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

Abstract

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/6 J 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 M1 signature genes CD32, CD86, IL-1β, 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 NFΚB pathway. Pharmacological targeting of AMP kinase activity, which is known to block microglia/macrophages M1 polarization, appears promising to improve stroke recovery in CKD.

• Authors: Lucie Hénaut, Maria Grissi, François Brazier, Maryam Assem, Sabrina Poirot-Leclercq, Gaëlle Lenglet, Cédric Boudot, Carine Avondo, Agnès Boullier, Gabriel Choukroun, Ziad A Massy, Saïd Kamel, Jean-Marc Chillon
• Journal: Scientific reports (Sci Rep) Vol. 9 Issue 1 Pg. 6432 (04 23 2019) ISSN: 2045-2322 [Electronic] England
• PMID: 31015533 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD
• Ccl2 protein, mouse
• Chemokine CCL2
• IL1B protein, mouse
• Interleukin-1beta
• Interleukin-6
• NF-kappa B
• interleukin-6, mouse
• Adenylate Kinase

Topics

• Adenylate Kinase (genetics, metabolism)
• Animals
• Antigens, CD (genetics, metabolism)
• Apoptosis (genetics)
• Brain Ischemia (complications, genetics, metabolism, physiopathology)
• Chemokine CCL2 (genetics, metabolism)
• Disease Models, Animal
• Electrocoagulation
• Female
• Gene Expression Regulation
• Humans
• Interleukin-1beta (genetics, metabolism)
• Interleukin-6 (genetics, metabolism)
• Kidney Cortex (metabolism, pathology)
• Mice
• Mice, Inbred C57BL
• Muscle Weakness (complications, genetics, metabolism, physiopathology)
• NF-kappa B (genetics, metabolism)
• Neuroglia (metabolism, pathology)
• Neurons (metabolism, pathology)
• Renal Insufficiency, Chronic (complications, genetics, metabolism, physiopathology)
• Rotarod Performance Test
• Severity of Illness Index
• Stroke (complications, genetics, metabolism, physiopathology)