弥漫性轴突损伤胆碱能纤维改变的实验研究

目的通过大鼠弥漫性脑损伤模型观察海马及乳头体内的轴突损伤,了解轴突损伤后上述结构中胆碱酯酶纤维的变化,探讨轴突损伤与伤后记忆功能障碍的相关性.方法用Marmarou介绍的落体打击装置致伤动物,对海马和乳头体区脑组织进行胆碱酯酶(AChE)纤维染色.结果该模型较好地模拟了轴突损伤的表现,简便实用.在这个模型中轴突损伤的最常见部位为桥脑基底部和小脑上脚,其次为大脑半球白质、海马和乳头体.海马结构内含有大量胆碱酯酶阳性染色纤维.与对照组相比中,损伤10天海马CA1区,CA3区,齿状回分子层和乳头体内纤维密度明显低于对照组大鼠(P＜0.01).结论大鼠损伤后海马区和乳头体内胆碱酯酶阳性纤维明显减少,这可能是弥漫性轴突损伤病人记忆功能损害的原因.     

直线加速度所致的猫弥漫性轴突损伤

目的：为了解直线加速度在颅脑损伤特别是在弥漫性轴突损伤（ＤＡＩ）中的作用。方法：用一套撞击装置对２６只猫进行实验。结果：直线加速度可以导致几乎所有类型的颅脑损伤，包括颅骨骨折、蛛网膜下腔出血、硬膜下血肿、硬膜外血肿、脑挫伤、脑干损伤，特别是ＤＡＩ。ＤＡＩ的特征性改变－轴突回缩球在２４小时内死亡的动物脑标本中看不到，２４小时后可见到，７２小时则多而典型，７天时仍然存在。结论：凡能使脑的神经纤维受到广泛剪力和（或）张力的任何形式的外部作用均可产生ＤＡＩ。     

闭合性颅脑损伤后持续植物生存状态：42例病人的临床及磁共振成像所见

在本文的回顾性研究中作者对42例闭合性头部伤后持续植物生存状态病人的发生频率、解剖分布和脑部创伤的形状进行了分析。 用头部磁共振成像(MRI)检查(脑部)损伤数目,损伤数目最少为5处,最多为19处,平均为9处。MRI扫描证实全部病例均有弥漫性轴突损伤(diffuse axonal injury),并伤及胼胝体。弥漫性轴突损伤第二个常见部位是腹侧的脑干背外侧部(74％)。此外,65％的病人有额叶、颞叶和放射冠的白质损伤。基底神经节或丘脑损伤分别占病例数的52％和40％。MRI扫描显示脑皮质挫伤的病人占48％;额叶和颞叶是最常见的受损部位。伤及海马旁回(parahippocampal gyrus)的病人占45％;在本组病例中中脑对侧大脑脚(contralateral peduncular)的损伤发生率为80％     

大鼠头颅瞬间旋转致脑弥漫轴索损伤的形态学观察与机理探讨

目的：观察大鼠头颅瞬间旋转引起脑神经轴索损伤的形态学改变并探讨其机理。方法：ＳＤ大鼠２１只（对照组３只，损伤组１８只）。采用自制头颅旋转致伤装置，将损伤组大鼠头颅于３ｍｓ内在冠状面绕脑中心右向旋转９０°造成剪力伤，于伤后６、１２、２４、７２、１４４小时分批处死动物制脑切片，行镀银及ＨＥ染色，光镜下观察神经轴索变化。结果：伤后即刻大鼠均意识丧失。３只１５分钟内死亡，肉眼亦见蛛网膜下腔广泛出血。其余存活大鼠在伤后６至１４４小时，肉眼见蛛网膜下腔广泛出血，光镜下见脑干、胼胝体、大脑脚等部的神经轴索有程度不同的肿胀、断裂、轴缩球形成等征象，以脑干纵行纤维受损最重并伴纤维束间点状出血。延髓和中脑的上述变化分别在伤后６及２４小时最重。结论：本研究成功地建立了大鼠头颅瞬间旋转脑弥漫轴索损伤模型，表明剪力可引起轴索损伤，脑微血管变化是加重轴索损伤的重要因素。     

