MOG-IgG在补体参与下介导脱髓鞘损伤体外模型的建立及应用

目的 通过建立髓鞘少突胶质细胞糖蛋白抗体相关疾病（MOGAD）体外脱髓鞘模型探讨MOGAD的发病机制并筛选疾病治疗药物。方法 采用基于转染细胞的亲和层析方法纯化患者来源的髓鞘少突胶质细胞糖蛋白自身抗体（MOG-IgG）。基于大鼠小脑切片和神经元-少突胶质细胞共培养的髓鞘模型,通过MOG-IgG和补体共同作用建立MOGAD体外脱髓鞘模型,将髓鞘碱性蛋白（MBP）的表达量及与神经微丝蛋白（NF）共定位情况作为评估髓鞘形成和损伤的指标。分析多发性硬化促髓鞘再生药物在该模型中的髓鞘修复作用。结果 应用转染细胞的亲和层析方法可获得高特异MOG-IgG。经抗体补体作用后,MOG-IgG组MBP表达水平降低（P = 0.003）,MBP-NF共定位程度降低（P < 0.001）。经药物作用后,氯马斯汀组和多潘立酮组MBP表达水平上升（P = 0.030,P = 0.001）,MBP-NF共定位程度增加（P均< 0.001）。结论 应用该法获得患者来源的高特异MOG-IgG在补体的参与下直接介导髓鞘损伤。氯马斯汀和多潘立酮在MOGAD体外脱髓鞘模型中能促进髓鞘再生。     

Restoration of conduction in the spinal roots correlates with clinical recovery from experimental autoimmune encephalomyelitis

In the Lewis rat, acute experimental autoimmune encephalomyelitis (EAE) induced by inoculation with myelin basic protein (MBP) and adjuvants is characterized by tail and hindlimb weakness that resolves spontaneously after several days. In rats with neurological signs of this form of EAE (MBP-EAE) we have previously demonstrated demyelination and nerve conduction block in the proximal peripheral nervous system (PNS) and in the central nervous system (CNS). The present study was performed to assess conduction in the PNS and CNS, after recovery from acute MBP-EAE, using direct recordings from surgically exposed spinal roots and spinal cord dorsal columns. The study revealed that 1–2 weeks after clinical recovery from tail paralysis there was almost complete restoration of conduction in the sacral spinal roots but persistent severe conduction abnormalities in the dorsal columns. Significant restoration of conduction through the dorsal columns occurred over the following 2 weeks. These findings indicate that PNS conduction block due to a demyelinating polyradiculitis is a major cause of the neurological signs of acute MBP-EAE in the Lewis rat.© 1995 John Wiley & Sons, Inc.     

Gelatinase B is present in the cerebrospinal fluid during experimental autoimmune encephalomyelitis and cleaves myelin basic protein

Gelatinases in inflammatory demyelinating diseases of the central nervous system (CNS) were studied using actively induced experimental autoimmune encephalomyelitis (EAE) in mice as a model system. Clinical disease scores correlated in time and in intensity with pathology parameters such as cytosis in the cerebrospinal fluid (CSF), inflammatory infiltrates, and demyelination in the CNS. Zymographic analysis was employed to measure gelatinases A and B in the CSF from individual animals. According to their apparent molecular weight (MW), gelatinases A and B appeared with a MW of 65 and 95 kDa, respectively. The 65 kDa form was present in all samples, even in those derived from non-induced animals, whereas the 95 kDa form was present only in samples from animals developing EAE. The levels of 95 and 65 kDa gelatinase correlated with the CSF cytosis. In vitro digestion of myelin basic protein (MBP) with gelatinase B and analysis of the cleavage products by protein sequence analysis pinpointed two cleavage sites in conserved regions of MBP. Gelatinase production within the CNS may constitute an important pathogenic mechanism for both the disruption of the blood-brain barrier and the destruction of myelin, as observed in several neuroinflammatory disorders. © 1993 Wiley-Liss, Inc.     

Homozygous hypertrophic hereditary motor and sensory neuropathies

We compared 25 autosomal dominant hereditary motor and sensory neuropathy (HMSN) type I patients with 7 subjects affected by hypertrophic HMSN with non-dominant inheritance. All the autosomal dominant HMSN I cases carried the chromosome 17p11.2 duplication, providing evidence that it is widely represented in HMSN I families. The second group included: Two siblings born to unrelated, unaffected parents and suffering from hypertrophic HMSN of strikingly different severity; two sisters with HMSN I phenotype, born to first-cousin unaffected parents; two brothers with HMSN III phenotype born to unrelated parents both showing HMSN II phenotype; a child with classic HMSN III phenotype, born to unrelated, unaffected parents. The 17p11.2 duplication was not found in any of the patients of the second series or in their parents. Our data provide further evidence that: HMSN III is heterogeneous and encompasses the homozygous expressions of different neuropathic genes; it is advisable to separate autosomal recessive hypertrophic HMSN from dominant HMSN Ia, because they appear to be due to different DNA mutations. DNA analyses were supported by grants from P.F. Biotecnologie CNR, Telethon, Murst 40% and 60%.     

