急性运动性轴索型格林-巴利综合征兔模型坐骨神经巨噬细胞免疫组化研究

目的：探讨急性运动性轴索型（AMAN型）格林-巴利综合征（GBS）兔模型坐骨神经巨噬细胞免疫组化染色的改变。方法：采用免疫组化方法对实验兔坐骨神经进行CD68免疫组化染色。结果：发病兔坐骨神经单核巨噬细胞呈阳性表达，坐骨神经内有散在单核巨噬细胞浸润，单核巨噬细胞吞噬含铁血黄素局部神经轴索疏松和消失。结论：本实验证明了单核巨噬细胞参与AMAN型GBS的发病过程，为空肠弯曲菌（Cj）感染和体液免疫反应与AMAN型GBS的发病关系提供了一个可靠证据。     

薄束轴索变性小鼠轴索内淀粉样β蛋白蓄积的研究

目的：探讨薄束轴索变性（GAD）小鼠薄束路系统的轴索变性和Aβ沉积的相互关系，方法：用免疫组织化学染色和HE染色镜像切片对照方法。结果：在GAD小鼠薄束路系统的轴索变性部位，有呈Aβ强阳性的类圆形沉积物，在4周龄时，延髓的薄束核区已出现球状沉积物（sphroid)，但Aβ染色呈阴性，9周龄时，该区的部分sphroid，呈Aβ染色强阳性的类圆形沉积物，伴随着加更为明显，并与轴索进行性变性进展序至一致地出现，结论：Aβ沉积与轴索变性密切相关，是神经轴索变性后继发产生的结果。     

腊肠体样周围神经病的临床和病理

报告４例经腓肠神经活检病理证实的腊肠体样周围神经病，以提高该病的临床认识和诊断能力。方法局麻下做腓肠神经活检，活检标本分别做ＨＥ和Ｍａｓｓｏｎ染色；髓鞘染色；剥离单神经；半薄和超薄切片，分别在光镜或电镜下观察。结果４例均为男性，１３～２１岁发病，其中３例有家族史，临床特征为反复发生的轻微机械性压迫或牵拉后单神经麻痹。电生理检查显示广泛性周围神经损害，传导速度明显减慢。临床符合遗传性压迫易感性麻痹神经病和痛性臂丛神经病。腓肠神经活检可见少数明显增粗的有髓纤维，直径达２０～２８μｍ，髓鞘增厚，而轴索正常，还可见到薄髓纤维。剥离单神经纤维可见局灶性髓鞘增厚，形似腊肠样。电镜下见到髓鞘板层层数增多，无轴索变性，雪旺细胞和无髓纤维未见明显异常。结论腊肠体样周围神经病有周围神经髓鞘发育缺陷，使周围神经易于损伤，是多发性单神经病的病因之一。     

腓骨肌萎缩症的病理和超微结构改变

目的　总结腓骨肌萎缩症 (HMSNⅠ型和Ⅱ型 )周围神经的病理改变及其特征。　　方法　采用单纤维分离、光镜及电镜观察 5例HMSNⅠ型、2例HMSNⅡ型腓肠神经的病理改变。　　结果　光镜下HMSNⅠ型患者大直径有髓纤维几乎完全消失 ,HMSNⅡ型部分保留 ,Ⅰ型各例均可见大量洋葱头样结构 ,Ⅱ型则无。电镜观察同样见到Ⅰ型患者有大量洋葱头样结构 ,并有较多膜性结构和雪旺氏细胞胞浆突起成分。Ⅱ型可见髓鞘坏变、塌陷 ,轴索内空泡变性。　　结论　HMSNⅠ型的基本病理改变为雪旺氏细胞病变 ,Ⅱ型则为轴索变性。     

剔除小鼠神经微管运动蛋白Kif1b基因产生轴索型神经退行性病变

目的 研究杂合子小鼠Kif1b基因剔除后神经系统的病理改变,为Charcot-Marie-Tooth(CMT)病动物模型的分型提供病理学依据.方法用PCR和Southern blotting检测基因型和验证同源重组,通过脊髓前角细胞HE染色和坐骨神经甲苯胺蓝染色及电镜标本制备观察病理改变.结果 Kif1b基因组DNA用Southern blotting检测表明,PCR法挑选的19只小鼠全部发生了同源重组.杂合子Kif1b基因剔除小鼠的坐骨神经内,粗径有髓纤维轴索变性,数量减少.在光镜和电镜下可见轴索的限局性肿胀,肿胀处可见壅堵的细胞器,但未见髓鞘的改变、节段性脱髓鞘和"洋葱球"样改变;其脊髓前角细胞体中,HE染色可以看到典型的嗜酸性球状体变性,电镜下显示为各种细胞器堵塞在核周和在细胞通往轴索的出口处,包括排列紊乱的神经丝、线粒体、空泡及多室小体.脊髓前角细胞数目明显减少.结论杂合子Kif1b基因剔除小鼠的病理改变与人类CMT2A具有相似性.     

