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4.1 Clinical relevance of the CLP model The CLP model was selected for its unique ability to recapitulate core clinical features of SAE: polymicrobial sepsis, hippocampal neurodegeneration, and chronic cognitive impairment ( 4.2 Microglia-mediated oxidative neuronal injury Microglial activation initiates neuronal damage, and a previous study revealed that the microglial inhibitor minocycline reduces neuronal apoptosis ( in vivo oxidative stress ( Mechanistically, a microglial inflammation-oxidative stress feedforward loop perpetuates injury: Activated microglia secrete neurotoxins, impairing neuronal mitochondrial function and antioxidant capacity (such as GPX4), thus increasing ROS leakage

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The CCBL2 encoded protein was formerly known as kynurenine aminotransferase III (KAT III or KAT3)

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