Evaluation of the effect of intrathecal GM1 in 24, 48, and 72 hours after acute spinal cord injury in rats

Abstract Objective The aim of this study was to evaluate the best timing and feasibility of intrathecal application of sodium monosialoganglioside (GM1) after spinal cord contusion in Wistar rats as an experimental model. Methods Forty Wistar rats were submitted to contusion spinal cord injury after laminectomy. The animals were randomized and divided into four groups: Group 1 - Intrathecal application of GM1 24 hours after contusion; Group 2 - Intrathecal application of GM1 48 hours after contusion; Group 3 - intrathecal application of GM1 72 hours after contusion; Group 4 - Sham, with laminectomy and intrathecal application of 0.5 mL of 0.9% saline solution, without contusion. The recovery of locomotor function was evaluated at seven different moments by the Basso, Beattie, and Bresnahan (BBB) test. They were also assessed by the horizontal ladder, with sensory-motor behavioral assessment criteria, pre-and postoperatively. Results This experimental study showed better functional scores in the group submitted to the application of GM1, with statistically significant results, showing a mean increase when evaluated on known motor tests like the horizontal ladder and BBB, at all times of evaluation (p < 0.05), especially in group 2 (48 hours after spinal cord injury). Also, fewer mistakes and slips over the horizontal ladder were observed, and many points were achieved at the BBB scale analysis. Conclusion The study demonstrated that the intrathecal application of GM1 after spinal cord contusion in Wistar rats is feasible. The application 48 hours after the injury presented the best functional results.

Clinical and CLB1 gene mutations analysis of GM1 gangliosidosis in a patient / 中华神经科杂志

Objective@#To investigate the clinical and CLB1 gene mutation characteristics of GM1 gangliosidosis patient.@*Methods@#The clinical data of one GM1 gangliosidosis patient from Children′s Hospital Affiliated to Zhengzhou University in March 2018 were reviewed and analyzed. The patient was diagnosed by gene detection and enzymatic activity.@*Results@#The patient is a 4 years and 1 month old boy, mainly presented psychomotor retrogression. His β-galactosidase activity was low (8.0 nmol·g-1·min-1). Two splice site mutations (c.458-2A(IVS4)>G and c.1068+5G(IVS10)>A) of patient′s CLB1 gene were screened by targeted next generation sequencing. The results of Sanger sequencing showed that the mutations are compound heterozygous and both are first reported. The mutation c.1068+5G(IVS10)>A was derived from patient′s mother, and the other one is de nove.@*Conclusion@#GM1 gangliosidosis is a rare neurodegenerative disease, which could be accurately diagnosed by the next generation sequencing and enzyme assay.

Clinical and CLB1 gene mutations analysis of GM1 gangliosidosis in a patient / 中华神经科杂志

Objective To investigate the clinical and CLB1 gene mutation characteristics of GM1 gangliosidosis patient. Methods The clinical data of one GM1 gangliosidosis patient from Children′s Hospital Affiliated to Zhengzhou University in March 2018 were reviewed and analyzed. The patient was diagnosed by gene detection and enzymatic activity. Results The patient is a 4 years and 1 month old boy, mainly presented psychomotor retrogression. His β?galactosidase activity was low (8.0 nmol·g-1·min-1). Two splice site mutations (c.458?2A(IVS4)>G and c.1068+5G(IVS10)>A) of patient′s CLB1 gene were screened by targeted next generation sequencing. The results of Sanger sequencing showed that the mutations are compound heterozygous and both are first reported. The mutation c.1068+5G(IVS10)>A was derived from patient′s mother, and the other one is de nove. Conclusion GM1 gangliosidosis is a rare neurodegenerative disease, which could be accurately diagnosed by the next generation sequencing and enzyme assay.

Study on the absorption of monosialotetrahexosylganglioside sodium in rats with in situ cycle intestinal perfusion methods / 中国医师杂志

Objective To investigate the duodenum absorptive character of monosialotetrahexosylganglioside sodium (GM1) in rats.Methods The contents of phenolsulfonphthalein (as indicators) and GM1 were determined with ultraviolet-visible (UV) method and high performance liquid chromatography (HPLC) method in rats with in situ cycle intestinal perfusion model.Results The ratio of duodenum absorption of GM1 was 10％ in 2 h after cycle and 22％ in 6 h after cycle,respectively.The Ka was (0.030± 0.012)h,and absorption t1/2 was (25.50 ± 8.56)h in 8 h after cycle.Conclusions GM1 is absorption in rat duodenum,and the accumulate absorption of GM1 is almost linearly related to the cycle time.The absorption dynamics of GM1 may be first-order kinetic process.

