Blockade of Rho-associated kinase prevents inhibition of axon regeneration of peripheral nerves induced by anti-ganglioside antibodies

Anti-ganglioside antibodies are associated with delayed/poor clinical recovery in Guillain-Barrèsyndrome,mostly related to halted axon regeneration.Cross-linking of cell surface gangliosides by anti-ganglioside antibodies triggers inhibition of nerve repair in in vitro and in vivo paradigms of axon regeneration.These effects involve the activation of the small GTPase Rho A/ROCK signaling pathways,which negatively modulate growth cone cytoskeleton,similarly to well stablished inhibitors of axon regeneration described so far.The aim of this work was to perform a proof of concept study to demonstrate the effectiveness of Y-27632,a selective pharmacological inhibitor of ROCK,in a mouse model of axon regeneration of peripheral nerves,where the passive immunization with a monoclonal antibody targeting gangliosides GD1a and GT1b was previously reported to exert a potent inhibitory effect on regeneration of both myelinated and unmyelinated fibers.Our results demonstrate a differential sensitivity of myelinated and unmyelinated axons to the pro-regenerative effect of Y-27632.Treatment with a total dosage of 9 mg/kg of Y-27632 resulted in a complete prevention of anti-GD1a/GT1b monoclonal antibody-mediated inhibition of axon regeneration of unmyelinated fibers to skin and the functional recovery of mechanical cutaneous sensitivity.In contrast,the same dose showed toxic effects on the regeneration of myelinated fibers.Interestingly,scale down of the dosage of Y-27632 to 5 mg/kg resulted in a significant although not complete recovery of regenerated myelinated axons exposed to anti-GD1a/GT1b monoclonal antibody in the absence of toxicity in animals exposed to only Y-27632.Overall,these findings confirm the in vivo participation of Rho A/ROCK signaling pathways in the molecular mechanisms associated with the inhibition of axon regeneration induced by anti-GD1a/GT1b monoclonal antibody.Our findings open the possibility of therapeutic pharmacological intervention targeting Rho A/Rock pathway in immune neuropathies associated with the presence of anti-ganglioside antibodies and delayed or incomplete clinical recovery after injury in the peripheral nervous system.

Gangliosides in nervous system development,regeneration,and pathologies

Gangliosides,sialic acid-containing sphingolipids,are major constituents of neuronal membranes.According to the number of sialic acids and the structure of the oligosaccharide chain,gangliosides can be classified as simple or complex and grouped in different ganglio-series.Hundreds of gangliosides have been identified in vertebrate cells,with different expression patterns during development and related to several physiological processes,especially in the nervous system.While GD3 and its O-acetylated form,9acGD3,are highly expressed in early developmental stages,GM1,GD1a,GD1b,and GT1b are the most abundant ganglioside species in the mature nervous system.Mutations in enzymes involved in ganglioside metabolism can lead to the accumulation of specific species,a condition termed gangliosidosis and usually marked by severe neurological impairment.Changes in ganglioside levels have also been described in several neurodegenerative diseases,such as Alzheimer’s and Parkinson’s.In this review,we summarized recent information about the roles of GD3,9acGD3,GM1,GD1a,GD1b,GT1b,and other ganglioside species in nervous system development and regeneration,as well as clinical trials evaluating possible therapeutic applications of these molecules.

Influence of ganglioside combined with methylprednisolone sodium succinate on efficacy and neurological function in patients with acute myelitis

