A self-perpetuating neuron-intrinsic GSDMD–mtDNA–AIM2 inflammasome axis drives neuronal pyroptosis and cognitive impairment after traumatic brain injury

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Traumatic brain injury (TBI) leads to acute neurological deficits and long-term cognitive impairment due to neuroinflammation.
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The AIM2 inflammasome, primarily studied in myeloid cells, is activated in neurons after TBI, driving pyroptosis and cognitive decline.
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Mechanical injury causes early release of mitochondrial DNA (mtDNA) that activates the AIM2 inflammasome, leading to neuronal loss.
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Knockdown of AIM2 in hippocampal neurons reduces neuronal loss and improves cognitive performance in various behavioral assays.
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A self-perpetuating GSDMD–mtDNA–AIM2 axis is identified as a key driver of TBI-induced cognitive decline and neuroinflammation.

Frontiers In Immunology

by Tian Li, Siyu Huang, Junjun Zhang, Xueer Liu, Lihong Zhu, Yue Li, Runmin Lin, Xiaoxuan Chen, Kangsheng Li, Weiqiang Chen, Jiangtao Sheng
June 19, 2026

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