The effect of monosialoganglyoside (GM-1) administration in spinal cord injury / Efeito da administração do monosialogangliosídeo (GM-1) no trauma raquimedular

Objetivo: Avaliar o efeito do uso de monosialogangliosídeo (GM-1) nospacientes vítimas de trauma raquimedular atendidos em nosso serviço que não foram tratados com metilprednisolona. Métodos: Trinta pacientes vítimas de trauma raquimedular agudo foram divididos randomicamente em dois grupos. No Grupo 1, os pacientes receberam200 mg de GM-1 no atendimento inicial e a partir daí receberam 100mg endovenoso por dia durante 30 dias e o Grupo 2 (controle) recebeu soro fisiológico. Os pacientes foram avaliados periodicamente(com 6 semanas, 6 meses, um ano e 2 anos), utilizando-se a padronização de avaliação neurológica da American Spinal Injuty Association/International Spinal Cord Society. Resultados: A análise estatística comparativa dos índices motores, sensitivo para dor e sensitivo paratato de acordo com a padronização da ASIA/ISCOS mostrou que nas avaliações com 6 semanas, 6 meses e 2 anos os pacientes do Grupo GM-1 apresentaram índices superiores em relação ao grupo controle em relação a sensibilidade para dor e tato, não havendo diferença estatisticamente significativa em relação ao índice motor. Conclusão: A avaliação funcional demonstrou melhora nos índices sensitivos dos pacientes tratados com GM1 após lesão medularpós-traumática em relação aos pacientes que receberam placebo.Nível de Evidência IV, Estudo Prospectivo de Série de Casos.

Objective: To evaluate the effect of monosialoganglioside (GM-1)in spinal cord trauma patients seen in our service who have notbeen treated with methylprednisolone. Methods: Thirty patientswith acute spinal cord trauma were randomly divided into twogroups. In Group 1, patients received 200 mg GM-1 in the initialassessment and thereafter received 100 mg intravenous per dayfor 30 days and Group 2 (control) received saline. Patients wereevaluated periodically (at 6 weeks, 6 months, one year and twoyears), using a standardized neurological assessment of theAmerican Spinal Injury Association / International Spinal CordSociety. Results: The comparative statistical analysis of motorindices, sensitive indices for pain and touch according to thestandardization of ASIA / ISCOS showed that the assessmentsat 6 weeks, 6 months and 2 years, GM-Group 1 patients hadhigher rates than the control group regarding sensitivity to painand touch, with no statistically significant difference from themotor index. Conclusion: The functional assessment showedimprovement in the sensitive indices of patients treated withGM1 after post-traumatic spinal cord injury compared to patientswho received placebo. Level of Evidence IV, Prospective CaseStudies Series.

The role of pharmacotherapy in modifying the neurological status of patients with spinal and spinal cord injuries / O papel da farmacoterapia na modificação do estado neurológico de traumatizados vértebro-medulares

The aim here was to conduct a review of the literature on pharmacological therapies for modifying the neurological status of patients with spinal cord injuries. The PubMed database was searched for articles with the terms "spinal cord injury AND methylprednisolone/GM1/apoptosis inhibitor/calpain inhibitor/naloxone/tempol/tirilazad", in Portuguese or in English, published over the last five years. Older studies were included because of their historical importance. The pharmacological groups were divided according to their capacity to interfere with the physiopathological mechanisms of secondary injuries. Use of methylprednisolone needs to be carefully weighed up: other anti-inflammatory agents have shown benefits in humans or in animals. GM1 does not seem to have greater efficacy than methylprednisolone, but longer-term studies are needed. Many inhibitors of apoptosis have shown benefits inin vitro studies or in animals. Naloxone has not shown benefits. Tempol inhibits the main consequences of oxidation at the level of the spinal cord and other antioxidant drugs seem to have an effect superior to that of methylprednisolone. There is an urgent need to find new treatments that improve the neurological status of patients with spinal cord injuries. The benefits from treatment with methylprednisolone have been questioned, with concerns regarding its safety. Other drugs have been studied, and some of these may provide promising alternatives. Additional studies are needed in order to reach conclusions regarding the benefits of these agents in clinical practice.

