PMID- 25241340 OWN - NLM STAT- MEDLINE DCOM- 20151117 LR - 20200905 IS - 1532-8511 (Electronic) IS - 1052-3057 (Linking) VI - 23 IP - 10 DP - 2014 Nov-Dec TI - Telmisartan reduces progressive accumulation of cellular amyloid beta and phosphorylated tau with inflammatory responses in aged spontaneously hypertensive stroke resistant rat. PG - 2580-2590 LID - S1052-3057(14)00268-7 [pii] LID - 10.1016/j.jstrokecerebrovasdis.2014.05.023 [doi] AB - BACKGROUND: In addition to reducing the level of blood pressure (BP), telmisartan was expected to show the long-term neuroprotective effects preventing accumulation of cellular amyloid beta peptide (Abeta) and phosphorylated tau (ptau) by ameliorating neuroinflammation. METHODS: We examined effects of telmisartan on cellular Abeta and ptau with inflammatory responses in the brain of a spontaneously hypertensive stroke resistant (SHR-SR) rat by giving either telmisartan at 0 (vehicle), .3 mg/kg/day or 3 mg/kg/day, orally, from 3 months of age and performed immunohistologic analysis at 6, 12, and 18 months. Compared with normotensive Wistar rats, numbers of Abeta- and ptau-positive neurons in the cerebral cortex progressively increased with age until 18 months in the SHR-SR rats, as did the numbers of ionized calcium-binding adapter molecule 1 (Iba-1)-positive microglia, tumor necrosis factor alpha (TNF-alpha)-positive neurons, and monocyte chemotactic protein 1 (MCP-1)-positive neurons. RESULTS: Low-dose telmisartan significantly decreased the numbers of Abeta- and ptau-positive neuron as well as the numbers of TNF-alpha-positive neurons, Iba-1-positive microglia, and MCP-1-positive neurons at 6, 12, and 18 months. High-dose telmisartan reduced BP and showed a further reduction of cellular Abeta and ptau. CONCLUSIONS: The present study suggests that accumulation of cellular Abeta and ptau and the inflammatory responses were decreased via improving metabolic syndrome with low-dose telmisartan and improving both metabolic syndrome and hypertension with high-dose telmisartan. CI - Copyright (c) 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved. FAU - Kurata, Tomoko AU - Kurata T AD - Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan. FAU - Lukic, Violeta AU - Lukic V AD - Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan. FAU - Kozuki, Miki AU - Kozuki M AD - Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan. FAU - Wada, Daisuke AU - Wada D AD - Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan. FAU - Miyazaki, Kazunori AU - Miyazaki K AD - Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan. FAU - Morimoto, Nobutoshi AU - Morimoto N AD - Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan. FAU - Ohta, Yasuyuki AU - Ohta Y AD - Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan. FAU - Deguchi, Kentaro AU - Deguchi K AD - Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan. FAU - Ikeda, Yoshio AU - Ikeda Y AD - Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan. FAU - Kamiya, Tatsushi AU - Kamiya T AD - Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan. FAU - Abe, Koji AU - Abe K AD - Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan. Electronic address: toko11@cc.okayama-u.ac.jp. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140916 PL - United States TA - J Stroke Cerebrovasc Dis JT - Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association JID - 9111633 RN - 0 (Aif1 protein, rat) RN - 0 (Amyloid beta-Peptides) RN - 0 (Angiotensin II Type 1 Receptor Blockers) RN - 0 (Benzimidazoles) RN - 0 (Benzoates) RN - 0 (Calcium-Binding Proteins) RN - 0 (Chemokine CCL2) RN - 0 (Microfilament Proteins) RN - 0 (Neuroprotective Agents) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (tau Proteins) RN - U5SYW473RQ (Telmisartan) SB - IM MH - Age Factors MH - Amyloid beta-Peptides/*metabolism MH - Angiotensin II Type 1 Receptor Blockers/*pharmacology MH - Animals MH - Benzimidazoles/administration & dosage/*pharmacology MH - Benzoates/administration & dosage/*pharmacology MH - Calcium-Binding Proteins/metabolism MH - Cerebral Cortex/cytology/drug effects MH - Chemokine CCL2/metabolism MH - Inflammation/drug therapy MH - Male MH - Microfilament Proteins/metabolism MH - Microglia/drug effects/*metabolism MH - Neurons/drug effects/*metabolism MH - Neuroprotective Agents/administration & dosage/pharmacology MH - Phosphorylation/drug effects MH - Rats MH - Rats, Inbred SHR MH - Rats, Wistar MH - Telmisartan MH - Time Factors MH - Treatment Outcome MH - Tumor Necrosis Factor-alpha/metabolism MH - tau Proteins/*metabolism OTO - NOTNLM OT - Alzheimer's disease OT - inflammation OT - spontaneously hypertensive rat OT - telmisartan EDAT- 2014/09/23 06:00 MHDA- 2015/11/18 06:00 CRDT- 2014/09/22 06:00 PHST- 2014/01/22 00:00 [received] PHST- 2014/05/20 00:00 [revised] PHST- 2014/05/29 00:00 [accepted] PHST- 2014/09/22 06:00 [entrez] PHST- 2014/09/23 06:00 [pubmed] PHST- 2015/11/18 06:00 [medline] AID - S1052-3057(14)00268-7 [pii] AID - 10.1016/j.jstrokecerebrovasdis.2014.05.023 [doi] PST - ppublish SO - J Stroke Cerebrovasc Dis. 2014 Nov-Dec;23(10):2580-2590. doi: 10.1016/j.jstrokecerebrovasdis.2014.05.023. Epub 2014 Sep 16.