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

研究梭曼暴露后白细胞介素 1 受体拮抗剂 (IL-1Ra) 的神经保护潜力

• 批准号: NE/V019848/1
• 负责人: Stuart Allan
• 金额: $ 1.5万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=NE%2FV019848%2F1
• 关键词: Investigating; neuroprotective; potential; interleukin; receptor

"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.

“MRC DTP：Ioana - Emilia Mosneag：MR/N013751/1”有机磷化合物（有机磷酸盐）由于农药中毒或作为化学武器的替代用途而在全球造成大量死亡。强效有机磷酸酯，例如梭曼，具有剧毒，可导致瘫痪、癫痫发作、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，导致大脑血流量减少和脑细胞死亡。接触梭曼后，大脑中白介素 1 (IL-1)（一种引起炎症的蛋白质）会增加，这可能会导致细胞死亡。先前的研究使用经过基因改造的啮齿动物来阻止 IL-1 发挥作用，结果表明，暴露于梭曼后脑细胞的死亡减少，而增强 IL-1 的作用则加剧了细胞死亡。 IL-1 受体拮抗剂 (IL-1Ra) 是一种阻断 IL-1 作用的药物，该项目将研究啮齿类动物暴露于梭曼后，接受 IL-1Ra 治疗后细胞死亡和大脑血流的变化。假设的结果是在有机磷中毒的情况下使用 IL-1Ra，这可能使农民、士兵和平民受益。