104例格林-巴利综合征电生理分型及病理分析

目的 :研究 10 4例格林 巴利综合征 (GBS)的电生理分型及病理特点。方法 :分析 10 4例GBS病人的电生理和临床资料 ,对 19例进行腓肠神经活检和电镜研究。结果 :10 4例GBS病人有病前感染 60 3 7%、有机磷农药密切接触 49 0 3 %。电生理分型 :脱髓鞘型 64例 ,轴索型 3 1例 ,神经失电位型 9例。 19例腓肠神经活检以脱髓鞘为主 ,伴轴索变性 13例。结论 :10 4例GBS病人以原发性脱髓鞘型为主要发病形式 ,消化道感染为主。有机磷农药与GBS轴索型发病有关     

实验性糖尿病大鼠坐骨神经病理形态学的动态变化

目的通过HE染色在光镜及电镜下观察不同时期实验性糖尿病大鼠(DM大鼠)坐骨神经内膜毛细血管及坐骨神经的形态学改变,来揭示实验性糖尿病大鼠坐骨神经病理学的动态变化。方法采用大鼠腹腔内注射链脲菌素(STZ)溶液,制备实验性糖尿病大鼠模型。将80只Wistar大鼠随机分为正常对照组(NC组),成模即刻(0w)组、成模后4w组、8w组、12w组。应用HE染色在光镜和电镜下观察大鼠下肢坐骨神经病理形态学改变。结果造模前DM组和NC组大鼠病理形态学无显著差异;HE染色显示DM组大鼠从4w开始出现神经内膜毛细血管管壁逐渐增厚,管腔不规则,内皮细胞肿胀、变形,随病程延长而逐渐加重;同时也从4w开始出现坐骨神经有髓及无髓神经纤维排列松散,且随病程进展逐渐出现髓鞘变薄、分离、空泡形成,并伴有轴索萎缩。电镜观察结果显示DM组大鼠从4w开始出现毛细血管内皮增厚,基底膜不清楚,周围有炎细胞浸润;同时有髓神经纤维髓鞘板层薄厚不一、分离或脱落,无髓神经纤维轴索内神经丝减少,线粒体肿胀,粗面内质网扩张,可见髓样小体,且随病程延长而逐渐加重。结论DM大鼠早期4w时周围神经即可出现明显的病理形态学改变,且其损伤程度随病程的延长而加重。     

大鼠脑弥漫性轴索损伤不同轴索损伤类型的形态学观察

目的 观察脑弥漫性轴索损伤(DAI)急性期轴索损伤的类型和形态学改变,并探讨其相关机制. 方法 SD大鼠24只随机数字表法分为实验组(n=16)和对照组(n=8).实验组又按损伤后不同时间(6、24 h)分为2组,每组8只,运用自制联合损伤装置致实验组大鼠DAI模型,于损伤后急性期不同时间点行HE染色,免疫荧光染色检测脑组织轴浆运输障碍标志物β-淀粉样前体蛋白(β-APP)和神经微丝结构破坏标志物(NF-68)的表达,并在电镜下观察损伤轴索的超微结构变化.结果与对照组[(6.5±1.0)min]相比,实验组[(11.9±2.7)min]大鼠伤后出现昏迷时间延长,差异有统计学意义(P<0.05).β-APP免疫组化染色显示轴索肿胀扭曲、膨胀断裂及轴索球形成;NF-68免疫荧光染色显示轴索缩窄变细呈分割状.电镜下肿胀类型的轴索骨架溶解絮乱、细胞器聚集,而另一类损伤轴索骨架排列仍较清晰,但轴索内有较多空泡形成及神经微丝汇聚. 结论 DAI急性期损伤轴索存在着轴浆运输障碍和神经微丝结构破坏等病理生理过程,相应损伤轴索的形态不同.多种检测方法的使用能更全面地评估轴索损伤的严重程度及轴索对损伤的复杂反应.     

