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AMPK activation alleviates stroke severity in mice with chronic kidney disease

Abstract : Background and aims: Ischemic stroke is highly prevalent in patients with chronic kidney disease (CKD) and has been associated with poor outcomes. In experimental studies, CKD mice display wider and more inflammatory ischemic lesions as well as poorer functional outcomes than mice with normal renal function. Our group recently showed that adenosine-monophosphate-activated protein kinase (AMPK) activation is impaired within ischemic lesions of CKD mice. In rodents with normal renal function, AMPK activation by metformin, an anti-diabetic drug, improved stroke outcomes. This work aimed to investigate whether a 5-week pre-conditioning with metformin can restore AMPK activity and improve functional recovery in mice with CKD. Methods: . 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 received metformin (200 mg/kg/day) or vehicle in drinking water. The treatment began 1 week after CKD induction and was given for 5 weeks until stroke induction by transient middle cerebral artery occlusion (tMCAO). Results: . Exposure to metformin rescued AMPK activation, decreased ischemic lesion size and improved neurological score, grip strength and prehensile abilities in CKD mice. Ischemic hemisphere of CKD mice exposed to metformin displayed decreased microglia/macrophages pro-inflammatory M1 signature genes’ expression (i.e. CD32, CD16, CD86, IL-1b and iNOS) as well as reduced activation of the canonical NF-KB pathway. Conclusions: . These data demonstrate that the AMPK could be a promising therapeutic target to decrease brain inflammation and improve stroke recovery in CKD
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https://hal-u-picardie.archives-ouvertes.fr/hal-03555472
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Soumis le : jeudi 3 février 2022 - 16:16:00
Dernière modification le : mercredi 4 mai 2022 - 16:48:02

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Distributed under a Creative Commons Paternité 4.0 International License

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  • HAL Id : hal-03555472, version 1

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M. Grissi, C. Boudot, M. Assem, S. Poirot-Leclercq, M. Lando, et al.. AMPK activation alleviates stroke severity in mice with chronic kidney disease. International Journal of Stroke, Wiley, 2020, https://journals.sagepub.com/doi/pdf/10.1177/1747493020963387, 15 (1S), pp.150. ⟨hal-03555472⟩

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