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ABSTRACT Objectives: To evaluate the functional and immunohistochemical effects of ganglioside GM1 and erythropoietin following experimental spinal cord injury. Methods: Thirty-two male BALB/c mice were subjected to experimental spinal cord injury using the NYU Impactor device and were randomly divided into the following groups: GM1 group, receiving standard ganglioside GM1 (30 mg/kg); erythropoietin group, receiving erythropoietin (1000 IU/kg); combination group, receiving both drugs; and control group, receiving saline (0.9%). Animals were evaluated according to the Basso Mouse Scale (BMS) and Hindlimb Mouse Function Score (MFS). After euthanasia, the immunohistochemistry of the medullary tissue of mice was analyzed. All animals received intraperitoneal treatment. Results: The GM1 group had higher BMS and MFS scores at the end of the experiment when compared to all other groups. The combination group had higher BMS and MFS scores than the erythropoietin and control groups. The erythropoietin group had higher BMS and MFS scores than the control group. Immunohistochemical tissue analysis showed a significant difference among groups. There was a significant increase in myelinated axons and in the myelinated axon length in the erythropoietin group when compared to the other intervention groups (p < 0.01). Conclusion: Erythropoietin and GM1 have therapeutic effects on axonal regeneration in mice subjected to experimental spinal cord injury, and administration of GM1 alone had the highest scores on the BMS and MFS scales.
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After De’s pivotal demonstration in 1959 of a diarrhoeogenic exo-enterotoxin in cell-free culture filtrates from Vibrio cholerae (of classical biotype), much insight has been gained about cholera toxin (CT), which is arguably now the best known of all microbial toxins. The subunit structure and function of CT, its receptor (the GM1 ganglioside), and its effects on the cyclic AMP system and on intestinal secretion were defined in the 1970s, and the essential aspects of the genetic organization in the 1980s. Recent findings have generated additional perspectives. The 3D-crystal structure of CT has been established, the CT-encoding operon has been shown to be carried by a non-lytic bacteriophage, and in depth knowledge has been gained on how the bacterium controls CT gene expression in response to cell density and various environmental signals. The mode of entry into target cells and the intracellular transport of CT are becoming clearer. CT has become the prototype enterotoxin and a widely used tool for elucidating important aspects of cell biology and physiology, e.g., cell membrane receptors, the cyclic AMP system, G proteins, as well as normal and pathological ion transport mechanisms. In immunology, CT has emerged as a potent, widely used experimental adjuvant, and the strong oral-mucosal immunogenicity of the non-toxic B-subunit (CTB) has led to the use of CTB as a protective antigen together with killed vibrios in a widely licensed oral cholera vaccine. CTB has also been shown to promote immunological tolerance against certain types of mucosally co-administered antigens, preferably tissue antigens linked to the CTB molecule; this has stimulated research and development to use CTB in this context for treatment of autoimmune and allergic diseases. In summary, in the 50 years after De’s discovery of CT, this molecule has emerged from being the cholera patient’s “foe” to also becoming a highly useful scientist’s “friend”.
Subject(s)
Cholera Toxin/chemistry , Cholera Toxin/genetics , Cholera Toxin/metabolism , Cholera Vaccines/immunology , Humans , Immunity, Mucosal/immunology , Models, Molecular , Protein Conformation , Protein Subunits/chemistry , Protein Subunits/genetics , Vibrio cholerae/chemistry , Vibrio cholerae/pathogenicityABSTRACT
ObjectiveTo investigate the curative effect of neural stem cells (NSCs) transplantation combined with monosialotetrahexosyl ganglioside (GMi) in treatment of acute spinal cord injury in rats.MethodsCompressive spinal cord injury model at T8 segment was established in the adult SD rats that were then randomly divided into three groups, ie, control group, NSCs transplantation group and NSCs + GM1 group.Continuous observation was performed at 1,2, 4 and 8 weeks.Functional neurological recovery of the injured spinal cord was evaluated with motor function scale, pathology, transmission electron microscopy and somatosensory evoked potential (SEP).ResultsThe motor function of the lower extremities was recovered at different degrees in three groups.While the motor function recovery level of the animals and the positive staining cells of the calcitonin gene-related peptide (CGRP) in the NSCs + GM1 group were higher than those in the other two groups at 4 and 8 weeks (P ＜ 0.01).Compared with control group and NSCs group, focal necrosis and small vessel regeneration were observed only in the center of the injured segment in the NSCs + GM1 group at 8 weeks.Electron microscope scan showed edema under the membrane of the large myelin sheath in the control group, much intact myelin sheath, well-differentiated neurons and many kinds of synapse vesicles in the NSCs + GM1 group.The latent period of SEP was shortened markedly in the NSCs + GM1 group two weeks after transplantation (P ＜0.05).The latent period shortening was apparent in the NSCs group at 4 and 8 weeks after transplantation but was still longer than that in the control group.ConclusionsTransplantation of neural stem cells combined with use of GM1 can protect the nervous tissues after spinal cord injury, when GM1 reconstructs the spinal cord through promoting differentiation of the transplanted stem cells and linking with the host cells.
