Telmisartan reduces progressive oxidative stress and phosphorylated α-synuclein accumulation in stroke-resistant spontaneously hypertensive rats after transient middle cerebral artery occlusion

Kota Sato, Toru Yamashita, Tomoko Kurata, Violeta Lukic, Yusuke Fukui, Nozomi Hishikawa, Kentaro Deguchi, Koji Abe

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Abstract

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.

Original languageEnglish
Pages (from-to)1554-1563
Number of pages10
JournalJournal of Stroke and Cerebrovascular Diseases
Volume23
Issue number6
DOIs
Publication statusPublished - Jul 2014

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Keywords

  • Parkinson's disease
  • Spontaneously hypertensive rat
  • oxidative stress
  • phosphorylated α-synuclein
  • telmisartan

ASJC Scopus subject areas

  • Surgery
  • Rehabilitation
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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