Diffuse vascular injury in fatal road traffic accident victims: its relationship to diffuse axonal injury

The authors have reported a macro- and microscopic study of brain lesions in 120 victims of fatal road traffic accidents, independent of the survival time. Diffuse vascular injury (DVI) was found in 14 patients (11.7%). All patients with DVI died within 24 h after the accident. The 14 patients with DVI also showed severe (Grade 2 or 3) diffuse axonal injury (DAI). Since DVI is restricted to road traffic accidents and incompatible with life, the high frequency observed in our series could be explained by the fact that all 120 patients were victims of road traffic accidents, and 69.2% had died within 24 h after the accident. The association between DVI and severe DAI (Grades 2 and 3) suggests that both lesions depend on the same mechanism, with the degree of axonal and vascular damage being determined by the intensity of the head acceleration. Our results show a relationship between DVI and DAI that suggest there may be a spectrum or at least a continuum between these entities as distinct from DVI being a separate entity.     

弥漫性轴索损伤的研究进展

弥漫性轴索损伤（diffuse axonal injury,DAI）以脑白质轴索弥漫性损伤为主要特征,迄今其形成机制尚未完全阐明,不同学科诊断标准迥异,是法医学和神经科学亟待解决的难题。磁共振弥散张量成像（diffusion tensor imaging,DTI）通过检测弥散参数及纤维束成像（fibre tracking,FT）可准确地反映轴索损伤部位及损伤程度,具有广泛的法医学应用前景。本文综述DAI发生机制及诊断方法的研究进展,尤其DTI技术在DAI诊断中的应用。     

Diffuse axonal injury by simple fall.

Diffuse axonal injury (DAI) is the second most common lethal head trauma after subdural hematoma and probably the most frequent cause of traumatic coma in the absence of an expanding intracranial mass lesion. Though it occurs most often in traffic accidents, it may occasionally result from falls from a height. Previously, it has not been associated with a simple fall or a fall of a distance not more than the victim's own height. We report herein a case of DAI from a simple fall.     

Modification of the Marmarou and Foda model of diffuse axonal injury (DAI) improves percentage survival of rats at 24 h and increases the amount of DAI identified

More than two decades ago, Marmarou published a valid model for producing diffuse axonal injury (DAI) in rats. Since then, both mild and severe injuries have been obtained by researchers using the original method and a weight of 450 g. However, the diffuse brain injuries produced in rats were only similar to those seen in humans when the rats sustained severe brain injuries. In these cases, rat mortality in the original article was around 50%, and the cause of death was prolonged apnea post-impact. Rat survival after impact is critical for studying the progression of DAI. In order to explain the cause of death in human victims with cranial trauma who do not show gross brain injury, testing for the presence of DAI is essential. Thus, in order to minimize local and cervical injuries to increase rat survival, attention should be paid to the following aspects: a wider head protector disc should be used, the head of the rat should be elevated at the time of impact, and the foam bed should be soft enough to allow the movement caused by acceleration. With our modified method, rat survival increased by 30% compared to the original model (80% versus 50%). Moreover, 85.7% of rats demonstrated DAI after 24 h of survival. With these modifications, injuries appear in the same locations as in humans; thus, the method is suitable for the study of traumatic DAI in humans.     

Delayed sudden death in an infant following an accidental fall: a case report with review of the literature

Several controversies exist regarding ultimately lethal head injuries in small children. Death from short falls, timing of head injury, lucid intervals, presence of diffuse axonal injury (DAI), and subdural hematoma (SDH) as marker of DAI are the most recent controversial topics of debate in this evolving field of study. In this area of debate, we present a case of delayed death from a witnessed fall backwards off a bed in a 9-month-old black male child who struck his head on a concrete floor and was independently witnessed as "healthy" postfall for 72 hours until he was discovered dead in bed. Grandmother, babysitter, and mother all independently corroborated under police investigation that the child "acted and behaved normally" after the fall until death. Autopsy showed a linear nondisplaced parietal skull fracture, diastasis of adjacent occipital suture, subgaleal hemorrhage with evidence of aging, small posterior clotting SDH, marked cerebral edema, and a small tear of the midsuperior body of the corpus callosum consistent with focal axonal injury (FAI). No DAI was seen, and there were no retinal hemorrhages. All other causes of death were excluded upon thorough police and medical examiner investigation. Although this seems to be a rare phenomenon, a delayed, seemingly symptom-free interval can occur between a clinically apparent mild head injury and accidental death in a young child.     