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O objetivo deste trabalho foi avaliar os efeitos do monossialogangliosídio (GM1), da câmara de oxigenoterapia hiperbárica e de ambos no tratamento da lesão medular experimental em ratos. Trinta e dois ratos Wistar com lesão medular foram divididos em 4 grupos: um grupo recebeu o monossialogangliosídio (GM1), um segundo foi submetido à oxigenoterapia hiperbárica, um terceiro recebeu os dois tratamentos e um quarto não recebeu tratamento (controle). Não houve diferença significativa entre os grupos na análise histológica, em todas as variáveis (necrose, hemorragia, hiperemia e degeneração cística, p>0,06). Também não houve nenhuma diferença na comparação entre os lados direito e esquerdo nos testes funcionais (p>0,06 para todos). Não foram encontradas diferenças nos testes motores, na comparação entre os grupos após 2, 7 21 e 28 dias de lesão medular. Mas, na avaliação após 14 dias, o Grupo 3, o qual recebeu a terapia combinada, mostrou um escore BBB significantemente maior que os outros grupos (p=0,015). Na avaliação de 28 dias, houve uma tendência dos Grupos 1 (GM1) e 3 (terapia combinada) apresentarem um escore BBB maior que o do Grupo 4 (controle), embora sem significância estatística (p=0,057). Concluiu-se que, quanto aos índices motores, a utilização do GM-1 tem efeito benéfico, embora sem diferença estatisticamente significante e que o efeito benéfico do GM-1 é antecipado através da utilização concomitante da oxigênio terapia hiperbárica.
The objectives were to evaluate the effect of GM1 ganglioside, hyperbaric oxygen, and both in combination, in the treatment of experimental spinal cord lesions in rats. Thirty-two Wistar rats with spinal cord lesions were divided into four groups: one group received GM1 ganglioside, one was submitted to hyperbaric oxygen therapy, the third received both treatments, and the fourth received no treatment (control). There were no significant differences between the groups in the histological analysis, for any of the variables (necrosis, hemorrhage, hyperemia, cystic degeneration, p > 0.06). Neither were there any significant differences in the comparison of left and right sides in the functional tests (p > 0.06 for all). No significant differences were found in the locomotor ratings, in the comparison of groups at 2 days, 7 days, 21 days and 28 days after the surgical procedure. However, in the evaluation on day 14, Group 3, which received the combined therapy, showed a significantly higher BBB score than the other groups (p = 0.015). In the evaluation on day 28, there was a trend to Group 1 (GM1) and 3 (combined therapy) showed a higher BBB score than the group 4 (control), but with no significance (p=0,057). In conclusion, the is a benefit in the use of GM1 ganglioside, but with no significance and the therapeutic effect of GM1 in locomotor evaluation of rats submitted to spinal cord lesion is anticipated by hyperbaric oxygen therapy.
Subject(s)
Animals , Guinea Pigs , Rats , G(M1) Ganglioside , Oxygen Inhalation Therapy , Rats, Wistar , Spinal Cord InjuriesABSTRACT
@#ObjectiveTo evaluate the safety and efficacy of GM1 ganglioside treatment for persons with Parkinson's disease.Methods33 Parkinson's disease patients with a fluctuating response to levodopa received 100 mg GM1 ganglioside (used as add-on agent to the previous medication regimen) daily. Unified Parkinson's disease Rating scale (UPDRS) motor score and Activities of Daily Living (ADL) score were measure before and 2, 3 or 4 weeks after treatment. The side-effect of GM1 during treatment were observed. ResultsAfter 2, 3, 4 weeks of treatment, There was significant improvement in patients with GM1 treament on the UPDRS motor scores were (23.5±8.9), (22.8±8.3) and (22.5±9.1) respectively, which was improved compared with that before (36.7±10.2) (P<0.01). The ADL portion of the UPDRS at these time were (21.4±10.9), (20.3±9.5) and (20.6±10.2) respectively, also showed significant improvement compared with the baseline (30.5±12.1) (P<0.01). However, there was no significant differece between the scores that measured at the time spots 2 weeks after treatment.No side-effect had been observed.ConclusionGM1 ganglioside can improve neurologic function significantly in PD patients with fluctuating response to levodopa.
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@#ObjectiveTo evaluate the safety and efficacy of GM1 ganglioside treatment for persons with Parkinson's disease.Methods33 Parkinson's disease patients with a fluctuating response to levodopa received 100 mg GM1 ganglioside (used as add-on agent to the previous medication regimen) daily. Unified Parkinson's disease Rating scale (UPDRS) motor score and Activities of Daily Living (ADL) score were measure before and 2, 3 or 4 weeks after treatment. The side-effect of GM1 during treatment were observed. ResultsAfter 2, 3, 4 weeks of treatment, There was significant improvement in patients with GM1 treament on the UPDRS motor scores were (23.5±8.9), (22.8±8.3) and (22.5±9.1) respectively, which was improved compared with that before (36.7±10.2) (P<0.01). The ADL portion of the UPDRS at these time were (21.4±10.9), (20.3±9.5) and (20.6±10.2) respectively, also showed significant improvement compared with the baseline (30.5±12.1) (P<0.01). However, there was no significant differece between the scores that measured at the time spots 2 weeks after treatment.No side-effect had been observed.ConclusionGM1 ganglioside can improve neurologic function significantly in PD patients with fluctuating response to levodopa.
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OBJECTIVE:To investigate the anti-apoptosis effect and the mechanism of GM 1 ganglioside on nerve cell af?ter the spinal cord injury.METHODS:The rats with compressed injury at the T8.9level of spinal cord were employed as the model.Then the rats were divided into two groups at random,one for the control and one for GMI treatment.The rats in each group were administrated normal saline solution(20?l)and GM 1 (30?g,20?l)intrathecally10minutes after injury,respective?ly.The apoptosis of nerve cells in the injured spinal cord were examined by TUNEL and flow cytometry with nerve cells labeled with Annexin V/PI;and Caspase3activity was measured by fluorometric immunosorbent enzyme assay.RESULTS:The apoptotic cells appeared in both groups at4h and reached their peak on3rd day after the injury.The proportion of apoptotic cells and the intracelluar Caspase3activity in the GM 1 treated group were significant lower than those in the control group(P