Fievisohn Elizabeth M, Sajja Venkata Siva Sai Sujith, Vandevord Pamela J, Hardy Warren N
a Virginia Tech-Wake Forest University, School of Biomedical Engineering and Sciences, Center for Injury Biomechanics, Virginia Polytechnic Institute and State University , Blacksburg , Virginia.
Traffic Inj Prev. 2014;15 Suppl 1:S81-7. doi: 10.1080/15389588.2014.929670.
Two novel injury devices were used to characterize impact-induced traumatic brain injury (TBI). One imparts pure translation, and the other produces combined translation and rotation. The objective of this study was to evaluate the neuropathology associated with two injury devices using proton magnetic resonance spectroscopy (1H-MRS) to quantify metabolic changes and immunohistochemistry (IHC) to evaluate axonal damage in the corpus callosum.
Young adult female Göttingen minipigs were exposed to impact-induced TBI with either the translation-input injury device or the combined-input injury device (n=11/group). Sham animals were treated identically except for the injury event (n=3). The minipigs underwent 1H-MRS scans prior to injury (baseline), approximately 1 h after injury, and 24 h post injury, at which point the brains were extracted for IHC. Metabolites of interest include glutamate (Glu), glutamine (Gln), N-acetylaspartate (NAA), N-acetylaspartylglutamate (NAAG), and γ-aminobutyric acid (GABA). Repeated measures analysis of variance with a least significant difference post hoc test were used to compare the three time points. IHC was performed on paraffin-embedded sections of the corpus callosum with light and heavy neurofilament antibodies. Stained pixel percentages were compared between shams and 24-h survival animals.
For the translation-input group (27.5-70.1 g), 16 significant metabolite differences were found. Three of these include a significant increase in Gln, both 1 h and 24 h postinjury, and an increase in GABA 24 h after injury. For the combined-input group (40.1-95.9 g; 1,014.5-3,814.9 rad/s2; 7.2-10.8 rad/s), 20 significant metabolite differences were found. Three of these include a significant increase in Glu, an increase in the ratio Glu/Gln, and an increase in the ratio Glu/NAAG 24 h after injury. The IHC analysis revealed significant increases in light and heavy neurofilament for both groups 24 h after injury.
Only five metabolite differences were similar between the input modes, most of which are related to inflammation or myelin disruption. The observed metabolite differences indicate important dissimilarities. For the translation-input group, an increase in Gln and GABA suggests a response in the GABA shunt system. For the combined-input group, an increase in Glu, Glu/Gln, and Glu/NAAG suggests glutamate excitotoxicity. Importantly, both of these input modes lead to similar light and heavy neurofilament damage, which indicates axonal disruption. Identifying neuropathological changes that are unique to different injury mechanisms is critical in defining the complexity of TBI and can lead to improved prevention strategies and the development of effective drug therapies.
使用两种新型损伤装置来表征撞击所致的创伤性脑损伤（TBI）。一种施加单纯平移，另一种产生平移与旋转的组合。本研究的目的是使用质子磁共振波谱（1H-MRS）量化代谢变化，并使用免疫组织化学（IHC）评估胼胝体中的轴突损伤，以评价与这两种损伤装置相关的神经病理学。
成年雌性哥廷根小型猪分别使用平移输入损伤装置或组合输入损伤装置暴露于撞击所致的TBI（每组n = 11）。假手术动物除不进行损伤操作外，其他处理相同（n = 3）。小型猪在损伤前（基线）、损伤后约1小时和损伤后24小时接受1H-MRS扫描，之后取出大脑进行IHC。感兴趣的代谢物包括谷氨酸（Glu）、谷氨酰胺（Gln）、N-乙酰天门冬氨酸（NAA）、N-乙酰天门冬氨酰谷氨酸（NAAG）和γ-氨基丁酸（GABA）。采用重复测量方差分析及最小显著差异事后检验来比较三个时间点。对胼胝体石蜡包埋切片用轻链和重链神经丝抗体进行IHC。比较假手术组和存活24小时动物组的染色像素百分比。
对于平移输入组（27.5 - 70.1 g），发现16个显著的代谢物差异。其中三个包括损伤后1小时和24小时Gln显著增加，以及损伤后24小时GABA增加。对于组合输入组（40.1 - 95.9 g；1,014.5 - 3,814.9 rad/s2；7.2 - 10.8 rad/s），发现20个显著的代谢物差异。其中三个包括损伤后24小时Glu显著增加、Glu/Gln比值增加以及Glu/NAAG比值增加（原文此处有误，Glu/Gln和Glu/NAAG是比值，前面不应加“an increase in the ratio”，应改为“an increase in Glu/Gln ratio和an increase in Glu/NAAG ratio”）。IHC分析显示两组在损伤后24小时轻链和重链神经丝均显著增加。
两种输入模式之间只有五个代谢物差异相似，其中大多数与炎症或髓鞘破坏有关。观察到的代谢物差异表明存在重要的不同之处。对于平移输入组，Gln和GABA增加表明GABA分流系统有反应。对于组合输入组，Glu、Glu/Gln比值和Glu/NAAG比值增加表明谷氨酸兴奋性毒性。重要的是，这两种输入模式都会导致相似的轻链和重链神经丝损伤，这表明轴突中断。识别不同损伤机制所特有的神经病理学变化对于界定TBI的复杂性至关重要，并且可以带来更好的预防策略和有效的药物治疗的发展。
