Metformin prevents stroke damage in non-diabetic female mice with chronic kidney disease

Abstract Chronic kidney disease (CKD) worsens ischemic stroke severity in both patients and animals. In mice, these poorer functional outcomes are associated with decreased brain activity of AMP-activated protein kinase (AMPK), a molecule that recently emerged as a potential therapeutic target for i...

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Autores principales:	Maria Grissi, Cédric Boudot, Maryam Assem, Alexandre Candellier, Mathilde Lando, Sabrina Poirot-Leclercq, Agnès Boullier, Youssef Bennis, Gaëlle Lenglet, Carine Avondo, Jean-Daniel Lalau, Gabriel Choukroun, Ziad A. Massy, Saïd Kamel, Jean-Marc Chillon, Lucie Hénaut
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9f8a2ca6c26c45778bd5905ec65b06e4
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spelling	oai:doaj.org-article:9f8a2ca6c26c45778bd5905ec65b06e42021-12-02T13:27:04ZMetformin prevents stroke damage in non-diabetic female mice with chronic kidney disease10.1038/s41598-021-86905-92045-2322https://doaj.org/article/9f8a2ca6c26c45778bd5905ec65b06e42021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86905-9https://doaj.org/toc/2045-2322Abstract Chronic kidney disease (CKD) worsens ischemic stroke severity in both patients and animals. In mice, these poorer functional outcomes are associated with decreased brain activity of AMP-activated protein kinase (AMPK), a molecule that recently emerged as a potential therapeutic target for ischemic stroke. The antidiabetic drug metformin, a well-known activator of AMPK, has improved stroke outcomes in diabetic patients with normal renal function. We investigated whether chronic metformin pre-conditioning can rescue AMPK activity and prevent stroke damage in non-diabetic mice with CKD. Eight-week-old female C57BL/6J mice were assigned to CKD or SHAM groups. CKD was induced through right kidney cortical electrocautery, followed by left total nephrectomy. Mice were then allocated to receive metformin (200 mg/kg/day) or vehicle for 5 weeks until stroke induction by transient middle cerebral artery occlusion (tMCAO). The infarct volumes were lower in CKD mice exposed to metformin than in vehicle-treated CKD mice 24 h after tMCAO. Metformin pre-conditioning of CKD mice improved their neurological score, grip strength, and prehensile abilities. It also enhanced AMPK activation, reduced apoptosis, increased neuron survival and decreased microglia/macrophage M1 signature gene expression as well as CKD-induced activation of the canonical NF-κB pathway in the ischemic lesions of CKD mice.Maria GrissiCédric BoudotMaryam AssemAlexandre CandellierMathilde LandoSabrina Poirot-LeclercqAgnès BoullierYoussef BennisGaëlle LengletCarine AvondoJean-Daniel LalauGabriel ChoukrounZiad A. MassySaïd KamelJean-Marc ChillonLucie HénautNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Maria Grissi Cédric Boudot Maryam Assem Alexandre Candellier Mathilde Lando Sabrina Poirot-Leclercq Agnès Boullier Youssef Bennis Gaëlle Lenglet Carine Avondo Jean-Daniel Lalau Gabriel Choukroun Ziad A. Massy Saïd Kamel Jean-Marc Chillon Lucie Hénaut Metformin prevents stroke damage in non-diabetic female mice with chronic kidney disease
description	Abstract Chronic kidney disease (CKD) worsens ischemic stroke severity in both patients and animals. In mice, these poorer functional outcomes are associated with decreased brain activity of AMP-activated protein kinase (AMPK), a molecule that recently emerged as a potential therapeutic target for ischemic stroke. The antidiabetic drug metformin, a well-known activator of AMPK, has improved stroke outcomes in diabetic patients with normal renal function. We investigated whether chronic metformin pre-conditioning can rescue AMPK activity and prevent stroke damage in non-diabetic mice with CKD. Eight-week-old female C57BL/6J mice were assigned to CKD or SHAM groups. CKD was induced through right kidney cortical electrocautery, followed by left total nephrectomy. Mice were then allocated to receive metformin (200 mg/kg/day) or vehicle for 5 weeks until stroke induction by transient middle cerebral artery occlusion (tMCAO). The infarct volumes were lower in CKD mice exposed to metformin than in vehicle-treated CKD mice 24 h after tMCAO. Metformin pre-conditioning of CKD mice improved their neurological score, grip strength, and prehensile abilities. It also enhanced AMPK activation, reduced apoptosis, increased neuron survival and decreased microglia/macrophage M1 signature gene expression as well as CKD-induced activation of the canonical NF-κB pathway in the ischemic lesions of CKD mice.
format	article
author	Maria Grissi Cédric Boudot Maryam Assem Alexandre Candellier Mathilde Lando Sabrina Poirot-Leclercq Agnès Boullier Youssef Bennis Gaëlle Lenglet Carine Avondo Jean-Daniel Lalau Gabriel Choukroun Ziad A. Massy Saïd Kamel Jean-Marc Chillon Lucie Hénaut
author_facet	Maria Grissi Cédric Boudot Maryam Assem Alexandre Candellier Mathilde Lando Sabrina Poirot-Leclercq Agnès Boullier Youssef Bennis Gaëlle Lenglet Carine Avondo Jean-Daniel Lalau Gabriel Choukroun Ziad A. Massy Saïd Kamel Jean-Marc Chillon Lucie Hénaut
author_sort	Maria Grissi
title	Metformin prevents stroke damage in non-diabetic female mice with chronic kidney disease
title_short	Metformin prevents stroke damage in non-diabetic female mice with chronic kidney disease
title_full	Metformin prevents stroke damage in non-diabetic female mice with chronic kidney disease
title_fullStr	Metformin prevents stroke damage in non-diabetic female mice with chronic kidney disease
title_full_unstemmed	Metformin prevents stroke damage in non-diabetic female mice with chronic kidney disease
title_sort	metformin prevents stroke damage in non-diabetic female mice with chronic kidney disease
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/9f8a2ca6c26c45778bd5905ec65b06e4
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Metformin prevents stroke damage in non-diabetic female mice with chronic kidney disease

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