格林—巴利综合征冷冻蚀刻电镜研究

探讨格林－巴利综合征（ＧＢＳ）病变神经元各种生物膜超微结构变化特征。方法利用冷冻蚀刻电镜技术对３例ＧＢＳ尸检材料进行研究。结果ＧＢＳ病灶中多处可见巨噬细胞和淋巴细胞浸润；神经纤维髓鞘板层之间多处出现空泡或不同程度脱失，严重者轴索呈裸露状态，而轴索相对完好；轴索内神经微丝、微管形态和数量与正常人相同；髓鞘板层表面出现膜蛋白颗粒，且大小不一，分布不均；施万细胞有的处于激活状态具有吞噬功能，参与破坏髓鞘；有的成为免疫应答所攻击的目标而受到破坏，处于机能衰退状态。结论从冷冻蚀刻电镜角度认为经典型ＧＢＳ主要累及施万细胞和髓鞘。且施万细胞在神经元脱髓机制中起着重要作用。     

脑出血大鼠锥体束显微和超微结构改变

目的研究脑出血大鼠锥体束病理变化规律及特点。方法使用Ⅳ型胶原酶．肝素诱导大鼠基底节脑出血,采用劳克坚牢蓝（LFB）染色、神经丝蛋白（NF）免疫组化和电镜对内囊后肢进行观察。结果Ⅳ型胶原酶-肝素能成功建立具有典型神经功能缺损的大鼠脑出血模型。光镜发现锥体束髓鞘损伤在脑出血1～3d逐渐加重,7d开始再生修复,1～7d轴突损伤持续加重,14d轴突光度值（0．09±0．01）有所增加,但与7d（0．10±0．02）相比无显著性差异（P〉0．05）。电镜显示脑出血1d锥体束髓鞘松解,轴突水肿,部分无髓轴突崩解坏死消失,3d髓鞘松解、空泡样变性,局部髓鞘消失、厚薄不均,轴突水肿严重,甚至坏死崩解。结论大鼠脑出血后1w内锥体束损伤呈进行性加重,提示应早期和超早期予以干预治疗以减轻损伤和促进修复。     

运动轴索型格林-巴利综合征患者血清对神经轴索损害作用的研究

应用含有高效价空肠弯曲菌抗体的急性运动性轴索型格林-巴利综合征病人的血清浸泡8只在体新西兰兔坐骨神经。14天后病理检查显示4只兔的坐骨神经均有20%～30%的纤维发生轴索变性,而髓鞘相对正常。而其他神经疾病组血清、健康成人组血清做同样实验获阴性病理结果。本实验表明:AMAN 患者血清中含有致病因子,此致病因子可能是抗空肠弯曲菌抗体并介导了神经轴索的损害。     

空肠弯曲菌抗体对兔周围神经致病作用的研究

目的探讨空肠弯曲菌（Ｃｊ）及其抗体在急性运动性轴索型格林－巴利综合征（ＡＭＡＮ）中的免疫致病作用。方法经外科手术将含与不含Ｃｊ抗体的血清滴注、浸泡两组各８只兔的坐骨神经。１４ｄ后取浸泡处的坐骨神经．进行病理检查。结果Ｃｊ抗体阳性血清致局部神经损害,５只兔的坐骨神经有２０～３０％的纤维发生轴索变性。而Ｃｊ抗体阴性血清未引起上述病变。结论Ｃｊ抗体可能是ＧＢＳ的致病因子之一并介导了神经轴索的损害。     

Severe Guillain-Barré syndrome: sorting out the pathological hallmark in an electrophysiological axonal case

Abstract   We describe a clinicopathological study of a patient presenting with severe and electrophysiological axonal Guillain-Barré syndrome (GBS). An 83-year-old man had a 2-day history of distal acroparesthesias and ascending weakness culminating in quadriplegia, the patient dying 1 month after onset. On day 3, motor conduction velocity (MCV) and distal motor latency values were normal or minimally delayed; most F waves were present with latencies normal or barely delayed. Compound muscle action potential (CMAP) amplitudes were variably reduced. On day 10, there was reduction of CMAPs with relative preservation of MCV. On histological study, the density of myelinated fibers was normal in L5 ventral and dorsal roots, where outstanding lesions included dark fibers, scattered macrophage infiltration, and occasional images of de-remyelination or axonal degeneration. In the fifth spinal nerve, there was widespread loss of myelinated fibers with focal areas showing almost complete fiber loss and variable fascicular combination of extensive de-remyelination and axonal degeneration. Wallerian-like degeneration predominated in femoral and sciatic nerves. Peripheral neuron cell bodies showed central chromatolysis. We conclude that the pathological hallmark of this electrophysiological axonal GBS case is extensive but variable de-remyelination of proximal nerve trunks with superimposed nerve ischemia and axonal degeneration.     