O objetivo deste trabalho foi fazer uma revisão da literatura sobre a terapia farmacológica para a modificação do estado neurológico de traumatizados vértebro-medulares. Foi feita uma na base de dados Pubmed por artigos com os termos "spinal cord injury AND methylprednisolone/GM1/apoptosis inhibitor/calpain inhibitor/naloxone/tempol/tirilazad", em português ou em inglês, publicados nos últimos cinco anos. Trabalhos mais antigos foram incluídos pela sua importância histórica. Os grupos farmacológicos foram divididos em função da sua capacidade para interferir nos mecanismos fisiopatológicos da lesão secundária. O uso de metilprednisolona deve ser cuidadosamente ponderado. Outros anti-inflamatórios mostraram benefícios em humanos ou em animais. O GM1 não aparenta ter maior eficácia do que a MP, mas estudos em mais longo prazo são necessários. Muitos inibidores da apoptose têm mostrado benefício em estudos in vitro ou em animais. A naloxona não deu mostras de benefício. O tempol inibe as principais consequências da oxidação no nível da medula e outros fármacos antioxidantes aparentam ter um efeito superior ao da metilprednisolona. É urgente encontrar novos tratamentos que melhorem o estado neurológico dos traumatizados vértebro-medulares. Os benefícios do tratamento com metilprednisolona têm sido questionados, há preocupações em relação à sua segurança. Outros fármacos têm sido estudados, podem alguns deles ser opções promissoras. Estudos adicionais são necessários para tirar conclusões sobre o benefício desses agentes na prática clínica.

Effectof monosialoganglioside on hippocampal Akt/GSK-3β signaling pathway in rats undergoing cardiopulmonary bypass / 中华麻醉学杂志

Objective To evaluate the effect of monosialoganglioside (GM-1) on hippocampal protein kinase B (Akt) /glycogen synthase kinase 3β (GSK-3β) signaling pathway in the rats undergoing cardiopulmonary bypass (CPB).Methods Eighteen healthy male Sprague-Dawley rats, aged 6 months, weighing 400-500 g, were randomly divided into 3 groups (n =6 each) using a random number table:control group (group C), CPB group and GM-1 group.GM-1 20 mg/kg was added to the priming solution in group GM-1, while the equal volume of normal saline was given in group CPB.At 3 h after termination of CPB, blood samples were taken from the jugular vein for determination of plasma neuron-specific enolase (NSE) and S-100β protein concentrations using enzyme-linked immunosorbent assay.After blood sampling, the rats were sacrificed, and the hippocampi were isolated for microscopic examination of the ultrastructure of the hippocampal neurons (with electron microscope), and for detection of neuronal apoptosis (with light microscope) and phosphorylation of Akt and GSK-3β (by Western blot).Results Compared with group C, the concentrations of plasma NSE and S-100β protein, and the number of apoptotic neurons were significantly increased in CPB and GM-1 groups, the phosphorylation of Akt and GSK-3β was decreased in group CPB, and the phosphorylation of Akt and GSK-3β was increased in group GM-1 (P＜0.05).Compared with group CPB, the concentrations of plasma NSE and S-100β protein, and the number of apoptotic neurons were significantly decreased, the phosphorylation of Akt and GSK-3β was increased (P＜0.05), and the pathological changes were reduced in group GM-1.Conclusion GM-1 can reduce apoptosis in hippocampal neurons through activating Akt/GSK-3β signaling pathway, thus mitigating CPB-induced brain injury in rats.