Mg2+对大鼠弥漫性轴索损伤脑干NF-68KD的影响

目的探讨Mg2+对脑弥漫性轴索损伤(DAI)轴索细胞骨架神经丝(NF-68KD)是否有影响.方法选健康成年雄性SD大鼠(体重350～450 g)随机分为实验组、对照组、空白组,各组又分为6 h、24 h两个亚组.采用改良Marmarou模型制作DAI模型,伤后30 min分别给予MgSO4(250μmol/kg),生理盐水(0.2 ml),伤后6 h、24 h处死.用免疫组化技术行NF-68KD染色,分别累计脑干阳性轴索数,计算阳性轴索个数/mm2行统计分析.结果伤后6 h、24 h,实验组脑干NF-68KD阳性表达强度(阳性轴索个数/mm2)均明显低于对照组(P＜0.01).对照组伤后6 h、24 h均可见明显的轴索肿胀、断裂、回缩球,而实验组仅见轴索肿胀,未见轴索断裂及回缩球.结论Mg2+可在轴索细胞骨架蛋白水平阻止轴索的继发性损害,对DAI具有一定的保护作用.     

弥漫性轴突损伤早期超微结构改变

目的通过观察弥漫性轴突损伤(DAI)患者伤后早期轴突的超微结构变化以探索DAI的发生机理.方法对12例DAI患者的14份活体脑组织标本进行透射电镜检查.结果 DAI患者在伤后早期可发生多方面的轴突改变,包括(1)轴突的细胞骨架破坏;(2)轴膜改变;(3)膜性细胞器的变化;(4)髓鞘的改变;(5)轴突出现肿胀和离断,轴突近侧断端呈现球状.结论在DAI的发生中,可能有多种机理参与.推测,在受到足够强的外力作用时,一些管径较细的轴突可能会立即断裂;其它受损轴突则会出现进行性的延迟性轴突断裂.在此演化过程中,细胞骨架破坏和轴膜受损继而通透性改变可能是造成轴突局灶性轴浆转运障碍最终离断的最重要的因素.     

椎动脉造影对小脑桥脑角肿瘤的诊断(附7例分析)

本文分析7例小脑桥脑角肿瘤经选择性导管法椎动脉造影的血管改变,主要为基底动脉侧移,惠侧小脑上功脉脚间-脚段与环中脑段向内上移位,伴边缘支和半球支伸长拉直,小脑后下动脉向内下及向后移位,大脑后动脉近段向内上移位等。其中以小脑上动脉脚间-脚段的抬高、内移为最主要而特异的征象,且是鉴别脑内外占位病变的特有征象。并简要复习后颅窝动脉的正常X线解剖。     

外伤性急性弥漫性脑肿胀的相关危险因素分析

目的 通过对外伤性急性弥漫性脑肿胀的临床流行病学调查,探讨其相关危险因素及发病机制,为院前急救及后期救治提供依据.方法 对54例外伤性弥漫性脑肿胀(病例组)与270例同期未发生外伤性弥漫性脑肿胀(对照组)患者的性别、年龄、受伤至入院时间、着力部位、误吸、低血压、高血压病史、原发脑干伤、合并多发伤、颅底骨折等因素进行病例对照研究.结果 原发脑干伤、低血压、着力部位(枕部)、误吸、年龄等因素与外伤性弥漫性脑肿胀的发生密切相关.结论 原发脑干伤、低血压、着力部位(枕部)、误吸是外伤性急性弥漫性脑肿胀的危险因素;高龄是外伤性急性弥漫性脑肿胀的保护因素.     