BACKGROUND Acute myelitis(AM)can lead to sudden sensory,motor and autonomic nervous dysfunction,which negatively affects their daily activities and quality of life,so it is necessary to explore optimization from a therapeutic perspective to curb the progression of the disease.AIM To investigate the effect of ganglioside(GM)combined with methylprednisolone sodium succinate(MPSS)on the curative effect and neurological function of patients with AM.METHODS First,we selected 108 AM patients visited between September 2019 and September 2022 and grouped them based on treatment modality,with 52 patients receiving gamma globulin(GG)+MPSS and 56 patients receiving GM+MPSS,assigned to the control group(Con)and observation group(Obs),respectively.The therapeutic effect,neurological function(sensory and motor function scores),adverse events(AEs),recovery(time to sphincter function recovery,time to limb muscle strength recovery above grade 2,and time to ambulation),inflammatory factors(IFs)[interleukin(IL)-6,C-reactive protein(CRP),and tumor necrosis factor(TNF)-α]and other data of the two groups were collected for evaluation and comparison.RESULTS The Obs had:(1)A significantly higher response rate of treatment than the Con;(2)Higher scores of sensory and motor functions after treatment that were higher than the baseline(before treatment)and higher than the Con levels;(3)Lower incidence rates of skin rash,gastrointestinal discomfort,dyslipidemia,osteoporosis and other AEs;(4)Faster posttreatment recovery of sphincter function,limb muscle strength and ambulation;and(5)Markedly lower posttreatment IL-6,CRP and TNF-αlevels than the baseline and the Con levels.CONCLUSION From the above,it can be seen that GM+MPSS is highly effective in treating AM,with a favorable safety profile comparable to that of GG+MPSS.It can significantly improve patients’neurological function,speed up their recovery and inhibit serum IFs.

Curative effect of ganglioside sodium for adjuvant therapy on acute severe craniocerebral injury

Objective: To study the effect of adjuvant therapy of ganglioside sodium on intracranial pressure (ICP), partial pressure of brain tissue oxygen (PbtO2), nerve injury molecules, nerve protection molecules and indexes of oxidative stress in patients with acute severe craniocerebral injury. <br> Methods: Forty-seven patients with severe craniocerebral injury treated in the emergency department of our hospital during the period time from December 2012 to October 2015 were selected for retrospective analyses. They were divided into the ganglioside group and the normal treatment group according to the usage of ganglioside sodium in the process of the emergency treatment. At days 1, 3, 5 and 7 before and after treatment, theICP and PbtO2 in patients of the two groups were measured. After 7 days of treatment, the nerve injury molecules, nerve protection molecules and the indexes of oxidative stress in serum of the patients of the two groups were determined. <br> Results: At days 1, 3, 5 and 7 before and after treatment, theICP in patients of the ganglioside group were all significantly lower than those of the normal treatment group, while the PbtO2 were all significantly higher than those of normal treatment group. After 7 days of treatment, the contents of serum methane dicarboxylic aldehyde, advanced oxidation protein products, 8-hydroxy-2'-deoxyguanosine urine, S100β, glial fibrillary acidic portein, neuron specific enolase, myelin basic protein, neuroglobin and ubiquitin carboxyl-terminal hydrolase L1 in patients of the ganglioside group were notably lower than those of the normal treatment group, while the contents of superoxidase dismutase, glutathione peroxidase, catalase, nerve growth factor and brain derived neurotrophic factor were significantly higher than those of the normal treatment group. <br> Conclusions: The adjuvant therapy of ganglioside sodium in patients with severe craniocerebral injury can effectively reduceICP, improve PbtO2 and alleviate the injuries of neurons and glial cells caused by oxidative stress.

Ganglioside promotes the bridging of sciatic nerve defects in cryopreserved peripheral nerve allografts

Previous studies have shown that exogenous gangliosides promote nervous system regeneration and synapse formation. In this study, 10 mm sciatic nerve segments from New Zealand rabbits were thawed from cryopreservation and were used for the repair of left sciatic nerve defects through allograft bridging. Three days later, 1 mL ganglioside solution （1 g/L） was sub- cutaneously iniected into the right hind leg of rabbits. Compared with non-injected rats, muscle wet weight ratio was increased at 2-12 weeks after modeling. The quantity of myelinated fibers in regenerated sciatic nerve, myelin thickness and fiber diameter were elevated at 4-12 weeks after modeling. Sciatic nerve potential amplitude and conduction velocity were raised at 8 and 12 weeks, while conduction latencies were decreased at 12 weeks. Experimental findings indicate that ganglioside can promote the regeneration of sciatic nerve defects after repair with cryopre- served peripheral nerve allografts.

