Long-term effect of telmisartan on Alzheimer's amyloid genesis in SHR-SR after tMCAO

Transl Stroke Res. 2015 Apr;6(2):107-15. doi: 10.1007/s12975-013-0321-y. Epub 2014 Jan 17.

Abstract

Telmisartan is expected to reduce not only the level of blood pressure but also neuroinflammation and neurotoxicity via pleiotrophic effects as a metabo-sartan. We examined the effects of telmisartan on Alzheimer's disease (AD) pathology in spontaneously hypertensive rat stroke resistant (SHR-SR) after transient middle cerebral artery occlusion (tMCAO) by giving either telmisartan at 0 (vehicle), 0.3 mg/kg/day (low dose, with no reduction of blood pressure), or 3 mg/kg/day (high dose, with a significant reduction of blood pressure) p.o. from 3 months (M) of age, and performed immunohistological analysis at 6, 12, and 18 M of age. The numbers of amyloid β (Aβ)-positive neurons in the cerebral cortex and hippocampus and senile plaque (SP) in the ipsilateral cerebral cortex progressively increased with age until 18 M in the SHR-SR after tMCAO. On the other hand, low-dose telmisartan significantly reduced the number of Aβ-positive neuron as well as SP at 6, 12, and 18 M. High-dose telmisartan showed further reductions of the above AD pathology. The present study suggests that telmisartan reduced both intracellular Aβ and extracellular SP accumulations after tMCAO in SHR-SR, with a further improvement by combined BP lowering. Such a strong effect of telmisartan could provide a preventative approach for AD in post-stroke patients with hypertension.

MeSH terms

  • Age Factors
  • Amyloid beta-Peptides / metabolism*
  • Analysis of Variance
  • Animals
  • Antihypertensive Agents / therapeutic use*
  • Benzimidazoles / therapeutic use*
  • Benzoates / therapeutic use*
  • Blood Pressure / drug effects
  • Body Weight / drug effects
  • Brain / drug effects
  • Brain / pathology
  • Cholesterol / blood
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Functional Laterality
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Infarction, Middle Cerebral Artery / drug therapy*
  • Infarction, Middle Cerebral Artery / etiology
  • Infarction, Middle Cerebral Artery / pathology*
  • Longitudinal Studies
  • Male
  • Plaque, Amyloid / pathology*
  • Rats
  • Rats, Inbred SHR
  • Telmisartan
  • Triglycerides / blood

Substances

  • Amyloid beta-Peptides
  • Antihypertensive Agents
  • Benzimidazoles
  • Benzoates
  • Triglycerides
  • Cholesterol
  • Telmisartan