CPCGI Alleviates Neural Damage by Modulating Microglial Pyroptosis After Traumatic Brain Injury.

Area of Science:

• Neuroscience
• Immunology
• Pharmacology

Background:

• Traumatic brain injury (TBI) is a leading cause of death and disability globally, with limited treatment options.
• Microglial pyroptosis, a programmed cell death pathway, exacerbates neuroinflammation and secondary injury post-TBI.
• The therapeutic potential of Compound Porcine Cerebroside Ganglioside Injection (CPCGI) in TBI, particularly its effects on pyroptosis, is largely unexplored.

Purpose of the Study:

• To investigate the efficacy of CPCGI in mitigating TBI-induced neuroinflammation and neuronal damage.
• To elucidate the underlying mechanisms of CPCGI's action, focusing on microglial pyroptosis and the NLRP3 inflammasome pathway.

Main Methods:

• Established TBI using a controlled cortical impact (CCI) model in vivo and lipopolysaccharide (LPS)-induced microglial activation in vitro.
• Assessed CPCGI's effects on microglial pyroptosis, inflammatory cytokines, and neuronal injury using immunofluorescence, flow cytometry, Western blotting, and qRT-PCR.
• Investigated the role of the NLRP3 inflammasome by manipulating its expression and using a specific agonist (BMS-986299).

Main Results:

• CPCGI treatment significantly improved neurobehavioral outcomes, reduced lesion volume, and decreased neuronal loss in TBI models.
• CPCGI inhibited TBI-induced microglial pyroptosis and suppressed the release of pro-inflammatory cytokines.
• CPCGI's inhibitory effect on pyroptosis and its neuroprotective benefits were dependent on the NLRP3 inflammasome pathway.

Conclusions:

• CPCGI demonstrates significant neuroprotective effects in TBI by targeting NLRP3 inflammasome-mediated microglial pyroptosis.
• CPCGI improves the neuroinflammatory microenvironment, promoting neurological recovery after TBI.
• CPCGI represents a promising therapeutic candidate for treating traumatic brain injury.