Metformin prevents stroke damage in non-diabetic female mice with chronic kidney disease
| Autor: | Maria Grissi, Jean-Marc Chillon, Gaëlle Lenglet, Mathilde Lando, Alexandre Candellier, Youssef Bennis, Ziad A. Massy, Lucie Hénaut, Maryam Assem, Carine Avondo, Saïd Kamel, Sabrina Poirot-Leclercq, Gabriel Choukroun, Agnès Boullier, Jean-Daniel Lalau, Cédric Boudot |
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| Přispěvatelé: | Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, CHU Amiens-Picardie, Périnatalité et Risques Toxiques - UMR INERIS_I 1 (PERITOX), Institut National de l'Environnement Industriel et des Risques (INERIS)-Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Hôpital Ambroise Paré [AP-HP], HAL UVSQ, Équipe |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Brain Infarction
medicine.medical_specialty Science [SDV]Life Sciences [q-bio] Urology Diseases Apoptosis urologic and male genital diseases Models Biological Article Grip strength medicine Animals Gliosis Renal Insufficiency Chronic Ischemic Preconditioning Stroke Neurons Kidney Multidisciplinary Microglia business.industry Macrophages Adenylate Kinase Body Weight NF-kappa B AMPK Infarction Middle Cerebral Artery medicine.disease Metformin [SDV] Life Sciences [q-bio] Enzyme Activation Mice Inbred C57BL medicine.anatomical_structure Neurology Gene Expression Regulation Nephrology Medicine Female business Kidney disease medicine.drug |
| Zdroj: | Scientific Reports Scientific Reports, 2021, 11 (1), ⟨10.1038/s41598-021-86905-9⟩ Scientific Reports, Vol 11, Iss 1, Pp 1-14 (2021) |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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