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

“MRC DTP：Ioana-Emily Mosneag：MR/N013751/1”有机磷化合物(有机磷)在全球范围内因农药中毒或作为化学武器替代使用而造成大量死亡。强效有机磷，如梭曼，是剧毒的，会导致瘫痪、癫痫、呼吸衰竭和死亡。接触亚致死剂量的梭曼会立即导致惊厥发作，导致大脑血流量减少和脑细胞死亡。接触梭曼后，大脑中可引起炎症的蛋白质白介素1(IL-1)增加，这可能导致细胞死亡。之前使用转基因啮齿动物来阻止IL-1发挥作用的研究表明，接触梭曼后减少了脑细胞的死亡，而增强IL-1的作用会加剧细胞死亡。IL-1受体拮抗剂(IL-1ra)是一种阻断IL-1作用的药物，本项目将研究啮齿动物接触梭曼后IL-1ra治疗后细胞死亡和脑血流的变化。假设的结果是在有机磷中毒的情况下使用IL-1ra，这可能会使农民、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.