Monossialogangliosídeo transdérmico com laser no tratamento de lesão medular espinal de ratos / Transdermal monosialoganglioside with laser in the treatment of spinal cord lesion in rats

Objetivos: Avaliar os efeitos de monossialogangliosídeos (GM1) administrados com laser por via transdérmica na recuperação da lesão da medula espinal de ratos. Métodos: Quarenta ratos Wistar machos foram submetidos a contusão da medula espinal usando NYU Impactor. No Grupo 1, os ratos receberam 0,2 ml de solução salina diária por via intraperitoneal; no Grupo 2, GM1 foi administrada intraperitonealmente em concentração de 30 mg/kg por dia; no Grupo 3, os ratos foram tratados diariamente com o laser a baixa temperatura sobre a pele, e no Grupo 4, a sessão de laser diária também continha GM1. Todos os grupos foram tratados durante 42 dias. Os animais foram avaliados pela escala funcional de Basso, Baettie e Bresnahan (BBB) nos dias 7, 14, 21, 28, 35 e 42 após a lesão, e por histopatologia e potencial motor evocado 42 dias depois da lesão. Resultados: Os animais do Grupo 4 apresentaram escores BBB mais elevados em comparação com os outros grupos. Não houve diferenças entre os grupos ou nas comparações ao longo do tempo. A avaliação histológica não mostrou diferenças, e tampouco foram encontradas diferenças significativas no potencial evocado. Conclusão: A GM1 associada ao uso de laser a baixa temperatura não mostra resultados superiores no tratamento de lesões da medula espinal de ratos. Nível de Evidência I, Experimental, Estudo Controlado de Animais.

Objectives: To evaluate the effects of monosialoganglioside (gm1) administered transdermally with laser in the recovery of spinal cord injury in rats. methods: forty male wistar rats underwent spinal cord contusion using the nyu impactor. in group 1, the rats received 0,2 ml of saline intraperitoneally daily; in group 2, GM1 was administered intraperitoneally at a concentration of 30 mg/kg per day; in group 3, rats were treated daily with laser at low temperature on the skin, and in group 4, the daily laser session also contained gm1. all the groups were treated for 42 days. the animals were evaluated by the Basso, Baettie and Bresnahan (BBB) functional scale on days 7, 14, 21, 28, 35 and 42 after the injury, and by histopathology and motor evoked potential after 42 days of injury. Results: the animals in group 4 had higher BBB scores compared with the other groups. there were no differences between the groups, or in the comparisons over time. Histological evaluation showed no differences, and no differences were found in the motor evoked potential tests either. conclusion: gm1 associated with the use of low-temperature laser shows no superior functional, neurological or histological results in the treatment of spinal cord lesions in rats. Evidence Level I, Experimental, Controlled, Animal Study.

Effects of Monosialoganglioside on the Expression of Fas in Hippocampus of Cerebral Ischemia-Reperfusion Rats / 天津医药

0bjective To study the expression of Fas in hippocampus of cerebral ischemia-reperfusion rats after treatment with monosialoganglioside (GM1). Methods Seventy-two SD rats were randomly divided into sham group (n=8), GM1 treatment group (n=32) and ischemia-reperfusion (I/R) group (n=32). According to the different time points (6 h, 12 h, 24 h and 3 d) of I/R, there were four subgroups in GM1 and I/R groups respectively. The expression of Fas in hippocampus was examined by immunochemistry and Western blot methods in all groups. Results Results of immunochemistry method showed that there was a little expression of Fas (the mean optical density was 0.17±0.02) in hippocampus of sham group, and the positive expression of Fas at different time points were increased significantly after reperfusion. The mean values of opti-cal density at different time points were 0.42±0.11, 0.51±0.13, 0.55±0.13 and 0.62±0.15 in I/R group, which reached to the peak at 3 d . The positive expression of Fas at different time points were significantly decreased in GM1 group (0.29 ± 0.09, 0.34±0.11, 0.37±0.12 and 0.43±0.12) than that of I/R group (P＜0.05). Conclusion Monosialoganglioside participated in the pathogenesis of cerebral ischemia-reperfusion injury by down-regulating the expression of Fas.

Efficacy of intrathecally administered monosialoganglioside for treatment of bupivacaine spinal anesthesia-induced neurotoxicity to rat spinal cord / 中华麻醉学杂志

