Cellular and molecular mechanisms associated with ischemic stroke severity in female mice with chronic kidney disease

Lucie Henaut (1) , Maria Grissi (1) , Francois Brazier (1, 2) , Maryam Assem (1, 2) , Sabrina Poirot-Leclercq (1) , Gaëlle Lenglet (1) , Cedric Boudot (1) , Carine Avondo (1) , Agnes Boullier (1, 2) , Gabriel Choukroun (2, 1) , Ziad A. Massy (3, 4) , Saïd Kamel (1, 2) , Jean-Marc Chillon (1, 2)

1 MP3CV - Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517
2 CHU Amiens-Picardie
3 Hôpital Ambroise Paré [AP-HP]
4 CESP - Centre de recherche en épidémiologie et santé des populations

Ischemic stroke is highly prevalent in chronic kidney disease (CKD) patients and has been associated with a higher risk of neurological deterioration and in-hospital mortality. To date, little is known about the processes by which CKD worsens ischemic stroke. This work aimed to investigate the cellular and molecular mechanism associated with ischemic stroke severity in an in vivo model of CKD. CKD was induced through right kidney cortical electrocautery in 8-week-old female C57BL/6J mice followed by left total nephrectomy. Transient middle cerebral artery occlusion (tMCAO) was performed 6 weeks after left nephrectomy. Twenty-four hours after tMCAO, the infarct volumes were significantly wider in CKD than in SHAM mice. CKD mice displayed decreased neuroscore, impaired ability to remain on rotarod device, weaker muscular strength and decreased prehensile score. Apoptosis, neuronal loss, glial cells recruitment and microglia/macrophages M-1 signature genes CD32, CD86, IL-1 beta, IL-6, MCP1 and iNOS were significantly increased within ischemic lesions of CKD mice. This effect was associated with decreased AMP kinase phosphorylation and increased activation of the NFKB pathway. Pharmacological targeting of AMP kinase activity, which is known to block microglia/macrophages M-1 polarization, appears promising to improve stroke recovery in CKD.

Domaines: Sciences du Vivant [q-bio]

Lucie Henaut, Maria Grissi, Francois Brazier, Maryam Assem, Sabrina Poirot-Leclercq, et al.. Cellular and molecular mechanisms associated with ischemic stroke severity in female mice with chronic kidney disease. Scientific Reports, 2019, 9, ⟨10.1038/s41598-019-42933-0⟩. ⟨hal-03568253⟩