脑源性神经营养因子基因转染可促进弥漫性轴突损伤神经元修复和轴突再生

应用脂质体将外源脑源性神经营养因子基因导入弥漫性轴突损伤模型大鼠脑内,力图通过脑源性神经营养因子促进神经元再生及修复的作用,促进损伤大鼠的形态功能恢复。结果显示基因转染后弥漫性轴突损伤额叶皮质神经元的形态得到改善,额叶皮质组织神经丝蛋白表达增加,证实脑源性神经营养因子可促进弥漫性轴突损伤后神经元的修复及轴突的再生。     

对弥漫性轴突损伤的认识

弥漫性轴突损伤（diffuse axonal injury，DAI）是一种常见的脑损伤类型，是造成重型脑损伤患者不良预后的主要原因之一。1956年Strieh发现脑外伤后5—15个月死亡患者的脑白质纤维缺失和变性，随后又观察到存活48h的病例存在DAI的特征性病理改变“轴突回缩球”，1982年Adamas等将这种独特的损伤类型命名为“弥漫性轴突损伤”。现今DAI作为独立的脑损伤类型已被写入教科书，但对其致伤机理、伤情演化过程及特异性诊断仍不明确，治疗上也无特效方法，有些问题还存在认识上的误区。     

脑弥漫性轴索损伤轴索内钙超载及钙拮抗剂的治疗作用

目的探讨脑弥漫性轴索损伤(DAI)轴索内Ca2+超载及Ca2+拮抗剂的治疗作用.方法 SD大鼠14只,分损伤组、用药组(伤后立即静注尼莫通)、对照组.用自制头颅瞬间侧向旋转装置,制作大鼠DAI模型.伤后2～24小时取延髓组织,行Ca2+电镜细胞化学处理(草酸钾-焦锑酸钾法)和观察.结果 (1)损伤组神经轴索髓鞘板层断裂、间隙扩大,轴膜与髓鞘脱离,细胞器边聚,轴浆空泡形成,线粒体稀少.受损髓鞘内有大量细小钙颗粒,髓鞘损害程度与钙颗粒数量呈正相关;伤后晚期轴浆内可见粗大钙颗粒.神经元胞体及血管内皮细胞空泡化,也有钙颗粒沉着,内皮细胞管腔面出现微绒毛.(2)用药组轴索髓鞘损伤趋于局部,线粒体数量、形态、分布近于正常,髓鞘及轴浆钙颗粒罕见,神经元胞体及血管内皮细胞空泡变明显减轻.结论 DAI中轴索存在Ca2+超载,这是导致DAI发生发展的重要因素;Ca2+拮抗剂尼莫通可改善DAI.     

弥漫性轴索损伤在重型脑损伤中的意义

在15例闭合性脑损伤尸检中,病理诊断弥漫性轴索损伤(DAI)5例。根据病理研究结果和文献报道,分析了530例急性脑外伤病人脑CT表现,发现DAI61例。其CT表现为大脑皮髓质交界处、基底节内囊区域、胼胝体、脑干或小脑有一个或多个直径≤2cm的出血灶,脑室内出血及急性弥漫性脑肿胀。本文把DAI分为高颅压型和非高颅压型,后者又分的脑干损伤型和局灶性损伤型。这种分型对指导治疗和判断预后均有重要意义。DAI预后较差,是目前脑外伤病人死亡率高的重要原因之一。     

Ultrastructural evidence of axonal shearing as a result of lateral acceleration of the head in non-human primates

Summary The concept of shearing of axons at the time of non-impact injury to the head was first suggested in the middle of this century. However, no experimental model of diffuse axonal injury (DAI) has provided morphological confirmation of this concept. Evidence from experiments on invertebrate axons suggests that membrane resealing after axonal transection occurs between 5 and 30 min after injury. Thus, ultrastructural evidence in support of axonal shearing will probably only be obtained by examination of very short-term survival animal models. We have examined serial thin sections from the corpus callosum of non-human primates exposed to lateral acceleration of the head under conditions which induce DAI. Tearing or shearing of axons was obtained 20 and 35 min after injury, but not at 60 min. Axonal fragmentation occurred more frequently at the node/paranode but also in the internodal regions of axons. Fragmentation occurred most frequently in small axons. Axonal shearing was associated with dissolution of the cytoskeleton and the occurrence of individual, morphologically abnormal membranous organelles. There was no aggregation of membranous organelles at 20 and 35 min but small groups did occur in some axons at 60 minutes. We suggest that two different mechanisms of injury may be occurring in non-impact injury to the head. The first is shearing of axons and sealing of fragmented axonal membranes within 60 min. A second mechanism occurs in other fibres where pertubation of the axon results in axonal swelling and disconnection at a minimum of 2 h after injury.Supported by NIH grant number NS-08803-21, the Wellcome Trust, the Royal Society, London and the Institute of Neurological Sciences, University of Glasgow. Part of this work was presented at the Ist International Neurotrauma Symposium, Fukishima, Japan and the IVth European Meeting of Neuropathology, Berlin Dedication: The authors would like this work to be a tribute to Professor J. H. Adams upon his retiral. His research into diffuse axonal injury inspired the authors to undertake this study.     

