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Updated: Jul 10, 2026
Three-dimensional Confocal Analysis of Microglia/macrophage Markers of Polarization in Experimental Brain Injury
Published on: September 4, 2013
Loss of Plxdc2 exacerbates microglia-mediated neuroinflammation and ischemic brain injury
Lixuan Yang1, Yang Geng1, Yi Qian1
1Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210000, China.
Abstract:
Microglia are the supervisors maintaining intracerebral homeostasis, which function importantly in determining the outcome of ischemic stroke. Plxdc2 is a single-transmembrane protein and mainly studied in the development of central nervous system and cancers, whereas its role in the function of microglia remains elusive. In this study, based on our previous scRNA-seq of ischemic brain and transcriptomic analysis of microglia isolated from the ischemic brain, we found that Plxdc2 was abundantly expressed in microglia and remarkably downregulated after stroke. Further, with adeno-associated virus (AAV) overexpressing or lentivirus interfering Plxdc2 in microglia in vivo, Plxdc2 was proved to protect against ischemic brain injury. Plxdc2 helps maintain microglial homeostatic state both in vitro and in vivo, and downregulation of Plxdc2 exacerbated microglial inflammatory response. In addition, we found that Plxdc2 participated in regulating the activation of NF-κB p65 signaling, and also modulated microglial lipid metabolism. Moreover, Plxdc2 was found to facilitate the activation of PPARγ, which might account for its impact on NF-κB p65 signaling and lipid metabolism in microglia. Overall, our results illustrated a vital role of Plxdc2 in modulating post-stroke microglial activation, which holds potential to be a novel target for immunomodulation in ischemic stroke.
Insights
Plxdc2 protein protects against ischemic stroke by maintaining microglial homeostasis. Downregulation of Plxdc2 worsens inflammation, highlighting its potential as a therapeutic target for stroke immunomodulation.
Area of Science:
- Neuroscience
- Immunology
- Molecular Biology
Background:
- Microglia are crucial for brain homeostasis and stroke outcomes.
- Plxdc2's role in microglial function is largely unknown.
- Previous studies linked Plxdc2 to CNS development and cancer.
Purpose of the Study:
- Investigate the role of Plxdc2 in microglial function after ischemic stroke.
- Determine if Plxdc2 influences microglial activation and inflammatory responses.
- Explore Plxdc2's potential as a therapeutic target for stroke.
Main Methods:
- Single-cell RNA sequencing (scRNA-seq) of ischemic brain tissue.
- Transcriptomic analysis of isolated microglia.
- In vivo manipulation of Plxdc2 levels in microglia using AAV and lentivirus.
- In vitro and in vivo assessment of microglial homeostatic state and inflammatory response.
- Analysis of NF-κB p65 signaling and lipid metabolism pathways.
- Investigation of PPARγ activation.
Main Results:
- Plxdc2 is highly expressed in microglia and downregulated post-stroke.
- Overexpression of Plxdc2 protects against ischemic brain injury.
- Plxdc2 maintains microglial homeostatic state and reduces inflammatory response.
- Plxdc2 modulates NF-κB p65 signaling and microglial lipid metabolism.
- Plxdc2 facilitates PPARγ activation.
Conclusions:
- Plxdc2 plays a vital role in regulating microglial activation post-stroke.
- Plxdc2 maintains microglial homeostasis and mitigates inflammatory responses.
- Plxdc2 represents a potential novel target for immunomodulation in ischemic stroke treatment.
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