Increased catabolism and decreased unsaturation of ganglioside in patients with inflammatory bowel disease

AIM: To investigate whether accelerated catabolism of ganglioside and decreased ganglioside content contribute to the etiology of pro-inflammatory intestinal disease. METHODS: Intestinal mucosa from terminal ileum or colon was obtained from patients with ulcerative colitis or inflammatory Crohn's disease(n = 11) undergoing bowel resection and compared to control samples of normal intestine from patients with benign colon polyps(n = 6) and colorectal cancer(n = 12) in this observational case-control study. Gangliosides and phospholipids of intestinal mucosa were characterized by class and ceramide or fatty acid composition using liquid chromatography triple-quad mass spectrometry. Content and composition of ganglioside classes GM1, GM3, GD3, GD1 a, GT1 and GT3 were compared among subject groups. Content and composition of phospholipid classes phosphatidylcholine(PC) and phosphatidylethanolamine were compared among subject groups. Unsaturation index of individual ganglioside and phospholipid classes was computed and compared among subject groups. Ganglioside catabolism enzymes beta-hexosaminidase A(HEXA) and sialidase-3(NEU3) were measured in intestinal mucosa using western blot and compared among subject groups. RESULTS: Relative GM3 ganglioside content was 2-fold higher(P < 0.05) in intestine from patients with inflammatory bowel disease(IBD) compared to control intestine. The quantity of GM3 and ratio of GM3/GD3 was also higher in IBD intestine than control tissue(P < 0.05). Control intestine exhibited 3-fold higher(P < 0.01) relative GD1 a ganglioside content than IBD intestine. GD3 and GD1 a species of ganglioside containing three unsaturated bonds were present in control intestine, but were not detected in IBD intestine. The relative content of PC containing more than two unsaturated bonds was 30% lower in IBD intestine than control intestine(P < 0.05). The relative content of HEXA in IBD intestine was increased 1.7-fold(P < 0.05) and NEU3 was increased 8.3-fold(P < 0.01) compared to normal intestine. Intestinal mucosa in IBD is characterized by increased GM3 content, decreased GD1 a, and a reduction in polyunsaturated fatty acid constituents in GD3, GD1 a and PC.CONCLUSION: This study suggests a new paradigm by proposing that IBD occurs as a consequence of increased metabolism of specific gangliosides.

Protective effects of exogenous gangliosides on ROS-induced changes in human spermatozoa

This article summarizes the available evidence on the efficacy of gangliosides to reduce the degree of reactive oxygen species （ROS）-mediated damage. The antioxidative efficacy of exogenous gangliosides in protecting different cells encouraged us to examine their ability to protect human spermatozoa. Gangliosides are sialic acid-containing glycosphingolipids with strong amphiphilic character due to the bulky headgroup made of several sugar rings with sialic acid residues and the double-tailed hydrophobic lipid moiety. The amphiphilicity of gangliosides allows them to exist as micelles in aqueous media when they are present at a concentration above their critical micellar concentration. The protective effect of ganglioside micelles on spermatozoa is believed to stem from their ability to scavenge free radicals and prevent their damaging effects, In our study, we particularly focused our attention on the protective effect of ganglioside micelles on DNA in human spermatozoa exposed to cryopreservation. The results indicate that ganglioside micelles can modulate the hydrophobic properties of the sperm membrane to increase tolerance to DNA fragmentation, thus protecting the DNA from cryopreservation-induced damage. Further actions of ganglioside micelles, which were documented by biochemical and biophysical studies, included （i） the modulation of superoxide anion generation by increasing the diffusion barrier for membrane events responsible for signal translocation to the interior of the cell; （ii） the inhibition of iron-catalysed hydroxyl radical formation due to the iron chelation potential of gangliosides; and （iii） inhibition of hydrogen peroxide diffusion across the sperm membrane.

