Post-stroke angiotensin II type 2 receptor activation provides long-term neuroprotection in aged rats

by Douglas M. Bennion, Jacob D. Isenberg, Allison T. Harmel, Kelly DeMars, Alex N. Dang, Chad H. Jones, Megan E. Pignataro, Justin T. Graham, U. Muscha Steckelings, Jon C. Alexander, Marcelo Febo, Eric G. Krause, Annette D. de Kloet, Eduardo Candelario-Jalil, Colin Sumners Activation of the angiotensin II type 2 receptor (AT2R) by administration of Compound 21 (C21), a selective AT2R agonist, induces neuroprotection in models of ischemic stroke in young adult animals. The mechanisms of this neuroprotective action are varied, and may include direct and indirect effec ts of AT2R activation. Our objectives were to assess the long-term protective effects of post-stroke C21 treatments in a clinically-relevant model of stroke in aged rats and to characterize the cellular localization of AT2Rs in the mouse brain of transgenic reporter mice following stroke. Intraperit oneal injections of C21 (0.03mg/kg) after ischemic stroke induced by transient monofilament middle cerebral artery occlusion resulted in protective effects that were sustained for up to at least 3-weeks post-stroke. These included improved neurological function across multiple assessments and a sign ificant reduction in infarct volume as assessed by magnetic resonance imaging. We also found AT2R expression to be on neurons, not astrocytes or microglia, in normal female and male mouse brains. Stroke did not induce altered cellular localization of AT2R when assessed at 7 and 14 days post-stroke. These findings demonstra...
Source: PLoS One - Category: Biomedical Science Authors: Source Type: research

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Source: Acta Neurologica Belgica - Category: Neurology Source Type: research
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Source: The International Journal of Cardiovascular Imaging - Category: Radiology Source Type: research
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Source: Cerebrovascular Diseases Extra - Category: Neurology Source Type: research
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Source: Clinical Imaging - Category: Radiology Authors: Tags: Neuroradiology Source Type: research
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Source: Anesthesia and Analgesia - Category: Anesthesiology Authors: Tags: Anesth Analg Source Type: research
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Source: Neural Plasticity - Category: Neurology Authors: Tags: Neural Plast Source Type: research
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Source: Frontiers in Neurology - Category: Neurology Source Type: research
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Source: Biological and Pharmaceutical Bulletin - Category: Drugs & Pharmacology Authors: Tags: Biol Pharm Bull Source Type: research
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Source: Medicine - Category: Internal Medicine Tags: Research Article: Clinical Case Report Source Type: research
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