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Updated: Apr 30, 2026
Author Spotlight: A Unique Mouse Model of Asphyxia-Induced Cardiac Arrest
Published on: April 14, 2023
FPS-ZM1 Exerts Neuroprotection in Cardiac-Arrest Mice through Inhibiting Oxidative Stress and Pyroptosis via the
Ying Zhu1,2, Qianhui Lin1,2, Yanping Wu1,2
1Department of Critical Care Medicine, Renmin Hospital of Wuhan University, 430060 Wuhan, Hubei, China.
Background:
Cardiac arrest (CA) is a widespread public health problem with high mortality, severe neurological sequelae, and limited pharmacological therapies. We investigated the neuroprotective effect of a novel drug, FPS-ZM1 (FPS), on CA and explored its potential mechanism.
Methods:
A potassium chloride-induced CA was induced for 9.5 min in mice, with i.p. injections of FPS or vehicle administered 24 and 1 h before induction. Postoperative assessments included survival rate, body weight change, neurological scores, and neuronal pathological damage. The expression levels of the high mobility group box 1 (HMGB1)/receptor for advanced glycation end products (RAGE) axis, pyroptosis-related molecules, oxidative stress markers, and the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) axis were evaluated.
Results:
Post-CA brain injury (PCABI) activated the HMGB1/RAGE axis, triggering intensified oxidative stress and aggravated pyroptosis. In contrast, pretreatment with FPS attenuated CA-induced injuries. FPS pretreatment was found to suppress the activation of the HMGB1/RAGE axis, alleviate pyroptosis and the release of associated inflammatory mediators, and enhance the Nrf2/HO-1 antioxidant axis after PCABI.
Conclusion:
FPS pretreatment mitigated PCABI by concurrently modulating the HMGB1/RAGE inflammatory axis and the Nrf2/HO-1 antioxidant pathway, suggesting that RAGE antagonism represents a promising therapeutic strategy for PCABI.
Insights
A novel drug, FPS-ZM1, protects the brain after cardiac arrest by reducing inflammation and oxidative stress. This neuroprotective effect suggests RAGE antagonism as a potential therapeutic strategy for post-cardiac arrest brain injury.
Area of Science:
- Neuroscience
- Pharmacology
- Cardiology
Background:
- Cardiac arrest (CA) presents a significant public health challenge with high mortality and severe neurological deficits.
- Current pharmacological therapies for CA are limited, necessitating novel treatment strategies.
Purpose of the Study:
- To investigate the neuroprotective effects of the novel drug FPS-ZM1 (FPS) in a mouse model of cardiac arrest.
- To explore the underlying mechanisms of FPS-ZM1's action, focusing on inflammatory and oxidative stress pathways.
Main Methods:
- Cardiac arrest was induced in mice using potassium chloride, with FPS or vehicle administered pre-induction.
- Postoperative assessments included survival, body weight, neurological scores, and neuronal damage.
- Key molecular pathways evaluated included high mobility group box 1 (HMGB1)/receptor for advanced glycation end products (RAGE), pyroptosis, oxidative stress markers, and the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) axis.
Main Results:
- Post-cardiac arrest brain injury (PCABI) activated the HMGB1/RAGE axis, leading to increased oxidative stress and pyroptosis.
- FPS pretreatment significantly attenuated CA-induced brain injuries.
- FPS suppressed HMGB1/RAGE activation, alleviated pyroptosis and inflammation, and enhanced the Nrf2/HO-1 antioxidant axis.
Conclusions:
- FPS pretreatment mitigated PCABI by modulating both the HMGB1/RAGE inflammatory axis and the Nrf2/HO-1 antioxidant pathway.
- RAGE antagonism emerges as a promising therapeutic strategy for treating post-cardiac arrest brain injury.
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