Meta-analysis evaluation of the treatment of neonatal hypoxic-ischemic encephalopathy with ganglioside

The efficacy and safety of ganglioside in the treatment of neonates who suffer from hypoxic-ischemic encephalopathy(HIE)needs to be fully evaluated.We searched the following databases:PubMed,ScienceDirect,LISTA,CNKI,Chinese biomedical literature database and Wanfang digital journals of full-text database to determine the inclusion and exclusion criteria of papers and a total of 12 papers were included after quality evaluation.Then we conducted the meta-analysis with RevMan5.0 software.The results showed that compared with the control group,the abnormal rate declined in the ganglioside-treated group(relative risk(RR)=0.27,95%confidence interval(CI)=0.05-1.96).NBNA records of the 7,10-14d neonates were improved effectively:RR(95%CI)were 2.28(0.86-3.42)and 2.53(1.04-2.92)respectively.Neural system sequelae incidence was reduced significantly:RR(95%CI)=0.35:(0.15-0.79).Ganglioside treatment could effectively reduce the abnormality rate of head size,improve the neurological score,reduce the incidence of neurological sequelae,and significantly prompt clinical recovery for neonates with HIE.

Effect of ganglioside sodium on stress, neural injury degree, rebuilding related factors of neural function and coagulation index in patients with severe craniocerebral injury

Objective:To investigate the effect of ganglioside sodium on stress, neural injury degree, rebuilding related factors of neural function and coagulation index in patients with severe craniocerebral injury.Methods: From June 2016 to March 2018, 90 cases of severe craniocerebral injury in our hospital were randomly divided into 45 cases of ganglioside sodium group (group GM1) and 45 cases of control group. The levels of stress [including norepinephrine (NE) and cortisol (Cor)], nerve injury [including neuron-specific enolase (NSE), astrocyte-derived protein (S100beta), ubiquitin carboxyl terminal hydrolase L1 (UCH-L1), glial fibrillary acidic protein (GFAP)], nerve function reconstruction [including brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF)] and coagulation function [including prothrombin time (PT), thrombin time (TT), activated partial prothrombin time (APTT) and fibrinogen (FIB)] were observed and compared between the two groups. Results:Before treatment, there was no significant difference in stress hormone, nerve injury degree, nerve function reconstruction and coagulation function between the two groups.After treatment, the levels of cytokines and FIB in the two groups were significantly higher than those before treatment, and the levels of stress hormone, nerve injury molecule and TT were significantly lower than those before treatment.The levels of cytokines and FIB in GM1 group were significantly higher than those in the control group. The levels of stress hormone, nerve injury molecule and TT in GM1 group were significantly lower than those in the control group. There was no significant difference in the levels of PT and APTT between the two groups before and after treatment.Conclusions: The treatment of severe craniocerebral injury with ganglioside sodium on the basis of routine treatment can relieve body stress and nerve damage, also, facilitate nerve function reconstruction and improve coagulation function.

Effects of exogenous ganglioside-1 on learning and memory in a neonatal rat model of hypoxia-ischemia brain injury

