A self-perpetuating neuron-intrinsic GSDMD–mtDNA–AIM2 inflammasome axis drives neuronal pyroptosis and cognitive impairment after traumatic brain injury
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By
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Tian Li
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Siyu Huang
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Junjun Zhang
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Xueer Liu
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Lihong Zhu
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Yue Li
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Runmin Lin
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Xiaoxuan Chen
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Kangsheng Li
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Weiqiang Chen
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Jiangtao Sheng
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June 19, 2026
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Clinical Scorecard: An Intrinsic Neuronal GSDMD–mtDNA–AIM2 Inflammasome Pathway Promotes Pyroptosis and Cognitive Decline Following Traumatic Brain Injury
At a Glance
| Category | Detail |
|---|
| Condition | Traumatic Brain Injury (TBI) |
| Key Mechanisms | GSDMD–mtDNA–AIM2 inflammasome pathway driving neuronal pyroptosis and cognitive decline. |
| Target Population | Individuals with traumatic brain injury. |
| Care Setting | Neuroscience and neurotrauma research. |
Key Highlights
- AIM2 inflammasome activation occurs in cortical and hippocampal neurons post-TBI.
- Neuron-specific AIM2 knockdown reduces neuronal loss and improves cognitive performance.
- Mechanical injury leads to early release of mitochondrial DNA into the cytosol.
- Caspase-1 inhibition attenuates late-phase mtDNA release and neuronal injury.
- A self-perpetuating GSDMD–mtDNA–AIM2 axis is identified as a driver of cognitive decline.
Guideline-Based Recommendations
Diagnosis
- Assess cognitive function and neurological status following TBI.
Management
- Consider neuron-targeted AIM2 silencing as a therapeutic strategy.
Monitoring & Follow-up
- Monitor for signs of neuroinflammation and cognitive decline post-TBI.
Risks
- Potential for sustained neuroinflammation and cognitive impairment following TBI.
Patient & Prescribing Data
Patients with traumatic brain injury experiencing cognitive dysfunction.
AIM2 silencing may limit post-TBI neuroinflammation and cognitive decline.
Clinical Best Practices
- Utilize behavioral and molecular assays to assess neuronal health post-TBI.
- Implement early intervention strategies targeting neuroinflammation.
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