduces progressive oxidative stress and phosphorylated α-synuclein accumulation in stroke-resistant spontaneously hypertensive rats after transient middle cerebral artery occlusion
AU - Sato, Kota
AU - Yamashita, Toru
AU - Kurata, Tomoko
AU - Lukic, Violeta
AU - Fukui, Yusuke
AU - Hishikawa, Nozomi
AU - Deguchi, Kentaro
AU - Abe, Koji
N1 - Funding Information:
This work was partly supported by a Grant-in-Aid for Scientific Research (B) 21390267 from the Ministry of Education, Science, Culture, and Sports of Japan , and by Grants-in-Aid from the Research Committee of CNS Degenerative Diseases (I. Nakano) and grants (H. Mizusawa, M. Nishizawa, H. Sasaki, G. Sobue) from the Ministry of Health, Labour, and Welfare of Japan .
PY - 2014/7
Y1 - 2014/7
N2 - Telmisartan is an angiotensin receptor blocker with high lipid solubility, also called metabosartan, which exerts a special protective effect on both acute brain damage and chronic neurodegeneration. We examined the effects of telmisartan on oxidative stress by advanced glycation end product (AGE) and 4-hydroxynonenal (4-HNE) assays and the accumulation of phosphorylated α-synuclein (pSyn) in the brain of stroke-resistant spontaneously hypertensive rats (SHR-SR). At the age of 12 weeks, SHR-SR received transient middle cerebral artery occlusion (tMCAO) for 90 minutes and were divided into the following 3 groups: the vehicle group, the low-dose telmisartan group (.3 mg/kg/day), and the high-dose telmisartan group (3 mg/kg/day, postoperatively). Immunohistologic analysis was performed when rats were 6, 12, and 18 months old. AGE, 4-HNE, and pSyn-positive cells (per square millimeter) increased with age in the cerebral cortex and hippocampus of the vehicle group, in the low-dose telmisartan group, these parameters decreased without lowering blood pressure (BP), and in the high-dose telmisartan group, these parameters increased with lowering BP. The present study suggests that a persistent hypertension after tMCAO caused a progressive oxidative stress with the abnormal accumulation of pSyn, and that telmisartan reduced oxidative stress and the accumulation of pSyn without lowering BP (low dose) or improved these conditions with a reduction in BP (high dose) via its pleiotropic effects through a potential peroxisome proliferator-activated receptor gamma stimulation in the brain of SHR-SR.
AB - Telmisartan is an angiotensin receptor blocker with high lipid solubility, also called metabosartan, which exerts a special protective effect on both acute brain damage and chronic neurodegeneration. We examined the effects of telmisartan on oxidative stress by advanced glycation end product (AGE) and 4-hydroxynonenal (4-HNE) assays and the accumulation of phosphorylated α-synuclein (pSyn) in the brain of stroke-resistant spontaneously hypertensive rats (SHR-SR). At the age of 12 weeks, SHR-SR received transient middle cerebral artery occlusion (tMCAO) for 90 minutes and were divided into the following 3 groups: the vehicle group, the low-dose telmisartan group (.3 mg/kg/day), and the high-dose telmisartan group (3 mg/kg/day, postoperatively). Immunohistologic analysis was performed when rats were 6, 12, and 18 months old. AGE, 4-HNE, and pSyn-positive cells (per square millimeter) increased with age in the cerebral cortex and hippocampus of the vehicle group, in the low-dose telmisartan group, these parameters decreased without lowering blood pressure (BP), and in the high-dose telmisartan group, these parameters increased with lowering BP. The present study suggests that a persistent hypertension after tMCAO caused a progressive oxidative stress with the abnormal accumulation of pSyn, and that telmisartan reduced oxidative stress and the accumulation of pSyn without lowering BP (low dose) or improved these conditions with a reduction in BP (high dose) via its pleiotropic effects through a potential peroxisome proliferator-activated receptor gamma stimulation in the brain of SHR-SR.
KW - Parkinson's disease
KW - Spontaneously hypertensive rat
KW - oxidative stress
KW - phosphorylated α-synuclein
KW - telmisartan
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U2 - 10.1016/j.jstrokecerebrovasdis.2013.12.051
DO - 10.1016/j.jstrokecerebrovasdis.2013.12.051
M3 - Article
C2 - 24780412
AN - SCOPUS:84902531967
SN - 1052-3057
VL - 23
SP - 1554
EP - 1563
JO - Journal of Stroke and Cerebrovascular Diseases
JF - Journal of Stroke and Cerebrovascular Diseases
IS - 6
ER -