Axonal Guillain-Barré syndrome: carbohydrate mimicry and pathophysiology

Abstract   Acute motor axonal neuropathy (AMAN), an axonal subtype of Guillain-Barré syndrome (GBS), is characterized by pure motor involvement, frequent antecedent infection by Campylobacter jejuni , association with anti-GM1 or anti-GD1a immunoglobulin G (IgG) antibodies, and the electrophysiological features of axonal degeneration and reversible conduction block. Molecular mimicry exists between GM1 and GD1a gangliosides and lipooligosaccharides (LOSs) of C. jejuni isolates from AMAN. Sensitization of rabbits with GM1 or C. jejuni LOS induces anti-GM1 IgG antibodies and subsequent flaccid paralysis. Pathological changes seen in rabbit model peripheral nerves are identical to those in human AMAN. Immunohistochemistry of AMAN rabbits shows disruption of nodal sodium channel clusters and detachment of paranodal myelin terminal loops, similar to paranodal demyelination, which would significantly reduce the safety factor for impulse transmission and might be responsible for the rapidly reversible conduction block frequently present in human AMAN. C. jejuni sialyltransferase (Cst-II), which functions in the biosynthesis of ganglioside-like LOSs, determines the transferase activity. Strains with cst-II (Thr51) express GM1 and GD1a epitopes, whereas GBS patients infected with cst-II (Thr51) strains have anti-GM1 or anti-GD1a IgG antibodies. The cst-II gene is responsible for the development of GBS. Immunological, pathological, electrophysiological, and bacteriological studies have provided strong evidence of carbohydrate mimicry being a cause of AMAN and clarified the mechanisms of nerve conduction failure in AMAN.     

Physiologic-pathologic correlation in Guillain-Barré syndrome in children

OBJECTIVE: To correlate electrophysiologic patterns with sural nerve pathology in children with Guillain-Barré syndrome (GBS). BACKGROUND: Based on electrophysiologic and pathologic observations, GBS has been divided into demyelinating and axonal subtypes. The acute motor axonal neuropathy (AMAN) involves predominantly motor nerve fibers with a physiologic pattern suggesting axonal damage, whereas the acute inflammatory demyelinating polyneuropathy (AIDP) involves both motor and sensory nerve fibers with a physiologic pattern suggesting demyelination. In this study, we sought to confirm these observations by correlating sural nerve pathology with electrophysiologic findings in GBS patients. METHODS: Biopsies of sural nerve from 29 of 50 prospectively studied GBS patients were obtained. Nerves were examined by light and electron microscopy, and with immunocytochemistry for macrophages, lymphocytes, and complement activation products. RESULTS: Sural nerves from AMAN patients were normal or had only a few (0.1% to 0.7%) degenerating fibers without lymphocytic infiltration or complement activation. One patient with reduced sural sensory nerve action potential classified as acute motor sensory axonal neuropathy (AMSAN) had many degenerating fibers (2.3%) in the sural nerve. All three AIDP patients displayed active demyelination, and in two patients, lymphocytic infiltration and complement activation products were observed on the abaxonal Schwann cell surface. CONCLUSION: Classification of Guillain-Barré syndrome subtypes based on motor conduction studies correlates closely with pathologic changes seen in sural nerve. In acute motor axonal neuropathy cases, the sural nerve is almost completely spared pathologically. In acute inflammatory demyelinating polyneuropathy cases, macrophage-mediated demyelination and lymphocytic infiltration are common in the biopsies of sural nerves.     

A pathological study of a peripheral nerve in a case of neonatal adrenoleukodystrophy

Summary The pathological findings for a sural nerve biopsy specimen in a case of neonatal adrenoleukodystrophy are described. The density and total number of myelinated fibers in the patient showed no significant changes compared with controls. On electric microscopy, however, thickness of the myelin was smaller in the patient than in controls. Some linear or trilamellar inclusion bodies were found in Schwann cells and fibroblasts, similar to those found in X-linked adrenoleukodystrophy. Büngner's bands were also seen on electron microscopy, and myelin ovoids and balls were seen in teased fibers. These results show that a sural nerve biopsy is useful for the diagnosis of neonatal adrenoleukodystrophy. We suspect that axonal or neuronal degeneration occurs with changes in myelin in neonatal adrenoleukodystrophy.     

