Cerebral Hemorrhage-Related Inflammatory Response Mediated by NINJ1 and the Protective Effects of Atorvastatin

Guanghui Yang1, Nan Li1, Zeming Li1

  • 1Department of Neurosurgery, Taiyuan Central Hospital/The Ninth Clinical Medical School of Shanxi Medical University, Taiyuan, Shanxi, China.

Insights

Ninja-1 (NINJ1) exacerbates neuroinflammation in cerebral hemorrhage. Atorvastatin mitigates this by inhibiting NINJ1-mediated NLRP3 activation, offering a new therapeutic target for stroke treatment.

Area of Science:

  • Neuroscience
  • Immunology
  • Pharmacology

Background:

  • Cerebral hemorrhage triggers inflammatory responses that contribute to neurological damage.
  • The role of Ninja-1 (NINJ1) in cerebral hemorrhage-induced inflammation and the protective mechanisms of atorvastatin remain incompletely understood.

Purpose of the Study:

  • To investigate the relationship between NINJ1 and the inflammatory response in cerebral hemorrhage.
  • To explore the protective effects of atorvastatin in this context.
  • To elucidate the underlying molecular mechanisms involving NLRP3 inflammasome activation.

Main Methods:

  • Established a collagenase-induced cerebral hemorrhage mouse model.
  • Evaluated neurological function using behavioral tests (open field, Y-maze, mNSS).
  • Assessed inflammatory markers via ELISA, histological analysis (H&E, Nissl), and Western blotting.
  • Investigated protein interactions using co-immunoprecipitation (IP).

Main Results:

  • NINJ1 transgenic mice exhibited exacerbated inflammatory responses and neurological deficits compared to wild-type mice.
  • Treatment with NINJ1 monoclonal antibody and atorvastatin reduced NINJ1-mediated NLRP3 activation and tissue inflammation.
  • Atorvastatin inhibited BV2 cell inflammation and directly interacted with NINJ1, suppressing NLRP3 activation.

Conclusions:

  • NINJ1 promotes NLRP3 activation and subsequent neuroinflammation in cerebral hemorrhage.
  • Atorvastatin exerts neuroprotective effects by interacting with NINJ1 and inhibiting NLRP3 activation.
  • NINJ1 represents a novel therapeutic target for cerebral hemorrhage, and atorvastatin offers a new pharmacological approach.

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