Crucial Role for the Myelin-associated Glycoprotein in the Maintenance of Axon-Myelin Integrity

It has recently been shown that mice deficient in the gene for myelin-associated glycoprotein develop normal myelin sheaths in the peripheral nervous system. Here we report that in mutant mice older than 8 months the maintenance of axon-myelin units is disturbed, resulting in both axon and myelin degeneration. Morphological features include those typically seen in human peripheral neuropathies, where demyelination-induced Schwann cell proliferation and remyelination lead to the formation of so-called onion bulbs. Expression of tenascin-C, a molecule indicative of peripheral nerve degeneration, was up-regulated by axon-deprived Schwann cells and regenerating axons were occasionally seen. Myelin-associated glycoprotein thus appears to play a crucial role in the long-term maintenance of the integrity of both myelin and axons.     

The membrane attack complex of complement mediates peripheral nervous system demyelination in vitro

The present study used cocultures of rat dorsal root ganglia (DRG) and peritoneal macrophages to define the role of activated complement components during demyelination. The complement cascade was activated in vitro by treatment of the cultures with natural rat serum and lipopolysaccharides. Complement activation was examined by detection of the membrane attack complex of complement (MAC) with an antibody directed against rat C5–9. Detection of MAC in vitro by immunoelectron microscopy was associated with morphological changes of the myelin sheath. The sheath's regular structure was disrupted. Myelin lamellae were split and showed signs of decompaction. These changes were followed by a selective macrophage attack on myelin sheaths resulting in demyelination. Schwann cell viability was not affected by complement activation. Axons and sensory ganglion cells also survived this attack. The specificity of the complement effect was tested in experiments using treatment regimens with natural rat serum or lipopolysaccharides alone. In these experiments, no morphological changes of the myelin sheath were observed as well as no macrophage attack on myelin.     

Osmotic demyelination syndrome with a dysequilibrium syndrome: reversible MRI findings

Abstract Neurological disorders may be seen in end-stage renal disease patients due to uraemia or to complications of dialysis. A dysequilibrium syndrome may be seen, usually soon after or towards the end of haemodialysis. This group of patients has no particular findings on MRI. On the other hand, the osmotic demyelination syndrome has definitive MRI findings, not to date reported with the dysequilibrium syndrome. We report a patient with end-stage renal disease and the dysequilibrium syndrome who showed findings of osmotic demyelination on MRI. The patient had a convulsion after a first haemodialysis, with quadriparesis and hyperactive deep tendon reflexes and bilateral Babinski signs. The upper motor neurone signs lasted for a week. Meanwhile, he was also dysarthric and had dysphagia. He recovered neurologically without any residuum following appropriate treatment and there was improvement on MRI. Received: 25 March 1997 Accepted: 17 September 1997     

KINKY HAIR SYNDROME

Abstract. Møllekær, A. M. (Department of Paediatrics and the Department of Neuropathology, århus University School of Medicine, århus, Denmark). Kinky Hair Syndrome. Acta Paediat Scand, 63289, 1974.–Two brothers with Kinky Hair Syndrome are described. Both of them had hypothermia. In the younger boy low levels of serum copper and ceruloplasrnin were demonstrated. At autopsy the most surprising finding was a demyelinating process in the brain. The fact that the younger boy showed signs of Kinky Hair syndrome at birth makes it difficult to accept an 'intestinal malabsorption of copper as the only underlying defect in the disease.     

Establishment and characterization of a mouse Schwann cell line which produces myelin in vivo.

A Schwann cell line (MSC 80) was established from purified mouse Schwann cell cultures using large doses of serum. MSC 80 cell line is an aneuploid cell line which has a doubling time of 17 hr and has been maintained through more than 110 passages. Most of MSC 80 cells are of bipolar or stellate (3-5 processes) shape. A few others are irregular in shape, gigantic, and multinucleated. All MSC 80 cells express antigens of myelin-forming Schwann cells such as S-100, 224/58, laminin, and other glycoproteins of the extracellular matrix. However, they also express the non-myelin-forming Schwann cell antigen GFAP. By time-lapse cinematography, MSC 80 cells exhibit the Schwann cell characteristic rhythmical undulations. When induced to form aggregates in agar, they form intercellular junctions and basement membrane-like structures. In addition, after transplantation in or at a distance from a lysolecithin induced lesion, MSC 80 cells form myelin around the host demyelinated axons. MSC 80 cells thus express, when isolated in vitro, some of the normal myelin-forming Schwann cell phenotype. In addition, they present the major advantage of forming myelin when associated with axons in vivo.     

Acute polyradiculoneuritis associated with demyelinated plaques in the central nervous system: Report of a case

Summary A report is given of a woman who developed acute idiopathic polyradiculoneuritis and was found at necropsy 9 weeks later to have in addition multiple recent demyelinated lesions in the central nervous system (CNS), resembling those of multiple sclerosis (MS). The possibility that in such a case there might be an immunological reaction against one or more components of myelin common to the CNS and PNS has to be considered.