BACKGROUND： Exogenous ganglioside-1 （GM1） can cross the blood-brain barrier and play a protective role against hypoxia-ischemia-induced brain damage. OBJECTIVE： To examine the possible mechanisms of exogenous GM1 protection in hypoxia-ischemia-induced brain damage in a neonatal rat model by measuring changes in brain mass, pathological morphology, growth-associated protein-43 expression, and neurobehavioral manifestations. DESIGN, TIME AND SETTING： A randomized block-design study was performed at the Immunohistochemistry Laboratory of the Pediatric Research Institute, Children＇s Hospital of Chongqing Medical University from August 2005 to August 2006. MATERIALS： A total of 36 neonatal, 7-day-old, Sprague Dawley rats were used in this experiment. The hypoxia-ischemia-induced brain damage model was established by permanently occluding the right carotid artery, followed by oxygen inhalation at a low concentration （8% O2, 92% N2） for 2 hours, METHODS： All rats were randomly divided into the following groups： GMI, model, and sham operation, with 12 rats each group. Rats in the GM 1 and model groups received hypoxic/ischemic-induced brain damage. Rats in the GM1 group received injections of GM1 （i.p., 20 mg/kg） at 0, 24, 48, 72, 96, 120, and 144 hours following models established, and rats in the model group were administered （i.p.） the same amount of saline. The right carotid artery was separated, but not ligated, in the sham operation group rats. MAIN OUTCOME MEASURES： At 1 week after surgery, expression of growth-associated protein-43, a marker of neural development and plasticity, was detected in the hippocampal CA3 region by immunohistochemistry. Brain mass was measured, and the pathological morphology was observed. At 4 weeks after surgery, behavioral changes in the remaining rats were tested by Morris water maze, and growth-associated protein-43 expression was measured. RESULTS： （1） In the GMI and sham operation groups, growth-associated protein-43 expression was greater in the hippocampal CA3 region compared to the model group 1 week after surgery （P 〈 0.05）. In all three groups, brain weight of the right hemisphere was significantly less than the left hemisphere, in particular in the model group （P 〈 0.05）. In the GMI group, the weight difference between two hemispheres, as well as the extent of damage in the right hemisphere, was less than the model group （P 〈 0.01 ）. In the sham operation Uoup, brain tissue consisted of integrated structures and ordered cells. In the model group, the cerebral cortex layers of the right hemisphere were not defined, neurons were damaged, and neurons were disarranged in the hippocampal area. In the GM1 group, neurons were dense in the right cerebral cortex and hippocampal area, with no significant change in glial proliferation. （2） The average time of escape latency in the GM1 group was shortened 4 weeks alter surgery, and significantly less than the model group （P 〈 0.05）. In addition, the frequency platform passing in the GMI group was significantly greater than the model group （P 〈 0.01）. CONCLUSION： Exogenous GM1 may reduce brain injury and improve learning and memory in hypoxia-ischemia-induced brain damage rats. This protection may be associated with increased growth-associated protein-43 expression, which is involved in neuronal remodeling processes.

CAPILLARY ELECTROPHORETIC SEPARATION OF GANGLIOSIDES USING CYCLODEXTRIN AS BUFFER ADDITIVE

A new method for the rapid separation of gangliosides(GLS)by capillary electrophoresis(CE)is described which is based on the use of β—cyclodextrin(β—CD)as buffer additive.The effects of β—CD concentration,pH,electrolyte composition were dis- cussed.Under optimum conditions,the complete separation of a mixture of GM1,GD1a, GD1b and GT1b was obtained within 5 min.

Mechanism of gangliosides GD3 increment in hepatocellular carcinoma tissue

Determination of sialidase activity in hepatocellular carcinoma (HCC) to complete the mechanism study of GD3 change in HCC. A sensitive assay for ganglioside sialidase activity was used based on the specific binding of ricinus communis agglutinin Ⅱ (RCAⅡ) to lactose reside. The substrate used for sialidase assay was ganglioside GM3 coated on a 96- well microtiterplate. After removing static acids from the terminal positions of the ganglioside glycans by sialidase, the glycans were subjected to biotin-labeled RCAⅡ. Then, the ABC assay was used to determine the activity of sialidase. The activities of sialidase with both soluble form and membrane-bound form in HCC decreased significantly as compared with those in peritumor tissue. Our results indicated that the increase in ganglioside GD3 in HCC is not only due to the enhancement of GD3 sythase activity but also due to the decrease in the sialidase

Application of Simple Head Cooling Combined with Gangliosides in Neonatal Hypoxic-ischemic Encephalopathy

