Midkine-Mediated Microglia Activation after Renal Injury Promotes Cognitive Impairment Following Ischemic Renal Injury.

ABSTRACT: Acute kidney injury (AKI) is associated with a high prevalence of cognitive impairment, the underlying mechanisms remain elusive. This study explores the role of midkine (MDK), upregulated in renal injury, in mediating cognitive dysfunction following post-ischemic renal injury. Using a mouse model of unilateral renal ischemia-reperfusion injury, cognitive deficits and blood-brain barrier disruption is observed. Single-cell RNA sequencing and ligand-receptor interaction analysis reveals a strengthened MDK-LRP1 axis in both the kidneys and hippocampus of mice subjected to ischemic renal injury. MDK, mainly from injured renal tubular cells and fibroblasts, is enriched in peripheral blood and the hippocampus, correlating with increased activation of hippocampal microglia and upregulation of c.

SUBMITTER: Lu L 

PROVIDER: S-EPMC12806390 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature