Effect of IL-18BP on anxiety-like behavior in traumatic brain injury rats and its mechanism

Objective To evaluate the effect of IL-18 binding protein （IL-18BP） on anxiety-like behavior after traumatic brain injury （TBI） in rats and its related mechanism. Methods Seventy-two adult male SD rats were divided into 3 groups（all n = 24） using the random number table method： sham-operated （Sham） group， TBI group， traumatic brain injury plus IL-18BP （TBI+IL-18BP） group. The skull was exposed and skin incisions were then closed without TBI in sham group. The rodent model of TBI was established using the weight-drop method. In TBI+IL-18BP group， IL-18BP was administered by tail vein at a dose of 1.5 mg/kg immediately after TBI. The changes in anxiety-like behaviors in rats were measured by the open field and elevated plus maze tests. The number of neuron and activated astrocytes as well as the percentage of NLRP3 and IL-18 positive astrocytes in amygdala region were detected by immunofluorescence assay. The concentration of IL-18 in serum and cerebrospinal fluid was detected by ELISA. The expression levels of NLRP3， activated Caspase-1（cl-Caspase-1）， N-GSDMD in the amygdala were detected using western blot. Results At 30 d post-TBI， compared with the Sham group， rats in the TBI and TBI+IL-18BP groups had statistically less entry times and shorter time spending in the central square of the open field， significantly lower percentage of open arm entries and percentage of open arm time in the elevated plus maze tests， significantly increased concentration of IL-18 in the serum and cerebrospinal fluid， up-regulated activation of astrocytes in the amygdala， higher percentage of NLRP3 and IL-18 positive astrocytes， as well as up-regulated expression levels of the pyroptosis-related proteins including NLRP3， cl-Caspase-1 and N-GSDMD （all P < 0.05）. While compared with the TBI group， rats in the TBI+IL-18BP group had statistically more entry times and longer time spending in the central square of the open field， significantly higher percentage of open arm entries and percentage of open arm time in the elevated plus maze tests， significantly lower concentration of IL-18 in the serum and cerebrospinal fluid， down-regulated activation of astrocytes in the amygdala， lower percentage of NLRP3 and IL-18 positive astrocytes， and down-regulated expression levels of the pyroptosis-related proteins （all P < 0.05）. Conclusions IL-18BP can alleviate TBI-induced anxiety-like behaviors to certain extent in rats， probably associated with the inhibition of pyroptosis associated with NLRP3 inflammasome in astrocytes.