An anti-ganglioside antibody-secreting hybridoma induces neuropathy in mice

Immune responses against gangliosides are strongly implicated in the pathogenesis of some variants of Guillain-Barré syndrome (GBS). For example, IgG antibodies against GM1, GD1a, and related gangliosides are frequently present in patients with post-Campylobacter acute motor axonal neuropathy (AMAN) variant of GBS, and immunization of rabbits with GM1 has produced a model of AMAN. However, the role of anti-ganglioside antibodies in GBS continues to be debated because of lack of a passive transfer model. We recently have raised several monoclonal IgG anti-ganglioside antibodies. We passively transfer these antibodies by intraperitoneal hybridoma implantation and by systemic administration of purified anti-ganglioside antibodies in mice. Approximately half the animals implanted with an intraperitoneal clone of anti-ganglioside antibody-secreting hybridoma developed a patchy, predominantly axonal neuropathy affecting a small proportion of nerve fibers. In contrast to hybridoma implantation, passive transfer with systemically administered anti-ganglioside antibodies did not cause nerve fiber degeneration despite high titre circulating antibodies. Blood-nerve barrier studies indicate that animals implanted with hybridoma had leaky blood-nerve barrier compared to mice that received systemically administered anti-ganglioside antibodies. Our findings suggest that in addition to circulating antibodies, factors such as antibody accessibility and nerve fiber resistance to antibody-mediated injury play a role in the development of neuropathy.     

Recessive hereditary sensory neuropathy.

Clinical features in 2 cases of a recessive form of hereditary sensory neuropathy and the light and electron microscopy of sural nerve biopsy in 1 of them are described. The patients showed symptoms typical of this form of the disease; it should be stressed however that the loss of cutaneous sensation appeared to be limited to the distal parts of the lower extremities and involved all modalities of cutaneous sensation. Histological examination of sural nerve revealed a marked reduction in the number of myelinated fibres due to Wallerian-like axonal degeneration, of which various stages were represented. In addition, segmental demyelination, probably secondary to axonal changes, was seen. The unmyelinated fibres were also involved but to a lesser degree than the myelinated fibres. The observations indicate a progressive nature of the pathological process.     

IDPN NEUROPATHY IN THE CAT: COEXISTENCE OF PROXIMAL AND DISTAL AXONAL SWELLINGS

Administration of beta,beta'-iminodipropionitrile (IDPN) to rodents has previously been shown to produce neurofilament-filled axonal swellings in the proximal regions of motor and sensory nerve fibers. Because of the distinctive distribution of these swellings, IDPN has been classed as a proximal axonopathy and thereby distinguished from other disorders in which similar axonal swellings occur in the distal parts of the axon (distal axonopathies). This report describes the pathology in the peripheral nerves of cats which received intermittent injections of IDPN and calls attention to two previously undescribed pathological changes. First, in addition to the typical proximal swellings associated with IDPN, these animals developed numerous axonal swellings within the distal branches of the sciatic nerve. Distal swellings were present as early as 23 days after initiation of intoxication, indicating that they formed locally (rather than developing in the proximal axon and undergoing transport into the distal regions). The second finding was Wallerian-like degeneration within the affected nerve branches. These changes in the distal sciatic nerve and its branches closely resembled the pathology of the distal axonopathies produced by agents such as the neurotoxic hexacarbons and carbon disulfide. The pathological similarities suggest that IDPN may share with these agents pathogenetic mechanisms to an extent not previously suspected.     

Quantitative, histological and ultrastructural studies of peripheral nerve in arteriosclerotic non-diabetic patients

The superficial peroneal nerve was taken from 12 arteriosclerotic non-diabetic patients just after amputation of a leg. Preparations of teased fibers were performed in 8 cases. Specimens were studied by light and electron microscopy in all cases. Histograms of myelinated fibers in transverse semi-thin sections showed that depletion of myelinated fibers varied from case to case, with no selective vulnerability in either the large or the small diameter group. There was a dramatic loss of myelinated fibers in only one case. No real nerve infarct was observed. In most cases, regions of Wallerian-like degeneration were prevalent; however, myelino-axonal changes were severe only in a few cases. Axons with organelle aggregates were seen in some cases. Figures of segmental demyelination were not numerous in this series. Unmyelinated fibers were also damaged, and the degree of involvement differed from case to case. Pathological changes observed in this study confirm the relative resistance of peripheral nerve to ischemia.