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Published on: January 17, 2013
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.
Abstract:
We investigated the relationship between NINJ1 and the inflammatory response in cerebral hemorrhage, as well as the relationship with the protective effects of atorvastatin. A cerebral hemorrhage model was constructed using injection of Type IV collagenase, and open field tests, Y-maze, and mNSS were used to evaluate the behavioral and neurological functions of mice. Enzyme-linked immunosorbent assays were used to detect the expression of tissue inflammatory factors. H&E and Nissl staining were used to detect tissue pathological changes. Western blotting was used to detect the relative expression levels of proteins. NINJ1 transgenic mice showed a more severe inflammatory response and neurological damage compared to wild-type mice, but intervention with NINJ1 monoclonal antibody Ab and atorvastatin could reduce the activation of NLRP3 mediated by NINJ1, decrease tissue inflammation, and, at the cellular level, atorvastatin could inhibit BV2 inflammation. IP experiment results showed that atorvastatin could interact with NINJ1 and inhibit its mediation of NLRP3 activation. Our research results show that NINJ1 in cerebral hemorrhage can promote the activation of NLRP3, further promoting neuroinflammation. Atorvastatin can interact with NINJ1, inhibiting its mediation of NLRP3 activation. NINJ1 is a new target for the treatment of cerebral hemorrhage, and we have revealed a new pharmacological mechanism and target for atorvastatin.
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