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Two-photon Imaging of Cellular Dynamics in the Mouse Spinal Cord
Published on: February 22, 2015
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Type 2 Diabetes Promotes the Microglial Pyroptosis by Activating NLRP3 Inflammasome to Impede Remyelination After
Jingyu Xu1, Li Fang1, Tao Wei1
1The Institute of Life Sciences, Engineering Laboratory of Zhejiang Province for Pharmaceutical Development of Growth Factors, Wenzhou University, Wenzhou, Zhejiang 325035, China.
Research (Washington, D.C.)
|April 16, 2026
Summary
Type 2 diabetes (T2D) impairs spinal cord injury (SCI) recovery by causing excessive microglial pyroptosis. This process, driven by the RAGE-ROS-NLRP3 axis, hinders nerve repair and remyelination, suggesting microglial pyroptosis as a therapeutic target.
Area of Science:
- Neuroscience
- Immunology
- Metabolic Disorders
Background:
- Spinal cord injury (SCI) recovery is significantly hindered by diabetes.
- Microglial function is critical for SCI repair, but diabetes's impact on this is not fully understood.
- Type 2 diabetes (T2D) presents complex challenges in treating combined SCI.
Purpose of the Study:
- To investigate the role and regulatory mechanism of diabetes in microglial function during SCI recovery.
- To determine if T2D influences microglial function, thereby affecting nerve repair after SCI.
Main Methods:
- A mouse model of T2D combined with SCI was established.
- Microglial phagocytosis, pyroptosis, and the RAGE-ROS-TXNIP-NLRP3 inflammasome axis were analyzed.
- Pharmacological interventions (Verapamil, N-acetyl-l-cysteine, FPS-ZM1) and genetic knockout (Caspase-1) were employed.
Main Results:
- T2D significantly impaired nerve repair and remyelination post-SCI by blocking microglial phagocytosis.
- T2D induced excessive microglial pyroptosis via the RAGE-ROS-TXNIP-NLRP3 inflammasome axis.
- Inhibiting TXNIP, RAGE, or ROS, or blocking pyroptosis, ameliorated nerve damage and improved SCI recovery in T2D mice.
Conclusions:
- T2D exacerbates SCI by inducing microglial pyroptosis through the RAGE-ROS-NLRP3 axis, leading to impaired remyelination.
- Microglial pyroptosis is a key detrimental mechanism in T2D-complicated SCI.
- Targeting microglial pyroptosis presents a promising therapeutic strategy for treating SCI in diabetic patients.
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