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Intracerebral expression pattern of various transported protein through axons and proinflammatory cytokines after fatal traumatic brain injury

致命性脑外伤后各种轴突转运蛋白和促炎细胞因子的脑内表达模式

基本信息

批准号：
20890177
负责人：
HAYASHI Takahito
金额：
$ 2.1万
依托单位：
Kagoshima University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Young Scientists (Start-up)
财政年份：
2008
资助国家：
日本
起止时间：
2008 至 2009
项目状态：
已结题

项目摘要

This research aimed to establish the following three methods ; (1) new forensic diagnostic markers for diffuse traumatic axonal injury (TAI), (2) differential diagnosis between traumatic axonal injury and hypoxic one, (3) estimation for time interval after injury. For this purpose, we immunohistochemically examined intracerebral expressions of transported proteins through axons such as β-amyloid precursor protein (APP), Neuron-specific enolase (NSE), and expressions of proinflammatory cytokines such as Interleukin-8 (IL-8), Tumor necrosis factor-α (TNF-α). Sections of the corpus callosum from cases of head injury were immunostained for those markers. On both APP and NSE immunostained sections, two patterns of immunoreactivity were identified in several cases of head injury. The first pattern showed that labeled axons were oriented along with white matter bundles ; the second demonstrated that the axons were scattered irregularly. Our results suggested that the first and second pattern may represent traumatic axonal injury, and secondary hypoxic axonal injury, respectively. Moreover, NSE was more sensitive procedure for detecting TAI than APP, because NSE immunostaining could detect axonal injuries in cases of head injury that survived more than 2 hours (APP ; more than 9 hours). Furthermore, IL-8 and TNF-α immunostaining could detect axonal injuries in cases of head injury that survived more than 3 days and 4 days, respectively. Our results suggested that immunostaining of proinflammatory cytokines such as IL-8 and TNF-α in the corpus callosum could be a new useful marker for estimating time interval after traumatic axonal injury.

本研究旨在建立以下三种方法；（1）弥漫性外伤性轴突损伤（TAI）的新法医诊断标志物，（2）外伤性轴突损伤与缺氧性轴突损伤之间的鉴别诊断，（3）损伤后时间间隔的估计。为此，我们采用免疫组织化学方法检测了通过轴突转运蛋白的脑内表达，例如 β-淀粉样前体蛋白 (APP)、神经元特异性烯醇化酶 (NSE)，以及促炎细胞因子的表达，例如白介素-8 (IL-8)、肿瘤坏死因子-α (TNF-α)。对头部受伤病例的胼胝体切片进行了这些标记物的免疫染色。在 APP 和 NSE 免疫染色切片上，在几例头部损伤病例中发现了两种免疫反应模式。第一个模式显示标记的轴突与白质束一起定向；第二个表明轴突不规则地分散。我们的结果表明，第一种和第二种模式可能分别代表创伤性轴突损伤和继发性缺氧轴突损伤。此外，NSE 是比 APP 更敏感的 TAI 检测程序，因为 NSE 免疫染色可以在存活超过 2 小时（APP ；超过 9 小时）的头部损伤病例中检测到轴突损伤。此外，IL-8 和 TNF-α 免疫染色可以分别检测存活超过 3 天和 4 天的头部损伤病例中的轴突损伤。我们的结果表明，胼胝体中促炎细胞因子（例如 IL-8 和 TNF-α）的免疫染色可能是估计创伤性轴突损伤后时间间隔的新的有用标记。