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Updated: Jan 10, 2026
Renal Ischaemia Reperfusion Injury: A Mouse Model of Injury and Regeneration
Published on: June 7, 2014
Midkine-Mediated Microglia Activation after Renal Injury Promotes Cognitive Impairment Following Ischemic Renal
Li Lu1,2, Bixiao Liu1, Yu Yang1
1Department of Andrology, Nanjing Drum Tower Hospital, the Affiliated hospital of Nanjing University Medical School, Nanjing, Jiangsu, 210008, China.
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. It is demonstrated that MDK internalization into microglia via LRP1 upregulated P2ry12 expression, promoting microglial activation and phagocytosis. Inhibiting renal MDK expression with shRNA adenovirus ameliorated cognitive dysfunction and attenuated microglial activation after ischemic renal injury. These findings suggest the MDK-LRP1 pathway is a key mediator of cognitive dysfunction following ischemic renal injury and a potential therapeutic target for mitigating cognitive decline in AKI patients. It provides a mechanistic link between renal injury, neuroinflammation, and cognitive deficits, highlighting the potential of targeting MDK-LRP1 signaling to address cognitive impairment after ischemic renal injury.
Insights
Acute kidney injury (AKI) causes cognitive impairment via the midkine (MDK)-LRP1 pathway. Targeting this axis may mitigate brain dysfunction following kidney injury.
Area of Science:
- Nephrology
- Neuroscience
- Immunology
Background:
- Acute kidney injury (AKI) is linked to cognitive impairment, but mechanisms are unclear.
- Midkine (MDK), elevated during kidney injury, is investigated for its role in cognitive dysfunction.
- The MDK-LRP1 axis is implicated in mediating kidney injury-induced brain deficits.
Purpose of the Study:
- To investigate the role of midkine (MDK) in cognitive impairment following ischemic renal injury.
- To elucidate the MDK-LRP1 pathway's involvement in neuroinflammation and cognitive decline.
- To explore MDK-LRP1 signaling as a potential therapeutic target for AKI-related cognitive dysfunction.
Main Methods:
- A mouse model of unilateral renal ischemia-reperfusion injury was utilized.
- Single-cell RNA sequencing and ligand-receptor interaction analysis were performed.
- Inhibition of renal MDK expression using shRNA adenovirus was employed.
Main Results:
- Ischemic renal injury induced cognitive deficits and blood-brain barrier disruption.
- A strengthened MDK-LRP1 axis was identified in kidneys and hippocampus.
- MDK internalization into microglia via LRP1 upregulated P2ry12, promoting microglial activation.
Conclusions:
- The MDK-LRP1 pathway is a key mediator of cognitive dysfunction post-ischemic renal injury.
- Targeting the MDK-LRP1 pathway offers a potential therapeutic strategy for cognitive decline in AKI patients.
- This study establishes a mechanistic link between renal injury, neuroinflammation, and cognitive deficits.
Related Concept Videos
01:29Acute Kidney Injury II: Pathophysiology
01:22Acute Kidney Injury I: Introduction