Objective To investigate the effect of simple head cooling combined with ganglioside therapy on neonatal hypoxic-ischemic encephalopathy(HIE)and its clinical efficacy.Methods A total of 100 children with HIE admitted in the neonatal ward of our hospital from August 2018 to October 2020 were selected as the research objects,and were divided into control group and observation group according to the random number table method,with 50 cases in each group.The control group was treated with gangliosides,and the observation group was treated with simple head cooling combined with gangliosides.Observe and compare the clinical performance improvement time,the level of relevant hematological examination indexes before and after treatment,and the neonatal behavioral neurological assessment(NBNA),clinical efficacy,and adverse reactions.Results The improvement time of convulsions,disturbance of consciousness,pupil changes,hypotonia,and gastrointestinal dysfunction in the observation group was significantly lower than that in the control group(all P<0.001).After treatment,the NSE,IL-6,CK,CK-MB of the two groups of children were significantly lower than before treatment,and the serum calcium and NBNA scores were significantly higher than before treatment,and the decrease or increase in the observation group was significantly higher than that of the control Group(all P<0.001).The total effective rate of treatment of children in the observation group(82.00%)was higher than that of the control group(62.00%)(P<0.05).There were no obvious adverse reactions in both groups.Conclusion The simple head cooling combined with gangliosides in the treatment of HIE can improve the clinical symptoms,blood test index levels,and NBNA scores.The clinical effect is clear and superior to the single use of gangliosides.

Effects of gangliosides combined with family rehabilitation training on nerve injury, neurodevelopment and oxidative stress in children with HIE

Objective:To study the effects of gangliosides combined with family rehabilitation training on nerve injury, neurodevelopment and oxidative stress in children with HIE.Methods:Children with HIE who were treated in Zigong Third People's Hospital between March 2015 and October 2017 were selected and randomly divided into two groups, rehabilitation training group received gangliosides combined with family rehabilitation training and negative control group accepted gangliosides combined with conventional rehabilitation intervention. The contents of nerve injury molecules, neurotrophic molecules and oxidative stress molecules in serum were measured before intervention and 3 months after intervention.Results: Compared with those of same group before intervention, serum VILIP1, NSE, UCH-L1, TNF-α, IL-6, NO, DM and MDA levels of both groups of children were significantly lower whereas BDNF, TRKB, NTF, NGF, SOD and GSH-PX levels were significantly higher 3 months after intervention, and serum VILIP1, NSE, UCH-L1, TNF-α, IL-6, NO, DM and MDA levels of rehabilitation training group after intervention were lower than those of negative control group whereas BDNF, TRKB, NTF, NGF, SOD and GSH-PX levels were higher than those of negative control group.Conclusion: Gangliosides combined with family rehabilitation training can reduce the nerve injury, improve the neurodevelopment and inhibit the oxidative stress in children with HIE.

The influence of ganglioside on the blood gas analysis and serum inflammatory cytokines in newborns with anoxic ischemic encephalopathy

Objective:To observe the influence of ganglioside on the blood gas analysis and serum levels of inflammatory cytokines in newborns with anoxic ischemic encephalopathy.Method: A total of 100 newborns with anoxic ischemic encephalopathy in our hospital were selected and randomly divided into 2 groups: the control group and the observation group. Conventional oxygen inhalation, reducing intracranial pressure, controlling eclampsia and neurotrophic drug treatment were given to the observation group. Treatment of ganglioside was given to the control group on the basis of observation group. Blood gas analysis and serum levels of inflammatory cytokines were detected before treatment (T0), 3 d after treatment (T1), and 7 d after treatment (T2).Result: (1) The comparison of pH, PaO2, PaCO2, SaO2 in the two groups in T0 was not statistically significant. The comparison of pH, PaO2, PaCO2, SaO2 in T0, T1, T2 was considered to be statistically significant. Among these, the result of comparision of pH, PaO2, SaO2: T0<T1<T2. comparision of PaCO2: T0>T1>T2. The pH, PaO2, SaO2 in observation group were higher, PaCO2 in observation group was lower compared with that in control group in T1 and T2. The difference was considered to be statistically significant. (2) The comparision of IL-2, IL-6, hs-CRP, TNF-α in the two groups in T0 was not statistically significant. IL-2 in the observation in T1 and T2 was higher than that in the control group, IL-6, hs-CRP, TNF-α in the observation in T1 and T2 was lower than that in the control group. The difference was considered to be statistically significant.Conclusion: Ganglioside can improve blood gas analysis indexes, decrease the serum inflammatory cytokines in newborns with anoxic ischemic encephalopathy.

