Investigating the neuroprotective potential of interleukin-1 receptor antagonist (IL-1Ra) after soman exposure

“MRC DTP：约安娜-艾米莉亚·莫斯内格：MR/N 013751/1“有机磷化合物（有机磷酸盐）在全球范围内因农药中毒或作为化学武器的替代用途而造成大量死亡。强效有机磷，如梭曼，具有剧毒，可导致瘫痪、癫痫、呼吸衰竭和死亡。暴露于亚致死剂量的梭曼会导致立即惊厥性癫痫发作，导致脑血流量减少和脑细胞死亡。暴露于梭曼后，大脑中的白细胞介素-1（IL-1）（一种引起炎症的蛋白质）增加，这可能导致细胞死亡。以前的研究使用转基因啮齿动物来阻止IL-1的工作，显示梭曼暴露后脑细胞的死亡减少，而增强IL-1的作用则恶化了细胞死亡。IL-1受体拮抗剂（IL-1 Ra）是一种阻断IL-1作用的药物，本项目将研究啮齿动物在梭曼暴露后接受IL-1 Ra治疗后，脑中细胞死亡和血流量的变化。假设的结果是在有机磷中毒的情况下使用IL-1 Ra，这可能使农民，士兵和平民受益。

"MRC DTP : Ioana - Emilia Mosneag : MR/N013751/1"Organophosphorus compounds (organophosphates) cause numerous deaths globally due to pesticide poisoning or due to their alternative use as chemical weapons. Potent organophosphates, such as soman, are highly toxic inducing paralysis, seizures, respiratory failure and death. Exposure to sub-lethal soman doses results in immediate convulsive seizures, leading to decreased blood flow in the brain and the death of brain cells. Increases in interleukin-1 (IL-1), a protein that causes inflammation, are seen in the brain after soman exposure, which may contribute to cell death. Previous studies that used rodents genetically modified to stop IL-1 from working show reduced death of brain cells after soman exposure while enhancing the effects of IL-1 worsened the cell death. IL-1 receptor antagonist (IL-1Ra) is a drug that blocks the effects of IL-1 and this project will investigate changes in cell death and blood flow in the brain after IL-1Ra treatment post soman exposure in rodents. The postulated outcome is the use of IL-1Ra in situations of organophosphate poisoning, which could benefit farmers, soldiers and civilians.