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Updated: Sep 17, 2025
Identifying Microglia and Peripheral Infiltrating Macrophages in the Injured Spinal Cords Using Flow Cytometry
Published on: June 24, 2025
Piezo1 deletion ameliorates inflammation and functional recovery in spinal cord injury through altering
Weiwei Zheng1, Zeyu Han2, Zonghan Xu3
1Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou 215000 Jiangsu Province, China; Department of Orthopedics, the Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou 215000 Jiangsu Province, China.
Abstract:
Disruption of their homeostasis post-spinal cord injury (SCI) triggers severe secondary inflammation. This study focuses on Piezo1, a key mediator of macrophage/microglia-driven neuroinflammation. We aimed to promulgate the effect of deleting or inhibiting macrophage/microglial Piezo1 on the neural function after SCI in vitro and vivo. Here, we used C57BL/6J mice in which Piezo1 was specifically deleted in macrophages/microglia (Piezo1-CKO, Piezo1 [flox/flox, Cx3cr1-Cre]). We investigated the expression dynamics of Piezo1 following SCI, explored the phenotypic switching of macrophages/microglia under inflammatory cytokine stimulation, and examined the changes in hindlimb motor function in Piezo1-deficient mice. Our data demonstrated that macrophages/microglia in the injured segment gathered and activated after SCI, and the number of Pierzo1 + macrophages/microglia reached the peak at the 7th day. Piezo1 leads to pro-inflammatory response of macrophages/microglia with IFNγ/LPS stimulation, while inhibition of Piezo1 can lead to anti-inflammation under IL4/IL13 stimulation. Subsequently, Piezo1-CKO mice exhibited a faster and better recovery of neural function after SCI. These findings suggested that Piezo1 deletion ameliorates inflammation and functional recovery in spinal cord injury through altering microglia/macrophage phenotype.
Insights
Deleting Piezo1 in macrophages/microglia reduces neuroinflammation after spinal cord injury (SCI). This targeted approach improves neural function recovery in Piezo1-deficient mice.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Spinal cord injury (SCI) causes secondary inflammation, impacting neural function.
- Macrophages and microglia are key players in SCI-induced neuroinflammation.
- Piezo1 channels are implicated as mediators in this inflammatory process.
Purpose of the Study:
- To investigate the role of Piezo1 in macrophage/microglia-driven neuroinflammation post-SCI.
- To evaluate the therapeutic potential of deleting or inhibiting Piezo1 in macrophages/microglia for neural function recovery.
Main Methods:
- Utilized Piezo1-CKO (Cx3cr1-Cre) C57BL/6J mice with specific Piezo1 deletion in macrophages/microglia.
- Assessed Piezo1 expression dynamics and macrophage/microglia phenotypic switching in vitro and in vivo.
- Examined hindlimb motor function recovery in Piezo1-deficient mice post-SCI.
Main Results:
- Piezo1 expression peaked in activated macrophages/microglia at day 7 post-SCI.
- Piezo1 promoted pro-inflammatory responses under IFNγ/LPS stimulation.
- Inhibition of Piezo1 induced anti-inflammatory effects under IL4/IL13 stimulation.
- Piezo1-CKO mice showed accelerated and improved neural function recovery.
Conclusions:
- Piezo1 deletion in macrophages/microglia ameliorates inflammation following spinal cord injury.
- Targeting Piezo1 in these cells offers a promising strategy for enhancing functional recovery after SCI.