Effect of adjuvant ganglioside sodium therapy on nerve injury degree as well as cytokines and humoral immunity in patients with acute severe craniocerebral injury

Objective:To study the effect of adjuvant ganglioside sodium therapy on nerve injury degree as well as cytokines and humoral immunity in patients with acute severe craniocerebral injury. Methods:94 patients with severe craniocerebral injury treated in our hospital between March 2013 and March 2016 were selected and randomly divided into the ganglioside sodium group (GM1 group) and control group. Before treatment as well as after 4 weeks and 8 weeks of treatment, serum levels of nerve injury molecules, nerve injury cytokines, inflammatory cytokines and humoral immune molecules were determined respectively.Results: After 4 weeks and 8 weeks of treatment, serum neuron-specific enolase (NSE), S100β protein (S100β), ubiquitin carboxy-terminal hydrolase L1 (UCH L1), glial fibrillary acid protein (GFAP), hypersensitive C-reactive protein (hs-CRP), tumor necrosis factor α(TNF-α), and interleukin-6 (IL-6) content of both groups were significantly lower than those before treatment (P<0.05) while brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), IgG, IgM and IgA content were significantly higher than those before treatment (P<0.05), and serum NSE, S100β, UCH-L1, GFAP, hs-CRP, TNF-α and IL-6 content of GM1 group were significantly lower than those of control group (P<0.05) while BDNF, NGF, IgG, IgM and IgA content were significantly higher than those of control group (P<0.05).Conclusions: Adjuvant ganglioside sodium therapy can relieve the nerve injury, inhibit the inflammatory reaction and improve the humoral immune response in patients with acute severe craniocerebral injury.

Effect of gangliosides combined with hyperbaric oxygenation on neural functional recovery and oxidative stress injury after cerebral infarction intervention

Objective:To explore the effect of gangliosides combined with hyperbaric oxygenation on neural functional recovery and oxidative stress injury after cerebral infarction intervention. Methods:A total of 120 patients with cerebral infarction who received interventional therapy in our hospital between August 2013 and February 2016 were collected and divided into control group and observation group, 60 cases in each group. Control group received hyperbaric oxygenation after intervention, and the observation group received gangliosides combined with hyperbaric oxygenation after intervention. The differences in serum levels of neurotrophy indexes, nerve injury indexes and oxidative stress indexes were compared between two groups of patients before and after treatment.Results: Before intervention, differences in serum levels of neurotrophy indexes, nerve injury indexes and oxidative stress indexes were not statistically significant between two groups of patients. After intervention, serum neurotrophy indexes BDNF and NT-3 levels in observation group were higher than those in control group;serum nerve injury indexes S100B, NGB, NSE and GFAP levels were lower than those in control group;serum oxidative indexes MDA, MPO and LPO levels were lower than those in control group while antioxidant indexes SOD, GSH-Px, CAT and TAC levels were higher than those in control group.Conclusion: Gangliosides combined with hyperbaric oxygenation for patients with cerebral infarction after interventional therapy helps speed up the neural functional recovery and also reduce systemic inflammatory response.

