title: Long-term effect of telmisartan on Alzheimer's amyloid genesis in SHR-SR after tMCAO.
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.
authors.affiliation: Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikatacho, Kitaku, Okayama, 700-8558, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kurata
authors.forename: Violeta
authors.initials: V
authors.lastname: Lukic
authors.forename: Miki
authors.initials: M
authors.lastname: Kozuki
authors.forename: Daisuke
authors.initials: D
authors.lastname: Wada
authors.forename: Kazunori
authors.initials: K
authors.lastname: Miyazaki
authors.forename: Nobutoshi
authors.initials: N
authors.lastname: Morimoto
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Ohta
authors.forename: Kentaro
authors.initials: K
authors.lastname: Deguchi
authors.forename: Toru
authors.initials: T
authors.lastname: Yamashita
authors.forename: Nozomi
authors.initials: N
authors.lastname: Hishikawa
authors.forename: Kosuke
authors.initials: K
authors.lastname: Matsuzono
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Kamiya
authors.forename: Koji
authors.initials: K
authors.lastname: Abe
mesh_terms: D000367:Age Factors; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use*; D001565:Benzoates / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002784:Cholesterol / Q000097:blood; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007839:Functional Laterality; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology*; D008137:Longitudinal Studies; D008297:Male; D058225:Plaque, Amyloid / Q000473:pathology*; D051381:Rats; D011918:Rats, Inbred SHR; D000077333:Telmisartan; D014280:Triglycerides / Q000097:blood
chemical_list: D016229:Amyloid beta-Peptides; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001565:Benzoates; D014280:Triglycerides; D002784:Cholesterol; D000077333:Telmisartan