title: Transient Mild Cerebral Ischemia Significantly Deteriorated Cognitive Impairment in a Mouse Model of Alzheimer's Disease via Angiotensin AT1 Receptor.
abstract: BACKGROUND
  Ischemic stroke is suggested to be potentially associated with cognitive impairment in Alzheimer's disease (AD). We hypothesized that cerebral ischemia deteriorates cognitive impairment in AD, through angiotensin II.
  
  
  METHODS
  We used 5XFAD mouse, a model of AD with vascular and cerebral amyloid-β deposition. Transient cerebral ischemia of mice was induced by bilateral common carotid artery occlusion (BCCAO) for 17 minutes. The posttreatment with olmesartan, an ARB, or vehicle was started at 24 hours after BCCAO and was performed for 5 weeks. Experimental mice consisted of 5 groups: (i) wild-type mice, (ii) wild-type mice with BCCAO, (iii) 5XFAD mice, (iv) 5XFAD mice with BCCAO, (v) 5XFAD mice with BCCAO and olmesartan postadministration.
  
  
  RESULTS
  BCCAO in 5XFAD caused greater escape latency (P < 0.01) on water maze test than that in wild type, indicating that transient brief cerebral ischemia enhanced cognitive decline in 5XFAD mice. Posttreatment with olmesartan significantly reduced escape latency (P < 0.01) on water maze test, retention trial latency (P < 0.05) on passive avoidance test, and retention time of outer zone (P < 0.01) on open-field test in 5XFAD subjected to BCCAO. This protective effect of olmesartan against cognitive impairment in 5XFAD with BCCAO was associated with the protection of neuron and attenuation of oxidative stress in hippocampus and the suppression of blood-brain barrier disruption.
  
  
  CONCLUSIONS
  We obtained the evidence that transient brief cerebral ischemia deteriorated cognitive impairment in AD model through AT1 receptor.
authors: Departments of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
authors: Takashi
authors: T
authors: Nakagawa
authors: Departments of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
authors: Yu
authors: Y
authors: Hasegawa
authors: Departments of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
authors: Ken
authors: K
authors: Uekawa
authors: Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors: Satoru
authors: S
authors: Senju
authors: Division of Reproductive Engineering, Center for Animal Resources and Development, Kumamoto University, Kumamoto, Japan.
authors: Naomi
authors: N
authors: Nakagata
authors: Department of General and Community Medicine, Kumamoto University Hospital, Kumamoto, Japan.
authors: Kunihiko
authors: K
authors: Matsui
authors: Departments of Pharmacology and Molecular Therapeutics, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan; mitsuyam@gpo.kumamoto-u.ac.jp.
authors: Shokei
authors: S
authors: Kim-Mitsuyama
mesh_terms: D000544:Alzheimer Disease / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage; D000818:Animals; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D060825:Cognitive Dysfunction / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000008:administration & dosage*; D002546:Ischemic Attack, Transient / Q000150:complications* / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D013777:Tetrazoles / Q000008:administration & dosage*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D007093:Imidazoles; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; C437965:olmesartan
keywords: amyloid-β; angiotensin; blood pressure; blood–brain barrier; cognitive function; hypertension; oxidative stress; transient cerebral ischemia.