Objective To evaluate the efficacy of intrathecally administered monosialoganglioside (GM-1)for treatment of bupivacaine spinal anesthesia-induced neurotoxicity to rat spinal cord.Methods Adult male Sprague-Dawley rats,weighing 280-300 g,in which the intrathecal catheter was successfully inserted into the L3,4 intervertebral space and advanced toward the tail,were randomly divided into 4 groups (n =36 each):sham operation group (group S),GM-1 group,bupivacaine group (group B) and bupivacaine + GM-1 group (group BG).In B and BG groups,the rats received 5％ bupivacaine 20 μl via the intrathecal catheter 3 times at 1.5-hour intervals.GM-1 20 μg was injected intrathecally 24 h later once a day for 7 days in BG and GM-1 groups.Before bupivacaine injection and on days 1,3,5,7,14 and 28 after bupivacaine injection (T0-T6),tail flick latency (TFL) was measured,MPE (percentage of maximal possible effect) was calculated,and the locomotor recovery was evaluated using the Basso,Beattie,Bresnahan (BBB) Locomotor Rating Scale.Then six rats were randomly chosen and sacrificed in each group.Spinal cord was removed for histopathologic examination (with light and electronic microscope) and for determination of caspase-3 protein and mRNA expression (by immuno-histochemistry and RTPCR).The pathological changes of the spinal cord were scored.Results Compared with S and GM-1 groups,MPE,pathological scores,and caspase-3 protein and mRNA expression were significantly increased and BBB score was decreased at T1-6 in group B (P ＜ 0.05),and MPE was increased at T1-5 (P ＜ 0.05) and returned to the baseline value at T6 (P ＞ 0.05) and pathological scores,and caspase-3 protein and mRNA expression were significantly increased and BBB score was decreased at T1-6 in group BG (P ＜ 0.05).There were no significant differences in each parameter at each time point between S and GM-1 groups (P ＞ 0.05).Compared with group B,MPE and caspase-3 protein and mRNA expression were significantly decreased at T2-6,pathological scores were decreased at T3-6,and BBB score was increased at T4-6 in group BG (P ＜ 0.05).The pathological changes of spinal cord tissues were obvious at T1-6 in group B and at T1-3 in group BG,but the changes gradually recovered at T4-6 in group BG.Conclusion Intrathecally administered GM-1 has therapeutic effect against bupivacaine spinal anesthesia-induced neurotoxicity to rat spinal cord,and inhibition of neuronal apoptosis in the spinal cord may be involved in the underlying mechanism.

Effect of monosialoganglioside GM1 on cardiopulmonary bypass-induced inflammatory response in rats / 中华麻醉学杂志

Objective To investigate the effect of monosialoganglioside GM1 on cardiopulmonary bypass (CPB)-induced inflammatory response in rats.Methods Twenty-four adult male Sprague-Dawley rats,weighing 350-450 g,were randomly divided into 3 groups (n =8 each):sham operation group (group S),group CPB and CPB + GMi group (group G).GM1 20 mg/kg was added to the priming solution in group G.While the equal volume of normal saline was given in group CPB.Blood samples were collected from the jugular vein at 3 h after termination of CPB for determination of plasma concentrations of neuron-specific enolase (NSE) and S-100β protein (by ELISA) and tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) (by radioimmunoassay).The hippocampi were isolated to detect the expression of hippocampal matrix metalloproteinase-9 (MMP-9) and IL-10 and NF-κB activity in hippocampal tissues by Western blot.Results Compared with group S,the plasma concentrations of NSE,S-100β protein,TNF-α and IL-6 and NF-κB activity were significantly increased,the expression of MMP-9 was up-regulated,and the expression of IL-10 was down-regulated in groups CPB and G (P ＜ 0.05).Compared with group CPB,the plasma concentrations of NSE,S-100β protein,TNF-α and IL-6 and NF-κB activity were significantly decreased,the expression of MMP-9 was down-regulated,and the expression of IL-10 was upregulated in group G (P ＜ 0.05).Conclusion The mechanism by which GM1 reduces the CPB-induced brain damage may be related to reduction of the central and systemic inflammatory response in rats.

Effect of monosialoganglioside GM-1 on cardiopulmonary bypass-induced brain injury in rats / 中华麻醉学杂志