Diffuse axonal injury: Novel insights into detection and treatment

Diffuse axonal injury (DAI) is one of the most common and important pathologic features of traumatic brain injury. The definitive diagnosis of DAI, especially in its early stage, is difficult. In addition, most therapeutic agents for patients with DAI are non-specific. The CT scan is widely used to identify signs of DAI. Although its sensitivity is limited to moderate to severe DAI, it remains a useful first-line imaging tool that may also identify co-morbid injuries such as intracerebral hemorrhage. Recently, investigations have sought to apply advanced imaging techniques and laboratory techniques to detect DAI. Meanwhile, some potential specific treatments that may protect injured axons or stimulate axonal regeneration have been developed. We review some new diagnostic technologies and specific therapeutic strategies for DAI.     

Calcium overloading in traumatic axonal injury by lateral head rotation: a morphological evidence in rat model.

The study investigated morphologically axonal calcium overloading and its relationship with axonal structural changes. Twelve SD rats were divided into an injury and a sham group. The rat model of traumatic axonal injury (TAI) by lateral head rotation was produced. The oxalate-pyroantimonate technique for calcium localization was used to process the rat's medulla oblongata tissues with thin sections observed electron-microscopically for axonal structure and calcium precipitates on it. The axonal damage in medulla oblongata appeared at 2 h post-injury, gradually became diffuse and severe, and continued to exist at 24 hours. At 2 hours, calcium precipitates were deposited on separated lamellae and axolemma, but were rarely distributed in the axoplasm. At 6 hours, calcium precipitates occurred on separated lamellae and axolemma in much higher density, but on axoplasm in extremely small amounts. Some axons, though lacking structural changes of the myelin sheath, sequestered plenty of calcium deposits on their swollen mitochondria. At 24 hours, damaged axons presented with much more severe lamellae separation and calcium deposits. Axonal calcium overloading developed in rat TAI model using lateral head rotation. This was significantly related to structural damage in the axons. These findings suggest the feasibility of using calcium antagonists in cope the management of human DAI in its very early stage.     

Diffuse axonal injury and traumatic coma in the primate

Traumatic coma was produced in 45 monkeys by accelerating the head without impact in one of three directions. The duration of coma, degree of neurological impariment, and amount of diffuse axonal injury (DAI) in the brain were directly related to the amount of coronal head motion used. Coma of less than 15 minutes (concussion) occurred in 11 of 13 animals subjected to sagittal head motion, in 2 of 6 animals with oblique head motion, and in 2 of 26 animals with full lateral head motion. All 15 concussed animals had good recovery, and none had DAI. Conversely, coma lasting more than 6 hours occurred in none of the sagittal or oblique injury groups but was present in 20 of the laterally injured animals, all of which were severely disabled afterward. All laterally injured animals had a degree of DAI similar to that found in severe human head injury. Coma lasting 16 minutes to 6 hours occurred in 2 of 13 in the sagittal group, 4 of 6 in the oblique group, and 4 of 26 in the lateral group; these animals had less neurological disability and less DAI than when coma lasted longer than 6 hours. These experimental findings duplicate the spectrum of traumatic coma seen in human beings and include axonal damage identical to that seen in severe head injury in humans. Since the amount of DAI was directly proportional to the severity of injury (duration of coma and quality of outcome), we conclude that axonal damage produced by coronal head acceleration is a major cause of prolonged traumatic coma and its sequelae.