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http://hdl.handle.net/1843/63480
Type: | Artigo de Periódico |
Title: | Alamandine induces neuroprotection in ischemic stroke models |
Authors: | Sthéfanie Chaves de Almeida Gonçalves Beatriz Lopes Tecedor Bassi Lucas Miranda Kangussu Daniele Teixeira Alves Lorena Kelly Santiago Ramos Lorena Figueiredo Fernandes Marco Túllio Rodrigues Alves Rubén Dario Sinisterra Millán Gisele Eva Bruch Robson Augusto Souza dos Santos André Ricardo Massensini Maria Jose Campagnole dos Santos |
Abstract: | Background and Objective: Stroke, a leading cause of mortality and disability, characterized by neuronal death, can be induced by a reduction or interruption of blood flow. In this study, the role of Alamandine, a new peptide of the renin-angiotensin system, was evaluated in in-vitro and in-vivo brain ischemia models. Methods: In the in-vitro model, hippocampal slices from male C57/Bl6 mice were placed in a glucose-free aCSF solution and bubbled with 95% N2 and 5% CO2 to mimic brain ischemia. An Alamandine concentration-response curve was generated to evaluate cell damage, glutamatergic excitotoxicity, and cell death. In the in-vivo model, cerebral ischemia/ reperfusion was induced by bilateral occlusion of common carotid arteries (BCCAo-untreated) in SD rats. An intracerebroventricular injection of Alamandine was given 20–30 min before BCCAo. Animals were subjected to neurological tests 24 h and 72 h after BCCAo. Cytokine levels, oxidative stress markers, and immunofluorescence were assessed in the brain 72 h after BCCAo. Results: Alamandine was able to protect brain slices from cellular damage, excitotoxicity and cell death. When the Alamandine receptor was blocked, protective effects were lost. ICV injection of Alamandine attenuated neurological deficits of animals subjected to BCCAo and reduced the number of apoptotic neurons/cells. Furthermore, Alamandine induced anti-inflammatory effects in BCCAo animals as shown by reductions in TNFα, IL- 1β, IL-6, and antioxidant effects through attenuation of the decreased SOD, catalase, and GSH activities in the brain. Conclusion: This study showed, for the first time, a neuroprotective role for Alamandine in different ischemic stroke models. |
Subject: | Sistema renina-angiotensina Isquemia cerebral Acidentes vasculares cerebrais Citocinas Imunofluorescência |
language: | eng |
metadata.dc.publisher.country: | Brasil |
Publisher: | Universidade Federal de Minas Gerais |
Publisher Initials: | UFMG |
metadata.dc.publisher.department: | ICB - DEPARTAMENTO DE FISIOLOGIA E BIOFÍSICA ICB - DEPARTAMENTO DE MORFOLOGIA ICX - DEPARTAMENTO DE QUÍMICA |
Rights: | Acesso Restrito |
metadata.dc.identifier.doi: | https://doi.org/10.2174/0929867329666220204145730 |
URI: | http://hdl.handle.net/1843/63480 |
Issue Date: | 2022 |
metadata.dc.url.externa: | https://www.eurekaselect.com/article/120687 |
metadata.dc.relation.ispartof: | Current Medicinal Chemistry |
Appears in Collections: | Artigo de Periódico |
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