EXPERIMENTAL DIFFUSE AXONAL INJURY

实验性弥漫性轴突损伤

• 批准号: 5215013
• 负责人: THOMAS A GENNARELLI
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5215013
• 关键词: axon; brain imaging /visualization /scanning; brain injury; coma; creatine; cytoskeleton; disease /disorder model; histology; histopathology; magnesium; magnetic resonance imaging; miniature swine; model design /development; neuropharmacology; nuclear magnetic resonance spectroscopy

Because of the importance of traumatic damage to axons and of diffuse axonal injury (DAI) in specific, this project will continue to characterize a unique new model of DAI. The model was recently developed in this Center with only three animal experiments by first producing physical and mathematical models derived from biomechanics principles determined from previous research. DAI is created by applying a non- impact impulsive load to the snout of minipig thereby producing rotational acceleration to the brain. Preliminary studies show that traumatic axonal damage is produced in isolation and that at least some of this damage can be detected non-invasively by magnetic transfer imaging (MTI), a magnetic resonance technique sensitive to white matter changes. In-vivo biochemical changes determined by 31/P or 1/H magnetic resonance spectroscopy (MRS) show marked immediate reduction of intracellular magnesium that was temporary and of n-acetyl-aspartate which was not. These changes were very different if a contusion was superimposed on DAI around which cerebral blood flow (CBF), phosphocreatine (PCr), and the PCr/Pi ratio markedly decreased. We will extend these findings by further characterizing this model with MTI, MRS and CBF studies that have immediate clinical application.

由于创伤性损伤对轴突的重要性， 具体而言，轴突损伤（DAI），该项目将继续 描述了一种独特的DAI新模型。 该模型是最近开发的 在这个中心，只有三个动物实验， 从生物力学原理导出的物理和数学模型 根据以前的研究确定。 DAI是通过应用非 对小型猪的口鼻部施加冲击脉冲载荷， 旋转加速度传递到大脑 初步研究表明， 创伤性轴突损伤是孤立产生的， 这种损伤可以通过磁转移非侵入性地检测到， 成像（MTI），一种对白色物质敏感的磁共振技术 变化 通过31/P或1/H磁性测定的体内生化变化 核磁共振波谱（MRS）显示， 细胞内镁是暂时的， 其实不然 这些变化是非常不同的，如果挫伤是 叠加在DAI周围，脑血流（CBF）， 磷酸肌酸（PCr），PCr/Pi比值明显降低。 我们将 通过进一步用MTI、MRS表征该模型来扩展这些发现， 和具有直接临床应用的CBF研究。