Objective To investigate the effect of monosialoganglioside GM-1 on cardiopulmonary bypass (CPB)-induced brain injury in rats.Methods Twenty-seven adult male Sprague-Dawley rats,weighing 350-450 g,aged 15 months,were randomly divided into 3 groups (n=9 each): control group (C group),CPB group and GM-1 group.The animals were anesthetized with chloral hydrate,tracheostomized and mechanically ventilated.Right common carotid and right jugular vein were cannulated for closed-chest CPB.In groups CPB and GM-1,the rats underwent 1 h CPB.GM-1 20 mg/kg was added to the priming solution in group GM-1,while the equal volume of normal saline was given in group CPB.The animals were sacrificed at 3 h after termination of CPB or 3 h after the end of ventilation in group C,the brains were removed and the hippocampi isolated for microscopic examination and for determination of apoptosis (using TUNEL) and Bax and Bcl-2 protein expression (by immunohistochemistry and Western blot).Results Compared with group C,the number of apoptotic neurons and ratio of Bax/Bcl-2 were significantly increased,and the expression of Bcl-2 and Bax protein was up-regulated in groups CPB and GM-1 (P ＜ 0.05).Compared with group CPB,the number of apoptotic neurons and ratio of Bax/Bcl-2 were significantly decreased,the expression of Bax protein was down-regulated and the expression of Bcl-2 protein was up-regulated in group GM-1.The pathological changes were severe in group CPB and attenuated in group GM-1.Conclusion GM-1 can attenuate CPB-induced brain injury in rats and inhibition of the apoptosis in neurons may be involved in the mechanism.

Avaliação do emprego do GM1 após lesão medular experimental em ratos / Evaluando el uso de GM1 después de lesión experimental de médula espinal en ratones / Evaluation of the use of GM1 after experimental spinal cord injury in rats

OBJETIVO: Avaliar a eficácia do GM1, administrado por via intraperitoneal, após lesão medular experimental em ratos. MÉTODOS: Foram utilizados 20 ratos da raça Wistar machos, adultos jovens, com média de idade de 20 semanas, pesando em torno de 350 g, divididos em dois grupos de 10 animais. No grupo 1 foi administrado apenas soro fisiológico por via intraperitoneal. Ao grupo 2, administraram-se 30 mg/kg de GM1 diariamente por essa mesma via. As lesões foram produzidas seguindo-se o protocolo internacional MASCIS (Multicenter Animal Spinal Cord Injury Study), com o sistema NYImpactor. Os animais foram avaliados funcionalmente pela escala BBB nos dias 14, 28 e 42 após a lesão. O potencial evocado foi realizado em todos os animais, no 42º dia após o trauma. RESULTADOS: Utilizou-se um modelo de variância de dois fatores (ANOVA) e o teste t de Student. As avaliações funcionais e por meio de potencial evocado não demonstraram diferença estatisticamente significante entre os dois grupos. CONCLUSÃO: O emprego de GM1 intraperitoneal não demonstrou resultados satisfatórios após lesão medular experimental.

OBJECTIVE: To evaluate the efficacy of GM1, administered intraperitoneally after experimental spinal cord injury in rats. METHODS: A total of 20 Wistar rats, young adults, males, with a mean age of 20 weeks, weighting about 350g were divided into two groups of 10 animals. The group 1 was given only saline intraperitoneally. Group 2 received GM1 30mg/kg daily, also intraperitoneally. The lesions were produced by following the international protocol MASCIS (Multicenter Animal Spinal Cord Injury Study), using the system NY Impactor. The animals were evaluated functionally by the BBB scale at days 14, 28 and 42 after injury. The evoked potential was performed on all animals 42 days after trauma. RESULTS: We used a two-factor variance model (ANOVA) and the Student t test. The functional assessments as well as those by evoked potential showed no statistically significant difference between the two groups. CONCLUSION: The use of intraperitoneal GM1 was not efficient after experimental spinal cord injury.

OBJETIVO: Evaluar la eficacia del GM1, administrado por vía intraperitoneal, después de la lesión medular experimental en ratones. MÉTODOS: se utilizaron 20 ratones de la raza Wistar, machos, adultos jóvenes, con una edad promedio de 20 semanas, peso de 350 gramos, aproximadamente, que se dividieron en dos grupos de 10 animales. En el grupo 1 se usó solamente suero fisiológico por vía intraperitoneal. En el grupo 2, se administró por vía intraperitoneal 30 mg/kg de GM1 por día. Las lesiones fueron producidas siguiéndose el protocolo internacional MASCIS (estudio multicéntrico de lesión de médula espinal en animales) por sistema NYImpactor. Los animales se evaluaron funcionalmente por la escala BBB en los días 14, 28 y 42 después de la lesión. El potencial evocado se realizó en todos los animales a los 42 días después del traumatismo. RESULTADOS: se utilizó un modelo de variancia de dos factores (ANOVA) y la prueba t de Student. Las evaluaciones funcionales y de los potenciales evocados no mostraron diferencias estadísticamente significativas entre los dos grupos. CONCLUSIÓN: El uso de GM1 intraperitoneal no demostró resultados satisfactorios después de la lesión medular experimental.

