Microglial CARD19 ameliorates post-stroke neuroinflammation by stabilizing mitochondrial cristae

Yujie Hu1,2, Liwen Zhu1,3, Chao Zhou1,2

  • 1Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu Province, China.

PubMed
Abstract

No abstract available in PubMed .

Insights

Caspase activation and recruitment domain 19 (CARD19) in microglia protects against neuroinflammation after ischemic stroke. Targeting CARD19 may preserve mitochondria and reduce stroke damage.

Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • Microglia are key immune cells in the brain, activated after ischemic stroke.
  • Mitochondrial dysfunction worsens neuroinflammation mediated by microglia post-stroke.
  • Caspase activation and recruitment domain 19 (CARD19) is implicated in innate and inflammatory responses.

Purpose of the Study:

  • To investigate the role of CARD19 in microglial biology and its impact on ischemic stroke.
  • To determine CARD19 expression levels in microglia following ischemic stroke.

Main Methods:

  • Analysis of spatial transcriptomic sequencing data from ischemic brain tissue.
  • In vitro studies using microglial activation models.
  • Conditional knockdown of Card19 in a mouse model of ischemic stroke.
  • Mitochondrial ultrastructure and function analysis.

Main Results:

  • CARD19 expression was significantly elevated in microglia within the ischemic penumbra.
  • Microglial CARD19 deficiency exacerbated neuroinflammation and worsened neurological outcomes in mice.
  • CARD19 localizes to mitochondria, promoting intermembrane bridge assembly.
  • CARD19 deficiency led to mitochondrial cristae damage and an exaggerated inflammatory response.

Conclusions:

  • CARD19 plays a protective role in microglia following ischemic stroke.
  • CARD19 is crucial for maintaining mitochondrial integrity and function in microglia.
  • Targeting CARD19 may represent a novel therapeutic strategy to reduce neuroinflammation and ischemic damage.

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