Application of diffusion tensor imaging and 1H-magnetic resonance spectroscopy in diagnosis of traumatic brain injury

Mild traumatic brain injury (mTBI) is a common type of brain disorders among young adults. The dysfunction of the brain is often exacerbated due to diffuse axonal injury (DAI) which based on the injury of white matter fibers and axons. Since mild and moderate brain injury or DAI are diffuse and subtle, conventional CT and MRI are difficult to make a positive diagnosis. Recent clinical study indicated that functional magnetic resonance imaging has a high detection rate in the diagnosis of acute mild and moderate brain injury, especially the diffusion tensor imaging (DTI) and 1H-magnetic resonance spectroscopy (1H-MRS). This paper has reviewed the principles and characteristics of DTI and 1H-MRS, and recent research in the clinical and animal experiments on brain injury.     

实验性大鼠弥漫性轴索损伤的傅里叶红外光谱检测

目的探讨利用傅里叶红外光谱技术诊断弥漫性轴索损伤的可行性。方法利用HE染色、银染和β-APP免疫组化染色确认大鼠弥漫性轴索损伤模型,利用傅里叶变换显微红外光谱面扫描成像技术检测弥漫性轴索损伤区域酰胺Ⅱ带的光谱分布情况,得到弥漫性轴索损伤的红外光谱数据,绘制红外光谱病理图像。结果实验组与对照组的酰胺Ⅱ带红外光谱吸收度之间存在明显差异,红外光谱病理图像中酰胺Ⅱ带的高吸收区与弥漫性轴索损伤区符合。结论傅里叶红外光谱技术可对弥漫性轴索损伤进行病理形态学诊断。     

112例脑弥漫性轴索损伤分析

目的探讨脑弥漫性轴索损伤（diffuse axonal injury,DAI）与脑挫裂伤和原发性脑干损伤的关系。方法分析112例DAI伤者的法医临床学资料和影像学特点,对原发性脑损伤的特征进行比较。结果112例DAI伤者中70.5%为交通事故致伤,多次暴力致伤比较多见（60.7%）,伴脑挫裂伤者80例（71.4%）。CT或MRI发现出血灶者90例。结论DAI多伴有脑皮质挫裂伤和原发性脑损伤,CT或MRI有助于法医学死因分析和伤残程度鉴定。     

交通事故致弥漫性轴索损伤伤残等级鉴定89例分析

目的研究交通事故致弥漫性轴索损伤（diffuseaxonalinjury，DAI）的患者伤残等级鉴定结果，并探讨DAI对鉴定结果可能产生的影响。方法收集556例本鉴定中心2011年1月-2012年12月受理的交通事故致颅脑损伤案例，其中单纯性脑挫（裂）伤467例，临床诊断为DAI89例。再重新审阅被鉴定人颅脑CT及MRI检查结果，分为单纯DAI组、DAI合并脑挫（裂）伤组、无DAI脑挫（裂）伤组3组颅脑损伤，并对鉴定结果进行比较和统计学分析。结果单纯DAI组（20例）的伤残等级为7．72±1．09，DAI合并脑挫（裂）伤组（69例）的伤残等级为7．78±1．11，无DAI的脑挫（裂）伤组（467例）的伤残等级为8．86±0．66，前两组的伤残等级均高于无DAI的脑挫（裂）伤组（P〈0．05）。结论患有DAI的被鉴定人可能存在更为严重的脑功能损害．鉴定时应注意临床的漏诊和误诊，避免过于依赖CT、MRI等影像学表现。     

IL-1β和TNF-α在大鼠弥漫性轴索损伤中的作用

目的观察大鼠弥漫性轴索损伤后IL-1β和TNF-α蛋白表达的时序性变化,探讨其在大鼠弥漫性轴索损伤（diffuse axonal injury,DAI）中的作用。方法 55只健康雄性SD大鼠,随机分为正常对照组、手术对照组和DAI组,采用HE、Gless氏嗜银染色和免疫组织化学（SP法）观察不同时间（30min～7d）脑干组织病理学改变及IL-1β和TNF-α蛋白的表达情况。结果 HE染色显示DIA大鼠脑干组织结构疏松、水肿,Gless氏嗜银染色可见轴索肿胀、扭曲、收缩球形成等改变,证明弥漫性轴索损伤模型成功;IL-1β和TNF-α在正常对照组与假手术组大鼠脑干神经元内有低表达,而在DAI后30min～6h大鼠脑干神经元和小胶质细胞内表达迅速增加,于6h达高峰。结论大鼠弥漫性轴索损伤后IL-1β和TNF-α蛋白在脑干内表达的增加,与轴索继发性损伤有关。     

