The role of IL-18BP in alleviating anxiety-like behaviors after traumatic brain injury in rats by modulating astrocytic pyroptosis in amygdala

Primary objective: This study investigates the effect and underlying mechanisms of IL-18 binding protein (IL-18BP) on anxiety-like behaviors in rats following traumatic brain injury (TBI).

Methods and procedures: Thirty-six Sprague-Dawley rats were divided into three groups: sham, TBI, and TBI+IL-18BP. Anxiety-like behaviors were evaluated using the open field and elevated plus maze tests. Immunofluorescence staining was performed to assess the number of neurons, activated astrocytes, and the proportion of astrocytes positive for NLRP3 and IL-18. IL-18 levels in serum and cerebrospinal fluid (CSF) were quantified via ELISA. Western blot analysis was conducted to measure the expression of NLRP3, cleaved Caspase-1 (cl-caspase-1), and N-GSDMD in the amygdala.

Main outcomes and results: Thirty days post-TBI, both the TBI and TBI+IL-18BP groups exhibited increased anxiety-like behaviors, elevated IL-18 levels in serum and CSF, greater activation of astrocytes in the amygdala, a higher percentage of NLRP3 and IL-18-positive astrocytes, and upregulated expression of pyroptosis-related proteins compared to the sham group (p < 0.05). However, the TBI+IL-18BP group showed significant reductions in these parameters compared to the TBI group (p < 0.05).

Conclusions: IL-18BP appears to mitigate anxiety-like behaviors in TBI rats, likely through a mechanism that involves reducing astrocyte Apoptosis.

IL-18 binding protein; Traumatic brain injury; amygdala; anxiety; pyroptosis.