Neurovascular protection by telmisartan via reducing neuroinflammation in stroke-resistant spontaneously hypertensive rat brain after ischemic stroke.

Publisher: Saunders Country of Publication: United States NLM ID: 9111633 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1532-8511 (Electronic) Linking ISSN: 10523057 NLM ISO Abbreviation: J Stroke Cerebrovasc Dis Subsets: MEDLINE

Publication: Philadelphia, PA : Saunders
Original Publication: New York, NY : Demos Publications, [1991-

Angiotensin II Type 1 Receptor Blockers/*pharmacology ; Anti-Inflammatory Agents/*pharmacology ; Antihypertensive Agents/*pharmacology ; Benzimidazoles/*pharmacology ; Benzoates/*pharmacology ; Encephalitis/*prevention & control ; Hypertension/*drug therapy ; Infarction, Middle Cerebral Artery/*drug therapy ; Neuroprotective Agents/*pharmacology; Acetylglucosamine/metabolism ; Animals ; Blood Pressure/drug effects ; Carrier Proteins/metabolism ; Cerebral Cortex/drug effects ; Cerebral Cortex/metabolism ; Cerebral Cortex/pathology ; Collagen Type IV/metabolism ; Disease Models, Animal ; Encephalitis/etiology ; Encephalitis/metabolism ; Encephalitis/pathology ; Glial Fibrillary Acidic Protein/metabolism ; Hypertension/complications ; Hypertension/diagnosis ; Hypertension/physiopathology ; Infarction, Middle Cerebral Artery/complications ; Infarction, Middle Cerebral Artery/metabolism ; Infarction, Middle Cerebral Artery/pathology ; Inflammasomes/metabolism ; Male ; Matrix Metalloproteinase 9/metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein ; Rats, Inbred SHR ; Telmisartan ; Time Factors

Telmisartan is a highly lipid-soluble angiotensin receptor blocker (ARB), which improves insulin sensitivity and reduces triglyceride levels and, thus, is called metabo-sartan. We examined the effects of telmisartan on neurovascular unit (N-acetylglucosamine oligomer [NAGO], collagen IV, and glial fibrillary acidic protein [GFAP]) and neuroinflammation (matrix metalloproteinase-9 [MMP-9] and inflammasome) in brain of stroke-resistant spontaneously hypertensive rat (SHR-SR). At 12 weeks of age, SHR-SR received transient middle cerebral artery occlusion (tMCAO) for 90 minutes and were divided into the following 3 groups, that is, vehicle group, low-dose telmisartan group (.3 mg/kg/d), and high-dose telmisartan group (3 mg/kg/d, postoral). Immunohistologic analysis at ages 6, 12, and 18 months showed progressive decreases of NAGO-positive endothelium and collagen IV-positive basement membrane and progressive increases of MMP-9-positive neurons, GFAP-positive astrocytes, and NLRP3-positive inflammasome in the cerebral cortex of vehicle group. Low-dose telmisartan reduced such changes without lowering blood pressure (BP), and high-dose telmisartan further improved such changes with lowering BP. The present findings suggest that a persistent hypertension caused a long-lasting inflammation after tMCAO in SHR-SR, which accelerated neurovascular disruption and emergent inflammasome, and that telmisartan greatly reduced such inflammation and protected the neurovascular unit via its pleiotropic effects in living hypertensive rat brain after ischemic stroke.
(Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Keywords: Alzheimer disease; Spontaneously hypertensive rat; inflammasome; neurovascular unit; telmisartan

0 (Angiotensin II Type 1 Receptor Blockers)
0 (Anti-Inflammatory Agents)
0 (Antihypertensive Agents)
0 (Benzimidazoles)
0 (Benzoates)
0 (Carrier Proteins)
0 (Collagen Type IV)
0 (Glial Fibrillary Acidic Protein)
0 (Inflammasomes)
0 (NLR Family, Pyrin Domain-Containing 3 Protein)
0 (Neuroprotective Agents)
0 (Nlrp3 protein, rat)
EC 3.4.24.35 (Matrix Metalloproteinase 9)
EC 3.4.24.35 (Mmp9 protein, rat)
U5SYW473RQ (Telmisartan)
V956696549 (Acetylglucosamine)

Date Created: 20141224 Date Completed: 20160314 Latest Revision: 20181202

20221213

10.1016/j.jstrokecerebrovasdis.2014.09.037

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