磁敏感加权成像在出血性弥散性轴索损伤鉴定中的应用

目的探讨磁敏感加权成像(susceptibility weighted imaging,SWI)在出血性弥散性轴索损伤(diffuse axonal injury,DAI)法医学鉴定中的应用价值。方法对20例DAI的法医学鉴定资料进行回顾性分析,对其T1WI、T2WI、扩散加权成像(diffusion weighted imaging,DWI)、液体衰减反转恢复(fluid attenuated inversion recovery,FLAIR)、磁敏感加权成像(susceptibility weighted imaging,SWI)序列影像资料进行统计分析。结果 DAI出血灶多位于脑组织表浅区,SWI对出血性DAI的检出率最高,与其他序列成像之间的差异有统计学意义(P0.05)。结论 SWI在DAI法医学鉴定中具有重要的意义。     

Diffuse axonal injury

Diffuse axonal injury is a distinct form of head injury, induced by direct external forces at the time of the trauma, and not produced by secondary changes due to a primary injury. This type of lesion may be without conspicuous findings on gross brain examination, or may be found with coexisting conventional types of brain injuries. It is characterized by diffuse retraction balls (axonal swellings), hemorrhage or laceration of the corpus callosum, and hemorrhages in the brain stem. It is of utmost importance for forensic pathologists to be aware of this little-recognized entity. Five illustrative cases are presented.     

大鼠弥散性轴索损伤后β-APP的表达

目的观察大鼠DAI损伤后β-APP表达和Gless神经纤维轴索染色在诊断DAI损伤及判断损伤时间的价值。方法按Marmarou法复制大鼠DAI损伤模型,脑组织常规取材后进行β-APP及Gless氏神经纤维轴索染色观察。结果β-APP及Gless氏染色法在大鼠DAI损伤后0.5h即可见神经轴索断裂、扭曲变形、增粗膨大,12h以后可见到轴索收缩球。二种方法均显示DAI损伤的病理形态学变化,伤后12h明显,1d达到高峰,3d后开始修复,10d后基本恢复正常。β-APP表达强度在实验组不同时间存在着明显的差异,即3h呈明显阳性表达,1d达到高峰,3d后逐渐减弱,10d基本恢复正常。结论β-APP免疫组织化学染色法及Gless氏神经纤维轴索染色法,对DAI的早期诊断具有重要应用价值,并能从病理形态学上反映DAI损伤的时序性。β-APP表达强度变化是推断早期DAI损伤时间的重要参考指标。     

Preliminary Study on Diffuse Axonal Injury by Fourier Transform Infrared Spectroscopy Histopathology Imaging

The objective of this study was to evaluate the application of Fourier transform infrared (FTIR) spectroscopy for detecting diffuse axonal injury (DAI) in a mouse model. Brain tissues from DAI mouse model were prepared with H&E, silver, and β‐amyloid precursor protein (β–APP) immunohistochemistry stains and were also studied with FTIR. The infrared spectrum images showed high absorption of amide II in the subcortical white matter of the experimental mouse brain, while there was no obvious expression of amide II in the control mouse brain. The areas with high absorption of amide II were in the same distribution as the DAI region confirmed by the silver and β‐APP studies. The result suggests that high absorption of amide II correlates with axonal injury. The use of FTIR imaging allows the biochemical changes associated with DAI pathologies to be detected in the tissues, thus providing an important adjunct method to the current conventional pathological diagnostic techniques.     

大鼠弥漫性轴索损伤后海马热休克蛋白质70mRNA表达

目的 研究大鼠弥漫性轴索损伤(diffuse axonal injury,DAI)后大脑海马中热休克蛋白质(heat-shockproteins,HSP)70 mRNA的表达变化.方法 采用RT-PCR扩增,扩增产物用琼脂糖凝胶电泳检验,观察DAI后大鼠海马中HSP70 mRNA的表达变化.结果 损伤后4h,大鼠海马中...     

大鼠弥漫性轴索损伤后NGF表达

目的研究大鼠弥漫性轴索损伤后神经生长因子（NGF）表达的时间变化规律及意义。方法采用SD雄性大鼠复制弥漫性轴索损伤（DAI）模型,分别于伤后1、3、6、12、24、48h和3、7d取脑组织,应用免疫组织化学法对DAI后不同时间段大脑皮层、丘脑、小脑和海马部位NGF的表达变化进行观察并与正常组、假手术组对照。结果正常及假手术组大鼠大脑皮层、丘脑、小脑、海马均有少量NGF的表达。打击后1hNGF表达增强,12h达高峰,3d开始下降,7d降至正常。结论NGF参与弥漫性轴索损伤后的修复：NGF的时序性变化有望成为法医学脑损伤时间推断的客观指标。     

