Hemorrhagic shock and resuscitation (HSR) may lead to long-term neurological dysfunction, such as depression and anxiety. Carbon monoxide (CO) has emerged as an excellent neuroprotective agent against caspase-1-associated pyroptosis, following HSR. We evaluated the effects and determined the mechanism through which CO protects against emotional changes in a model of HSR, in rats. We subjected rats to treatments with an exogenous, CO-releasing compound (CORM-3, 4 mg/kg), in vivo, after HSR. We measured sucrose preference and performed tail suspension and open field tests 7 days after HSR, assessed brain magnetic resonance imaging 12 h after HSR and evaluated pyroptosis, and neuronal and astrocyte death in the amygdala 12 h post-HSR. We also measured changes in behavior and pathology, following an injection of recombinant murine interleukin (IL)-18 into the amygdala. HSR-treated rats displayed increased depression-like and anxiety-like behaviors, increased amygdalar injury, as indicated by T2-weighted magnetic resonance imaging (MRI) and cerebral blood flow with arterial spin labeling (CBF_ASL), associated with both neuronal and astrocytic death and pyroptosis, and upregulated IL-18 expression was observed in astrocytes. CORM-3 administration after resuscitation, via a femoral vein injection, provided neuroprotection against HSR, and this neuroprotective effect could be partially reversed by the injection of recombinant murine IL-18 into the amygdala. Therefore, CORM-3 alleviated HSR-induced neuronal pyroptosis and emotional changes, through the downregulation of IL-18 in astrocytes.

失血性休克和复苏 (HSR) 可能导致长期的神经功能障碍，例如抑郁和焦虑。在 HSR 之后，一氧化碳 (CO) 已成为对抗 caspase-1 相关细胞焦亡的出色神经保护剂。我们在大鼠的 HSR 模型中评估了效果并确定了 CO 防止情绪变化的机制。我们在体内对大鼠进行了外源性 CO 释放化合物 (CORM-3, 4 mg/kg) 的治疗, 在高铁之后。我们测量了蔗糖偏好并在 HSR 后 7 天进行了尾部悬吊和开放场测试，在 HSR 后 12 小时评估了脑磁共振成像，并评估了 HSR 后 12 小时杏仁核中的细胞焦亡、神经元和星形胶质细胞死亡。在将重组鼠白介素 (IL)-18 注射到杏仁核后，我们还测量了行为和病理学的变化。HSR 治疗的大鼠表现出更多的抑郁样和焦虑样行为，增加了杏仁核损伤，如 T2 加权磁共振成像 (MRI) 和动脉自旋标记脑血流 (CBF _{ASL) 所示})，与神经元和星形胶质细胞死亡和细胞焦亡有关，并且在星形胶质细胞中观察到 IL-18 表达上调。复苏后通过股静脉注射 CORM-3 提供了针对 HSR 的神经保护作用，这种神经保护作用可以通过将重组鼠 IL-18 注射到杏仁核中而部分逆转。因此，CORM-3 通过下调星形胶质细胞中的 IL-18 来减轻 HSR 诱导的神经元焦亡和情绪变化。