Experimental study of the effects of olfactory lamina propria transplantation and ganglioside GMI treatment on spinal curd injury / 中华老年医学杂志

Objective To observe the effects of olfactory lamina propria (OLP) transplantation and ganglioside GM1 treatment on spinal cord injury (SCI) in rats.Methods Totally 50 healthy pure breed female Sprague-Dawley (SD) rats after spinal cord hemiseetion were randomly divided into 5 groups and were given different treatments: (OLP + GM1) treatment group (group A), GM1 treatment group (group B), OLP treatment group (group C), spinal cord injury but without treatment group (group D) and healthy control group (group E). The recovery of neurological function was evaluated by somatosensory evoked potential (SEP) and pathological examination after surgery. Results In group A, in some rats an escaping response in right hind leg occurred, but in other groups, the motor function was not significantly improved. Histological examination showed that transplanted olfactory lamina propria survived in the transplantation area and expanded on certain routes. NF positive nerve fibers passed through the transplantation area. Compared with group B, C, D, the N1-wave latency was(4.71±0. 72)ms 4 weeks after operation(P<0. 01), and the NF density was(7. 31±0. 26) ×104/mm28 weeks after operation in group A(P<0. 05). Conclusions Olfactory lamina propria (OLP) transplantation and ganglioside GM1 treatment have a synergistic effect on SCI.

Ganglioside GM1 and central nervous system diseases / 国际脑血管病杂志

Gangliosides are sialic acid-containing glycosphingolipids and abundant in the brain. Some studies showed that glycosphingolipids not only could improve the differentiation of neurons, neurite outgrowth and synaptogenesis, but also could modulate neuronal plasticity and improve neurological function after cerebral damage. GM1 was so far most widely studied glycosphingolipids. It is believed that the regulatory functions for calcium homeostasis and the interaction between GM1 and neurotrophins are essential in the mechanisms underlying its neuroprotection. In addition, GM1 has also anti-excitotoxicity, anti-oxidation and vasodilation properties. Various forms of chronic neurodegenerative diseases and hypoxia/ischemic encepha-lopathy are characterized by progressive loss and apoptosis of neurons, the neuroprotective and neruotrophic effects of GM1 could play pivotal role in the treatment of these diseases. Nowadays, GM1 was widely used for the treatment of Parkinson's disease, stroke, hypoxia-ischemic encephalopathy, craniocerebral trauma, spinal cord injury and peripheral neuropathy. Further researches for the mechanisms of GM1 will provide new strategies for the treatment of central nervous system diseases.

Effects of GM1 on inducing adult rat bone marrow stromal cells to neural progenitor cells and their differentiation / 中华神经科杂志

Objective To investigate the effects of GMl on inducing adult rat MSCs to the neural progenitor cells and their descendants. Methods Purified MSCs were induced by basic fibroblast growth factor (bFGF) alone, GMl alone or by combination of bFGF and GMl. After 3 days of incubation, fibronectin and collagen I were detected by immunocytochemistry, and nestin by immunofluorescence. Neuron-specific enolase ( NSE) , glial fibrillary acidic protein ( GFAP) and galactose cerebroside ( GalC) were detected by immunocytochemistry after 7 days of incubation. Results After induction by bFGF alone or combination of bFGF and GM1, some MSCs exhibited the phenotypes of neural progenitor cells in 3 days, and then exhibited neurons and astrocytes in 7 days. In these two groups, cells positive for fibronectin and collagen I were decreased markedly after 3 days of induction. At the same time, cells positive for nestin were increased markedly. After 7 days of induction, NSE and GFAP-positive cells were increased significantly (22. 28% ?2. 97% and 26. 65%?3. 17% ). Furthermore, the combination of bFGF and GMl showed a maximal increase (30. 35%?3. 51% and 32. 22%?2. 68% ). But the GMl alone had shown no inductive effects. Conclusion Combination of bFGF and GMl might synergistically improve the neural induction of MSCs, showing a promising route for the application of MSCs.