实验性脑弥漫性轴索损伤的组织病理学变化

目的探讨钝力致脑弥漫性轴索损伤(DAI)的法医病理学鉴定依据。方法采用液压冲击方法建立钝力致家猫脑DAI模型;通过H．E．、Bodian、Kluver-Barrera普通组织化学染色及NF免疫组化染色,观察致伤后不同时间脑实质内轴索及其髓鞘的变化,并通过图像分析系统对轴索内NF免疫组化染色阳性反应物面积进行定量检测,所得数据用SPSS 11．5 for Windows软件进行统计学分析。结果致伤后1-2h,猫大脑皮质下白质、胼胝体及脑干轴索轻度肿胀、弯曲;4h轴索肿胀、弯曲显著,呈断续状,且在胼胝体、丘脑及脑干出血区周围出现收缩球,髓鞘开始疏松崩解。随着观察时间的延长,收缩球进一步变大,中心空泡出现,髓鞘疏松、水肿、崩解。经对轴索内NF免疫组化染色阳性反应物的图像分析数据进行统计学分析,对比组间差别具有非常显著性差异意义(P<0．01)。结论脑轴索肿胀、弯曲、增粗、离断以及收缩球的形成,是DAI法医病理学鉴定的依据。     

Crossbow suicide: mechanisms of injury and neuropathologic findings

Crossbow injuries are rarely reported events in modern times. Two cases of death due to self-inflicted crossbow injuries to the head are reported in 2 men aged 18 and 27 years, respectively. Despite relatively low velocity and concussive force, the sharpness and propulsion force of crossbow bolts may be sufficient to enable penetration of the skull at short range. Due to the relatively low concussive force of the crossbow bolt, however, death may not be instantaneous but may occur from intraparenchymal cerebral damage sometime thereafter. Detailed neuropathologic evaluation of such cases may therefore demonstrate "red cell" hypoxic injury, as well as axonal injury, not limited to the region of the missile tract, but widely distributed, even to the point of extensive brain stem involvement. These changes may result from primary mechanical deformation at the time of injury, from secondary hypoxic damage, or from a combination of both factors. Immunohistochemical staining of brains for amyloid precursor protein to delineate more clearly the pattern of axonal damage may assist in determining the extent of injury in such cases.     

应用iTRAQ-LC-MS/MS方法筛选大鼠DAI后脑组织差异表达蛋白质

目的应用相对和绝对定量同位素标记结合液相色谱-串联质谱法(isobaric tag for relative and absolute quantification-liquid chromatograph-mass spectrometer/mass spectrometer,iTRAQ-LC-MS/MS)筛选SD大鼠弥漫性轴索损伤(diffuse axonal injury,DAI)后脑组织差异表达的蛋白质,寻找诊断DAI的潜在生物标志物。方法参照Marmarou法建立DAI动物模型,分为空白对照组(n=4)、假打击组(n=4)和打击致死组(n=4),采用iTRAQ-LC-MS/MS技术对大鼠脑组织蛋白质进行检测,并对检测结果进行生物信息学分析及验证,筛选出差异表达的蛋白质。结果定量检测出2016种蛋白质,生物信息学分析显示其在细胞中分布广泛、功能多样,并且参与了多种生物过程,16种蛋白质在打击致死组具有差异表达,包括1种表达上调蛋白质和15种下调蛋白质;Western印迹法验证了iTRAQ-LC-MS/MS的结果。结论 iTRAQ-LC-MS/MS的检测技术筛选出大鼠DAI后脑组织中多个差异表达的蛋白质,不仅为深入探讨DAI后轴索损伤的发病机制提供了研究方向,也为DAI的诊断提供了潜在生物标志物。     

大鼠DAI脑细胞凋亡与Phospho-Ser^727 Stat1表达的相关性

目的探讨Stat1是否参与弥漫性轴索损伤（diffuse axonal injury,DAI）后神经细胞凋亡的病理生理过程。方法应用自由落体撞击模型复制大鼠DAI模型,分为正常对照组、假手术组和打击后不同时间组（6、12、24、48、72h,5d和10d）。采用HE染色和镀银染色观察大鼠脑组织的病理改变,用流式细胞检测脑组织中脑细胞的凋亡率,RT-PCR法测定脑组织中bax和bcl-2的表达变化,免疫组织化学法测定脑组织中不同脑区727位丝氨酸磷酸化的信号转导与转录激活子1（Phospho-Ser727 Stat1）的表达情况。结果DAI后HE染色未见脑挫裂伤,镀银染色可见神经轴索扭曲肿胀,个别断端膨大形成轴缩球;损伤组脑细胞的凋亡率和脑组织中bax和bcl-2 cDNA扩增产物的比值24h达到最大值,随后下降;不同脑区Phospho-Ser727 Stat1表达升高,24h达峰后下降,至10d较对照组仍有显著差异;阳性细胞主要是神经元,在不同脑区也有一定量的神经胶质细胞阳性表达。脑组织中Phospho-Ser727 Stat1表达变化与bax和bcl-2的cDNA扩增产物比值的变化具有正相关性,相关系数r为0.921。结论大鼠DAI后Stat1的激活和损伤后脑细胞的凋亡有关,应与损伤后二次打击有关。