Effect of Murine Nerve Growth Factor and Sodium Ganglioside on the Levels of NF-kB p56,TLR-4 and MyD88 in Hippocampus of Epileptic Rats

Objective:Epilepsy is a prevalent neurological condition,and NF-kB,TLR-4,and MyD88 are significant contributors to its development.Murine nerve growth factor(NGF)and monosialotetrahexosylganlioside sodium for injection(MSI)are essential neurotrophic medications,yet their regulatory mechanism in the pathogenesis of epilepsy remains uncertain.The aim of this research was to examine the impacts of NGF and MSI on nuclear factor-kB(NF-kB)p65,toll-like receptor 4(TLR-4),and myeloid differentiation primary response gene 88(MyD88)in order to clarify their mechanisms of action in the management of epilepsy.Methods:A total of 40 SD rats were randomly assigned to one of five groups:blank,model,NGF model,MSI model,and NGF+MSI model.Epileptic rat models were induced through intraperitoneal injection of lithium chloride and pilocarpine solution.The rats'body mass and behavioral traits were subsequently observed.The Western blotting technique was utilized to detect the levels of NF-kB p65,TLR-4,and MyD88.Results:The findings indicated a more pronounced increase in body mass among the four groups prior to sacrifice,as compared to the model group.Notably,the NGF+MSI model group exhibited significant enhancements in food intake,activity,and body weight.The frequency of seizures in NGF group,MSI group,and NGF+MSI group were(5.33±1.15),(4.33±1.03),and(2.66±1.33)times/7 d,respectively,with neuronal apoptosis rates being(23.17±2.91),(21.38±3.07),(18.19±2.14)%times/7 d,respectively,which were lower than those in the model group.The levels of NF-kB p56,TLR-4,and MyD88 in the hippocampus were reduced in the model group compared to the three treatment groups.Furthermore,the expression levels in the NGF+MSI model group closely resembled those in the control group(P>0.05).Conclusion:Thorough examination revealed that NGF and MSI,either individually or in conjunction,were capable of suppressing the activation of the NF-kB pathway and enhancing the TLR-4/MyD88 signaling pathway to exert an antiepileptic influence.Furthermore,the combined administration of NGF and MSI demonstrated greater efficacy in safeguarding hippocampal neurons in epileptic rats.

Physiology of gangliosides and the role of antiganglioside antibodies in human diseases

Gangliosides are structurally and functionally polymorphic sialic acid containing glycosphingolipids that are widely distributed in the human body.They play important roles in protecting us against immune attacks,yet they can become targets for autoimmunity and act as receptors for microbes,like the influenza viruses,and toxins,such as the cholera toxin.The expression patterns of gangliosides vary in different tissues,during different life periods,as well as in different animals.Antibodies against gangliosides(AGA)can target immune attack e.g.,against neuronal cells and neutralize their complement inhibitory activity.AGAs are important especially in acquired demyelinating immune-mediated neuropathies,like Guillain–Barrésyndrome(GBS)and its variant,the Miller–Fisher syndrome(MFS).They can emerge in response to different microbial agents and immunological insults.Thereby,they can be involved in a variety of diseases.In addition,antibodies against GM3 were found in the sera of patients vaccinated with Pandemrix®,who developed secondary narcolepsy,strongly supporting the autoimmune etiology of the disease.

Ganglioside GD3 synthase(GD3S),a novel cancer drug target

Gangliosides are a class of important glycosphingolipids containing sialic acid that are widely distributed on the outer surface of cells and are abundantly distributed in brain tissue. Disialoganglioside with three glycosyl groups(GD3) and disialoganglioside with two glycosyl groups(GD2) are markedly increased in pathological conditions such as cancers and neurodegenerative diseases. GD3 and GD2 were found to play important roles in cancers by mediating cell proliferation, migration, invasion, adhesion,angiogenesis and in preventing immunosuppression of tumors. GD3 synthase(GD3S) is the regulatory enzyme of GD3 and GD2 synthesis, and is important in tumorigenesis and the development of cancers.The study of GD3S as a drug target may be of great significance for the discovery of new drugs for cancer treatment. This review will describe the gangliosides and their roles in physiological and pathological conditions; the roles of GD3 and GD2 in cancers; the expression, functions and mechanisms of GD3S,and its potential as a drug target in cancers.